Skip to main content
NCBI home page
Journal of Mid-Life Health logoLink to Journal of Mid-Life Health
. 2026 Feb 1;17(Suppl 1):S12–S116. doi: 10.4103/jmh.jmh_302_25

Clinical Practice Guidelines for Menopause: *An Executive Summary and Recommendations: Indian Menopause Society 2026

Meeta Meeta 1,✉, M Anuradha 2, Asna Beg Ashraf 3, Kiran Aggarwal 4, Leela Digumarti 5, Tanvir Singh 6
PMCID: PMC12948155  PMID: 41767293

RESOURCE FACULTY

Akrishti Gupta

Alka Kumar

Anjan Pyal

Anita Kant

Annil Mahajan

Anita Shah

Asha Kapadia

Asif Sultan

Atul Munshi

Bipasa Sen

Bina Tandon

B Chandrashekar Reddy

Chellamma VK

Cherunur Ambuja

Ch Ratna Kishore

CH Trivedi

Duru Shah

Hara P Pattanaik

Hepshiba Khurabani

Jagmeet Madan

Jaideep Malhotra

Jignesh Shah

Jyotika Desai

Jyoti Hak

Jyoti M Shah

Jyothi Unni

K Madhulika Agarwal

Lakshmi Ratna

Madhu Babu

Madhukar Reddy

Mala Raj

Maninder Ahuja

Monal Shah

Navneet Takkar

Neelam Agarwal

Nidhi Gupta

C Nikhileshwar Reddy

N. Vivek

Padma Kurada

Pooja Shah

Prem Blaise Rejula

Pushpa Sethi

Rama A Vaidya

Rashmi Shah

Rashmi Banerjee

Ravi R Hebballi

Rohit Raina

Saroj Srivastava

Sabahat Rasool

Sai Deepak Yaranagula

Sai Praveen Haranath

Saket Kumar

Sharad Kumar

Sheela Mane

Shobhana Mohandas

Smrity Shailly Bagde Sonia Malik

Sudha Sharma

Sunila Khandelwal

Suvarna Khadilkar

Tanmaya Talukdar

Thanuja Mannava

Tripti Nagaria

Tushar Patel

Usha Rani Poli

Urvashi Prasad Jha

Urvashi Yavalkar

Vishal R Tandon

Yashodhara Pradeep

SECTION 1: GENERAL CONSIDERATIONS

Definition and biosociocultural aspects of menopause

1. Menopause is a dynamic physiological transition from the reproductive to the nonreproductive stage of a woman’s life. It involves systemic physiological adaptations affecting the neuroendocrine, cardiovascular, metabolic, musculoskeletal, genitourinary, and immune systems.[1,2]

2. Each woman experiences menopause uniquely, with distinct symptom trajectories varying in timing, severity, and duration. This individualized nature of the menopausal experience underscores the need for personalized care and understanding.[3,4]

3. All mammals undergo reproductive senescence and oophause, the irreversible depletion of ovarian follicles, and typically progress until the end of life, but only humans and a few cetaceans experience true menopause, the loss of fertility decades before death (<0.1% of mammals). Menopause continues to raise important evolutionary and biological questions.[5,6]

4. In India’s classical Ayurvedic tradition, menopause is described as Rajonivṛtti, a normal physiological transition. The text suggests that it typically occurs around the age of fifty. This unique cultural perspective on menopause in India adds a distinct layer to the understanding of menopause.[7,8]

Medicalization of menopause

5. The basis of the debate on menopause medicalization gained significance in the 1930s and 40s, in response to the popularization of menopause as a hormone deficiency state, with the isolation of estrogen and the rise of hormone replacement therapy (HRT) as an “elixir of youth”.[9,10] Meyer’s 2001 analysis documented how menopause is in the process of becoming medicalized, with midlife women being told that “natural menopause is a deficiency condition requiring replacement hormones.”[11]

6. However, substantial scientific evidence supports the view of menopause as a biological change with significant pathological potential, paralleling other life transitions such as puberty and pregnancy.[12,13]

7. Bell’s three models of menopause care: biological (physiological changes helped by hormone therapy), psychological (women’s inherent personalities relieved by cognitive behavioral therapy), and environmental (self-help) form the basis for guiding medical practice.[14]

8. Hickey et al. well described the final word on this debate in The Lancet 2024 that for most women, menopause should be viewed as a part of healthy aging rather than “framing this natural period of transition as a disease of estrogen deficiency” and prevent “overmedicalization” by promoting hormone therapy as empowerment.[15]

9. Rama Vaidya, Founder, President of the Indian Menopause Society (IMS), envisaged that the menopause society should work toward a holistic approach to menopausal health and not restrict research and implementation of menopausal health to medication (personal communication).

Menopause and the aging continuum

10. Menopause is associated with menopause symptoms and diverse physiological changes affecting multiple organ systems and metabolic processes, setting the stage for aging and increasing susceptibility to noncommunicable diseases (NCDs).[16]

11. Menopausal and age-related biological changes overlap substantially, making it challenging to distinguish menopause-specific effects from those of chronological aging.[17]

Early screening and preventive health

12. The menopause transition (MT) constitutes a biological window for preventive intervention, as highlighted by longitudinal studies and systematic reviews demonstrating that cardiovascular and metabolic risk trajectories accelerate around the final menstrual period (FMP) (Grade A).[18,19]

13. Suggested screening threshold for NCDs: In India, the “Start at 35” (awareness from age 35 and universal screening from 40 years) approach is based on the relatively early age at natural menopause (ANM) and the sharp rise in the prevalence of hypertension, diabetes, and low bone mass (Grade C).[20]

14. This recommendation is supported by national surveys, such as the National Family Health Survey, Round 5 (2019–21) (NFHS-5)[21] and the Longitudinal Ageing Study in India, Wave 1 (2017–18) (LASI),[22] and the Women’s Health Initiative (WHI; USA randomized clinical trial [RCT] program),[23] as well as large international cohorts, including the Study of Women’s Health Across the Nation (SWAN; USA longitudinal cohort).[24] Multiple meta-analyses and global studies have also demonstrated the early onset and higher burden of cardiometabolic risk factors in South Asian populations; however, prospective RCT evidence in Indian women remains limited.[25-27]

15. IMS “Club 35” initiative, active since 2007, is a nationwide public awareness program that promotes preventive midlife health among women aged ≥35 years. It emphasizes early screening, lifestyle changes, and health empowerment before menopause.[28]

Policy gaps and advocacy priorities

16. Menopause remains a critically underrepresented area in both undergraduate and postgraduate medical curricula and receives insufficient attention from policymakers.

17. This gap highlights the urgent need for structured sensitization and formal training of healthcare professionals in menopause medicine.[29,30]

18. Currently, there are no dedicated national health programs addressing the needs of women aged 40–60 years, highlighting a critical opportunity for policy integration within ongoing women’s health and NCD initiatives.[31]

Multidisciplinary models of menopause care

19. Establishing a structured three-tier healthcare system spanning primary, secondary, and tertiary levels of care would significantly reduce disability and improve the quality of life (QOL) in India’s growing aging population (Grade C).[27]

20. Menopausal health extends beyond obstetrics and gynecology and requires an integrated, multidisciplinary approach.

21. Hence, care should involve not only gynecologists but also dieticians, physiotherapists, psychologists, psychiatrists, physicians, cardiologists, endocrinologists, gynecologic oncologists, and orthopedic specialists, supported by an effective referral system.[4,32-35]

Proposed three-tier model of care

22. Level I: Primary care unit – First-contact care, screening, lifestyle counseling, basic management, and referral when indicated.

23. Level II: Primary gynecological unit – Comprehensive gynecological evaluation, initiation of hormonal and nonhormonal therapies, and management of gynecological comorbidities.

24. Level III: Menopause specialist and multidisciplinary unit – Advanced, risk-stratified care by menopause specialists in collaboration with multidisciplinary teams, including cross-specialty referrals.

TERMINOLOGY AND DIAGNOSIS

25. Natural or spontaneous menopause is recognized to have occurred after 12 months of amenorrhea, for which there are no obvious pathological causes. It occurs due to the depletion of ovarian follicles, resulting in near-complete but natural diminution of ovarian hormone secretion.[36,37] The ovary is among the first organs in the human body to undergo aging, owing to its finite, nonrenewable follicular pool and high metabolic demand.

26. The estimated average ANM of 46.6 years in India is supported by large, representative, and consistent data; however, its precision is constrained by recall bias, lack of hormonal confirmation, and regional variation. Robust longitudinal population-based studies are required to validate these cutoffs. Therefore, it should be interpreted as a population-level approximation, not an exact biological constant.[38-41]

27. The diagnosis of natural menopause should be based primarily on clinical history, including menstrual patterns, age, and symptoms. Menopause is diagnosed retrospectively after 12 consecutive months of amenorrhea following the last menstrual period in women aged ≥45 years, which is not attributable to other causes. Menstrual cycle irregularity is an objective marker of MT (Grade A).[42-44]

28. Biochemical markers such as follicle-stimulating hormone (FSH), 17 β-estradiol (E2), and anti-Müllerian hormone are not recommended for the diagnosis of natural menopause (Grade A).[45]

29. Biochemical markers for the diagnosis of menopause are preferably restricted for use in special situations such as premature ovarian insufficiency (POI), decision on hysterectomy at MT, uncertain menstrual history, fertility counseling, or for research (Grade C).[46]

30. FSH levels > 10 IU/L indicate a decline in ovarian function. FSH > 35–40 IU/L and E2 < 20 pg/mL are diagnostic of menopause (Grade C).[42,43,45-47]

31. Premenopause refers to the entire reproductive period, up to the FMP.[36]

32. Perimenopause: A broader clinical term covering the MT and the first 12 months following the FMP.[36,37]

33. MT: A term defined by the Stages of Reproductive Ageing Workshop (STRAW + 10), representing the progression from the onset of variable cycle length (≥7-day difference from normal) to the FMP. Clinically, MT is characterized by erratic menstruation, anovulatory cycles, reduced fertility, and the onset of symptoms affecting QOL. It typically lasts a median of 4 years but may extend for 8–10 years.

34. MT comprises early transition, characterized by persistent cycle variability (≥7-day difference), and late transition, defined by skipped cycles (≥60 days of amenorrhea) and increased vasomotor symptoms. Late MT is increasingly recognized as a critical physiological window, a period when accelerated biological and metabolic changes emerge. This window could potentially serve as a biomarker for chronic disease risk and a target for preventive health interventions.[42,44,48-50]

35. Climacteric literally means “rung of a ladder” and is often used interchangeably with perimenopause or MT. When accompanied by symptoms, it is referred to as climacteric syndrome. However, this term is not preferred in contemporary scientific literature.[37]

36. Postmenopause: This refers to the period of life beginning from the FMP onward, irrespective of whether menopause occurs spontaneously or is iatrogenic.[37]

37. POI: amenorrhea due to loss of ovarian function before the age of 40 years. Given the lower average ANM of 46 years, the statistical cutoff would correspond to <38 years; however, a <40 years definition is recommended for clinical consistency and global alignment.[19,51] POI is a state of female hypergonadotropic hypogonadism that can manifest as primary amenorrhea with onset before menarche or secondary amenorrhea.[19,51]

38. An FSH level >25 IU/L, measured on any day of the cycle, together with amenorrhea or irregular menstrual cycles for ≥4 months (after excluding secondary causes), is a reliable biochemical marker for the diagnosis of POI in women aged <40 years.[19,51] In cases of diagnostic uncertainty, FSH measurement should be repeated after 4–6 weeks to confirm the diagnosis.[51]

39. Early menopause (EM): The term EM (40–45 years) was introduced by the International Menopause Society and later endorsed by the North American Menopause Society (2014 and 2022) and the European Menopause and Andropause Society (2019 and 2022) to distinguish it from POI and ANM. In India, the statistical cutoff corresponds to <42 years, although the clinical definition remains <45 years for clinical consistency and global alignment.

40. Women with EM or POI (≤45 years) have an increased risk of cardiovascular disease (CVD), type 2 diabetes (T2DM), osteoporosis, fractures, and all-cause mortality (Grade B).[18,52-57] The long-term risk of cognitive impairment or dementia in women who undergo oophorectomy before natural menopause is approximately doubled; however, this risk is effectively mitigated when estrogen therapy is initiated soon after surgery and continued until at least the average ANM (Grade B).[58] For other associated health risks in women with EM, evidence for their prevention or mitigation through HRT remains limited, underscoring the need for further longitudinal and interventional studies (Grade C).[57,59,60]

41. EM is associated with reduced muscle mass, while POI is associated with reduced muscle strength and performance compared to the normal menopausal age. While large prospective Indian data are lacking, small cross-sectional studies suggest a similar pattern (Grade C).[61-64]

42. Late-onset or delayed menopause: It is typically defined as menopause occurring at or beyond 55 years; it lacks a uniform goal standard but clinically aligns with this threshold.[18,36] Late-onset menopause is associated with a higher risk of estrogen-dependent malignancies, including breast, endometrial, and specific ovarian cancers, due to prolonged estrogen exposure.[65-71] Conversely, delayed menopause is associated with a lower risk of osteoporosis and fractures, possibly favorable vascular aging, and reduced cardiovascular risk.[18,72-74]

43. Induced menopause: The cessation of menstruation follows bilateral oophorectomy or iatrogenic ablation of ovarian function.[37,75]

44. Transient ovarian failure: In rare cases, ovarian function may recover after an apparent period of failure due to reversible suppression of the HPO axis or survival of residual follicles. This can occur after chemotherapy, radiotherapy, autoimmune oophoritis, or severe stress.[43]

45. Recovery depends on age, type, and dose of gonadotoxic exposure and the residual follicular reserve. Even when menses resume, the ovarian reserve remains diminished, and the risk of EM persists (Grade C).[75]

46. Postmenopausal bleeding (PMB): PMB is clinically defined as any vaginal bleeding occurring ≥12 months after the FMP in women not taking HRT (Grade A).[76,77]

47. Genitourinary Syndrome of Menopause (GSM)[78]: Refer to Section 2.

48. Musculoskeletal health at menopause: The proposed “musculoskeletal syndrome of menopause” highlights the frequent coexistence of arthralgia, sarcopenia, bone loss, and osteoarthritis during MT; however, it remains a conceptual construct, not an established diagnostic entity.[79] Randomized evidence from the WHI shows that estrogen therapy modestly reduced joint pain and stiffness during active treatment. However, these benefits disappear or reverse after discontinuation, indicating symptomatic rather than structural relief.[80,81]

49. Staging system: The staging system of a physiological event improves the comparability of strategies and facilitates clinical decision-making.

50. In 1996, Anklesaria published a simple clinical method for staging menopause to understand and deal with the problems of the transition phase and beyond.[82] The IMS adopted Anklesaria’s staging of menopause after modification.[83]

51. The STRAW aimed to classify women’s lives into three phases (2001): reproductive, MT, and postmenopause, based on the menstrual cycle, endocrine parameters, and ovarian reserve markers. However, this applied only to healthy women.[48]

52. The 2011 STRAW + 10 provides greater clarity for menstrual patterns and applies to most women, except those with POI.[42]

53. Midlife: Generally defined as the period between ages 40 and 64, although this term is not used in the scientific literature.

54. Classifying older adults: The World Health Organization uses age-based cutoff points to classify older adults and considers 60-plus years as elderly, 80-plus years as the oldest old, 100-plus years as centenarians, and 110-plus years as super-centenarians.[37]

55. Medical professionals commonly use a four-tier system to classify adults over 45 years. Middle-aged: 45–64, young-old: 65–74, middle-old: 75–84, and the oldest-old: 85 years and above.[84,85]

56. Superagers: Superagers are individuals aged 80 or older whose memory and cognitive performance match or exceed that of people 30 years younger, typically those in their 50s or early 60s.[86-88]

DEMOGRAPHICS AND EPIDEMIOLOGY

57. The current population of India is 1,465,796,710 as of Sunday, October 19, 2025, based on Worldometer’s elaboration of the latest United Nations data.[89] This number is expected to increase to 1,679,589,259 by 2050.[89]

58. The life expectancy of Indian women has increased from 40.4 years in 1950 to approximately 73.6 years in 2023. Although India’s life expectancy has been increasing, it has generally remained below the global average.[90-92]

59. According to the UN World Population Prospects 2024 Revision (medium variant), India had approximately 46 million women aged 45–49 years in 2024 and is projected to have approximately 57 million in 2050, compared with 30 million in 2011.[89] Rising trends between 2005 and 2021 suggest an increasing burden of early ovarian aging in Indian women.[93-95]

60. Population-based Indian data (NFHS 3–5) show that the prevalence of POI is 1.5%–3% of women, while EM affects 8%-16%, with the national mean age at menopause as 46 years.[94] When surgical menopause is included, state-level data suggest an overall POI (natural + induced) prevalence of 8.7% in Telangana and 8.2% in Andhra Pradesh.[95] Regional prevalence is higher in southern and eastern states and among women with lower education, rural residence, poor nutrition, or prior tubal sterilization.[96,97]

Age at menopause: Determinants and health system implications

61. The estimated mean ANM in India is 46.6 years, approximately 4–5 years earlier than that in Caucasian women, whose mean ANM averages around 51 years.[40,41,98,99]

62. ANM is largely genetically determined (50%); smoking advances its onset by approximately 1–2 years in a dose-dependent manner (Grade A).[100,101] Undernutrition, reproductive factors (nulliparity, irregular cycles, or short cycles), and lower socioeconomic or educational status are consistently associated with earlier menopause in large cohort and pooled analyses (Grade B).[102-104]

Medical challenges

63. From the available Indian data, it is hypothesized that ANM predisposes women to chronic health disorders a decade earlier than Caucasian women. This earlier onset is attributed to a combination of genetic predisposition, higher central adiposity at a lower BMI, lifestyle factors, and possibly lower disease awareness, delayed diagnosis, and early ANM in women.[95,105,106]

64. Multimorbidity: It refers to having multiple chronic conditions, which also emerges earlier, with many women developing two or more chronic diseases by their mid-30s to mid-40s.[107-109]

65. NCDs: South Asian women, including those in India, experience myocardial infarction approximately a decade earlier than European women, reflecting the earlier onset and higher lifetime burden of atherosclerotic CVD in this population.[110] In India, the prevalence of CVD among adults is estimated at 11% (95% CI: 9%–12%), with markedly higher rates in urban and middle-aged women than in rural populations.[111]

66. Hypertension: The overall prevalence of hypertension in India is currently estimated at 22.6% among adults aged ≥15 years, with a higher prevalence in urban (25%) than in rural areas (21.4%).[112] Longitudinal data also indicate a rising trend, with rural prevalence increasing from approximately 34% to over 40% over a decade. Despite this, awareness, treatment, and control rates remain suboptimal, with less than one-third of individuals on treatment in most reports.[113]

67. T2DM in India shows a prevalence of 6.1% in adults aged ≥15 years, rising to nearly 20% among those aged 45 plus, and evidence suggests that Indians develop T2DM on average over a decade earlier than Caucasian populations.[114,115] The migrant population from the Indian subcontinent in the UK is known to be at a significantly higher risk of developing diabetes and CVD.[116]

68. Indian data consistently demonstrate that fragility fractures, particularly hip fractures, occur approximately a decade earlier (mean age 65–71 years) than in Western populations (>75–80 years).[117-120]

69. Cancers: Breast cancer occurs at younger ages in India: Indian hospital- and registry-based studies indicate that a large proportion of breast cancer cases in India occur in women aged 45–50 years, earlier than in the West, where the peak incidence tends to be in the 60–65 age group.[121-124]

70. In India, the median age at cervical cancer diagnosis is 55 years (range: 45–60), which is comparable to or slightly older than that in the U.S., where the median age is 50 years. This conclusion is supported by India’s Population-based Cancer Registers (PBCRs) and the U.S. Surveillance, Epidemiology, and End Results Program (SEER).[125]

71. In the U.S., the median age at endometrial cancer diagnosis is 64 years,[126] whereas Indian data indicate diagnosis in the mid-50s to early-60s. Nationwide PBCR-pooled figures are lacking, with available estimates from tertiary or regional registries.[126,127]

72. Ovarian cancer in rural central India: In the PBCR of Central Rural India (2010–2016), the age-standardized incidence rate of ovarian cancer was 4.61 per 100,000, with the majority of Indian cases (most ovarian malignancies) occurring in women aged 41–50 years. The above suggests a somewhat earlier onset age than Western populations, where the median age at diagnosis is 63 years.[128]

73. Obesity: The prevalence of obesity in India is 24%–28% among adults and is lower than that in Western populations (≥40%) in the United States.[20,129-131] However, related metabolic risks appear 5–10 years earlier than in Western populations and at lower BMI thresholds (≥23 for overweight and ≥25 for obesity), with NCDs such as T2DM and CVD emerging from the mid-30s onward.[20,129-131]

74. Health-seeking behavior: Few Indian studies on health-seeking behavior have limitations of geographical bias, sample size, and lack of cost analysis; yet, the influence of sociocultural factors is well demonstrated. Rural women demonstrate substantially lower healthcare utilization rates (25%–30%) than urban women (42%–48%). This disparity is attributed to multiple factors, including distance to healthcare facilities, financial constraints, and cultural barriers.[132]

75. Policy: Unlike the UK and Australia, India does not have a dedicated national policy on menopause. There is also limited government funding and policies for menopause-related research and program evaluations, gaps in the implementation of the National Program for Health Care of the Elderly, and a shortage of trained personnel in menopausal and geriatric medicine.[133-135]

76. Nongovernmental organizations, such as the IMS, are leading the charge in championing midlife health. IMS publishes and conducts regular community workshops, wellness camps, and public awareness programs for consumers under the “Club 35 Plus.”[136] The Federation of Obstetric and Gynecological Societies of India addresses this issue by focusing on the midlife committee.[137]

77. Social challenges: In India, key social challenges include an increasing aging population, erosion of traditional family support structures, rise of nuclear families, rural-to-urban and international migration, and a growing burden of NCDs and degenerative diseases.[138,139]

78. There is a need to retain and revive Eastern cultural strengths while integrating elements of the Scandinavian model, which emphasizes gender equity, preventive health, and state-supported well-being.[140,141]

Menopause and the workplace

79. Estimates indicate that approximately 9–11.6 million women aged ≥40 years work in India, with roughly 3–3.6 million in the government sector and 6–8 million in the private sector. This highlights their significant yet under-recognized contribution to the national workforce.[142,143] Barriers in the workforce include age–gender bias, career re-entry challenges, limited networking, work–life imbalance, and overrepresentation in informal, low-paid sectors, especially rural agriculture.[144]

80. Survey data show that nearly 82% of Indian women believe menopause impacts workplace well-being and career, while 18%–26% work through symptoms or take time off without disclosure.[145] A recent systematic review found that cognitive behavioral therapy, Raja Yoga, healthy lifestyle support, and menopause awareness interventions improve the well-being of menopausal women, and individuals or organizations can combine and tailor them to their needs.[146,147]

Transgender individuals and menopause

81. As the first generation of transgender women who initiated gender-affirming hormone therapy (GAHT) in adulthood reaches midlife and beyond, unique clinical considerations emerge, particularly regarding menopause and optimal hormone management strategies for aging transgender individuals.[148,149] Unlike cisgender women who experience natural menopause with declining estrogen levels, transgender women undergoing GAHT maintain exogenous hormone supplementation, creating distinct clinical scenarios that require specialized medical guidance.[148-150]

82. Living will: A step toward dignified death: In India, the “right to die with dignity” concept has gained legal and ethical validation. In a landmark 2023 ruling, the Supreme Court of India revised the 2018 guidelines on end-of-life care and legalized the use of “living wills” or advance medical directives.[151]

REFERENCES

  1. Hill K. The demography of menopause. Maturitas 1996;23:113-27.

  2. Muhammad YA. Reproductive aging in biological females: Mechanisms and immediate consequences. Front Endocrinol (Lausanne) 2025;16:1658592.

  3. Grub J, Willi J, Süss H, Ehlert U. The role of estrogen receptor gene polymorphisms in menopausal symptoms and estradiol levels in perimenopausal women – Findings from the Swiss perimenopause study. Maturitas 2024;183:107942.

  4. Meeta M, Digumarti L, Agarwal N, Vaze N, Shah R, Malik S. Clinical practice guidelines on menopause: *An executive summary and recommendations: Indian Menopause Society 2019-2020. J Midlife Health 2020;11:55-95.

  5. Rashidi A, Shanley D. Evolution of the menopause: Life histories and mechanisms. Menopause Int 2009;15:26-30.

  6. Skjærvø GR, Røskaft E. Menopause: No support for an evolutionary explanation among historical Norwegians. Exp Gerontol 2013;48:408-13.

  7. Yadav R, Dei L. Review of clinical studies on Rājōnivṛtti Āvasthā with special reference to menopausal syndrome. Int J Adv Med 2020;8:137-43.

  8. Kaur V, Manohar J, Sakshi. A critical analysis of Rajonivriti Lakshanas and their pathogenesis. Ayushdhara 2021;8:3466-72. Available from: https://ayushdhara.in/index.php/ayushdhara/article/view/792. [Last accessed on 2025 Oct 29].

  9. Moscucci O. Medicine, age and gender: The menopause in history. Menopause Int 1999;5:149-53.

  10. Avis NE, Kaufert PA, Lock M, McKinlay SM, Vass K. The evolution of menopausal symptoms. Baillieres Clin Endocrinol Metab 1993;7:17-32.

  11. Meyer VF. The medicalization of menopause: Critique and consequences. Int J Health Serv 2001;31:769-92.

  12. Santoro N, Sutton-Tyrrell K. The SWAN song: Study of women’s health across the nation’s recurring themes. Obstet Gynecol Clin North Am 2011;38:417-23.

  13. Munshi A, Garg R. The medicalization of menopause: Understanding the evolution of treatment approaches. J Midlife Health 2024;15:133-4.

  14. Bell SE. Changing ideas: The medicalization of menopause. Soc Sci Med 1987;24:535-42.

  15. Hickey M, LaCroix AZ, Doust J, Mishra GD, Sivakami M, Garlick D, et al. An empowerment model for managing menopause. Lancet 2024;403:947-57.

  16. Mishra GD, Kuh D. Health symptoms during midlife in relation to menopausal transition: British prospective cohort study. BMJ 2012;344:e402.

  17. Xiang Y, Meng Q, Huang Z, Zhang N, Zhang Y, Ding X, et al. Menopausal status, transition, and age at menopause with accelerated biological aging across multiple organ systems: Findings from two cohort studies. BMC Med 2025;23:461.

  18. Muka T, Oliver-Williams C, Kunutsor S, Laven JS, Fauser BC, Chowdhury R, et al. Association of age at onset of menopause and time since onset of menopause with cardiovascular outcomes, intermediate vascular traits, and all-cause mortality: A systematic review and meta-analysis. JAMA Cardiol 2016;1:767-76.

  19. Stuenkel CA, Davis SR, Gompel A, Lumsden MA, Murad MH, Pinkerton JV, et al. Treatment of symptoms of the menopause: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2015;100:3975-4011.

  20. International Institute for Population Sciences (IIPS) and ICF. National Family Health Survey (NFHS-5), 2019–21. Mumbai, India: IIPS; 2021.

  21. Kaur G, Chauhan AS, Prinja S, Teerawattananon Y, Muniyandi M, Rastogi A, et al. Cost-effectiveness of population-based screening for diabetes and hypertension in India: An economic modelling study. Lancet Public Health 2022;7:e65-73.

  22. International Institute for Population Sciences (IIPS), Harvard T.H. Chan School of Public Health, and University of Southern California. Longitudinal Aging Study in India (LASI), Wave 1, 2017–18: India Report. Mumbai: IIPS; 2020.

  23. Manson JE, Chlebowski RT, Stefanick ML, Aragaki AK, Rossouw JE, Prentice RL, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s health initiative randomized trials. JAMA 2013;310:1353-68.

  24. Avis NE, Crawford SL, Greendale G, Bromberger JT, Everson-Rose SA, Gold EB, et al. Duration of menopausal vasomotor symptoms over the menopause transition. JAMA Intern Med 2015;175:531-9.

  25. Kanis JA, Harvey NC, McCloskey E, Bruyère O, Veronese N, Lorentzon M, et al. Algorithm for the management of patients at low, high and very high risk of osteoporotic fractures. Osteoporos Int 2020;31:1-12.

  26. Yusuf S, Rangarajan S, Teo K, Islam S, Li W, Liu L, et al. Cardiovascular risk and events in 17 low-, middle-, and high-income countries. N Engl J Med 2014;371:818-27.

  27. World Health Organization. Global Action Plan for the Prevention and Control of NCDs 2013–2030. Geneva: WHO; 2013.

  28. Indian Menopause Society. Club 35 – Promoting Preventive Health from Age 35. New Delhi: IMS; 2007. Available from: https://www.indianmenopausesociety.org. [Last accessed on 2025 Oct 29].

  29. Meeta M, Guduru S, Tanvir T, Madan A. Awareness of menopause and menopause hormone therapy in India: Perspectives of healthcare providers and consumers. Climacteric 2025;28:286-95.

  30. Gudidevuni JD, Thakre A, Bondia A, Bhanushali M. Understanding the knowledge, attitudes, and practices of young obstetricians and gynecologists (OBGYNs) in menopause management: Unveiling insights from India. Cureus 2025;17:e84444.

  31. Press Information Bureau, Government of India. National Health Programmes List. PIB; 2019. Available from: https://www.pib.gov.in/PressNoteDetails.aspx?NoteId=154668&ModuleId=3&reg=3&lang=1. [Last accessed on 2015 Nov 25].

  32. Baber RJ, Panay N, Fenton A, IMS Writing Group. 2016 IMS recommendations on women’s midlife health and menopause hormone therapy. Climacteric 2016;19:109-50.

  33. North American Menopause Society (NAMS). The 2022 hormone therapy position statement of The North American Menopause Society. Menopause 2022;29:767-94.

  34. National Institute for Health and Care Excellence (NICE). Menopause: Diagnosis and Management. NICE Guideline [NG23]. London: NICE; 2023 update.

  35. Faubion SS, Larkin LC, Stuenkel CA, Bachmann GA, Chism LA, Kagan R, et al. Management of genitourinary syndrome of menopause in women with or at high risk for breast cancer: Consensus recommendations. Nat Rev Dis Primers 2015;1:15004.

  36. Research on the menopause in the 1990s. Report of a WHO Scientific Group. World Health Organ Tech Rep Ser 1996;866:1-107.

  37. Utian WH. The International Menopause Society menopause-related terminology definitions. Climacteric 1999;2:284-6.

  38. International Institute for Population Sciences (IIPS) and ICF. National Family Health Survey (NFHS-5), 2019–21: India. Mumbai: IIPS; 2021. Available from: https://dhsprogram.com/pubs/pdf/FR375/FR375.pdf. [Last accessed on 2025 Oct 29].

  39. International Institute for Population Sciences (IIPS), Harvard T.H. Chan School of Public Health, University of Southern California, and the United Nations Population Fund (UNFPA). Longitudinal Ageing Study in India (LASI) Wave 1, 2017–18. Mumbai: IIPS; 2020. Available from: https://www.iipsindia.ac.in/lasi. [Last accessed on 2025 Nov 10].

  40. Singh M. Early age of natural menopause in India, a biological marker for early preventive health programs. Climacteric 2012;15:581-6.

  41. Ahuja M. Age of menopause and determinants of menopause age: A PAN India survey by IMS. J Midlife Health 2016;7:126-31.

  42. Harlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW, et al. Executive summary of the stages of reproductive aging workshop + 10: Addressing the unfinished agenda of staging reproductive aging. J Clin Endocrinol Metab 2012;97:1159-68.

  43. Fritz MA, Speroff L, editors. Menopause and the perimenopausal transition. In: Clinical Gynecologic Endocrinology and Infertility. 8th ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2011. p. 621-88.

  44. Treloar AE, Boynton RE, Behn BG, Brown BW. Variation of the human menstrual cycle through reproductive life. Int J Fertil 1967;12:77-126.

  45. Burger HG, Hale GE, Robertson DM, Dennerstein L. A review of hormonal changes during the menopausal transition: Focus on findings from the Melbourne women’s midlife health project. Hum Reprod Update 2007;13:559-65.

  46. Welt CK. Primary ovarian insufficiency: Clinical manifestations and diagnosis. In: Post TW, editor. UpToDate. Wolters Kluwer Health; 2025.

  47. Santoro N, Randolph JF Jr. Reproductive aging and the menopause transition. Obstet Gynecol Clin North Am 2022;49:475-92.

  48. Soules MR, Sherman S, Parrott E, Rebar R, Santoro N, Utian W, et al. Executive summary: Stages of Reproductive Aging Workshop (STRAW). Climacteric 2001;4:267-72.

  49. McKinlay SM, Brambilla DJ, Posner JG. The normal menopause transition. Maturitas 1992;14:103-15.

  50. El Khoudary SR, Greendale G, Crawford SL, Avis NE, Brooks MM, Thurston RC, et al. The menopause transition and women’s health at midlife: A progress report from the study of women’s health across the nation (SWAN). Menopause 2019;26:1213-27.

  51. ESHRE, ASRM, CREWHIRL and IMS Guideline Group on POI, Panay N, Anderson RA, Bennie A, Cedars M, Davies M, et al. Evidence-based guideline: Premature ovarian insufficiency†‡. Climacteric 2024;27:510-20.

  52. Anagnostis P, Christou K, Artzouchaltzi AM, Gkekas NK, Kosmidou N, Siolos P, et al. Early menopause and premature ovarian insufficiency are associated with increased risk of type 2 diabetes: A systematic review and meta-analysis. Eur J Endocrinol 2019;180:41-50.

  53. Anagnostis P, Siolos P, Gkekas NK, Kosmidou N, Artzouchaltzi AM, Christou K, et al. Association between age at menopause and fracture risk: A systematic review and meta-analysis. Endocrine 2019;63:213-24.

  54. Hong JS, Yi SW, Kang HC, Jee SH, Kang HG, Bayasgalan G, et al. Age at menopause and cause-specific mortality in South Korean women: Kangwha Cohort Study. Maturitas 2007;56:411-9.

  55. Ossewaarde ME, Bots ML, Verbeek AL, Peeters PH, van der Graaf Y, Grobbee DE, et al. Age at menopause, cause-specific mortality and total life expectancy. Epidemiology 2005;16:556-62.

  56. Jones AR, Enticott J, Ebeling PR, Mishra GD, Teede HT, Vincent AJ. Bone health in women with premature ovarian insufficiency/early menopause: A 23-year longitudinal analysis. Hum Reprod 2024;39:1013-22.

  57. Xu Z, Chung HF, Dobson AJ, Wilson LF, Hickey M, Mishra GD. Menopause, hysterectomy, menopausal hormone therapy and cause-specific mortality: Cohort study of UK Biobank participants. Hum Reprod 2022;37:2175-85.

  58. Rocca WA, Grossardt BR, Shuster LT. Oophorectomy, estrogen, and dementia: A 2014 update. Mol Cell Endocrinol 2014;389:7-12.

  59. Savukoski SM, Niinimäki M. The long-term health effects of early menopause. Semin Reprod Med 2025;43:125-33.

  60. Coughlan GT, Betthauser TJ, Boyle R, Koscik RL, Klinger HM, Chibnik LB, et al. Association of age at menopause and hormone therapy use with tau and β-amyloid positron emission tomography. JAMA Neurol 2023;80:462-73.

  61. Divaris E, Anagnostis P, Gkekas NK, Kouidi E, Goulis DG. Early menopause and premature ovarian insufficiency may increase the risk of sarcopenia: A systematic review and meta-analysis. Maturitas 2023;175:107782.

  62. Li S, Ma L, Huang H, Lou Z, Qi T, Huang Y, et al. Loss of muscle mass in women with premature ovarian insufficiency as compared with healthy controls. Menopause 2023;30:122-7.

  63. Bhat G, Ireland A, Shah N, Gondhalekar K, Mandlik R, Kajale N, et al. Prevalence and factors associated with sarcopenia among urban and rural Indian adults in middle age: A cross-sectional study from Western India. PLOS Glob Public Health 2024;4:e0003553.

  64. Kalra S, Shaikh IA, Shende S, Kapoor N, Unnikrishnan AG, Sharma OP, et al. An Indian consensus on sarcopenia: Epidemiology, etiology, clinical impact, screening, and therapeutic approaches. Int J Gen Med 2025;18:1731-45.

  65. Abulajiang Y, Liu T, Wang M, Abulai A, Wu Y. The influence of menopause age on gynecologic cancer risk: A comprehensive analysis using NHANES data. Front Oncol 2025;15:1541585.

  66. Yiallourou A, Pantavou K, Markozannes G, Pilavas A, Georgiou A, Hadjikou A, et al. Non-genetic factors and breast cancer: An umbrella review of meta-analyses. BMC Cancer 2024;24:903.

  67. Verdiesen RM, Shokouhi M, Burgess S, Canisius S, Chang-Claude J, Bojesen SE, et al. Causal effects of breast cancer risk factors across hormone receptor breast cancer subtypes: A two-sample Mendelian randomization study. Cancer Epidemiol Biomarkers Prev 2025;34:933-43.

  68. Collaborative Group on Hormonal Factors in Breast Cancer. Menarche, menopause, and breast cancer risk: Individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies. Lancet Oncol 2012;13:1141-51.

  69. Dossus L, Allen N, Kaaks R, Bakken K, Lund E, Tjonneland A, et al. Reproductive risk factors and endometrial cancer: The European prospective investigation into cancer and nutrition. Int J Cancer 2010;127:442-51.

  70. Trabert B, Tworoger SS, O’Brien KM, Townsend MK, Fortner RT, Iversen ES, et al. The risk of Ovarian cancer increases with an increase in the lifetime number of ovulatory cycles: An analysis from the ovarian cancer cohort consortium (OC3). Cancer Res 2020;80:1210-8.

  71. Merritt MA, Abe SK, Islam MR, Rahman MS, Saito E, Katagiri R, et al. Reproductive factors and risk of epithelial ovarian cancer: Results from the Asia cohort consortium. Br J Cancer 2025;132:361-70.

  72. Farahmand M, Rahmati M, Saei Ghare Naz M, Amiri M, Noroozzadeh M, Farhadi-Azar M, et al. Fracture incidence in women: The impact of reproductive characteristics. BMC Public Health 2024;24:3409.

  73. Shin J, Kim KY, Park JH, Lee S, Noh OK, Choi YJ, et al. Fracture risk in Korean postmenopausal women: The influence of BMI, age, and bone density. Osteoporos Sarcopenia 2025;11:65-8.

  74. Darvish S, Murray KO, Ludwig KR, Avalani KH, Craighead DH, Freeberg KA, et al. Preservation of vascular endothelial function in late-onset postmenopausal women. Circ Res 2025;136:455-69.

  75. Nelson LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med 2009;360:606-14.

  76. Munro MG, Southern California Permanente Medical Group’s Abnormal Uterine Bleeding Working Group. Investigation of women with postmenopausal uterine bleeding: Clinical practice recommendations. Perm J 2014;18:55-70.

  77. FIGO Menstrual Disorders Working Group, Munro MG, Critchley HOD, Fraser IS. The FIGO classification of causes of abnormal uterine bleeding in the reproductive years. Fertil Steril 2011;95:2204-8, 2208.e1-3.

  78. Portman DJ, Gass ML, Vulvovaginal Atrophy Terminology Consensus Conference Panel. Genitourinary syndrome of menopause: New terminology for vulvovaginal atrophy from the International Society for the Study of Women’s Sexual Health and The North American Menopause Society. Climacteric 2014;17:557-63.

  79. Wright VJ, Schwartzman JD, Itinoche R, Wittstein J. The musculoskeletal syndrome of menopause. Climacteric 2024;27:466-72.

  80. Chlebowski RT, Cirillo DJ, Eaton CB, Stefanick ML, Pettinger M, Carbone LD, et al. Estrogen alone and joint symptoms in the Women’s health initiative randomized trial. Menopause 2013;20:600-8.

  81. Brunner RL, Aragaki A, Barnabei V, Cochrane BB, Gass M, Hendrix S, et al. Menopausal symptom experience before and after stopping estrogen therapy in the women’s health initiative randomized, placebo-controlled trial. Menopause 2010;17:946-54.

  82. Anklesaria BS, Soneji RM. Staging, symptoms and urological problems in the climacteric. In: Krishna UR, Shah D, editors. Menopause: Obstetrics and Gynecology in Perspective. 1st ed. Chennai: Orient Longman Pvt Ltd; 1996. p. 13.

  83. Anklesaria BS. The staging of menopause. In: Kumar P, Malhotra N, editors. Jeffcoate’s Principles of Gynecology. 7th ed. New Delhi: Jaypee Brothers Medical Publishers; 2008. p. 862-4.

  84. Lulle A. Midlife Geographies: Relational Transitions and Spatial Practices. U.K.: Bristol University Press, Routledge; 2025.

  85. Dodig S, Čepelak I, Pavić I. Hallmarks of senescence and aging. Biochem Med (Zagreb) 2019;29:030501.

  86. Harrison TM, Weintraub S, Mesulam MM, Rogalski E. Superior memory and higher cortical volumes in unusually successful cognitive aging. J Int Neuropsychol Soc 2012;18:1081-5.

  87. Cook Maher A, Makowski-Woidan B, Kuang A, Zhang H, Weintraub S, Mesulam MM, et al. Neuropsychological profiles of older adults with superior versus average episodic memory: The Northwestern “SuperAger” cohort. J Int Neuropsychol Soc 2022;28:563-73.

  88. Jin C, Wang X, Yang J, Kim S, Hudgins AD, Gamliel A, et al. Molecular and genetic insights into human ovarian aging from single-nuclei multi-omics analyses. Nat Aging 2025;5:275-90.

  89. United Nations, Department of Economic and Social Affairs, Population Division. World Population Prospects 2024: Summary of Results (Medium-fertility variant) New York: United Nations; 2024. Available from: https://population.un.org/wpp/. [Last accessed on 2025 Oct 18].

  90. Kumari M, Mohanty SK. Caste, religion and regional differentials in life expectancy at birth in India: Cross-sectional estimates from recent National Family Health Survey. BMJ Open 2020;10:e035392.

  91. Mishra V. India’s projected aged population (65+), projected life expectancy at birth and insecurities faced by aged population. Ageing Int 2020;45:72-84.

  92. Cao X, Hou Y, Zhang X, Xu C, Jia P, Sun X, et al. A comparative, correlate analysis and projection of global and regional life expectancy, healthy life expectancy, and their GAP: 1995-2025. J Glob Health 2020;10:020407.

  93. Perianayagam A, Bloom D, Lee J, Parasuraman S, Sekher TV, Mohanty SK, et al. Cohort profile: The longitudinal ageing study in India (LASI). Int J Epidemiol 2022;51:e167-76.

  94. Kundu S, Acharya SS. Exploring the triggers of premature and early menopause in India: A comprehensive analysis based on National Family Health Survey, 2019-2021. Sci Rep 2024;14:3040.

  95. Singh A, Govil D, Ladusingh L. Premature menopause among women in India: Evidence from NFHS-4. In: Proceedings of the International Population Conference 2021; Hyderabad, India. IUSSP; 2021. Available from: https://ipc2021.popconf.org/uploads/210152

  96. Halder P, Soni A, Seth A, Vijayakumar D, Das A, Sankhyan S, et al. Association of early menopause with indoor air pollution: A multilevel modelling analysis of the nationally representative cross-sectional study in India. J Family Med Prim Care 2025;14:173-83.

  97. Babbar K, Singh V, Sivakami M. Rising premature menopause and variations by education level in India. Sci Rep 2024;14:18238.

  98. Prasad JB, Tyagi NK, Verma P. Age at menopause in India: A systematic review. Diabetes Metab Syndr 2021;15:373-7.

  99. Gold EB. The timing of the age at which natural menopause occurs. Obstet Gynecol Clin North Am 2011;38:425-40.

  100. Day FR, Ruth KS, Thompson DJ, Lunetta KL, Pervjakova N, Chasman DI, et al. Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair. Nat Genet 2015;47:1294-303.

  101. Sun L, Tan L, Yang F, Luo Y, Li X, Deng HW, et al. Meta-analysis suggests that smoking is associated with an increased risk of early natural menopause. Menopause 2012;19:126-32.

  102. Zhu D, Chung HF, Pandeya N, Dobson AJ, Kuh D, Crawford SL, et al. Body mass index and age at natural menopause: An international pooled analysis of 11 prospective studies. Eur J Epidemiol 2018;33:699-710.

  103. Morris DH, Jones ME, Schoemaker MJ, McFadden E, Ashworth A, Swerdlow AJ. Body mass index, exercise, and other lifestyle factors in relation to age at natural menopause: Analyses from the breakthrough generations study. Am J Epidemiol 2012;175:998-1005.

  104. Schoenaker DA, Jackson CA, Rowlands JV, Mishra GD. Socioeconomic position, lifestyle factors and age at natural menopause: A systematic review and meta-analyses of studies across six continents. Int J Epidemiol 2014;43:1542-62.

  105. Peycheva D, Sullivan A, Hardy R, Bryson A, Conti G, Ploubidis G. Risk factors for natural menopause before the age of 45: Evidence from two British population-based birth cohort studies. BMC Womens Health 2022;22:438.

  106. Huang S, Gongye R, Zou S, Hee JY, Tang K. Menopausal status, age at menopause and risk of all-cause mortality among Chinese women: Findings from a 10-year prospective study. BMJ Public Health 2023;1:e000332.

  107. Puri P, Sinha A, Mahapatra P, Pati S. Multimorbidity among midlife women in India: Well-being beyond reproductive age. BMC Womens Health 2022;22:117.

  108. Puri P, Kothavale A, Singh SK, Pati S. Burden and determinants of multimorbidity among women in reproductive age group: A cross-sectional study based in India. Wellcome Open Res 2020;5:275.

  109. Mohanty SK, Rodgers J, Singh RR, Mishra RS, Kim R, Khan J, et al. Morbidity compression or expansion? A temporal analysis of the age at onset of non-communicable diseases in India. Geroscience 2021;43:409-22.

  110. Rejeleene R, Chidambaram V, Chatrathi M, Kumar A, Lu E, Pohlkamp P, et al. Addressing myocardial infarction in South-Asian populations: Risk factors and machine learning approaches. NPJ Cardiovasc Health 2025;2:4.

  111. Shannawaz M, Rathi I, Shah N, Saeed S, Chandra A, Singh H. Prevalence of CVD among Indian adult population: Systematic review and meta-analysis. Int J Environ Res Public Health 2025;22:539.

  112. Singh H, Rana RK, Sharma S, Goel S. Prevalence of hypertension among Indian adults based on global standards: Evidence from a nationally representative survey (NFHS-5). medRxiv; 2025. Available from: http://medrxiv.org/content/early/2025/09/17/2025.09.17.25335963.abstract. [Last accessed on 2025 Nov 25].

  113. Longkumer I, Yadav S, Rajkumari S, Saraswathy KN. Trends in hypertension prevalence, awareness, treatment, and control: An 8-year follow-up study from rural North India. Sci Rep 2023;13:9910.

  114. Maiti S, Akhtar S, Upadhyay AK, Mohanty SK. Socioeconomic inequality in awareness, treatment and control of diabetes among adults in India: Evidence from National Family Health Survey of India (NFHS), 2019-2021. Sci Rep 2023;13:2971.

  115. Sekher TV, Flood D, Green H, Hu P, Ali MK, Shete A, et al. Prevalence, awareness, treatment, and control of diabetes in India: A nationally representative survey of adults aged 45 years and older. Lancet Glob Health 2025;13:e1543-52.

  116. Smith GD, Morris JN, Shaw M. The independent inquiry into inequalities in health is welcome, but its recommendations are too cautious and vague. BMJ 1998;317:1465-6.

  117. Dhanwal DK, Siwach R, Dixit V, Mithal A, Jameson K, Cooper C. Incidence of hip fracture in Rohtak district, North India. Arch Osteoporos 2013;8:135.

  118. Dhanwal DK, Dennison EM, Harvey NC, Cooper C. Epidemiology of hip fracture: Worldwide geographic variation. Indian J Orthop 2011;45:15-22.

  119. Sahu RL, Bharti A. Epidemiological study of hip fractures in Eastern India. Indian J Orthop Surg 2015;1:13-7.

  120. Cooper C, Campion G, Melton LJ 3rd. Hip fractures in the elderly: A world-wide projection. Osteoporos Int 1992;2:285-9.

  121. Kulothungan V, Ramamoorthy T, Sathishkumar K, Mohan R, Tomy N, Miller GJ, et al. Burden of female breast cancer in India: Estimates of YLDs, YLLs, and DALYs at national and subnational levels based on the National Cancer Registry Programme. Breast Cancer Res Treat 2024;205:323-32.

  122. Mehrotra R, Yadav K. Breast cancer in India: Present scenario and the challenges ahead. World J Clin Oncol 2022;13:209-18.

  123. Leong SP, Shen ZZ, Liu TJ, Agarwal G, Tajima T, Paik NS, et al. Is breast cancer the same disease in Asian and Western countries? World J Surg 2010;34:2308-24.

  124. Ugai T, Sasamoto N, Lee HY, Ando M, Song M, Tamimi RM, et al. Is early-onset cancer an emerging global epidemic? Current evidence and future implications. Nat Rev Clin Oncol 2022;19:656-73.

  125. Sathishkumar K, Sankarapillai J, Mathew A, Nair RA, Gangane N, Khuraijam S, et al. Survival of patients with cervical cancer in India – Findings from 11 population based cancer registries under National Cancer Registry Programme. Lancet Reg Health Southeast Asia 2024;24:100296.

  126. National Cancer Institute (SEER). Cancer Stat Facts: Uterine (Endometrial) Cancer. SEER 21, 2018–2022.

  127. Agarwal S, Melgandi W, Sonkar DR, Ansari FA, Arora S, Rathi AK, et al. Epidemiological characteristics of endometrial cancer patients treated at a tertiary health center in National Capital Territory of India. J Cancer Res Ther 2023;19:452-6.

  128. Gangane NM, Patil BU, Ghongade PV. Ovarian cancer: A report from population-based cancer registry at central rural India. J Cancer Res Ther 2023;19: S857-62.

  129. Misra A, Chowbey P, Makkar BM, Vikram NK, Wasir JS, Chadha D, et al. Consensus statement for diagnosis of obesity, abdominal obesity and the metabolic syndrome for Asian Indians and recommendations for physical activity, medical and surgical management. J Assoc Physicians India 2009;57:163-70.

  130. Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, Lee A, et al. Health effects of overweight and obesity in 195 countries (1990–2015): Global Burden of Disease Study. N Engl J Med 2017;377:13-27.

  131. Ogden CL, Fryar CD, Martin CB, Freedman DS, Carroll MD, Gu Q, et al. Trends in obesity prevalence by race and Hispanic origin – United States, 1999-2000 to 2017-2020. JAMA 2022;327:234-43.

  132. Madhukumar S, Gaikwad V, Sudeepa D. A community based study on perceptions about menopausal symptoms and quality of life of post menopausal women in Bangalore rural. Indian J Community Med 2012;37:167-72.

  133. Perianayagam A. Gender disparities in health and wellbeing of older population in India. NPJ Women’s Health 2024;2:44.

  134. Joshi NK, Joshi V, Bajaj K. Strengths, weaknesses, opportunities, and threats (SWOT) analysis of NPHCE programme in India. J Indian Acad Geriatr 2023;11:19010. DOI: 10.4103/jiag.jiag_9_23.

  135. Dumka N, Mangat S, Ahmed T, Hannah E, Kotwal A. Adding health to years: A review of the National Programme for Health Care of the Elderly (NPHCE) in India. J Family Med Prim Care 2022;11:6654-9.

  136. Available from: https://www.indianmenopausesociety.org. [Last accessed on 2025 Nov 01].

  137. FOGSI. Activities of Midlife Management Committee (2022-2023). FOGSI. Available from: https://www.fogsi.org/wp-content/uploads/fogsi-activities-2022-2023/Midlife-Management-Committee-22-23.pdf. [Last aceessed on 2025 Oct 10].

  138. Mitra A, Murayama M. Rural to Urban Migration: A District Level Analysis for India. Institute of Developing Economies, Japan External Trade Organization (JETRO), IDE Discussion Papers; 2008. p. 5.

  139. Kumar R, Singh A, Tripathi VK, Mishra GC. Trend and pattern of rural-urban migration in India. Int J Curr Microbiol Appl Sci 2022;11:344-52.

  140. Menopause initiative saves millions in sick leave costs for Swedish… Nordic Labour Journal; 2024. Available from: www.nordiclabourjournal.org. [Last accessed on 2025 Nov 25].

  141. Azhar G. Future of healthcare in India: Lessons from Scandinavia. Glob J Med Public Health 2012;1:71-80.

  142. Ministry of Statistics and Programme Implementation. Periodic Labour Force Survey Annual Report 2022–23. New Delhi: Government of India; 2023. Available from: https://www.mospi.gov.in. [Last accessed on 2025 Sep 29].

  143. Employees’ Provident Fund Organisation. Payroll Reporting: Gender-wise and Age-Wise DISTRIBUTION of New Subscribers. New Delhi: EPFO; 2024. Available from: https://www.epfindia.gov.in. [Last accessed on 2025 Sep 29].

  144. Conti G, Ginja R, Persson P, Willage B. The Menopause “Penalty”. NBER Working Paper 33621. National Bureau of Economic Research; 2025. JEL No. I10, J01, J13.

  145. Abbott & Ipsos. Women@Work 2022 India: Survey on Women & Menopause Impact on Workplace. India: Abbott; 2022. Available from: https://www.abbott.in›Newsroom›Living Fully.

  146. Ndindeng AN. The impact of effective menopausal symptom management on workplace performance and well-being: A comprehensive analysis. Res Sq 2024. DOI: 10.21203/rs.3.rs-5036740/v1.

  147. Rees M, Bitzer J, Cano A, Ceausu I, Chedraui P, Durmusoglu F, et al. Global consensus recommendations on menopause in the workplace: A European Menopause and Andropause Society (EMAS) position statement. Maturitas 2021;151:55-62.

  148. Mehta JM, Kanell S, Borowicz CE, Fisher MA. Transgender patients and gender-affirming hormone therapy through midlife. Maturitas 2024;189:108093.

  149. Unger CA. Hormone therapy for transgender patients. Transl Androl Urol 2016;5:877-84.

  150. Majumder A, Chatterjee S, Maji D, Roychaudhuri S, Ghosh S, Selvan C, et al. IDEA Group consensus statement on medical management of adult gender incongruent individuals seeking gender reaffirmation as female. Indian J Endocrinol Metab 2020;24:128-35.

  151. Mani RK, Simha S, Gursahani R. Simplified legal procedure for end-of-life decisions in India: A new dawn in the care of the dying? Indian J Crit Care Med 2023;27:374-6.

SECTION 2: MENOPAUSE TRANSITION: “A WINDOW OF OPPORTUNITY”

1. Commonly recognized menopausal symptoms are thought to arise from neuroendocrine sensitivity to estrogen withdrawal, moderated and shaped by psychosocial stressors, coping capacity, and social determinants (Grade B).[1,2]

2. The decline in estrogen at menopause shifts the autonomic nervous system toward sympathetic dominance and reduced parasympathetic activity, contributing beyond vasomotor symptoms (VMSs) to increased cardiometabolic risk, hypertension, sleep disorders, urinary dysfunction, and chronic pain (Grade B).[3-5]

3. The menopause transition (MT), characterized by declining estrogen and relative androgen excess, is a well-established physiological process, and in genetically or metabolically predisposed women, it may accelerate the onset of noncommunicable diseases (NCDs), particularly cardiometabolic and musculoskeletal disorders (Grade B).[6,7] It must be recognized that NCDs are multifactorial in origin; alterations in different types of endogenous or exogenous estrogen exposure are neither primary causes nor definitive remedies, but act as system-specific, additive modulators of disease risk and management.

TIMING MATTERS: THE CRITICAL PHASE FOR MENOPAUSE CARE

4. Theories: The timing hypothesis proposes that menopause hormone therapy (MHT) is most effective when initiated during the late MT or early postmenopausal years, whereas delayed initiation beyond this window may offer diminished benefit or even adverse cardiovascular outcomes.[8]

5. This concept is supported by the Early versus Late Intervention Trial with Estradiol (ELITE) and builds upon Clarkson’s “timing hypothesis” derived from animal models and Hodis’ subsequent clinical translations.[9-11]

6. Analyses of robust pre-Women’s Health Initiative (WHI) and reanalysis of WHI data supported by the Danish Osteoporosis Study (DOPS) reinforced the understanding of the “critical window of opportunity.”[12-15]

7. Brinton’s “healthy cell bias” theory proposes that estrogen exerts protective and reparative effects only in metabolically healthy and functionally competent cells. In contrast, estrogen signaling may become ineffective or even detrimental in aged or metabolically compromised tissues.[16,17]

8. The timing hypothesis and Brinton’s healthy cell bias theory explain the variability in MHT outcomes across cardiovascular, neurological, musculoskeletal, and metabolic domains.

9. These models emphasize that both the timing of initiation and the metabolic health of target tissues determine estrogen’s benefit–risk profile, refining the understanding of its context-dependent actions and guiding individualized therapeutic decisions.[18-20]

10. MHT: Initiating MHT within 10 years of menopause or before the age of 60 years is associated with reduced all-cause mortality and cardiovascular events, supporting a “window of opportunity” effect; this benefit is not observed with later initiation (Grade A).[21-24]

11. Therapeutic lifestyle management (TLM): Adopting healthy lifestyle measures can enhance the benefits of HT, mitigate metabolic, cardiovascular, and cognitive risks, and may extend the “window of opportunity” by maintaining cell health and reducing end-organ vulnerability (Grade B).[25-28]

12. Education: Interventions, including structured therapeutic lifestyle programs, menopausal education, and coping skills training, significantly reduce symptom burden, improve quality of life (QOL), and enhance adaptation, serving as effective adjuncts to MHT (Grade B).[29,30]

SYMPTOMS OF MENOPAUSE

13. Menopausal symptoms are multidimensional, spanning vasomotor, somatic, neuropsychiatric, and genitourinary domains as captured by validated tools such as the Menopause Rating Scale.[31]

14. Strong hormone-linked evidence exists for VMS and genitourinary syndrome of menopause (GSM; Grade A),[32] moderate for sleep and mood disturbances (Grade B).[2,32-35]

15. Somatic complaints such as musculoskeletal pain, fatigue, and headache are common during the MT and may coincide with measurable declines in physical performance. Evidence from longitudinal cohorts such as SWAN suggests that these reflect the combined effects of estrogen deficiency, changes in body composition (BC), and psychosocial and metabolic stressors rather than hormonal change alone (Grade B).[36-39]

16. VMS: Global data demonstrate that VMSs are most prevalent in Western and African populations, whereas somatic complaints such as joint and muscle pain predominate in Asian regions, including India, Nepal, and China. This cultural and biological heterogeneity underscores the need for context-specific assessment and management strategies in Indian women (Grade B).[40]

17. There is a high overall prevalence of menopausal symptoms (70%–96.6%), with somatic complaints (mean: 73.7%) predominating, followed by psychological symptoms (63.0%), whereas urogenital symptoms were the less common (51.4%). The prevalence of VMSs showed wide regional variation (16.5%–88%), highlighting the need for standardized definitions and reporting criteria in future Indian studies.[41-43]

18. A 2023 global meta-analysis reported a pooled prevalence of sleep problems of 51.6% (95% confidence interval: 44.6%–58.5%) among postmenopausal women. Indian data confirm that the incidence of sleep problems increases from 16% to 42% in premenopause to 39%–47% at perimenopause and 35%–60% in postmenopause.[44]

19. VMSs include hot flushes, cold sweats, and night sweats, which may be accompanied by palpitations, anxiety, dizziness, headache, insomnia, or poor-quality sleep due to recurrent night sweats, leading to daytime fatigue.

20. VMS may impact the QOL by causing impaired concentration with mood swings, irritability, reduced work performance, anxiety, and embarrassment in social/professional settings and impaired sexual well-being if sweating/hot flushes interrupt intimacy.[45,46]

21. Typically, VMSs begin in the late MT, coincide with rapid estradiol decline and follicle-stimulating hormone (FSH) surge, may persist for 7–10 years on average, and generally peak and reach their maximum intensity during the first 2 years postmenopause.[47,48]

22. Recent pooled and cohort studies report that VMSs in midlife women are strongly associated with tobacco use, anxiety, menopause stage, and obesity.[47,49]

23. Moderate evidence supports the association with poor cardiorespiratory fitness, overweight, high fasting glucose, depressive symptoms, lower education, and African American ethnicity (Grade B).[47,50-52]

24. Genetic variants, particularly in the TACR3 gene, are modestly associated with VMSs in midlife women, with reported odds ratios of around 0.78–1.3, suggesting a small but significant contribution to symptom risk.[53]

25. Grading of VMS is important to plan management, follow-up, and research. The grades of hot flushes are classified as mild, feeling of heat without sweating; moderate, feeling of heat with sweating; and severe, feeling of heat with sweating and palpitation that disrupts usual activity.[54]

26. We need to exclude other causes of flushing before planning treatment.[55-58]

27. MHT: The most effective treatment for VMS is MHT (Grade A),[59,60] and low-dose combined oral contraceptives (COCs) may be used when contraception is needed (Grade C).[61-63] Other options are TLM, complementary and alternative therapies, cognitive behavioral therapy (CBT), hypnosis, and nonhormonal prescription therapies. Refer to Section 6.

28. Somatic symptoms: Begin in the early-to-late transition, paralleling fluctuating estrogen and psychosocial stress, and may persist into the early postmenopausal years; musculoskeletal pain can continue chronically due to sarcopenia, obesity, and inflammation of aging.[36,37,64]

29. Somatic symptoms are to be evaluated and managed when they are frequent, persistent, or sufficiently distressing to interfere with activities of daily living. Before attributing such symptoms to menopause, clinicians should exclude alternative medical causes such as Vitamin D deficiency, anemia, thyroid dysfunction, autoimmune disorders, or osteoarthritis.

30. Management: First-line management includes TLM and supportive measures such as exercise, sleep hygiene, balanced diet, weight management, analgesics, and physiotherapy for musculoskeletal symptoms.[65-68]

31. MHT may benefit women experiencing both vasomotor and somatic complaints; however, its effectiveness for isolated musculoskeletal or somatic symptoms is limited and inconsistent. The benefit appears modest, likely mediated by improved sleep, mood, and systemic inflammation rather than direct musculoskeletal effects.

32. Psychological symptoms include changes in mood, anxiety, irritability, emotional lability, sleep disturbance, and depressive features.

33. Mood and anxiety symptoms typically follow a bell-shaped trajectory: they begin to rise in the early perimenopausal stage, peak during the late transition, and tend to improve within 1 or 2 years after the final menstrual period (FMP).

34. These changes are influenced by fluctuating estrogen levels, psychosocial stressors, and individual coping capacity. Sleep disturbance and VMSs often exacerbate mood instability, while a prior history of depression or anxiety increases vulnerability.[69]

35. Cognitive complaints commonly described as “brain fog,” encompass difficulties with attention, memory retrieval for names, words, or numbers, and concentration rather than objective cognitive decline.[70]

36. Importantly, brain fog is transient, nonprogressive, and reversible, distinguishing it from pathological cognitive disorders such as mild cognitive impairment or dementia, which are characterized by progressive neurodegeneration and sustained cognitive loss.[71]

37. The etiology is multifactorial, involving the hormonal changes of the MT (especially estrogen decline), fragmented or poor-quality sleep, mood disturbances (anxiety/depression), vasomotor instability (hot flashes/night sweats), and psychosocial stressors (Grade B).[72-74]

38. Longitudinal studies, including the SWAN, demonstrate that cognitive performance may decline during perimenopause, particularly in verbal memory and processing speed, with gradual recovery within 1–2 years after menopause in early postmenopause (Grade A).[19,74,75]

39. Management: Screen for cognitive impairment using validated tools like short-form Montreal Cognitive Assessment, as needed.

40. Correct modifiable factors, including sleep, mood, vascular health, and social determinants, by lifestyle measures, including physical activity, cognitive training, adequate sleep, and vasomotor and mood symptoms management, to support mental health (Grade B).[76-78]

41. Current evidence does not support the routine use of MHT solely for the prevention of cognitive decline or dementia (Grade A).[19,79,80] MHT is safe for symptom management in healthy, recently postmenopausal women, but does not enhance or preserve cognition.[81] MHT initiated after 65 years may increase the risk of probable dementia.[82,83]

42. Depression: increased during the MT, when estradiol variability is most significant and remained elevated in the early postmenopause.[34,84-86]

43. Robust longitudinal and randomized trial evidence shows an increased risk of new-onset or recurrent depressive symptoms during the transition, independent of age or prior psychiatric history. The risk is most significant in the late reproductive and early MT phases, coinciding with unstable estradiol levels and irregular cycles.[69]

44. Precipitating factors include VMS, disturbed sleep, and psychosocial stressors such as caregiving, occupational pressures, and midlife role transitions. These factors interact with fluctuating estrogen and serotonin dopamine modulation, further predisposing to mood dysregulation.[87]

45. Mood symptoms are typically transient or moderate. However, they need treatment if symptoms persist beyond 2–4 weeks, impair daily functioning or interpersonal relationships, or exacerbate underlying anxiety or depressive disorders, and a primary major depressive disorder is ruled out.[85]

46. Management: Emphasize TLM, counseling, stress reduction techniques (Grade B), and CBT (Grade A).[76,88]

47. Antidepressants: Selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs) are effective and well-tolerated for moderate-to-severe or persistent depressive disorders in midlife women. They are also helpful for coexisting VMS and sleep disturbance and enhance the outcomes when given along with MHT. Refer to Section 6.[89,90]

48. MHT: Judicious, individualized MHT may be considered when mood symptoms are temporally linked to estrogen fluctuation and other contraindications are excluded. The best response is seen in women at early MT, where estrogen stabilization alleviates both vasomotor and affective symptoms. Treatment response becomes less predictable when initiated more than 5 years after menopause, likely reflecting long-standing neural adaptation to hypoestrogenism.[91,92]

49. Sleep disorders: follow a plateau–peak pattern, often beginning before the onset of VMSs, reaching maximum intensity around the FMP, and showing partial resolution in the later postmenopausal years. However, chronic insomnia may persist in predisposed women.[93,94]

50. These sleep problems are multifactorial in origin, arising from the combined effects of VMSs, mood and anxiety disorders, sleep-disordered breathing, circadian rhythm changes related to aging, and coexisting sleep conditions such as obstructive sleep apnea (OSA) and restless legs syndrome (RLS).[95]

51. Strong longitudinal evidence, including the SWAN, demonstrates that the MT is independently associated with increased risk of sleep complaints (Grade B).[94]

52. Sleep deprivation contributes to impaired mood, reduced work performance, increased musculoskeletal pain, and a higher risk of cardiovascular disease (CVD).[96]

53. Sleep health should be routinely evaluated in menopausal women. Where indicated, validated sleep questionnaires or sleep diaries should be used.[97]

54. Lifestyle factors such as caffeine, alcohol intake, irregular schedules, excessive gadget use, social stressors, and medical comorbidities should be identified and corrected (Grade C).[97,98]

55. When insomnia is present, secondary causes, including psychiatric illness, thyroid dysfunction, chronic pain, and medication effects, must be excluded and appropriately managed. Diagnosis and treatment of primary sleep disorders (OSA and RLS) are strongly recommended, as untreated comorbid sleep disorders exacerbate overall health risks and QOL impairment (Grade B).[98,99]

56. Neurological or respiratory disorders suspected on history or examination should prompt further investigations and specialist referral (Grade B).[96,97,100]

57. Sleep hygiene measures – Refer to Section 6.

58. CBT: According to the American-European clinical practice guidelines, CBT for insomnia is the first-line treatment for chronic insomnia and should also be considered in menopausal women (Grade A).[88,100,101]

59. Estrogens: All standard formulations are effective; however, transdermal preparations may be preferred for their ability to maintain stable serum estrogen levels and improve sleep quality among women with significant VMS (Grade B).[92,102] Micronized progesterone may have an additional benefit. MHT is not indicated as a primary therapy for insomnia (Grade B).[103]

60. Nonhormonal agents: SSRIs, SNRIs, and gabapentin (preferred) have demonstrated moderate efficacy in improving sleep and reducing nocturnal vasomotor events (Grade B).[89,90] Refer to Section 6.

61. Pharmacologic hypnotic therapy including benzodiazepines such as lorazepam (0.5–2 mg) or diazepam (2–5 mg) and nonbenzodiazepine GABA-A receptor agonists such as zolpidem (5–10 mg) should be reserved for short-term treatment of severe insomnia that is unresponsive to behavioral and nonhormonal measures. Treatment should generally be limited to 2–4 weeks and not exceed 3 months without specialist review. Therapy should employ the lowest effective dose, with regular reassessment, and consider intermittent or alternate-night dosing for maintenance, in order to minimize dependence, tolerance, and cognitive adverse effects (Grade A).[104,105]

62. Dual orexin receptor antagonists: Lemborexant, daridorexant, and suvorexant have favorable safety profiles and are potential future options for insomnia in midlife women; they can be continued long term with monitoring (Grade B).[106]

63. Melatonin and melatonin receptor agonists, such as ramelteon, may be considered for up to 3–6 months in selected women, with a structured follow-up every 3–6 months. Long-term, open-ended use >12 months lacks robust data and should only continue with periodic clinical review (Grade B).[107]

64. Current evidence for herbal or alternative remedies remains insufficient. Mind–body therapies such as yoga and tai chi have some evidence but need further rigorous studies to prove their effectiveness (Grade D).[101,108]

65. GSM: Previously known as vaginal atrophy, vulvovaginal atrophy (VVA), urogenital atrophy, or atrophic vaginitis, is defined as a collection of symptoms and signs caused by hypoestrogenic changes to the labia majora/minora, clitoris, vestibule/introitus, vagina, urethra, and bladder that occur in menopausal women. The syndrome may include, but is not limited to, genital symptoms of dryness, burning, and irritation; sexual symptoms of lack of lubrication, discomfort or pain, and impaired function; and urinary symptoms of urgency, frequency, dysuria, and recurrent urinary tract infections (UTIs).[109]

66. GSM is chronic, progressive, and persistent unless treated and increases with years since menopause.[109] Indian studies report GSM prevalence ranging from 31% to 79%, with vaginal dryness and lower urinary tract symptoms most frequent, increasing significantly across menopausal stages.[110-112]

67. Although GSM significantly affects QOL, many women do not volunteer these complaints; therefore, clinicians should actively ask targeted, suggestive questions during history-taking.[113] Symptomatic women may present with any of the above symptoms, which bother them (Grade A).[114]

68. Physical signs of GSM are variable and include reduced vulval fat, reduced vaginal rugae, and blood flow, leading to a pale appearance; a change from a normal moderately acidic range (pH: 3.5–5.0) to a neutral range (pH: 6.0–8.0) in the vaginal pH (measured by vaginal pH applicator strips); there is a shift in the Vaginal Maturation Index (VMI) to parabasal cells.[115,116]

69. Diagnosis: No universally accepted diagnostic criteria exist for GSM. For research purposes, the U.S. Food and Drug Administration mandates a standardized assessment using three core parameters: vaginal pH measurement, VMI, and identification of the patient’s most bothersome symptom. However, routine clinical practice often lacks access to pH measurement tools or VMI assessment capabilities, necessitating a practical minimum diagnostic approach.[117]

70. Physical examination has a strong clinical rationale and is essential for excluding alternative diagnoses, individualizing treatment, and monitoring therapeutic response (Grade B).[110]

71. Based on available evidence, we suggest the following criteria for diagnosing GSM:

  • Criterion 1: At least two genital or urinary bothersome symptoms (rate their severity on a four-point scale) after excluding nonestrogen deficiency causes[110]

  • Criterion 2: One symptom accompanied by vaginal pH of >5 and/or Vaginal Health Index (VHI) score ≤15.[118]

72. Exclude other causes, particularly infectious etiologies, vulvar dermatitis, vulvovaginal lichen planus and sclerosis, malignancy, and other etiologies of recurrent UTI.[119,120]

73. Management: The management of GSM is fundamentally patient-centered, aiming to relieve symptoms and, where possible, restore urogenital physiology. Clinical signs of urogenital atrophy often do not correlate directly with the symptoms reported by women, underscoring the need for individualized, need-based management, shared decision-making, and regular reassessment. The cornerstone of management is local estrogen therapy (LET).

74. It is essential to counsel patients that GSM is a chronic and progressive condition; unlike VMSs, it does not resolve spontaneously and typically requires ongoing, long-term treatment strategies (Grade B).[121,122]

75. Indications of LET in women with symptoms of GSM: LET is the most effective treatment for GSM.[123,124] It increases the blood flow and peripheral neuronal function, restores the VMI, and improves the VHI score. The details of LET are given below.

76. Systemic HT may cause urinary incontinence (UI) or worsen existing urinary symptoms.[125] Systemic estrogen therapy, prescribed primarily for VMS, also helps prevent or reduce the progression of GSM in many women.[126] However, some women on systemic HT may continue to experience urogenital symptoms and require additional LET for optimal control (Grade A).[127,128]

77. Sexual function: LET improves sexual function in postmenopausal women with GSM.[126]

78. Managing dyspareunia at penetration in women with GSM: apply a pea-sized amount of estradiol cream directly to the vulvar vestibule, combined with the use of a precoital silicone-based lubricant (Grade B).[129]

79. Recurrent UTI: LET is recommended to prevent recurrent UTI in postmenopausal women (Grade A).[123,124] Systemic estrogen therapy is not recommended (Grade B).[130-134]

80. Nonhormonal adjuncts, including cranberry extract, D-mannose (where available), and probiotics, may be considered before or alongside antibiotic therapy in uncomplicated recurrent UTI (Grade C).[135,136] We do not recommend routine antibiotic treatment for asymptomatic bacteriuria in postmenopausal women (Grade A).[136-138]

81. Urge incontinence: LET is recommended for postmenopausal women with urge UI or overactive bladder symptoms (OABs) associated with GSM (Grade A).[123,124] In postmenopausal women with idiopathic OAB or urge UI without GSM, evidence supports its use only as an adjunct to standard pharmacological or behavioral therapy, rather than as primary treatment (Grade B).[139-141]

82. Mixed UI: LET may be used as adjunctive therapy for mixed UI, particularly when GSM is present (Grade B). Systemic HT is not recommended for UI.[125,142]

83. Pelvic organ prolapse: In women with pelvic organ prolapse or UI, LET has uncertain benefit as a primary treatment, but it is recommended to prevent vaginal abrasions in those using pessaries (Grade B).[143,144]

84. Indications of LET in women without symptoms of GSM: Prior to vulvovaginal surgery, short preoperative courses improve vaginal vascularity and epithelial thickness, thereby facilitating surgical dissection and wound healing in vulvovaginal procedures (Grade B).[145,146]

85. Before performing a Pap smear in postmenopausal women with clinical atrophy or prior unsatisfactory/abnormal results, a short course of vaginal estrogen is reasonable to optimize epithelial maturity and specimen quality (Grade B).[147] This helps in false-positive or indeterminate cytologic interpretations that may arise from atrophic changes secondary to GSM, thereby preventing misdiagnosis of dysplasia.[147]

86. Long-term sequelae: Evidence indicates that untreated and worsening GSM leads to long-term sequelae like labial agglutination and introital narrowing which may need surgical correction along with LET.[148,149]

87. Follow-up: Clinical effectiveness is typically observed after 2 or more weeks, with maximal symptomatic improvement evident after 4–12 weeks of therapy. Follow-up visits are scheduled after 1 and 3 months. If, in 3 months, there is no improvement in signs and symptoms, stop the treatment and look for other causes.[126]

LOCAL ESTROGEN THERAPY IN GENITOURINARY SYNDROME OF MENOPAUSE: EVIDENCE, DOSING STRATEGIES, AND CLINICAL CONSIDERATIONS

88. LET includes a range of vaginally administered estrogen products approved with the indication to treat GSM.[150]

89. Comparative trials have also demonstrated that vaginal estrogen achieves a superior local effect with lower systemic absorption than oral preparations.[126]

90. A Cochrane systematic review confirmed that all licensed local estrogen preparations are equally effective in improving the symptoms and signs of VVA compared with placebo, with no significant difference in the overall efficacy among formulations (Grade A).[123] However, 17β-estradiol appears to provide greater improvement in patient-reported symptoms. In contrast, conjugated equine estrogen (CEE) produces more marked cytological changes and a slightly higher increase in serum estradiol levels,[151] with no clinically meaningful differences in overall efficacy. Estriol (E3) is a low-potency estrogen that is not converted to 17β estradiol (E2) and has modest efficacy (Grade B).[152]

91. Doses: The various doses of LET are shown in Table 1.

Table 1.

Doses of local estrogen therapy

Component Ultra-low-dose Low-dose Standard-dose
Estradiol 4–10 µg ≤50 µg >100 µg
Conjugated estrogens ≤0.3 mg 0.625–1.25 mg
Estriol 0.03 mg 0.5 mg
Open in a new tab

92. The doses for LET include CEEs 0.3–1.25 mg/day, estradiol 25 µg/day, and estriol cream 0.5 mg/day, depending on the severity of GSM (Grade A).[153]

93. A randomized study showed that ultra-low-dose E2 (4–10 µg) significantly improved vaginal maturation, restored vaginal pH, and reduced symptoms compared with placebo (Grade B).[154]

94. Regimen: The recommended regimen for LET consists of daily application to the lower vagina for 2–4 weeks, followed by a maintenance schedule of two to three applications per week for 2–6 months (Grade A).[150]

95. Absolute contraindications: are undiagnosed vaginal bleeding and active, untreated estrogen-sensitive malignancy (Grade A).[155-157]

96. Avoid: Hypersensitivity reactions to menopausal estrogen therapy are infrequent, with most documented cases including contact dermatitis, cyclical vulvitis, and drug eruptions.[158,159] Life-threatening events, including anaphylaxis, are infrequent and are primarily described in isolated case reports or hormone allergy reviews.[160]

97. Relative contraindications: Evidence supports a risk-stratified approach, with breast cancer survivors requiring mandatory oncology consultation, while patients with CVD or venous thromboembolism (VTE) history need individualized assessment (Grade B/C).[161-165]

98. General principles of LET use: Treatment should be started early to prevent irreversible atrophic changes (Grade B).[165-167]

99. Clinical consensus supports indefinite use when needed, based on longitudinal observational studies. However, robust safety data beyond 1 year of continuous use are limited for all available vaginal preparations (Grade B).[155,167-171]

100. A systematic review found no evidence of endometrial proliferation after 6–24 months of low-dose LET use (Grade A).[161] Transvaginal ultrasonography (TVS) and endometrial biopsy (EB) (Grade A) should be used to investigate unscheduled bleeding.[167] Progesterone supplement for endometrial protection is not needed along with the use of LET (Grade A).[165,168]

OTHER TREATMENT MODALITIES FOR GENITOURINARY SYNDROME OF MENOPAUSE

101. Tibolone: Significantly improved vaginal atrophy and cytology in comparison with placebo.[172]

102. Selective estrogen receptor modulators (SERMs): Ospemifene is currently the only approved oral treatment for GSM, with agonist activity on the vaginal epithelium and antagonist activity in breast and endometrial tissue (Grade A).[173,174]

103. Significantly, unlike other SERMs, ospemifene has not been associated with an increased risk of breast or endometrial cancer (EC), and available safety data suggest no excess risk of VTE.[175] Ospemifene may, therefore, be considered in women with a history of breast or EC, provided active treatment is complete and decisions are individualized.[176,177]

104. Postmenopausal women with GSM reported higher satisfaction and adherence for ospemifene compared to vaginal estrogen therapy, besides a lower number of missed doses in the treatment of moderate to severe GSM.[178]

105. Dehydroepiandrosterone (DHEA): is administered intravaginally once daily at bedtime. Within the vaginal mucosa, DHEA is locally converted into both estrogens and androgens (testosterone, androstenedione, and dihydrotestosterone), thereby improving epithelial maturation, vaginal pH, lubrication, and sexual function (Grade A).[179]

106. Lifestyle modifications such as smoking cessation, regular sexual activity, and pelvic floor exercises may help maintain urogenital health and reduce GSM severity (Grade B).[180]

107. Nonhormonal options are for women with mild GSM and/or willing to avoid HT or in high-risk individuals with a history of hormone-sensitive malignancy, such as breast cancer or EC.

108. Nonhormonal treatments, including vaginal moisturizers, lubricants, hyaluronic acid preparations, physical therapy, and energy-based therapies like laser, have demonstrated varying degrees of efficacy in symptom relief and QOL improvement.[181]

109. Vaginal lubricants can be recommended for the subjective symptom improvement of dyspareunia (Grade B).[182,183] Vaginal moisturizers can be offered for vaginal dryness and dyspareunia (Grade B).[184] Use vaginal lubricants, moisturizers, and hygiene products with physiologic pH and low osmolality (≤380 mOsm/kg); avoid high-osmolality products that exceed World Health Organization (WHO) recommendations, as they may irritate the epithelium and increase the infection risk (Grade B).[185]

110. Intravaginal phytoestrogens (isoflavone/genistein gels) may be considered a short-term, effective alternative to vaginal estrogen for GSM symptom relief (Grade B).[186-188]

111. Laser therapy: High-quality randomized trials are still required to provide definitive guidance on the efficacy and safety of vaginal laser therapy for various gynecological conditions (Grade C).[189-193]

112. Conclusion on management of GSM: LET, vaginal DHEA, vaginal moisturizers, and oral ospemifene have demonstrated efficacy in improving symptoms of GSM (Grade A).[193]

113. For women with contraindications to regular dose LET, effective nonhormonal alternatives, including hyaluronic acid and ultra-low-dose local estriol, are safe and beneficial (Grade B).[194,195]

114. Current evidence does not support the efficacy of energy-based therapies, vaginal or systemic testosterone, vaginal oxytocin, or oral SERMs such as raloxifene or bazedoxifene for the treatment of GSM (Grade C/D).[193]

URINARY INCONTINENCE

115. UI, an involuntary urine leakage, affects >50% of postmenopausal women and is a significant social problem.

116. There are five types of UI: stress, urge, mixed, overflow, and functional incontinence. Urge and mixed incontinence predominate in the older population.[196-198]

117. Diagnosis: Initial evaluation and diagnosis of a woman with UI can be based on symptoms alone to initiate conservative treatment.[198]

118. Urodynamics is not routinely recommended and is reserved for complicated UI requiring surgery to rule out mixed causes of voiding dysfunction (Grade A).[140,199,200]

119. Routine renal/bladder imaging or cystoscopy is not indicated in the initial evaluation of uncomplicated UI or overactive bladder. These investigations should be performed only in refractory, recurrent, or complex cases (Grade A).[201-203]

120. Management: Pelvic floor muscle training (PFMT), whether supervised or home-based, is recommended as first-line therapy for stress UI (SUI) and mixed incontinence (Grade B).[204,205]

121. All types of pelvic floor therapy are effective for SUI. At this point, no single therapy is superior to another (Grade B).[204]

122. Available interventions are PFMT, vaginal cone, biofeedback, electrical muscle stimulation, radiofrequency, and electroacupuncture.[204]

SEXUAL DYSFUNCTION

123. Sexual dysfunction affects 40%–60% of midlife women globally and is even more prevalent in India (66%–80%) (Grade B), with common issues being low desire, dyspareunia, and arousal difficulties.[206]

124. Cultural factors, stigma, and lack of awareness further contribute to underreporting in India.[207,208]

125. Sexual dysfunction is multifactorial and needs to be addressed accordingly. The biological factors are hypoestrogenism, chronic disease, and iatrogenic effects. The psychological factors are depression, anxiety, and body image concerns. Relationship factors are partner dysfunction, poor intimacy, and sociocultural barriers: myths, stigma, and low prioritization of sexual well-being (Grade B).[209-211]

126. Clinicians can play a pivotal role in addressing sexual health during midlife consultations by creating a safe, confidential, and nonjudgmental environment, normalizing discussion of sexuality, using open-ended questions, applying validated tools such as the Female Sexual Function Index (Refer to section 6), screening for medical and psychosocial comorbidities, and involving the partner when appropriate to enhance communication and shared decision-making.[211]

127. Management of sexual dysfunction in midlife women requires a multimodal approach.

128. Lifestyle and nonpharmacological strategies (Grade B), including regular physical activity, pelvic floor exercises, yoga, stress management, use of physiologic lubricants/moisturizers, and psychosocial interventions such as CBT, mindfulness, and sex therapy, improve body image, intimacy, and relationship satisfaction.[88,212]

129. Pharmacological therapies (Grade A) include local vaginal estrogen, vaginal DHEA, and oral ospemifene for GSM, while systemic MHT may be considered when vasomotor or bone indications coexist (Grade A).[213,214]

130. Tibolone: According to the 2023 Cochrane review, evidence for tibolone’s effect on sexual function is of low certainty and does not demonstrate a significant benefit over placebo or standard MHT (Grade C).[214]

131. Hypoactive sexual desire disorder (HSDD): HSDD, a non-GSM sexual dysfunction, requires a holistic approach. Management involves identification and treatment of contributory psychological, relational, and medical factors.

132. Pharmacological options may include bupropion, flibanserin, or selected SSRIs/SNRIs as adjuncts (Grade B).[215-217]

BODY COMPOSITION (BC), SKIN, AND METABOLIC CHANGES

133. BC: Overall, midlife weight and adiposity gain are driven mainly by aging and lifestyle rather than menopause (Grade C).[218,219]

134. However, the MT independently promotes adverse fat redistribution, with increased visceral and pericardial/epicardial fat beyond aging effects, contributing to metabolic syndrome and greater cardiometabolic risk after menopause.[220,221]

135. During the MT, estrogen deficiency accelerates bone loss (Grade A)[222] and reduces muscle mass and strength (Grade B),[223] while aging further impairs bone quality and muscle regeneration. Together, these processes especially in POI and early menopause increase the risk of osteoporosis, sarcopenia, and frailty.[224] Early lifestyle measures and, where appropriate, therapeutic interventions are essential to preserve bone and muscle health in midlife women and prevent adiposity (Grade B).[225-227]

136. Skin changes: Estrogen deficiency during and after the MT reduces collagen content in both skin and bone.[228] Loss of cutaneous collagen accelerates skin aging, wrinkling, and decreased elasticity (Grade B).[229] At the same time, hormonal imbalance with relative androgen excess after menopause may contribute to frontal balding and hirsutism in some women (Grade B).[230]

137. Metabolic changes: Refer to Section 3.

FERTILITY

138. Fertility: In women aged >40 years who fail to conceive after 1–2 cycles of controlled ovarian stimulation, in vitro fertilization (IVF) should be considered early, as success with conventional stimulation is poor (Grade B).[231,232]

139. The only effective treatment for ovarian aging with markedly reduced reserve is oocyte (donor egg) IVF, which yields pregnancy rates far superior to stimulation with autologous oocytes (Grade A).[233,234]

140. Counsel women aged ≥40 years about the exponential increase in chromosomal abnormalities, miscarriage, and mosaic embryos; offer individualized Preimplantation Genetic Testing for Aneuploidy (PGT-A) counseling and interpretation in collaboration with reproductive specialists (Grade A).[235,236]

141. Preconception counseling should emphasize weight optimization, control of hypertension, diabetes, thyroid disease, and identification of obstetric risks. Women aged >40 years require individualized counseling regarding maternal and perinatal complications (Grade B).[237,238]

142. Fertility preservation should be offered to women at risk of premature or treatment-induced menopause. Oocyte and embryo cryopreservation using vitrification is an established, effective, and safe technique (Grade A).[239,240]

143. Elective oocyte freezing may be considered before the age of 38 years after individualized counseling (Grade B).[241,242]

CONTRACEPTION

144. Contraceptive needs and choices during the MT should be individualized, taking into account a woman’s contraceptive requirements, menopausal symptoms, abnormal uterine bleeding (AUB), and presence or risk of comorbidities.[243,244]

145. Pregnancies in older women (>35 years) are associated with higher maternal and perinatal morbidity and mortality. Across all age groups, the annual risk of death associated with not using any method of contraception is substantially higher than the risk associated with using any contraceptive method.[245-247]

146. Reproductive autonomy is supported by shared decision-making between women and healthcare providers, using a person-centered approach to contraceptive choice (Grade A).[248]

147. Sterilization is a highly effective permanent method. Female tubal sterilization carries a very low mortality risk in well-controlled settings (1–2/100,000).[249]

148. Patients who are willing for a permanent method of contraception and who are at high risk for ovarian cancer may be counseled for bilateral salpingectomy at the time of permanent sterilization with the understanding that there is no scope for reversal (Grade C).[250-252]

149. Oral contraceptive pills (OCPs) are practical, easy to use, and reversible in healthy women. Low-dose OCPs have noncontraceptive health benefits with an increased safety profile (Grade A).[62,253-255]

150. The strength of association of increased breast cancer with OCP use is low (Grade B).[256] Estrogen-containing OCPs increase the risk of VTE by 2–4 times.[257]

151. For women aged over 35 years, careful personal and family history, accurate measurement of blood pressure (BP), breast examination, screening for diabetes, and lipid profile should be performed.[243,254,258]

152. For women aged 45–50 years and on combined hormonal contraception (CHC), if menopausal symptoms are present, consider transitioning to MHT for symptom relief. We recommend clinical age-based switching (without biomarker tests) due to increased risks of VTE with ethinyl estradiol (EE) (Grade B).[259-261]

153. For ongoing contraceptive needs, switch to a progestogen-only contraception (POP) method, pill, levonorgestrel-releasing intrauterine system (LNG-IUS), implant or a nonhormonal method like barrier methods, copper intrauterine contraceptive device (IUCD), or sterilization (Grade A).[262]

154. In women aged 50 years or older who are using progestogen-only pills (POP) and have no periods, menopause can be supported by two blood tests showing FSH levels ≥30 IU/L, taken at least 6 weeks apart.[263]

155. Diagnosis of menopause for women aged ≥50 years using COC: Discontinue hormones for 6 weeks, then measure serum FSH twice, 6 weeks apart; menopause is diagnosed if both FSH values are >35–40 IU/L (Grade C).[264,265] FSH/E2 testing when on CHCs is unreliable, since they suppress gonadotropins and estradiol (Grade A).[264,265]

156. For major surgery with prolonged immobilization (>30 min), COCs should ideally be discontinued 4–6 weeks before surgery to reduce the risk of VTE. If continued, appropriate perioperative VTE prophylaxis should be provided (Grade B).[243]

157. For minor or day-care surgery without prolonged immobilization, COCs may be safely continued (Grade A).[266,267]

158. Long-acting reversible contraception (LARC): Preinsertion assessment for IUCD insertion in a healthy woman, including body mass index, BP, cervical inspection, and bimanual examination, is a prerequisite. An opportunistic breast examination before initiating hormone-based LARC is advisable.

159. Management of irregular bleeding on LARC: Treatment may be repeated as needed. Options include antifibrinolytic agents (tranexamic acid), 5 days nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., mefenamic acid and celecoxib), 5–7 days, hormonal treatment (20–30 µg EE COCs or estrogen), short course. SERMs (e.g., tamoxifen 10 mg twice daily, 7–10 days.[243,259,268-272]

160. Progesterone-only contraceptives are ideal for women with a history of VTE and gallstones. Limitations are erratic and scanty periods. LNG-IUS, apart from being used as a contraception, is an effective HT for heavy menstrual bleeding (Grade A)[259,273,274] and for treating bleeding disturbances associated with endometrial hyperplasia (EH) (Grade B).[259,273,274]

161. Copper IUCD is a highly effective long-acting reversible contraceptive. However, it may be associated with increased menstrual bleeding and dysmenorrhea, particularly in the initial months after insertion (Grade B).[275-277]

162. Emergency contraception is an effective backup method, but it is less effective and less consistent than ongoing contraceptive use.[259]

163. The copper IUCD when inserted within 5 days of unprotected intercourse, has a failure rate <0.1% and is the most effective method of emergency contraception, while also providing ongoing protection for up to 10 years (Grade A).[259,278]

ABNORMAL UTERINE BLEEDING

164. PALM-COEIN: Use of the FIGO AUB System 2, derived from the PALM–COEIN classification, is recommended for the standardized categorization of AUB across reproductive and perimenopausal years (Grade A).[279]

165. The most common etiologies of AUB include anovulatory bleeding (43%), leiomyomas (15%), endometrial polyps (15%), endometrial hyperplasia (EH) (20%–30%), endometrial intraepithelial neoplasia (EIN) (3%–5%), and endometrial carcinoma (4%–6%; Grade B).[280,281]

166. Investigations: Endometrial biopsy (EB) is recommended in all women aged ≥40 years presenting with AUB. Given the high prevalence of EH (25%) and carcinoma (4%–6%) among Indian women aged ≥40 years presenting with AUB, routine EB is justified in this group. The diagnostic yield (one premalignant lesion per four biopsies; one carcinoma per 20–25 biopsies) meets the threshold for cost-effective evaluation in symptomatic population (Grade B).[282-285]

167. EB is recommended in younger women (<40 years) with persistent symptoms, failed medical therapy, or risk factors for unopposed estrogen exposure, obesity, polycystic ovary syndrome (PCOS), and diabetes (Grade C).[286]

168. Transvaginal ultrasonography (TVS) is the first-line investigation for perimenopausal AUB, providing assessment of the uterus, adnexa, and pelvic pathology.[287]

169. When endometrial visualization is suboptimal or a suspected focal lesion is present, saline infusion sonography (SIS) improves diagnostic accuracy (Grade A).[287-290]

170. If TVS shows no structural lesion, outpatient suction sampling (Pipelle biopsy) is performed as the first-line diagnostic test. It is a safe, quick, cost-effective, minimally invasive procedure with high diagnostic accuracy, providing >90% sensitivity and 100% specificity for detecting atypical EH or endometrial carcinoma (Grade A).[291-293]

171. Inadequate or nondiagnostic Pipelle samples (10%–15%) should be followed by hysteroscopy-guided EB for direct visualization and targeted sampling (Grade A).[291,294]

172. Hysteroscopy is the gold standard for diagnosing and treating intrauterine structural lesions.[295] If ultrasound identifies a focal or structural abnormality, hysteroscopy should be the first-line diagnostic and therapeutic procedure (Grade A).[296,297]

173. When hysteroscopy is unavailable, Pipelle EB, dilatation and curettage (D and C) are acceptable alternatives for endometrial sampling. These methods provide adequate diagnostic yield for hyperplasia and carcinoma, though they are less sensitive for focal lesions (Grade B).[298]

174. A benign or insufficient sample does not reliably exclude (pre) cancer or focal pathology, particularly in high-risk women, those aged ≥45 years, with persistent or intermenstrual bleeding, obesity, PCOS, diabetes, or tamoxifen use, or when imaging suggests a focal lesion. Such women should undergo targeted evaluation with outpatient hysteroscopy and directed biopsy ± SIS (Grade A).[291]

175. Pelvic magnetic resonance imaging (MRI) may be considered when hysteroscopy or SIS is inconclusive, or when deep myometrial, junctional-zone, or adnexal involvement is suspected (adenomyosis, endometrial carcinoma, or atypical hyperplasia with indeterminate ultrasound findings) (Grade B).[287,299]

176. Management in women with nonstructural benign AUB medical therapy is recommended as the first-line management (Grade A).[279,286]

177. Preferred options include the LNG-IUS, COCs, or oral/cyclic progestins (Grade A).[300-302] LNG-IUS is the first-line treatment to reduce menstrual blood loss in women with nonstructural AUB-O/AUB-E.[300] LNG-IUS is superior to oral medical therapies, including COCs, tranexamic acid, and oral progestins, in short and medium-term outcomes for blood loss reduction, symptom control, compliance, and patient satisfaction (Grade A).[301]

178. 17β-estradiol plus progesterone or COC may be used in perimenopausal women with AUB who also suffer from VMS, provided there are no contraindications to OCP use (Grade B).[302-304]

179. Nonhormonal therapies such as tranexamic acid or NSAIDs may be offered as second-line or adjunct options, especially in those with contraindications to hormonal agents (Grade A).[305]

180. Tranexamic acid is recommended for the management of heavy menstrual bleeding (HMB), leading to an average 40%–50% reduction in menstrual blood loss per cycle. It is most effective when taken only during active bleeding (1 g orally three times daily), typically up to 4–5 days per menstrual cycle, beginning on the 1st day of bleeding (Grade C).[306]

181. A Cochrane review and subsequent clinical trials found no significant increase in thromboembolic events in the general population (Grade A).Tranexamic acid should be used with caution in women with a personal history or active risk of venous or arterial thrombosis (Grade C).[305] It is contraindicated in women with current or past VTE/arterial thromboembolism or known thrombophilia (e.g., Factor V Leiden and antiphospholipid syndrome) (Grade B).[305]

182. NSAIDs (mefenamic acid, ibuprofen, naproxen) are recommended for women with HMB and no contraindications, reducing menstrual blood loss by 20%–50% and relieving dysmenorrhea when taken from the onset of menses for 3–5 days; use with caution in peptic ulcer disease, renal impairment, or platelet dysfunction (Grade B).[306]

183. Ethamsylate is an alternative for HMB when antifibrinolytics are contraindicated or unavailable. Taken from the onset of menses for 4–5 days, it provides a modest 20%–30% reduction in blood loss by improving platelet adhesiveness and capillary stability. However, it is less effective than tranexamic acid (Grade C).[307,308]

184. Transcervical endometrial ablation may be considered for recurrent bleeding with benign histopathology in women who have completed childbearing.[309,310]

185. Hysterectomy is reserved for refractory cases after failed medical or conservative surgical management, or for premalignant endometrial lesions (Grade B).[311]

186. Women with structural causes of AUB, such as endometrial polyps or submucous fibroids, should be managed with hysteroscopic removal, which allows simultaneous diagnosis and treatment with high success rates and low morbidity.[296] Moreover, it improves menstrual regularity, fertility outcomes, and QOL, and is superior to blind curettage for focal pathology (Grade A).[312]

187. Medical management of AUB-L, AUB-A, and endometriosis: The options are COCs, progesterones, tranexamic acid, gonadotropin-releasing hormone (GnRH) analogs, mifepristone, and restricted use of ulipristal for women who want to preserve fertility when waiting for surgery and as a transitional therapy when transitioning from MT to menopause. They have potential adverse effects that limit long-term use.

188. GnRH agonists: leuprolide, goserelin, and triptorelin may be used short term, ≤6 months, to achieve rapid reduction of uterine, fibroid, or adenomyotic volume and control bleeding, or for preoperative optimization/surgical deferral (Grade B).[313-315]

189. GnRH agonists are effective for endometriosis-associated pain; when used with concurrent add-back therapy, low-dose estrogen with progestogen to prevent bone loss, vasomotor, and urogenital symptoms without compromising efficacy. The 6–12 month courses are appropriate (Grade A).[313-315]

190. Oral GnRH antagonist: Elagolix may be offered for rapid control of bleeding and pain in women with fibroids or endometriosis (Grade A).[316,317] Elagolix improves hemoglobin and QOL and may allow surgical deferral. It causes rapid suppression of gonadotropins and ovarian sex hormones, inducing hypoestrogenism and amenorrhea (Grade B).[318-320]

191. Elagolix, when used with add-back therapy (estradiol 1 mg + norethindrone acetate 0.5 mg daily), is safe and well-tolerated for up to 24 months in women treated for endometriosis-or fibroid-associated symptoms (Grade A).[318-320] Concurrent low-dose estradiol plus progestogens are recommended to prevent bone loss, vasomotor and urogenital symptoms, without substantially compromising efficacy.[320]

192. Elagolix is contraindicated in women with osteoporosis, severe hepatic impairment, or hormone-dependent malignancy.[321] Obtain baseline and 12-month bone mineral density (BMD) when elagolix is used beyond short courses or when osteoporosis risk factors are present; ensure calcium/Vitamin D, weight-bearing exercise, and other bone-protective lifestyle measures (Grade A).[318,320,321]

193. Oral relugolix combination therapy (relugolix 40 mg + estradiol 1 mg + norethindrone acetate 0.5 mg once daily) is recommended for fibroid-associated heavy menstrual bleeding. It can be safely given up to 24 months (Grade A).[322,323] Routine monitoring of BMD is not recommended when on relugolix combination therapy given for <24 months (Grade B).[323,323]

194. Ulipristal acetate 5 mg daily for up to 3 months effectively reduces fibroid size and bleeding. However, its use is restricted due to the risk of severe liver injury; it may be considered only where liver function monitoring is feasible and regulatory approval exists (Grade B).[324-327]

195. Mifepristone: 25 mg daily for 3–6 months is a cost-effective selective progesterone receptor modulator (SPRM) shown to reduce bleeding, pain, and fibroid volume by 40%–50%, with improvement in hemoglobin and QOL; recurrence occurs after discontinuation (Grade B).[328,329]

POSTMENOPAUSAL BLEEDING

196. Definition (Refer to Section 1). The incidence of postmenopausal bleeding (PMB) is 10%. Women <50 years of age with PMB have a <1% chance of having EC, which increases to 24% in women more than 80 years.[330,331]

197. About 90% of the women with EC present with PMB. Therefore, all women with PMB should undergo prompt evaluation (Grade A).[330,332,333]

198. About 60%–80% of women presenting with PMB will have atrophic changes of the endometrium and/or the vaginal-urogenital tract.[334,335]

199. A detailed clinical and drug history should be obtained, as several over-the-counter herbal agents such as ginseng, soy, and red clover may induce vaginal bleeding due to phytoestrogenic effects (Grade C).[336]

200. A thorough general, pelvic, and rectovaginal examination should be performed to exclude nonuterine causes of bleeding, such as cervical, vaginal, vulval, urinary, or anal pathology, as well as atrophic vaginitis (Grade C).[337]

201. Women presenting with PMB should undergo TVS as the first-line investigation.[338,339]

202. TVS should include double-layer endometrial thickness (ET) measured as the maximum anteroposterior thickness of the double endometrial echo in the long axis (sagittal). Assess morphology by the echotexture (homogeneous vs. heterogeneous), focal or cystic areas, regularity of the endometrial–myometrial junction, and endocavitary fluid. Power Doppler mapping to evaluate the endometrial and sub-endometrial vascular pattern.[339]

203. Three-dimensional TVS is adjunctive and only provides moderate accuracy in assessing endometrial volume and focal abnormalities, but shows no consistent advantage over standard two-dimensional TVS for predicting EC (Grade B).[340,341]

204. SIS is complementary and offers high diagnostic accuracy for detecting focal intrauterine lesions, such as polyps and submucous fibroids, in women with PMB; however, it does not replace TVS-based ET triage for endometrial carcinoma and cannot substitute for histologic sampling for definitive diagnosis.[342]

205. In women presenting with PMB and no other high-risk factors, a TVS with an ET threshold between 3 and 5 mm provides a high negative predictive value for endometrial malignancy. However, assessment should include endometrial morphology, Doppler findings, and individual risk factors (Grade B).[336,337-340]

206. In women with p53-abnormal (p53abn) molecular subtype endometrial carcinoma, reliance on the standard ET cutoff ≤4 mm may lead to missed diagnoses, with false-negative rates reported up to 25% (Grade B).[343]

207. Women presenting with a first episode of PMB who have any of the following risk factors should undergo both TVS and endometrial sampling: obesity, diabetes, hypertension, tamoxifen use, increasing years since menopause, history of polyps, smoking, family history of EC, poor image definition, focal echogenicity, diffuse heterogeneity, or persistent bleeding (Grade B).[338,344]

208. Low-risk women (ET ≤3–4 mm, clearly defined homogeneous echo pattern, normal morphology and color Doppler, and good image quality) whose bleeding has ceased may be managed conservatively with shared decision-making and repeat TVS or biopsy only if bleeding recurs (Grade B).[339,344]

209. All women should receive documented counseling regarding the need for follow-up and to promptly report red-flag symptoms such as recurrent bleeding, abnormal discharge, pelvic pain, or unexplained weight loss (Grade A).[339,345]

210. In postmenopausal women at low risk for EC, presenting with global (nonfocal) endometrial pathology on imaging, an outpatient endometrial sampling using a suction device (e.g., Pipelle) (unless cervical stenosis or patient noncooperative) is an acceptable, low-cost, first-line diagnostic tool (Grade B).[346,347]

211. Office/outpatient, hysteroscopy-directed biopsy is a gold standard for diagnosing endometrial lesions.[348]

212. Hysteroscopy may be offered as the preferred diagnostic test in postmenopausal women with persistent or recurrent bleeding, focal/heterogeneous endometrial pathology on ultrasound, inadequate or nonrepresentative Pipelle/aspiration sampling, or poor-quality/uninterpretable TVS diagnostic accuracy over blind sampling (Grade B).[296,349]

213. It reduces unnecessary major surgery; this is especially relevant in India, where (i) endometrial polyps account for a large share of recurrent PMB and (ii) outpatient hysteroscopy is increasingly feasible in tertiary and many secondary centers at low cost without general anesthesia (Grade B).[296]

214. When the histopathology report from endometrial sampling is inconclusive, inadequate, or nonrepresentative, the woman should be re-evaluated with transvaginal TVS to assess ET and morphology (Grade A).[339,350]

215. If subsequent TVS reveals a thin endometrial stripe and the vaginal bleeding has ceased, no further invasive evaluation is necessary; a close follow-up strategy is advised (Grade B).[337]

216. Persistent bleeding or an unsatisfactory/poor-quality TVS necessitates further evaluation by pelvic MRI when malignancy is still suspected (Grade B) and an outpatient hysteroscopic evaluation if not done as the primary procedure (Grade B).[337]

217. Recurrent PMB is defined as any episode of vaginal bleeding occurring ≥6 weeks after the resolution of an initial episode of PMB (Grade C).[351] Reassessment is warranted, as up to 4%–5% may subsequently reveal EC or premalignant pathology. Endometrial polyps account for approximately one in four cases of PMB.

218. In women with recurrent PMB after an initial negative evaluation, a first-line investigation should focus on tests with high accuracy for focal intrauterine disease (such as outpatient hysteroscopy) because up to 20% may have endometrial polyps, and up to 4%–5% may reveal EC or premalignant pathology (Grade B).[337,352,353]

219. Asymptomatic postmenopausal women with thick endometrium: There is currently no clear ET threshold that can predict the risk of malignant transformation.[354-356]

220. Postmenopausal women without bleeding, no additional risk factors, and global endometrial thickening ≤11 mm on transvaginal ultrasonography do not require invasive endometrial investigation (Grade B).[335,355] In asymptomatic postmenopausal women, an ET >11 mm should prompt an EB (Grade B).[355] In an asymptomatic woman, the decision to biopsy if the ET is between 3/4 and 11 mm should depend on the patient’s individual risk factors, endometrial morphology, and power Doppler findings (Grade C).[355,356]

221. Women with or without PMB who are at increased risk for EC should be educated about early symptoms such as abnormal or recurrent vaginal bleeding, discharge, pelvic pain, or weight loss, and the importance of long-term follow-up even after a negative initial evaluation (Grade B).[356]

222. PMB in tamoxifen users – Refer to Section 5.

223. PMB in MHT users – Refer to Section 6.

QUALITY OF LIFE

224. The WHO defines QOL as “an individual’s perception of their position in life in the context of the culture and value system in which they live and in relation to their goals, expectations, standards, and concerns.” It encompasses various aspects of well-being, including physical, mental, emotional, social, and material health, as well as capabilities and the ability to participate in life events (Grade A).[357]

225. Validated tools to evaluate QOL: General– Global QOL is for a broad assessment of an individual’s overall well-being, including physical, psychological, social, cultural, and environmental dimensions. Moreover, health-related QOL (HRQOL) focuses on the impact of health status, disease, or treatment on physical, mental, and social functioning (Grade A).[358,359]

226. Work-related tools: Work Productivity and Activity Impairment (WPAI) for workplace productivity and Work Ability Index as occupational functioning tools (Grade B).[360,361]

227. When evaluating drug therapies, in addition to safety and efficacy, it is essential to assess the drug’s effect on QOL (Grade A).[362-364]

228. Moderate-to-severe VMSs (hot flashes and night sweats) are among the strongest determinants of reduced HRQOL in midlife women, affecting sleep quality, emotional well-being, daily functioning, and sexual health (Grade A).[365,366]

229. Sleep disturbance and psychological well-being are consistently reported as the most affected domains, followed by work productivity and sexual function (Grade A).[365-367]

230. The QOL domain most affected by bothersome vulvovaginal symptoms is sexual function, impacting 40% of women (Grade A).[368,369]

231. Metabolic diseases, CVD, cancers, fractures, and UI can severely impair QOL, affecting physical, psychological, and social domains.[370-373]

232. Studies using the WPAI scale have shown that hot flashes and night sweats impair daily activities more than working activities (Grade B).[374,375]

233. Indian studies consistently show that menopausal symptoms significantly impair HRQOL in both rural and urban women, affecting physical, psychological, vasomotor, and urogenital domains (Grade B).[376-384]

234. Menopause health education improves QOL and symptom control in menopausal women. Trusted educational programs facilitate emotional and physical well-being (Grade A).[381,385] Lifestyle changes such as exercise and yoga improve QOL. Exercise has been shown to reduce VMS severity and enhance QOL, although future rigorous randomized controlled trials are needed to establish optimal exercise prescription principles (Grade A).[61,386-388]

235. PFMT significantly improves HRQOL in women with GSM, with benefits for urinary symptoms, sexual health, and overall well-being (Grade A).[389]

236. MHT improves QOL in symptomatic menopausal women, mainly through relief of VMS, sleep, and psychological well-being (Grade A).[24,390-393]

237. Low-dose MHT significantly improves QOL in symptomatic women. In contrast, the HERS trial showed mixed effects among older women, and the WHI trial found no clinically meaningful improvement in HRQOL with estrogen plus progestin (Grade A).[394-396] An Indian study demonstrated that tibolone therapy improves HRQOL in menopausal women (Grade B).[397]

REFERENCES

  1. Logan NE, Gaudreau J, Owens B, Oaks BM, Ward-Ritacco CL, Sabik NJ. Heightened menopausal symptoms mediate the associations between stress and depressive symptoms among midlife women. Menopause 2025;32:956-65.

  2. Santoro N, Epperson CN, Mathews SB. Menopausal symptoms and their management. Endocrinol Metab Clin North Am 2015;44:497-515.

  3. Schwarz KG, Vicencio SC, Inestrosa NC, Villaseca P, Del Rio R. Autonomic nervous system dysfunction throughout menopausal transition: A potential mechanism underpinning cardiovascular and cognitive alterations during female ageing. J Physiol 2024;602:263-80.

  4. Joyner MJ, Barnes JN, Hart EC, Wallin BG, Charkoudian N. Neural control of the circulation: How sex and age differences interact in humans. Compr Physiol 2015;5:193-215.

  5. Lee E, Anselmo M, Tahsin CT, Vanden Noven M, Stokes W, Carter JR, et al. Vasomotor symptoms of menopause, autonomic dysfunction, and cardiovascular disease. Am J Physiol Heart Circ Physiol 2022;323: H1270-80.

  6. Torréns JI, Sutton-Tyrrell K, Zhao X, Matthews K, Brockwell S, Sowers M, et al. Relative androgen excess during the menopausal transition predicts incident metabolic syndrome in midlife women: Study of women’s health across the nation. Menopause 2009;16:257-64.

  7. Peacock K, Carlson K, Ketvertis KM. Menopause. [Updated 2023 Dec 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507826/. [Last accessed on 2026 Jan 19].

  8. El Khoudary SR, Aggarwal B, Beckie TM, Hodis HN, Johnson AE, Langer RD, et al. Menopause transition and cardiovascular disease risk: Implications for timing of early prevention: A scientific statement from the American Heart Association. Circulation 2020;142:e506-32.

  9. Clarkson TB. Estrogen effects on arteries vary with stage of reproductive life and extent of subclinical atherosclerosis progression. Menopause 2007;14:373-84.

  10. Clarkson TB, Meléndez GC, Appt SE. Timing hypothesis for postmenopausal hormone therapy: Its origin, current status, and future. Menopause 2013;20:342-53.

  11. Hodis HN, Mack WJ. The timing hypothesis and hormone replacement therapy: A paradigm shift in the primary prevention of coronary heart disease in women. Part 1: Comparison of therapeutic efficacy. J Am Geriatr Soc 2013;61:1005-10.

  12. Nudy M, Chinchilli VM, Foy AJ. A systematic review and meta-regression analysis to examine the ‘timing hypothesis’ of hormone replacement therapy on mortality, coronary heart disease, and stroke. Int J Cardiol Heart Vasc 2019;22:123-31.

  13. Gu Y, Han F, Xue M, Wang M, Huang Y. The benefits and risks of menopause hormone therapy for the cardiovascular system in postmenopausal women: A systematic review and meta-analysis. BMC Womens Health 2024;24:60.

  14. Boardman HM, Hartley L, Eisinga A, Main C, Roqué I Figuls M, Bonfill Cosp X, et al. Hormone therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database Syst Rev 2015;2015: CD002229.

  15. Schierbeck LL, Rejnmark L, Tofteng CL, Stilgren L, Eiken P, Mosekilde L, et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: Randomised trial. BMJ 2012;345:e6409.

  16. Brinton RD. The healthy cell bias of estrogen action: Mitochondrial bioenergetics and neurological implications. Trends Neurosci 2008;31:529-37.

  17. Nerattini M, Jett S, Andy C, Carlton C, Zarate C, Boneu C, et al. Systematic review and meta-analysis of the effects of menopause hormone therapy on risk of Alzheimer’s disease and dementia. Front Aging Neurosci 2023;15:1260427.

  18. Mauvais-Jarvis F, Manson JE, Stevenson JC, Fonseca VA. Menopausal hormone therapy and type 2 diabetes prevention: Evidence, mechanisms, and clinical implications. Endocr Rev 2017;38:173-88.

  19. Henderson VW, St John JA, Hodis HN, McCleary CA, Stanczyk FZ, Shoupe D, et al. Cognitive effects of estradiol after menopause: A randomized trial of the timing hypothesis. Neurology 2016;87:699-708.

  20. Fidecicchi T, Giannini A, Chedraui P, Luisi S, Battipaglia C, Genazzani AR, et al. Neuroendocrine mechanisms of mood disorders during menopause transition: A narrative review and future perspectives. Maturitas 2024;188:108087.

  21. Lobo RA, Gompel A. Management of menopause: A view towards prevention. Lancet Diabetes Endocrinol 2022;10:457-70.

  22. Salpeter SR, Walsh JM, Greyber E, Ormiston TM, Salpeter EE. Mortality associated with hormone replacement therapy in younger and older women: A meta-analysis. J Gen Intern Med 2004;19:791-804.

  23. Hodis HN, Mack WJ, Henderson VW, Shoupe D, Budoff MJ, Hwang-Levine J, et al. Vascular effects of early versus late postmenopausal treatment with estradiol. N Engl J Med 2016;374:1221-31.

  24. Rossouw JE, Aragaki AK, Manson JE, Szmuilowicz ED, Harrington LB, Johnson KC, et al. Menopausal hormone therapy and cardiovascular diseases in women with vasomotor symptoms. JAMA Intern Med 2025;185:1330.

  25. Pataky MW, Young WF, Nair KS. Hormonal and metabolic changes of aging and the influence of lifestyle modifications. Mayo Clin Proc 2021;96:788-814.

  26. Simpson EE, Doherty J, Timlin D. Menopause as a window of opportunity: The benefits of designing more effective theory-driven behaviour change interventions to promote healthier lifestyle choices at midlife. Proc Nutr Soc 2024;83:120-9.

  27. Anekwe CV, Cano A, Mulligan J, Ang SB, Johnson CN, Panay N, et al. The role of lifestyle medicine in menopausal health: A review of non-pharmacologic interventions. Climacteric 2025;28:478-96.

  28. Souza HC, Tezini GC. Autonomic cardiovascular damage during post-menopause: The role of physical training. Aging Dis 2013;4:320-8.

  29. Wang Y, Miao X, Viwattanakulvanid P. Effects of a therapeutic lifestyle modification intervention on cardiometabolic health, sexual functioning and health-related quality of life in perimenopausal Chinese women: Protocol for a randomised controlled trial. BMJ Open 2024;14:e082944.

  30. Khandehroo M, Salary M, Mahdizadeh M, Peyman N. Educational intervention and menopausal adapting: A randomized controlled trial. Health Sci Rep 2024;7:e70298.

  31. Schneider HP, Heinemann LA, Rosemeier HP, Potthoff P, Behre HM. The menopause rating scale (MRS): Reliability of scores of menopausal complaints. Climacteric 2000;3:59-64.

  32. Sherman S, Miller H, Nerukar L. NIH state-of-the-science conference on management of menopause-related symptoms, March 21–25, 2005. Am J Med 2005;118 Suppl 2:1-72.

  33. Freeman EW, Sammel MD, Lin H, Gracia CR, Pien GW, Nelson DB, et al. Symptoms associated with menopausal transition and reproductive hormones in midlife women. Obstet Gynecol 2007;110:230-40.

  34. Bromberger JT, Matthews KA, Schott LL, Brockwell S, Avis NE, Kravitz HM, et al. Depressive symptoms during the menopausal transition: The study of women’s health across the nation (SWAN). J Affect Disord 2007;103:267-72.

  35. Podfigurna A, Szeliga A, Męczekalski B. Climacteric syndrome. In: Female Reproductive Dysfunction. Cham: Springer International Publishing; 2020. p. 309-34.

  36. Khalaf A, Mathew R, Nayak SG. Exploring symptom clusters across the menopausal stages – Systematic review and meta-analysis. Sex Reprod Healthc 2025;45:101137.

  37. El Khoudary SR, Greendale G, Crawford SL, Avis NE, Brooks MM, Thurston RC, et al. The menopause transition and women’s health at midlife: A progress report from the study of women’s health across the nation (SWAN). Menopause 2019;26:1213-27.

  38. Brown WJ, Mishra GD, Dobson A. Changes in physical symptoms during the menopause transition. Int J Behav Med 2002;9:53-67.

  39. Greendale GA, Sternfeld B, Huang M, Han W, Karvonen-Gutierrez C, Ruppert K, et al. Changes in body composition and weight during the menopause transition. JCI Insight 2019;4:124865.

  40. Fang Y, Liu F, Zhang X, Chen L, Liu Y, Yang L, et al. Mapping global prevalence of menopausal symptoms among middle-aged women: A systematic review and meta-analysis. BMC Public Health 2024;24:1767.

  41. Shah A, Prajapati H. Menopause symptoms experienced by women in India: A systematic review. Int J Res Rev 2024;11:45-53.

  42. Anuradha S, Priyadarsini M, Sumithra P. A study to assess the menopausal symptoms among women in selected villages at Chandragiri Mandal, Andhra Pradesh. Int J Obstet Perinat Neonat Nurs 2020;6:14-9.

  43. Sivaprasad S, Kumar VR, Krishna MP, Sadakvali CH, Yusuf MD, Srikanth A. A crosssectional study on prevalence of menopausal symptoms in a tertiary care hospital, Telangana, India. Int J Pharm Sci Rev Res 2022;73:129-33. [doi: 10.47583/ijpsrr.2022.v73i02.024].

  44. Salari N, Hasheminezhad R, Hosseinian-Far A, Rasoulpoor S, Assefi M, Nankali S, et al. Global prevalence of sleep disorders during menopause: A meta-analysis. Sleep Breath 2023;27:1883-97.

  45. Freedman RR. Menopausal hot flashes: Mechanisms, endocrinology, treatment. J Steroid Biochem Mol Biol 2014;142:115-20.

  46. Avis NE, Crawford CS. Cultural differences in symptoms and attitudes toward menopause. Menopause Manage 2008;17:8.

  47. Gold EB, Colvin A, Avis N, Bromberger J, Greendale GA, Powell L, et al. Longitudinal analysis of the association between vasomotor symptoms and race/ethnicity across the menopausal transition: Study of women’s health across the nation. Am J Public Health 2006;96:1226-35.

  48. Thurston RC, Joffe H. Vasomotor symptoms and menopause: Findings from the study of women’s health across the nation. Obstet Gynecol Clin North Am 2011;38:489-501.

  49. Tijerina A, Barrera Y, Solis-Pérez E, Salas R, Jasso JL, López V, et al. Nutritional risk factors associated with vasomotor symptoms in women aged 40-65 years. Nutrients 2022;14:2587.

  50. Anderson DJ, Chung HF, Seib CA, Dobson AJ, Kuh D, Brunner EJ, et al. Obesity, smoking, and risk of vasomotor menopausal symptoms: A pooled analysis of eight cohort studies. Am J Obstet Gynecol 2020;222:478.e1-17.

  51. Freeman EW, Sammel MD. Anxiety as a risk factor for menopausal hot flashes: Evidence from the Penn ovarian aging cohort. Menopause 2016;23:942-9.

  52. Li RX, Ma M, Xiao XR, Xu Y, Chen XY, Li B. Perimenopausal syndrome and mood disorders in perimenopause: Prevalence, severity, relationships, and risk factors. Medicine (Baltimore) 2016;95:e4466.

  53. Ruth KS, Beaumont RN, Locke JM, Tyrrell J, Crandall CJ, Hawkes G, et al. Insights into the genetics of menopausal vasomotor symptoms: Genome-wide analyses of routinely-collected primary care health records. BMC Med Genomics 2023;16:231.

  54. Sloan JA, Loprinzi CL, Novotny PJ, Barton DL, Lavasseur BI, Windschitl H. Methodologic lessons learned from hot flash studies. J Clin Oncol 2001;19:4280-90.

  55. Guthrie JR, Dennerstein L, Taffe JR, Lehert P, Burger HG. Hot flushes during the menopause transition: A longitudinal study in Australian-born women. Menopause 2005;12:460-7.

  56. Avis NE, Crawford SL, Greendale G, Bromberger JT, Everson-Rose SA, Gold EB, et al. Duration of menopausal vasomotor symptoms over the menopause transition. JAMA Intern Med 2015;175:531-9.

  57. Freeman EW, Sammel MD, Sanders RJ. Risk of long-term hot flashes after natural menopause. Menopause 2014;21:924-32.

  58. Mishra GD, Kuh D. Health symptoms during midlife in relation to menopausal transition: British prospective cohort study. BMJ 2012;344:e402.

  59. MacLennan A, Lester S, Moore V. Oral oestrogen replacement therapy versus placebo for hot flushes. Cochrane Database Syst Rev 2001;(1): CD002978.

  60. Khan SJ, Kapoor E, Faubion SS, Kling JM. Vasomotor symptoms during menopause: A practical guide on current treatments and future perspectives. Int J Womens Health 2023;15:273-87.

  61. Nguyen AT, Curtis KM, Tepper NK, Kortsmit K, Brittain AW, Snyder EM, et al. U.S. medical eligibility criteria for contraceptive use, 2024. MMWR Recomm Rep 2024;73:1-126.

  62. ESHRE Capri Workshop Group. Noncontraceptive health benefits of combined oral contraception. Hum Reprod Update 2005;11:513-25.

  63. Duralde ER, Sobel TH, Manson JE. Management of perimenopausal and menopausal symptoms. BMJ 2023;382:e072612.

  64. Lu CB, Liu PF, Zhou YS, Meng FC, Qiao TY, Yang XJ, et al. Musculoskeletal pain during the menopausal transition: A systematic review and meta-analysis. Neural Plast 2020;2020:8842110.

  65. Chlebowski RT, Cirillo DJ, Eaton CB, Stefanick ML, Pettinger M, Carbone LD, et al. Estrogen alone and joint symptoms in the women’s health initiative randomized trial. Menopause 2013;20:600-8.

  66. Baber RJ, Panay N, Fenton A. 2016 IMS recommendations on women’s midlife health and menopause hormone therapy. Climacteric 2016;19:109-50.

  67. Greendale GA, Gold EB. Lifestyle factors: Are they related to vasomotor symptoms and do they modify the effectiveness or side effects of hormone therapy? Am J Med 2005;118 Suppl 12B:148-54.

  68. Wright VJ, Schwartzman JD, Itinoche R, Wittstein J. The musculoskeletal syndrome of menopause. Climacteric 2024;27:466-72.

  69. Bromberger JT, Kravitz HM. Mood and menopause: Findings from the study of women’s health across the nation (SWAN) over 10 years. Obstet Gynecol Clin North Am 2011;38:609-25.

  70. Russell JK, Jones CK, Newhouse PA. The role of estrogen in brain and cognitive aging. Neurotherapeutics 2019;16:649-65.

  71. Conde DM, Verdade RC, Valadares AL, Mella LF, Pedro AO, Costa-Paiva L. Menopause and cognitive impairment: A narrative review of current knowledge. World J Psychiatry 2021;11:412-28.

  72. Williams M, Maki PM. A review of cognitive, sleep, and mood changes in the menopausal transition: Beyond vasomotor symptoms. Obstet Gynecol 2025;146:350-9.

  73. Metcalf CA, Duffy KA, Page CE, Novick AM. Cognitive problems in perimenopause: A review of recent evidence. Curr Psychiatry Rep 2023;25:501-11.

  74. Greendale GA, Huang MH, Wight RG, Seeman T, Luetters C, Avis NE, et al. Effects of the menopause transition and hormone use on cognitive performance in midlife women. Neurology 2009;72:1850-7.

  75. Drogos LL, Rubin LH, Geller SE, Banuvar S, Shulman LP, Maki PM. Objective cognitive performance is related to subjective memory complaints in midlife women with moderate to severe vasomotor symptoms. Menopause 2013;20:1236-42.

  76. Ye M, Shou M, Zhang J, Hu B, Liu C, Bi C, et al. Efficacy of cognitive therapy and behavior therapy for menopausal symptoms: A systematic review and meta-analysis. Psychol Med 2022;52:433-45.

  77. Hunter MS, Chilcot J. Is cognitive behaviour therapy an effective option for women who have troublesome menopausal symptoms? Br J Health Psychol 2021;26:697-708.

  78. Ayers B, Smith M, Hellier J, Mann E, Hunter MS. Effectiveness of group and self-help cognitive behavior therapy in reducing problematic menopausal hot flushes and night sweats (MENOS 2): A randomized controlled trial. Menopause 2012;19:749-59.

  79. Andy C, Nerattini M, Jett S, Carlton C, Zarate C, Boneu C, et al. Systematic review and meta-analysis of the effects of menopause hormone therapy on cognition. Front Endocrinol (Lausanne) 2024;15:1350318.

  80. Maki PM. Critical window hypothesis of hormone therapy and cognition. Menopause 2013;20:695-709.

  81. Gleason CE, Dowling NM, Kara F, James TT, Salazar H, Ferrer Simo CA, et al. Long-term cognitive effects of menopausal hormone therapy: Findings from the KEEPS continuation study. PLoS Med 2024;21:e1004435.

  82. Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women. JAMA 2003;289:2651.

  83. Coughlan GT, Rubinstein Z, Klinger H, Lopez KA, Hsieh S, Boyle R, et al. Associations between hormone therapy use and tau accumulation in brain regions vulnerable to Alzheimer’s disease. Sci Adv 2025;11:eadt1288.

  84. Badawy Y, Spector A, Li Z, Desai R. The risk of depression in the menopausal stages: A systematic review and meta-analysis. J Affect Disord 2024;357:126-33.

  85. Clayton AH, Ninan PT. Depression or menopause? Presentation and management of major depressive disorder in perimenopausal and postmenopausal women. Prim Care Companion J Clin Psychiatry 2010;12: PCC.08r00747.

  86. Freeman EW, Sammel MD, Lin H, Nelson DB. Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry 2006;63:375-82.

  87. Bromberger JT, Kravitz HM, Chang YF, Cyranowski JM, Brown C, Matthews KA. Major depression during and after the menopausal transition: Study of women’s health across the nation (SWAN). Psychol Med 2011;41:1879-88.

  88. Green SM, Donegan E, Frey BN, Fedorkow DM, Key BL, Streiner DL, et al. Cognitive behavior therapy for menopausal symptoms (CBT-Meno): A randomized controlled trial. Menopause 2019;26:972-80.

  89. Huang AJ, Faubion S, Grady D. Nonhormonal treatment of menopausal vasomotor symptoms. JAMA Intern Med 2025;185:874-5.

  90. McCormick CA, Brennan A, Hickey M. Managing vasomotor symptoms effectively without hormones. Climacteric 2020;23:532-8.

  91. Schmidt PJ, Ben Dor R, Martinez PE, Guerrieri GM, Harsh VL, Thompson K, et al. Effects of estradiol withdrawal on mood in women with past perimenopausal depression: A randomized clinical trial. JAMA Psychiatry 2015;72:714-26.

  92. Gordon JL, Rubinow DR, Watkins L, Hinderliter AL, Caughey MC, Girdler SS. The effect of perimenopausal transdermal estradiol and micronized progesterone on markers of risk for arterial disease. J Clin Endocrinol Metab 2020;105:e2050-60.

  93. Xu Q, Lang CP. Examining the relationship between subjective sleep disturbance and menopause: A systematic review and meta-analysis. Menopause 2014;21:1301-18.

  94. Kravitz HM, Zhao X, Bromberger JT, Gold EB, Hall MH, Matthews KA, et al. Sleep disturbance during the menopausal transition in a multi-ethnic community sample of women. Sleep 2008;31:979-90.

  95. Tandon VR, Sharma S, Mahajan A, Mahajan A, Tandon A. Menopause and sleep disorders. J Midlife Health 2022;13:26-33.

  96. Yin J, Jin X, Shan Z, Li S, Huang H, Li P, et al. Relationship of sleep duration with all-cause mortality and cardiovascular events: A systematic review and dose-response meta-analysis of prospective cohort studies. J Am Heart Assoc 2017;6:e005947.

  97. Baker FC, Lampio L, Saaresranta T, Polo-Kantola P. Sleep and sleep disorders in the menopausal transition. Sleep Med Clin 2018;13:443-56.

  98. Qaseem A, Kansagara D, Forciea MA, Cooke M, Denberg TD, Clinical Guidelines Committee of the American College of Physicians. Management of chronic insomnia disorder in adults: A clinical practice guideline from the American College of Physicians. Ann Intern Med 2016;165:125-33.

  99. Baker FC, de Zambotti M, Colrain IM, Bei B. Sleep problems during the menopausal transition: Prevalence, impact, and management challenges. Nat Sci Sleep 2018;10:73-95.

  100. Riemann D, Baglioni C, Bassetti C, Bjorvatn B, Dolenc Groselj L, Ellis JG, et al. European guideline for the diagnosis and treatment of insomnia. J Sleep Res 2017;26:675-700.

  101. The 2023 nonhormone therapy position statement of The North American Menopause Society. Menopause 2023;30:573-90.

  102. Geiger PJ, Eisenlohr-Moul T, Gordon JL, Rubinow DR, Girdler SS. Effects of perimenopausal transdermal estradiol on self-reported sleep, independent of its effect on vasomotor symptom bother and depressive symptoms. Menopause 2019;26:1318-23.

  103. Nolan BJ, Liang B, Cheung AS. Efficacy of micronized progesterone for sleep: A systematic review and meta-analysis of randomized controlled trial data. J Clin Endocrinol Metab 2021;106:942-51.

  104. Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: An American academy of sleep medicine clinical practice guideline. J Clin Sleep Med 2017;13:307-49.

  105. Krystal AD. Current, emerging, and newly available insomnia medications. J Clin Psychiatry 2015;76:e1045.

  106. Kishi T, Ikuta T, Citrome L, Sakuma K, Hatano M, Hamanaka S, et al. Comparative efficacy and safety of daridorexant, lemborexant, and suvorexant for insomnia: A systematic review and network meta-analysis. Transl Psychiatry 2025;15:211.

  107. Rosenberg RP, Benca R, Doghramji P, Roth T. A 2023 update on managing insomnia in primary care: Insights from an expert consensus group. Prim Care Companion CNS Disord 2023;25:22nr03385.

  108. Verma K, Singh D, Srivastava A. The impact of complementary and alternative medicine on insomnia: A systematic review. Cureus 2022;14:e28425.

  109. Portman DJ, Gass ML. Genitourinary syndrome of menopause: New terminology for vulvovaginal atrophy from the international society for the study of women’s sexual health and The North American Menopause Society. Climacteric 2014;17:557-63.

  110. Ashraf AB, Meeta M, Chitra AB, Pahwa S, Shah J, Mohi M, et al. Genitourinary syndrome of menopause: A multicenter study from the Indian Midlife Registry. Climacteric 2025;28:329-36.

  111. Singh M. Early age of natural menopause in India, a biological marker for early preventive health programs. Climacteric 2012;15:581-6.

  112. Ulhe SC, Acharya N, Vats A, Singh A. Study of vulvovaginal atrophy and genitourinary syndrome of menopause and its impact on the quality of life of postmenopausal women in central India. Cureus 2024;16:e54802.

  113. Nappi RE, Palacios S, Panay N, Particco M, Krychman ML. Vulvar and vaginal atrophy in four European countries: Evidence from the European REVIVE survey. Climacteric 2016;19:188-97.

  114. Parish SJ, Nappi RE, Krychman ML, Kellogg-Spadt S, Simon JA, Goldstein JA, et al. Impact of vulvovaginal health on postmenopausal women: A review of surveys on symptoms of vulvovaginal atrophy. Int J Womens Health 2013;5:437-47.

  115. McEndree B. Clinical application of the vaginal maturation index. Nurse Pract 1999;24:48, 51-2, 55-6.

  116. Bachmann GA, Notelovitz M, Kelly SJ. Long-term nonhormonal treatment of vaginal dryness. Clin Pract Sex 1992;8:3-8.

  117. Food and Drug Administration. Guidance for Industry: Estrogen and Estrogen/Progestin Products to Treat Vasomotor Symptoms and Vulvar and Vaginal Atrophy Symptoms-Recommendation for Clinical Evaluation; 2022. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/estrogen-and-estrogenprogestin-drug-products-treat-vasomotor-symptoms-and-vulvar-and-vaginal-atrophy. [Last accessed on 2025 Sep 19].

  118. Mension E, Alonso I, Tortajada M, Matas I, Gómez S, Ribera L, et al. Genitourinary syndrome of menopause assessment tools. J Midlife Health 2021;12:99-102.

  119. NIH state-of-the-science conference statement on management of menopause-related symptoms. NIH Consens State Sci Statements 2005;22:1-38.

  120. Mitchell CM, Larson JC, Reed SD, Guthrie KA. The complexity of genitourinary syndrome of menopause: Number, severity, and frequency of vulvovaginal discomfort symptoms in women enrolled in a randomized trial evaluating treatment for genitourinary syndrome of menopause. Menopause 2023;30:791-7.

  121. Christmas M, Huguenin A, Iyer S. Clinical practice guidelines for managing genitourinary symptoms associated with menopause. Clin Obstet Gynecol 2024;67:101-14.

  122. Derzko CM, Röhrich S, Panay N. Does age at the start of treatment for vaginal atrophy predict response to vaginal estrogen therapy? Post hoc analysis of data from a randomized clinical trial involving 205 women treated with 10μg estradiol vaginal tablets. Menopause 2020;28:113-8.

  123. Lethaby A, Ayeleke RO, Roberts H. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev 2016;2016: CD001500.

  124. Krause M, Wheeler TL 2nd, Snyder TE, Richter HE. Local effects of vaginally administered estrogen therapy: A review. J Pelvic Med Surg 2009;15:105-14.

  125. Christmas MM, Iyer S, Daisy C, Maristany S, Letko J, Hickey M. Menopause hormone therapy and urinary symptoms: A systematic review. Menopause 2023;30:672-85.

  126. Long CY, Liu CM, Hsu SC, Wu CH, Wang CL, Tsai EM. A randomized comparative study of the effects of oral and topical estrogen therapy on the vaginal vascularization and sexual function in hysterectomized postmenopausal women. Menopause 2006;13:737-43.

  127. Suckling J, Lethaby A, Kennedy R. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev 2006;(4): CD001500.

  128. Faubion SS, Crandall CJ, Davis L, El Khoudary SR, Hodis HN, Lobo RA, et al. The 2022 hormone therapy position statement of The North American Menopause Society. Menopause 2022;29:767-94.

  129. Goetsch MF, Garg B, Lillemon J, Clark AL. Treating where it hurts-a randomized comparative trial of vestibule estradiol for postmenopausal dyspareunia. Menopause 2023;30:467-75.

  130. Porcari I, Uccella S, Casprini C, Bosco M, Zorzato PC, Garzon S. Vulvovaginal estrogen therapy for urinary symptoms in postmenopausal women: a review and meta-analysis. Climacteric 2025:1-10.

  131. Chen YY, Su TH, Lau HH. Estrogen for the prevention of recurrent urinary tract infections in postmenopausal women: A meta-analysis of randomized controlled trials. Int Urogynecol J 2021;32:17-25.

  132. Muiños Fernández N, Martínez Salamanca JI, Pardo González de Quevedo JI, Diz Morales MP, Palomo Alameda L, Duce Tello S, et al. Efficacy and safety of an ultra-low-dose 0.005 % estriol vaginal gel in the prevention of urinary tract infections in postmenopausal women with genitourinary syndrome of menopause: A randomized double-blind placebo-controlled trial. Maturitas 2024;190:108128.

  133. Fox KA, Lokken EM, Reed SD, Rahn DD. Evaluation of systemic estrogen for preventing urinary tract infections in postmenopausal women. Menopause 2021;28:836-44.

  134. Ferrante KL, Wasenda EJ, Jung CE, Adams-Piper ER, Lukacz ES. Vaginal estrogen for the prevention of recurrent urinary tract infection in postmenopausal women: A randomized clinical trial. Female Pelvic Med Reconstr Surg 2021;27:112-7.

  135. Pugliese D, Acampora A, Porreca A, Schips L, Cindolo L. Effectiveness of a novel oral combination of D-mannose, pomegranate extract, prebiotics and probiotics in the treatment of acute cystitis in women. Arch Ital Urol Androl 2020;92:34-8.

  136. Raz R. Urinary tract infection in postmenopausal women. Korean J Urol 2011;52:801-8.

  137. Nicolle LE, Gupta K, Bradley SF, Colgan R, DeMuri GP, Drekonja D, et al. Clinical practice guideline for the management of asymptomatic bacteriuria: 2019 update by the infectious diseases society of America. Clin Infect Dis 2019;68:e83-110.

  138. Zalmanovici Trestioreanu A, Lador A, Sauerbrun-Cutler MT, Leibovici L. Antibiotics for asymptomatic bacteriuria. Cochrane Database Syst Rev 2015;4: CD009534.

  139. Cody JD, Jacobs ML, Richardson K, Moehrer B, Hextall A. Oestrogen therapy for urinary incontinence in post-menopausal women. Cochrane Database Syst Rev 2012;10: CD001405.

  140. Russo E, Caretto M, Giannini A, Bitzer J, Cano A, Ceausu I, et al. Management of urinary incontinence in postmenopausal women: An EMAS clinical guide. Maturitas 2021;143:223-30.

  141. Anger J, Lee U, Ackerman AL, Chou R, Chughtai B, Clemens JQ, et al. Recurrent uncomplicated urinary tract infections in women: AUA/CUA/SUFU guideline. J Urol 2019;202:282-9.

  142. Robinson D, Cardozo LD. The role of estrogens in female lower urinary tract dysfunction. Urology 2003;62:45-51.

  143. Taithongchai A, Johnson EE, Ismail SI, Barron-Millar E, Kernohan A, Thakar R. Oestrogen therapy for treating pelvic organ prolapse in postmenopausal women. Cochrane Database Syst Rev 2023;7: CD014592.

  144. Zhou Y, Yin R, Zhang Y, Wang X, Jin F, Li X, et al. Effects of intravaginal conjugated oestrogen on pessary continuation for pelvic organ prolapse: Multicentre, randomised, double blind, placebo controlled trial. BMJ 2025;389:e084418.

  145. Rahn DD, Good MM, Roshanravan SM, Shi H, Schaffer JI, Singh RJ, et al. Effects of preoperative local estrogen in postmenopausal women with prolapse: A randomized trial. J Clin Endocrinol Metab 2014;99:3728-36.

  146. Vodegel EV, Kastelein AW, Jansen CH, Limpens J, Zwolsman SE, Roovers JW, et al. The effects of oestrogen on vaginal wound healing: A systematic review and meta-analysis. Neurourol Urodyn 2022;41:115-26.

  147. Mourtada S, Shepherd Y, Pevida M. Abnormal Pap Smears as Early Signs of GSM: Effect of Local Estrogen Therapy. Poster Presented at The Menopause Society Annual Meeting; 2024. Available from: https://menopause.org/wp-content/uploads/2024/09/2024-Oral-and-Poster-Presentation-Abstracts.pdf#:~:text=Abnormal%20PAP%20smears%20are%20one,Shepherd1%2C%20Monica%20Pevida%2C%20medical%20student1%2C. [Last acessed on 2025 Dec 10].

  148. Carlson K, Nguyen H. Genitourinary Syndrome of Menopause. [Updated 2024 Oct 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559297/. [Last acessed on 2025 Dec 28].

  149. Cucinella L, Tiranini L, Cassani C, Martini E, Cumetti A, Memoli S, et al. Insights into the vulvar component of the genitourinary syndrome of menopause (GSM). Maturitas 2024;186:108006.

  150. Ali A, Iftikhar A, Tabassum M, Imran R, Shaid MU, Hashmi MR, et al. Efficacy and safety of intravaginal estrogen in the treatment of atrophic vaginitis: A systematic review and meta-analysis. J Menopausal Med 2024;30:88-103.

  151. Griesser H, Skonietzki S, Fischer T, Fielder K, Suesskind M. Low dose estriol pessaries for the treatment of vaginal atrophy: A double-blind placebo-controlled trial investigating the efficacy of pessaries containing 0.2mg and 0.03mg estriol. Maturitas 2012;71:360-8.

  152. Santen RJ, Mirkin S, Bernick B, Constantine GD. Systemic estradiol levels with low-dose vaginal estrogens. Menopause 2020;27:361-70.

  153. Hirschberg AL, Sánchez-Rovira P, Presa-Lorite J, Campos-Delgado M, Gil-Gil M, Lidbrink E, et al. Efficacy and safety of ultra-low dose 0.005% estriol vaginal gel for the treatment of vulvovaginal atrophy in postmenopausal women with early breast cancer treated with nonsteroidal aromatase inhibitors: A phase II, randomized, double-blind, placebo-controlled trial. Menopause 2020;27:526-34.

  154. Simon J, Nachtigall L, Gut R, Lang E, Archer DF, Utian W. Effective treatment of vaginal atrophy with an ultra-low-dose estradiol vaginal tablet. Obstet Gynecol 2008;112:1053-60.

  155. Biehl C, Plotsker O, Mirkin S. A systematic review of the efficacy and safety of vaginal estrogen products for the treatment of genitourinary syndrome of menopause. Menopause 2019;26:431-53.

  156. Deli T, Orosz M, Jakab A. Hormone replacement therapy in cancer survivors – Review of the literature. Pathol Oncol Res 2020;26:63-78.

  157. Cagnacci A, Villa P, Grassi GP, Biglia N, Gambacciani M, Di Carlo C, et al. Systemic hormone therapy after breast and gynecological cancers: An Italian expert group consensus opinion. Climacteric 2025;28:4-14.

  158. Fischer G, Ayer B, Frankum B, Spurrett B. Vulvitis attributed to hypersensitivity to estrogen. A report of 11 cases. J Reprod Med 2000;45:493-7.

  159. Yang F, Xu Y, Li X. Estradiol valerate tablets caused rare severe drug eruption: The first reported case. Clin Cosmet Investig Dermatol 2024;17:2277-81.

  160. Untersmayr E, Jensen AN, Walch K. Sex hormone allergy: Clinical aspects, causes and therapeutic strategies – Update and secondary publication. World Allergy Organ J 2017;10:45.

  161. Beste ME, Kaunitz AM, McKinney JA, Sanchez-Ramos L. Vaginal estrogen use in breast cancer survivors: A systematic review and meta-analysis of recurrence and mortality risks. Am J Obstet Gynecol 2025;232:262-70.e1.

  162. Abou-Ismail MY, Citla Sridhar D, Nayak L. Estrogen and thrombosis: A bench to bedside review. Thromb Res 2020;192:40-51.

  163. Crandall CJ, Hovey KM, Andrews CA, Chlebowski RT, Stefanick ML, Lane DS, et al. Breast cancer, endometrial cancer, and cardiovascular events in participants who used vaginal estrogen in the women’s health initiative observational study. Menopause 2018;25:11-20.

  164. Bhupathiraju SN, Grodstein F, Stampfer MJ, Willett WC, Crandall CJ, Shifren JL, et al. Vaginal estrogen use and chronic disease risk in the nurses’ health study. Menopause 2018;26:603-10.

  165. Kaufman MR, Ackerman AL, Amin KA, Coffey M, Danan E, Faubion SS, et al. The AUA/SUFU/AUGS guideline on genitourinary syndrome of menopause. J Urol 2025;214:242-50.

  166. Nappi RE, Palacios S. Impact of vulvovaginal atrophy on sexual health and quality of life at postmenopause. Climacteric 2014;17:3-9.

  167. Sturdee DW, Panay N, International Menopause Society Writing Group. Recommendations for the management of postmenopausal vaginal atrophy. Climacteric 2010;13:509-22.

  168. Stanczyk FZ, Mandelbaum RS, Matharu H, Dancz CE, Sherman ME. Endometrial safety of low-dose vaginal estrogens. Menopause 2023;30:650-8.

  169. Bachmann G, Bouchard C, Hoppe D, Ranganath R, Altomare C, Vieweg A, et al. Efficacy and safety of low-dose regimens of conjugated estrogens cream administered vaginally. Menopause 2009;16:719-27.

  170. Pitkin J, British Menopause Society Medical Advisory Council. BMS – Consensus statement. Post Reprod Health 2018;24:133-8.

  171. Da Silva AS, Baines G, Araklitis G, Robinson D, Cardozo L. Modern management of genitourinary syndrome of menopause. Fac Rev 2021;10:25.

  172. Swanson SG, Drosman S, Helmond FA, Stathopoulos VM. Tibolone for the treatment of moderate to severe vasomotor symptoms and genital atrophy in postmenopausal women: A multicenter, randomized, double-blind, placebo-controlled study. Menopause 2006;13:917-25.

  173. Portman DJ, Bachmann GA, Simon JA, Ospemifene Study Group. Ospemifene, a novel selective estrogen receptor modulator for treating dyspareunia associated with postmenopausal vulvar and vaginal atrophy. Menopause 2013;20:623-30.

  174. Bruyniks N, Biglia N, Palacios S, Mueck AO. Systematic indirect comparison of ospemifene versus local estrogens for vulvar and vaginal atrophy. Climacteric 2017;20:195-204.

  175. Simon JA, Altomare C, Cort S, Jiang W, Pinkerton JV. Overall safety of ospemifene in postmenopausal women from placebo-controlled phase 2 and 3 trials. J Womens Health (Larchmt) 2018;27:14-23.

  176. Hussain I, Talaulikar VS. A systematic review of randomised clinical trials – The safety of vaginal hormones and selective estrogen receptor modulators for the treatment of genitourinary menopausal symptoms in breast cancer survivors. Post Reprod Health 2023;29:222-31.

  177. Cai B, Simon J, Villa P, Biglia N, Panay N, Djumaeva S, et al. No increase in incidence or risk of recurrence of breast cancer in ospemifene-treated patients with vulvovaginal atrophy (VVA). Maturitas 2020;142:38-44.

  178. Sánchez-Borrego R, de Diego Pérez de Zabalza MV, Alfageme Gullón MJ, Alija Castrillo ML, Sánchez Prieto M, Palacios S, et al. Satisfaction and medication adherence in women with vulvovaginal atrophy: The CRETA. Climacteric 2023;26:437-44.

  179. Labrie F. Intracrinology: The new science of sex steroid physiology in women. In: Birkhaeuser M, Genazzani A, editors. Pre-Menopause, Menopause and Beyond. ISGE Series. Cham, Switzerland: Springer; 2018. p. 3-15.

  180. Aarshageetha P, Janci PR, Tharani ND. Role of alternate therapies to improve the quality of life in menopausal women: A systematic review. J Midlife Health 2023;14:153-8.

  181. Pitsouni E, Grigoriadis T, Douskos A, Kyriakidou M, Falagas ME, Athanasiou S. Efficacy of vaginal therapies alternative to vaginal estrogens on sexual function and orgasm of menopausal women: A systematic review and meta-analysis of randomized controlled trials. Eur J Obstet Gynecol Reprod Biol 2018;229:45-56.

  182. Angelou K, Grigoriadis T, Diakosavvas M, Zacharakis D, Athanasiou S. The genitourinary syndrome of menopause: An overview of the recent data. Cureus 2020;12:e7586.

  183. Shim S, Park KM, Chung YJ, Kim MR. Updates on therapeutic alternatives for genitourinary syndrome of menopause: Hormonal and non-hormonal managements. J Menopausal Med 2021;27:1-7.

  184. Sarmento AC, Kamilos MF, Costa AP, Vieira-Baptista P, Eleutério J Jr., Gonçalves AK. Use of moisturizers and lubricants for vulvovaginal atrophy. Front Reprod Health 2021;3:781353.

  185. WHO UF 360. Use and Procurement of Additional Lubricants for Male and Female Condoms: WHO/UNFPA/FHI360 Advisory Note. Department of Reproductive Health and Research. WHO RHR/1233; 2012. Available from: https://iris.who.int. [Last accessed on 2025 Oct 19].

  186. Na Takuathung M, Inpan R, Yaja K, Ruansit W, Teekachunhatean S, Koonrungsesomboon N. Isoflavones improve vaginal atrophy, skin health, and sex-related hormones in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials. Menopause 2025. doi: 10.1097/GME.0000000000002619. Epub ahead of print.

  187. Mishra V, Chaudhary S, Rajender G, Chaudhary D. A prospective study to investigate the 12-week efficacy of soy isoflavone vaginal gel (0.5%) in postmenopausal women with symptoms of vulvovaginal atrophy. J South Asian Fed Obstet Gynaecol 2023;15:308-12.

  188. Lima SM, Yamada SS, Reis BF, Postigo S, Galvão da Silva MA, Aoki T. Effective treatment of vaginal atrophy with isoflavone vaginal gel. Maturitas 2013;74:252-8.

  189. Salvatore S, Ruffolo AF, Phillips C, Athanasiou S, Cardozo L, Serati M, et al. Vaginal laser therapy for GSM/VVA: Where we stand now – A review by the EUGA working group on laser. Climacteric 2023;26:336-52.

  190. Gottlieb S. Statement from FDA Commissioner on Efforts to Safeguard Women’s Health from Deceptive Health Claims and Significant Risks Related to Devices Marketed for Use in Medical Procedures for “Vaginal Rejuvenation. FDA Website; 2018. Available from: https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-efforts-safeguard-womens-health-deceptive-health-claims. [Last accessed on 2025 Oct 10].

  191. Lőczi LL, Vleskó G, Éliás M, Turan C, Kajtár P, Tóth R, et al. Effect of vaginal laser and topical therapies on vulvovaginal atrophy symptoms in breast cancer patients: A systematic review and meta-analysis. J Clin Med 2024;13:6131.

  192. Jafarzade A, Biri A, Ekiz OU, Mungan T. Vaginal LASER and estrogen comparison in genitourinary syndrome of menopause. Continence 2025;13:101724. Available from: https://www.sciencedirect.com/science/article/pii/S2772973724009998?via%3Dihub. [Last accessed on 2025 Dec 24].

  193. Danan ER, Diem S, Sowerby C, Ullman K, Ensrud K, Landsteiner A, et al. Genitourinary Syndrome of Menopause: A Systematic Review. Rockville (MD): Agency for Healthcare Research and Quality (US); 2024.

  194. Jafarzade A, Mungan T, Aghayeva S, Yıldırım Baydemir B, Ekiz OU, Biri A. A comparison of hyaluronic acid and estradiol treatment in vulvovaginal atrophy. Eur Rev Med Pharmacol Sci 2024;28:571-6.

  195. Albalawi NS, Almohammadi MA, Albalawi AR. Comparison of the efficacy of vaginal hyaluronic acid to estrogen for the treatment of vaginal atrophy in postmenopausal women: A systematic review. Cureus 2023;15:e44191.

  196. Barnaś E, Barańska E, Gawlik B. Factors most significantly affecting quality of life in women with urinary incontinence. HYGEIA Public Health 2015;50:643-8.

  197. Sultana A, Najeeya AG, Rahman K, Saeedi R, Khanam M. Mixed urinary incontinence (MUI) in women: From evidence to clinical practice. J Health Sci Res 2021;5:39-50. Available from: https://jhsronline.com/index.php/jhsr/article/view/21. [Last accessed on 2023 Feb 22].

  198. Leslie SW, Tran LN, Puckett Y. Urinary incontinence. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559095/. [Last updated on 2024 Aug 11].

  199. Nager CW, Brubaker L, Litman HJ, Zyczynski HM, Varner RE, Amundsen C, et al. A randomized trial of urodynamic testing before stress-incontinence surgery. N Engl J Med 2012;366:1987-97.

  200. Kobashi KC, Albo ME, Dmochowski RR, Ginsberg DA, Goldman HB, Gomelsky A, et al. Surgical treatment of female stress urinary incontinence: AUA/SUFU guideline. J Urol 2017;198:875-83.

  201. Urinary incontinence and pelvic organ prolapse in women: management. London: National Institute for Health and Care Excellence (NICE); 2019. (NICE Guideline, No. 123.). Available from: https://www.ncbi.nlm.nih.gov/books/NBK542416/.

  202. Cameron AP, Chung DE, Dielubanza EJ, Enemchukwu E, Ginsberg DA, Helfand BT, et al. The AUA/SUFU guideline on the diagnosis and treatment of idiopathic overactive bladder. J Urol 2024;212:11-20.

  203. Gormley EA, Lightner DJ, Faraday M, Vasavada SP, American Urological Association, Society of Urodynamics, Female Pelvic Medicine. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline amendment. J Urol 2015;193:1572-80.

  204. Malinauskas AP, Bressan EF, de Melo AM, Brasil CA, Lordêlo P, Torelli L. Efficacy of pelvic floor physiotherapy intervention for stress urinary incontinence in postmenopausal women: Systematic review. Arch Gynecol Obstet 2023;308:13-24.

  205. Srinivasan A, Sanghavi P. Effectiveness of home-based pelvic floor muscle training on stress urinary incontinence and quality of life in multiparous women. Natl J Community Med 2023;14:506-11.

  206. Jain N, Mehra R, Goel P, Chavan BS. Sexual health of postmenopausal women in North India. J Midlife Health 2019;10:70-4.

  207. Meeta M, Majumdar S, Tanvir T, Sharma S, Shah J, Aggarwal N, et al. Effects of menopause on sexual function in Indian women: A McCoy’s questionnaire-based assessment. J Midlife Health 2021;12:144-54.

  208. Thomas HN, Thurston RC. A biopsychosocial approach to women’s sexual function and dysfunction at midlife: A narrative review. Maturitas 2016;87:49-60.

  209. Mernone L, Fiacco S, Ehlert U. Psychobiological factors of sexual functioning in aging women – Findings from the women 40+ healthy aging study. Front Psychol 2019;10:546.

  210. Perelman MA, Giraldi A, Parish S, Wittmann D, Fisher W, Bober SL, et al. How has the biopsychosocial model fared in sexual medicine and sex therapy? Sex Med Rev 2025;13:663-73.

  211. Kingsberg SA, Schaffir J, Faught BM, Pinkerton JV, Parish SJ, Iglesia CB, et al. Female sexual health: Barriers to optimal outcomes and a roadmap for improved patient-clinician communications. J Womens Health (Larchmt) 2019;28:432-43.

  212. Danan ER, Sowerby C, Ullman KE, Ensrud K, Forte ML, Zerzan N, et al. Hormonal treatments and vaginal moisturizers for genitourinary syndrome of menopause: A systematic review. Ann Intern Med 2024;177:1400-14.

  213. Marchetti G, Taithongchai A, Robinson D. Ospemifene for genitourinary syndrome of menopause: Patient selection. Int J Womens Health 2024;16:1049-53.

  214. Lara LA, Cartagena-Ramos D, Figueiredo JB, Rosa-E-Silva AC, Ferriani RA, Martins WP, et al. Hormone therapy for sexual function in perimenopausal and postmenopausal women. Cochrane Database Syst Rev 2023;8: CD009672.

  215. Gao Z, Yang D, Yu L, Cui Y. Efficacy and Safety of flibanserin in women with hypoactive sexual desire disorder: A systematic review and meta-analysis. J Sex Med 2015;12:2095-104.

  216. Kennedy SH, Rizvi S. Sexual dysfunction, depression, and the impact of antidepressants. J Clin Psychopharmacol 2009;29:157-64.

  217. Razali NA, Sidi H, Choy CL, Roos NA, Baharudin A, Das S. The role of bupropion in the treatment of women with sexual desire disorder: A systematic review and meta-analysis. Curr Neuropharmacol 2022;20:1941-55.

  218. Greendale GA, Han W, Finkelstein JS, Burnett-Bowie SM, Huang M, Martin D, et al. Changes in regional fat distribution and anthropometric measures across the menopause transition. J Clin Endocrinol Metab 2021;106:2520-34.

  219. Samargandy S, Matthews KA, Brooks MM, Barinas-Mitchell E, Magnani JW, Janssen I, et al. Abdominal visceral adipose tissue over the menopause transition and carotid atherosclerosis: The SWAN heart study. Menopause 2021;28:626-33.

  220. El Khoudary SR, Shields KJ, Janssen I, Hanley C, Budoff MJ, Barinas-Mitchell E, et al. Cardiovascular fat, menopause, and sex hormones in women: The SWAN cardiovascular fat ancillary study. J Clin Endocrinol Metab 2015;100:3304-12.

  221. Opoku AA, Abushama M, Konje JC. Obesity and menopause. Best Pract Res Clin Obstet Gynaecol 2023;88:102348.

  222. Greendale GA, Sowers M, Han W, Huang MH, Finkelstein JS, Crandall CJ, et al. Bone mineral density loss in relation to the final menstrual period in a multiethnic cohort: Results from the study of women’s health across the nation (SWAN). J Bone Miner Res 2012;27:111-8.

  223. Cauley JA, Robbins J, Chen Z, Cummings SR, Jackson RD, LaCroix AZ, et al. Effects of estrogen plus progestin on risk of fracture and bone mineral density: The women’s health initiative randomized trial. JAMA 2003;290:1729-38.

  224. Divaris E, Anagnostis P, Gkekas NK, Kouidi E, Goulis DG. Early menopause and premature ovarian insufficiency may increase the risk of sarcopenia: A systematic review and meta-analysis. Maturitas 2023;175:107782.

  225. Mesinovic J, Hurst C, Leung GK, Ryan JR, Daly RM, Scott D. Exercise and dietary recommendations to preserve musculoskeletal health during weight loss in adults with obesity: A practical guide. Rev Endocr Metab Disord 2025;26:785-803.

  226. McPhee C, Aninye IO, Horan L. Recommendations for improving women’s bone health throughout the lifespan. J Womens Health (Larchmt) 2022;31:1671-6.

  227. Ranjan P, Vikram NK, Choranur A, Pradeep Y, Ahuja M, Meeta M, et al. Executive summary of evidence and consensus-based clinical practice guidelines for management of obesity and overweight in midlife women: An AIIMS-DST initiative. J Midlife Health 2022;13:34-49.

  228. Brincat MP, Baron YM, Galea R. Estrogens and the skin. Climacteric 2005;8:110-23.

  229. Rivera R, Guerra-Tapia A. Management of androgenetic alopecia in postmenopausal women. Actas Dermosifiliogr 2008;99:257-61.

  230. Affinito P, Palomba S, Sorrentino C, Di Carlo C, Bifulco G, Arienzo MP, et al. Effects of postmenopausal hypoestrogenism on skin collagen. Maturitas 1999;33:239-47.

  231. Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L, et al. ESHRE consensus on the definition of ‘poor response’ to ovarian stimulation for in vitro fertilization: The Bologna criteria. Hum Reprod 2011;26:1616-24.

  232. Practice Committee of the American Society for Reproductive Medicine Electronic Address: Asrm@asrmorg, Practice Committee of the American Society for Reproductive Medicine. Evidence-based treatments for couples with unexplained infertility: A guideline. Fertil Steril 2020;113:305-22.

  233. ESHRE Guideline Group on Female Fertility Preservation, Anderson RA, Amant F, Braat D, D’Angelo A, Chuva de Sousa Lopes SM, et al. ESHRE guideline: Female fertility preservation. Hum Reprod Open 2020;2020:hoaa052.

  234. ESHRE Working Group on Reproductive Donation, Kirkman-Brown J, Calhaz-Jorge C, Dancet EA, Lundin K, Martins M, et al. Good practice recommendations for information provision for those involved in reproductive donation. Hum Reprod Open 2022;2022:hoac001.

  235. Viotti M, McCoy RC, Griffin DK, Spinella F, Greco E, Madjunkov M, et al. Let the data do the talking: The need to consider mosaicism during embryo selection. Fertil Steril 2021;116:1212-9.

  236. Besser AG, Mounts EL, Grifo JA. Evidence-based management of preimplantation chromosomal mosaicism: Lessons from the clinic. Fertil Steril 2021;116:1220-4.

  237. Harper T, Kuohung W, Sayres L, Willis MD, Wise LA. Optimizing preconception care and interventions for improved population health. Fertil Steril 2023;120:438-48.

  238. Saccone G, Gragnano E, Ilardi B, Marrone V, Strina I, Venturella R, et al. Maternal and perinatal complications according to maternal age: A systematic review and meta-analysis. Int J Gynaecol Obstet 2022;159:43-55.

  239. Practice Committee of the American Society for Reproductive Medicine Electronic Address: Asrm@asrmorg. Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: A committee opinion. Fertil Steril 2019;112:1022-33.

  240. Cobo A, García-Velasco JA, Coello A, Domingo J, Pellicer A, Remohí J. Oocyte vitrification as an efficient option for elective fertility preservation. Fertil Steril 2016;105:755-64.e8.

  241. Chronopoulou E, Raperport C, Sfakianakis A, Srivastava G, Homburg R. Elective oocyte cryopreservation for age-related fertility decline. J Assist Reprod Genet 2021;38:1177-86.

  242. Mesen TB, Mersereau JE, Kane JB, Steiner AZ. Optimal timing for elective egg freezing. Fertil Steril 2015;103:1551-6.e1.

  243. Faculty of Sexual & Reproductive Healthcare (FSRH). Faculty of Sexual & Reproductive Healthcare (FSRH). FSRH Guideline: Contraception for Women Aged Over 40 Years. London: FSRH; 2017. Available from: https://www.fsrh.org/standards-and-guidance/documents/fsrh-guidance-contraception-for-women-aged-over-40-years-2017/. [Last accessed on 2025 Nov 01].

  244. Meeta M, Digumarti L, Agarwal N, Vaze N, Shah R, Malik S. Clinical practice guidelines on menopause: An executive summary and recommendations. J Midlife Health 2013;4:77-106.

  245. Kuppusamy P, Prusty RK, Kale DP. High-risk pregnancy in India: Prevalence and contributing risk factors – A national survey-based analysis. J Glob Health 2023;13:04116.

  246. Tambvekar SE, Adki S, Sheriar NK. Pregnancies in elderly mothers over 40 years: What to expect from the rising new age high-risk cohort? J Obstet Gynaecol India 2023;73:358-62.

  247. Bateman BT, Simpson LL. Higher rate of stillbirth at the extremes of reproductive age: A large nationwide sample of deliveries in the United States. Am J Obstet Gynecol 2006;194:840-5.

  248. Dehlendorf C, Krajewski C, Borrero S. Contraceptive counseling. Clin Obstet Gynecol 2014;57:659-73.

  249. Schwingl PJ, Guess HA. Safety and effectiveness of vasectomy. Fertil Steril 2000;73:923-36.

  250. Indian Council of Medical Research. Collaborative Study on Sequelae of Tubal Sterilization. New Delhi: Indian Council of Medical Research; 1982. Available from: https://openlibrary.org/books/OL3006889M/Collaborative_study_on_sequelae_of_tubal_sterilization. [Last accessed on 2025 Oct 10].

  251. Mor-Hadar D, Wilailak S, Berek J, McNally OM, FIGO Committee on Women’s Cancer. FIGO position statement on opportunistic salpingectomy as an ovarian cancer prevention strategy. Int J Gynaecol Obstet 2024;167:976-80.

  252. Siegler AM, Hulka J, Peretz A. Reversibility of female sterilization. Fertil Steril 1985;43:499-510.

  253. Schrager S, Larson M, Carlson J, Ledford K, Ehrenthal DB. Beyond birth control: Noncontraceptive benefits of hormonal methods and their key role in the general medical care of women. J Womens Health (Larchmt) 2020;29:937-43.

  254. Curtis KM, Tepper NK, Jatlaoui TC, Berry-Bibee E, Horton LG, Zapata LB, et al. U.S. medical eligibility criteria for contraceptive use, 2016. MMWR Recomm Rep 2016;65:1-103.

  255. Ratnam SS, Campana A. First Consensus Meeting on Menopause in the East Asian Region. Geneva: Medical Forum International, Foundation for Medical Education and Research; 1997.

  256. Shapiro S, Rosenberg L, Hoffman M, Truter H, Cooper D, Rao S, et al. Risk of breast cancer in relation to the use of injectable progestogen contraceptives and combined estrogen/progestogen contraceptives. Am J Epidemiol 2000;151:396-403.

  257. Oedingen C, Scholz S, Razum O. Systematic review and meta-analysis of the association of combined oral contraceptives on the risk of venous thromboembolism: The role of the progestogen type and estrogen dose. Thromb Res 2018;165:68-78.

  258. Curtis KM, Nguyen AT, Tepper NK, Zapata LB, Snyder EM, Hatfield-Timajchy K, et al. U.S. selected practice recommendations for contraceptive use, 2024. MMWR Recomm Rep 2024;73:1-77.

  259. World Health Organization. Medical Eligibility Criteria for Contraceptive Use. 5th ed. Geneva: World Health Organization; 2015. Available from: https://www.ncbi.nlm.nih.gov/books/nbk321151/. [last accessed on 2025 Sep 10].

  260. Lidegaard Ø, Løkkegaard E, Svendsen AL, Agger C. Hormonal contraception and risk of venous thromboembolism: National follow-up study. BMJ 2009;339:b2890.

  261. Roach RE, Helmerhorst FM, Lijfering WM, Stijnen T, Algra A, Dekkers OM. Combined oral contraceptives: The risk of myocardial infarction and ischemic stroke. Cochrane Database Syst Rev 2015;2015: CD011054.

  262. Wood AJ, Baird DT, Glasier AF. Hormonal contraception. N Engl J Med 1993;328:1543-9.

  263. Creinin MD. Laboratory criteria for menopause in women using oral contraceptives. Fertil Steril 1996;66:101-4.

  264. van Heusden AM, Fauser BC. Activity of the pituitary-ovarian axis in the pill-free interval during use of low-dose combined oral contraceptives. Contraception 1999;59:237-43.

  265. Mishell DR Jr., Nakamura RM, Crosignani PG, Stone S, Kharma K, Nagata Y, et al. Serum gonadotropin and steroid patterns during the normal menstrual cycle. Am J Obstet Gynecol 1971;111:60-5.

  266. Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 2016;149:315-52.

  267. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins-Gynecology. Prevention of venous thromboembolism in gynecologic surgery: ACOG practice bulletin, number 232. Obstet Gynecol 2021;138:e1-15.

  268. Lukes AS, Kouides PA, Moore KA. Tranexamic acid: A novel oral formulation for the treatment of heavy menstrual bleeding. Womens Health (Lond) 2011;7:151-8.

  269. Abdel-Aleem H, d’Arcangues C, Vogelsong KM, Gaffield ML, Gülmezoglu AM. Treatment of vaginal bleeding irregularities induced by progestin only contraceptives. Cochrane Database Syst Rev 2013;(7): CD003449.

  270. Alvarez-Sanchez F, Brache V, Thevenin F, Cochon L, Faundes A. Hormonal treatment for bleeding irregularities in norplant implant users. Am J Obstet Gynecol 1996;174:919-22.

  271. Edelman AB, Kaneshiro B, Simmons KB, Hauschildt JL, Bond K, Boniface ER, et al. Treatment of unfavorable bleeding patterns in contraceptive implant users: A randomized controlled trial. Obstet Gynecol 2020;136:323-32.

  272. Simmons KB, Edelman AB, Fu R, Jensen JT. Tamoxifen for the treatment of breakthrough bleeding with the etonogestrel implant: A randomized controlled trial. Contraception 2017;95:198-204.

  273. Lethaby A, Hussain M, Rishworth JR, Rees MC. Progesterone or progestogen-releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database Syst Rev 2015;(4): CD002126.

  274. Orbo A, Vereide A, Arnes M, Pettersen I, Straume B. Levonorgestrel-impregnated intrauterine device as treatment for endometrial hyperplasia: A national multicentre randomised trial. BJOG 2014;121:477-86.

  275. Grimes DA, Lopez LM, Manion C, Schulz KF. Cochrane systematic reviews of IUD trials: Lessons learned. Contraception 2007;75: S55-9.

  276. Winner B, Peipert JF, Zhao Q, Buckel C, Madden T, Allsworth JE, et al. Effectiveness of long-acting reversible contraception. N Engl J Med 2012;366:1998-2007.

  277. Hubacher D, Chen PL, Park S. Side effects from the copper IUD: Do they decrease over time? Contraception 2009;79:356-62.

  278. Cleland K, Zhu H, Goldstuck N, Cheng L, Trussell J. The efficacy of intrauterine devices for emergency contraception: A systematic review of 35 years of experience. Hum Reprod 2012;27:1994-2000.

  279. Munro MG, Critchley HO, Fraser IS, FIGO Menstrual Disorders Committee. The two FIGO systems for normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive years: 2018 revisions. Int J Gynaecol Obstet 2018;143:393-408.

  280. Wang L, Quan S, Bai E, Yang X. Analysis of clinical data of different endometrial pathological types in perimenopausal women with abnormal uterine bleeding. Front Oncol 2024;14:1370681.

  281. Kumar V, Kumari R, Ghosh Kar A. Histopathological spectrum of endometrial biopsies in abnormal uterine bleeding: An audit from a tertiary care center. Int J Pharm Qual Assur 2025;16:178-82.

  282. Amin R, Kazmi J, Jeelani B, Khursheed R. Prevalence of endometrial hyperplasia among patients with abnormal uterine bleeding: An analysis from a single centre. J Adv Med Med Res 2024;36:231-5.

  283. Vaidya R, Vinayachandran S, Devi S, Prejisha B, Lekshminath GL, Sreedharan S, et al. Prevalence of abnormal uterine bleeding and its associated risk factors in women of perimenopausal age group A retrospective study. J Clin Diagn Res 2022;16: QC09-13.

  284. Pidigundla D, Junutula B, Naik VS. Diagnostic value of endometrial samples in women with abnormal uterine bleeding at a teritiary care centre. Indian J Pathol Oncol 2023;10:366-70.

  285. Jha S, Singh A, Sinha HH, Bhadani P, Anant M, Agarwal M. Rate of premalignant and malignant endometrial lesion in “low-risk” premenopausal women with abnormal uterine bleeding undergoing endometrial biopsy. Obstet Gynecol Sci 2021;64:517-23.

  286. Dreisler E, Frandsen CS, Ulrich L. Perimenopausal abnormal uterine bleeding. Maturitas 2024;184:107944.

  287. Expert Panel on GYN and OB Imaging, Robbins JB, Sadowski EA, Maturen KE, Akin EA, Ascher SM, et al. ACR appropriateness criteria® abnormal uterine bleeding. J Am Coll Radiol 2020;17: S336-45.

  288. Wouk N, Helton M. Abnormal uterine bleeding in premenopausal women. Am Fam Physician 2019;99:435-43.

  289. Kim MJ, Kim JJ, Kim SM. Endometrial evaluation with transvaginal ultrasonography for the screening of endometrial hyperplasia or cancer in premenopausal and perimenopausal women. Obstet Gynecol Sci 2016;59:192-200.

  290. Selvam V, Lakshminarayanan P. A comprehensive approach: correlating ultrasound imaging with endometrial histopathological analysis in perimenopausal women with heavy menstrual bleeding. Cureus 2024;16:e57201.

  291. van Hanegem N, Prins MM, Bongers MY, Opmeer BC, Sahota DS, Mol BW, et al. The accuracy of endometrial sampling in women with postmenopausal bleeding: A systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 2016;197:147-55.

  292. Gou J, Li ZY. Accuracy of endometrial biopsy by Pipelle: A systematic review and meta-analysis. Ann Oncol 2019;30:ix84-5.

  293. Clark TJ, Mann CH, Shah N, Khan KS, Song F, Gupta JK. Accuracy of outpatient endometrial biopsy in the diagnosis of endometrial cancer: A systematic quantitative review. BJOG 2002;109:313-21.

  294. Sakna NA, Elgendi M, Salama MH, Zeinhom A, Labib S, Nabhan AF. Diagnostic accuracy of endometrial sampling tests for detecting endometrial cancer: A systematic review and meta-analysis. BMJ Open 2023;13:e072124.

  295. Moore JF, Carugno J. Hysteroscopy. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2025.

  296. Telang M, Shetty TS, Puntambekar SS, Telang PM, Panchal S, Alnure Y. Three thousand cases of office hysteroscopy: See and treat an Indian experience. J Obstet Gynaecol India 2020;70:384-9.

  297. Carugno J, Grimbizis G, Franchini M, Alonso L, Bradley L, Campo R, et al. International consensus statement for recommended terminology describing hysteroscopic procedures. Facts Views Vis Obgyn 2021;13:287-94.

  298. Senturk S, Aydin G, Bayrak CC, Hatirnaz S, Stojković M, Sparic R, et al. Endometrial sampling in the absence of hysteroscopy: Insights from more than 1000 dilatation and curettage cases. Int J Gynaecol Obstet 2025. doi: 10.1002/ijgo.70459. Epub ahead of print.

  299. Leal CR, Vannuccini S, Jain V, Dolmans MM, Di Spiezio Sardo A, Al-Hendy A, et al. Abnormal uterine bleeding: The well-known and the hidden face. J Endometr Uterine Disord 2024;6:100071.

  300. Eralil GJ. The effectiveness of levonorgestrel-releasing intrauterine system in the treatment of heavy menstrual bleeding. J Obstet Gynaecol India 2016;66:505-12.

  301. Chen S, Liu J, Peng S, Zheng Y. LNG-IUS versus medical treatments for women with heavy menstrual bleeding: A systematic review and meta-analysis. Front Med (Lausanne) 2022;9:948709.

  302. Lethaby A, Wise MR, Weterings MA, Bofill Rodriguez M, Brown J. Combined hormonal contraceptives for heavy menstrual bleeding. Cochrane Database Syst Rev 2019;2: CD000154.

  303. Jensen JT, Parke S, Mellinger U, Machlitt A, Fraser IS. Effective treatment of heavy menstrual bleeding with estradiol valerate and dienogest: A randomized controlled trial. Obstet Gynecol 2011;117:777-87.

  304. Gordon JL, Rubinow DR, Eisenlohr-Moul TA, Xia K, Schmidt PJ, Girdler SS. Efficacy of transdermal estradiol and micronized progesterone in the prevention of depressive symptoms in the menopause transition: A randomized clinical trial. JAMA Psychiatry 2018;75:149-57.

  305. Bryant-Smith AC, Lethaby A, Farquhar C, Hickey M. Antifibrinolytics for heavy menstrual bleeding. Cochrane Database Syst Rev 2018;4: CD000249.

  306. Bonnar J, Sheppard BL. Treatment of menorrhagia during menstruation: Randomised controlled trial of ethamsylate, mefenamic acid, and tranexamic acid. BMJ 1996;313:579-82.

  307. Deeksha DT, Kumar MA, Suresh G. A comparative study of tranexamic acid and ethamsylate in dysfunctional uterine bleeding. Indian J Pharm Pract 2021;14:205-10.

  308. Patel N, Pandya M. A comparative study of tranexamic acid and ethamsylate in menorrhagia. Int J Basic Clin Pharmacol 2012;1:85.

  309. Lethaby A, Hickey M, Garry R, Penninx J. Endometrial resection/ablation techniques for heavy menstrual bleeding. In: Lethaby A, editor. Cochrane Database of Systematic Reviews. Chichester, UK: John Wiley & Sons, Ltd.; 2009.

  310. Subbaiah M, Selvest N, Maurya DK. Comparison of bipolar ball endometrial ablation and transcervical resection of the endometrium in the treatment of heavy menstrual bleeding: A randomized clinical trial. Gynecol Minim Invasive Ther 2021;10:143-7.

  311. Mikes BA, Vadakekut ES, Sparzak PB. Abnormal uterine bleeding. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532913/. [Last updated on 2025 Feb 21].

  312. Bosteels J, van Wessel S, Weyers S, Broekmans FJ, D’Hooghe TM, Bongers MY, et al. Hysteroscopy for treating subfertility associated with suspected major uterine cavity abnormalities. Cochrane Database Syst Rev 2018;12: CD009461.

  313. Gurusamy KS, Vaughan J, Fraser IS, Best LM, Richards T. Medical therapies for uterine fibroids – A systematic review and network meta-analysis of randomised controlled trials. PLoS One 2016;11:e0149631.

  314. Chen I, Kives S, Randle E, Rattray D, Sanders A, Vilos G. Guideline no. 461: The management of uterine fibroids. J Obstet Gynaecol Can 2025;47:102970.

  315. Sohn GS, Cho S, Kim YM, Cho CH, Kim MR, Lee SR, et al. Current medical treatment of uterine fibroids. Obstet Gynecol Sci 2018;61:192-201.

  316. Wang X, Li J, Liu Y, Zheng Y, Wang X, Liu G. A systematic review and meta-analysis comparing the use of elagolix therapy alone or in combination with add-back therapy to treat women with uterine fibroid associated heavy menstrual bleeding. Gland Surg 2025;14:60-73.

  317. Schlaff WD, Ackerman RT, Al-Hendy A, Archer DF, Barnhart KT, Bradley LD, et al. Elagolix for heavy menstrual bleeding in women with uterine fibroids. N Engl J Med 2020;382:328-40.

  318. Taylor HS, Giudice LC, Lessey BA, Abrao MS, Kotarski J, Archer DF, et al. Treatment of endometriosis-associated pain with elagolix, an Oral GnRH antagonist. N Engl J Med 2017;377:28-40.

  319. Muneyyirci-Delale O, Archer DF, Owens CD, Barnhart KT, Bradley LD, Feinberg E, et al. Efficacy and safety of elagolix with add-back therapy in women with uterine fibroids and coexisting adenomyosis. F S Rep 2021;2:338-46.

  320. U.S. Food and Drug Administration. Orilissa® (elagolix) Prescribing Information. Silver Spring (MD): FDA; 2018. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210450s000lbl. [Last accessed on 2025 Sep 19].

  321. Becker CM, Bokor A, Heikinheimo O, Horne A, Jansen F, Kiesel L, et al. ESHRE guideline: Endometriosis. Hum Reprod Open 2022;2022:hoac009.

  322. Al-Hendy A, Lukes AS, Poindexter AN 3rd, Venturella R, Villarroel C, McKain L, et al. Long-term relugolix combination therapy for symptomatic uterine leiomyomas. Obstet Gynecol 2022;140:920-30.

  323. Al-Hendy A, Lukes AS, Poindexter AN 3rd, Venturella R, Villarroel C, Critchley HO, et al. Treatment of uterine fibroid symptoms with relugolix combination therapy. N Engl J Med 2021;384:630-42.

  324. Kounidas G, Kastora SL, Barnott E, Black L, Robinson-Burke T, Gould A, et al. Efficacy of ulipristal acetate in women with fibroid induced menorrhagia: A systematic review and meta-analysis. J Gynecol Obstet Hum Reprod 2021;50:102173.

  325. Donnez J, Tatarchuk TF, Bouchard P, Puscasiu L, Zakharenko NF, Ivanova T, et al. Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med 2012;366:409-20.

  326. European Medicines Agency (EMA). PRAC Recommends Revoking Marketing Authorization of Ulipristal Acetate for Uterine Fibroids Due to Risk of Liver Injury. [EMA News Release]; 2020. European Medicines Agency. Available from: https://www.ema.europa.eu›Home›News. [Last accessed on 2025 Oct 19].

  327. Whitaker LH, Middleton LJ, Daniels JP, Williams AR, Priest L, Odedra S, et al. Ulipristal acetate versus levonorgestrel-releasing intrauterine system for heavy menstrual bleeding (UCON): A randomised controlled phase III trial. EClinicalMedicine 2023;60:101995.

  328. Esteve JL, Acosta R, Pérez Y, Rodriguez B, Seigler I, Sanchez C, et al. Mifepristone versus placebo to treat uterine myoma: A double-blind, randomized clinical trial. Int J Womens Health 2013;5:361-9.

  329. Kulshrestha V, Kriplani A, Agarwal N, Sareen N, Garg P, Hari S, et al. Low dose mifepristone in medical management of uterine leiomyoma – An experience from a tertiary care hospital from North India. Indian J Med Res 2013;137:1154-62.

  330. Astrup K, Olivarius Nde F. Frequency of spontaneously occurring postmenopausal bleeding in the general population. Acta Obstet Gynecol Scand 2004;83:203-7.

  331. Crosbie EJ, Kitson SJ, McAlpine JN, Mukhopadhyay A, Powell ME, Singh N. Endometrial cancer. Lancet 2022;399:1412-28.

  332. Bengtsen MB, Veres K, Nørgaard M. First-time postmenopausal bleeding as a clinical marker of long-term cancer risk: A Danish nationwide cohort study. Br J Cancer 2020;122:445-51.

  333. Clarke MA, Long BJ, Del Mar Morillo A, Arbyn M, Bakkum-Gamez JN, Wentzensen N. Association of endometrial cancer risk with postmenopausal bleeding in women: A systematic review and meta-analysis. JAMA Intern Med 2018;178:1210-22.

  334. Kumari K, Paswan MK, Kundan M, Ambedkar SN. A prospective study of endometrial histopathology in post-menopausal women in Jharkhand. J Family Med Prim Care 2024;13:1696-700.

  335. Van Den Bosch T, Verbakel JY, Valentin L, Wynants L, De Cock B, Pascual MA, et al. Typical ultrasound features of various endometrial pathologies described using International Endometrial Tumor Analysis (IETA) terminology in women with abnormal uterine bleeding. Ultrasound Obstet Gynecol 2021;57:164-72.

  336. Paik DJ, Lee CH. Review of cases of patient risk associated with ginseng abuse and misuse. J Ginseng Res 2015;39:89-93.

  337. ACOG committee opinion no. 734: The role of transvaginal ultrasonography in evaluating the endometrium of women with postmenopausal bleeding. Obstet Gynecol 2018;131:e124-9.

  338. Gupta JK, Chien PF, Voit D, Clark TJ, Khan KS. Ultrasonographic endometrial thickness for diagnosing endometrial pathology in women with postmenopausal bleeding: A meta-analysis. Acta Obstet Gynecol Scand 2002;81:799-816.

  339. Timmermans A, Opmeer BC, Khan KS, Bachmann LM, Epstein E, Clark TJ, et al. Endometrial thickness measurement for detecting endometrial cancer in women with postmenopausal bleeding: A systematic review and meta-analysis. Obstet Gynecol 2010;116:160-7.

  340. Xydias EM, Kalantzi S, Tsakos E, Ntanika A, Beis N, Prior M, et al. Comparison of 3D ultrasound, 2D ultrasound and 3D Doppler in the diagnosis of endometrial carcinoma in patients with uterine bleeding: A systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 2022;277:42-52.

  341. Epstein E, Van Holsbeke C, Mascilini F, Måsbäck A, Kannisto P, Ameye L, et al. Gray-scale and color Doppler ultrasound characteristics of endometrial cancer in relation to stage, grade and tumor size. Ultrasound Obstet Gynecol 2011;38:586-93.

  342. Kaveh M, Sadegi K, Salarzaei M, Parooei F. Comparison of diagnostic accuracy of saline infusion sonohysterography, transvaginal sonography, and hysteroscopy in evaluating the endometrial polyps in women with abnormal uterine bleeding: A systematic review and meta-analysis. Wideochir Inne Tech Maloinwazyjne 2020;15:403-15.

  343. Wagar MK, Mojdehbakhsh RP, Reetz E, Huang D, Kao MJ, Al-Niaimi AN, et al. Ultrasonography-based measurements of endometrial thickness in patients with p53 abnormal endometrial carcinomas. Obstet Gynecol 2025;146:881-7.

  344. Goldstein SR. Abnormal uterine bleeding: The role of ultrasound. Radiol Clin North Am 2006;44:901-10.

  345. van Maldegem LD, van der Zande JA, van Werkhoven LA, Ewing-Graham PC, Heemskerk-Gerritsen BA, van Doorn HC. Recurrent postmenopausal bleeding: Pathological findings and predictive factors. A multicenter, prospective, observational study. Acta Obstet Gynecol Scand 2024;103:1283-91.

  346. Rotenberg O, Doulaveris G, Goldberg GL, Renz M, Whitney K, Dar L, et al. Combining ultrasonography and endometrial aspiration as a one-stop screening for endometrial neoplasia. Obstet Gynecol 2024;144:801-9.

  347. Terzic MM, Aimagambetova G, Terzic S, Norton M, Bapayeva G, Garzon S. Current role of Pipelle endometrial sampling in early diagnosis of endometrial cancer. Transl Cancer Res 2020;9:7716-24.

  348. Di Spiezio Sardo A, Saccone G, Carugno J, Pacheco LA, Zizolfi B, Haimovich S, et al. Endometrial biopsy under direct hysteroscopic visualisation versus blind endometrial sampling for the diagnosis of endometrial hyperplasia and cancer: Systematic review and meta-analysis. Facts Views Vis Obgyn 2022;14:103-10.

  349. Tandulwadkar S, Deshmukh P, Lodha P, Agarwal B. Hysteroscopy in postmenopausal bleeding. J Gynecol Endosc Surg 2009;1:89-93.

  350. Duffy A, Ní Bhuinneain M, Burke N, Murphy C. National Clinical Practice Guideline: Assessment and Management of Postmenopausal Bleeding. National Women and Infants Health Programme and the Institute of Obstetricians and Gynaecologists; 2022. Available from: https://www.rcpi.ie/faculties/obstetricians-and-gynaecologists/national-clinical-guidelines-in-obstetricsand-gynaecology/. [Last accessed on 2025 Oct 28].

  351. Smith PP, O’Connor S, Gupta J, Clark TJ. Recurrent postmenopausal bleeding: A prospective cohort study. J Minim Invasive Gynecol 2014;21:799-803.

  352. Ghoubara A, Sundar S, Ewies AA. Endometrial pathology in recurrent postmenopausal bleeding: Observational study of 385 women. Climacteric 2018;21:391-6.

  353. Zhang L, Guo Y, Qian G, Su T, Xu H. Value of endometrial thickness for the detection of endometrial cancer and atypical hyperplasia in asymptomatic postmenopausal women. BMC Womens Health 2022;22:517.

  354. Li JX, Chan F, Johansson CY. Can a higher endometrial thickness threshold exclude endometrial cancer and atypical hyperplasia in asymptomatic postmenopausal women? A systematic review. Aust N Z J Obstet Gynaecol 2022;62:190-7.

  355. Smith-Bindman R, Weiss E, Feldstein V. How thick is too thick? When endometrial thickness should prompt biopsy in postmenopausal women without vaginal bleeding. Ultrasound Obstet Gynecol 2004;24:558-65.

  356. Li Z, Li L. Risk of malignancies among asymptomatic postmenopausal women with thickened endometrium: A cohort study. Medicine (Baltimore) 2019;98:e14464.

  357. The World Health Organization quality of life assessment (WHOQOL): Position paper from the World Health Organization. Soc Sci Med 1995;41:1403-9.

  358. Burckhardt CS, Anderson KL. The quality of life scale (QOLS): Reliability, validity, and utilization. Health Qual Life Outcomes 2003;1:60.

  359. Cieza A, Stucki G. Content comparison of health-related quality of life (HRQOL) instruments based on the international classification of functioning, disability and health (ICF). Qual Life Res 2005;14:1225-37.

  360. Theis S, Baumgartner SJ, Janka H, Kolokythas A, Skala C, Stute P. Quality of life in menopausal women in the workplace – A systematic review. Climacteric 2023;26:80-7.

  361. Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and activity impairment instrument. Pharmacoeconomics 1993;4:353-65.

  362. Hirt J, Dembowska K, Woelfle T, Axfors C, Granziera C, Kuhle J, et al. Clinical trial evidence of quality-of-life effects of disease-modifying therapies for multiple sclerosis: A systematic analysis. J Neurol 2024;271:3131-41.

  363. Rolfes L, van Hunsel F, Taxis K, van Puijenbroek E. The impact of experiencing adverse drug reactions on the patient’s quality of life: A retrospective cross-sectional study in the Netherlands. Drug Saf 2016;39:769-76.

  364. Sampogna G, Di Vincenzo M, Giuliani L, Menculini G, Mancuso E, Arsenio E, et al. A systematic review on the effectiveness of antipsychotic drugs on the quality of life of patients with schizophrenia. Brain Sci 2023;13:1577.

  365. Nappi RE, Kroll R, Siddiqui E, Stoykova B, Rea C, Gemmen E, et al. Global cross-sectional survey of women with vasomotor symptoms associated with menopause: Prevalence and quality of life burden. Menopause 2021;28:875-82.

  366. Williams RE, Levine KB, Kalilani L, Lewis J, Clark RV. Menopause-specific questionnaire assessment in US population-based study shows negative impact on health-related quality of life. Maturitas 2009;62:153-9.

  367. Avis NE, Colvin A, Bromberger JT, Hess R, Matthews KA, Ory M, et al. Change in health-related quality of life over the menopausal transition in a multiethnic cohort of middle-aged women. Menopause 2009;16:860-9.

  368. Hirschberg AL. Enhancing quality of life: Addressing vulvovaginal atrophy and urinary tract symptoms. Climacteric 2025;28:400-7.

  369. Nappi RE, Cucinella L, Martella S, Rossi M, Tiranini L, Martini E. Female sexual dysfunction (FSD): Prevalence and impact on quality of life (QoL). Maturitas 2016;94:87-91.

  370. Dixit J, Gupta N, Kataki A, Roy P, Mehra N, Kumar L, et al. Health-related quality of life and its determinants among cancer patients: Evidence from 12,148 patients of Indian database. Health Qual Life Outcomes 2024;22:26.

  371. Shah P, Mehta M, Oza F, Makwana P. Prevalence of quality of life and physical activity in patients with different stages of heart failure – An observational cross-sectional study. J Indian Coll Cardiol 2023;13:154-9.

  372. Papaioannou A, Morin S, Cheung AM, Atkinson S, Brown JP, Feldman S, et al. 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: Summary. CMAJ 2010;182:1864-73.

  373. Coyne KS, Sexton CC, Irwin DE, Kopp ZS, Kelleher CJ, Milsom I. The impact of overactive bladder, incontinence and other lower urinary tract symptoms on quality of life, work productivity, sexuality and emotional well-being in men and women: Results from the EPIC study. BJU Int 2008;101:1388-95.

  374. DePree B, Shiozawa A, King D, Schild A, Zhou M, Yang H, et al. Association of menopausal vasomotor symptom severity with sleep and work impairments: A US survey. Menopause 2023;30:887-97.

  375. Todorova L, Bonassi R, Guerrero Carreño FJ, Hirschberg AL, Yuksel N, Rea C, et al. Prevalence and impact of vasomotor symptoms due to menopause among women in Brazil, Canada, Mexico, and Nordic Europe: A cross-sectional survey. Menopause 2023;30:1179-89.

  376. Punitha VC, Pavithra E, Shankar K. Assessment of menopause-related quality of life and effectiveness of health education on health-seeking behaviour among rural perimenopausal women. JCHR 2024;14:2440-51.

  377. Kang HK, Kaur A, Dhiman A. Menopause-specific quality of life of rural women. Indian J Community Med 2021;46:273-6.

  378. Manrisha PV, Madhu B, Lakshmi NG. Assessment of quality of life among postmenopausal women in a rural area of Mysuru. Int J Sci Res 2025;14.

  379. Nissy VL, Bhaskaran GG, Lal SS, Mini GK. Menopause-specific quality of life among rural women: A community-based cross-sectional study in Kerala, India. J Midlife Health 2025;16:67-75.

  380. Sivapragasam R, Rajini S, Rajalakshmi S, Priyanga K, Rajesh V, Priyadharshini R. A community-based cross-sectional study about the quality of life in postmenopausal women in rural Puducherry. Indian J Community Med 2020;45:96-9.

  381. Yerra AK, Bala S, Yalamanchili RK, Bandaru RK, Mavoori A. Menopause-related quality of life among urban women of Hyderabad, India. J Midlife Health 2021;12:161-7.

  382. Madan U, Chhabra P, Gupta G, Madan J. Menopausal symptoms and quality of life in women above 40 years in an urban resettlement colony of East Delhi. Int J Med Sci Public Health 2019;8:514-9.

  383. Muhseenah, Nallapu SS. Evaluating the quality of life among menopausal women in the Urban Field practice area of a medical college in Guntur. J Midlife Health 2025;16:76-82.

  384. Sharma S, Mahajan N. Menopausal symptoms and its effect on quality of life in urban versus rural women: A cross-sectional study. J Midlife Health 2015;6:16-20.

  385. Keye C, Varley J, Patton D. The impact of menopause education on quality of life among menopausal women: A systematic review with meta-analysis. Climacteric 2023;26:419-27.

  386. Liu T, Chen S, Mielke GI, McCarthy AL, Bailey TG. Effects of exercise on vasomotor symptoms in menopausal women: A systematic review and meta-analysis. Climacteric 2022;25:552-61.

  387. Jayabharathi B, Judie A. Complementary health approach to quality of life in menopausal women: A community-based interventional study. Clin Interv Aging 2014;9:1913-21.

  388. Chattha R, Nagarathna R, Padmalatha V, Nagendra HR. Effect of yoga on cognitive functions in climacteric syndrome: A randomised control study. BJOG 2008;115:991-1000.

  389. Nguyen TT, Hsu YY, Sari YP. The effect of pelvic floor muscle training on health-related quality of life in postmenopausal women with genitourinary syndrome: A systematic review and meta-analysis. J Nurs Res 2024;32:e316.

  390. Tang Y, Ma R, Zhang L, Sun X, Wang Y. Effectiveness and safety of hormone replacement therapy in the treatment of menopausal syndrome: A meta-analysis. Am J Transl Res 2025;17:1-15.

  391. Zhang GQ, Chen JL, Luo Y, Mathur MB, Anagnostis P, Nurmatov U, et al. Menopausal hormone therapy and women’s health: An umbrella review. PLoS Med 2021;18:e1003731.

  392. Welton AJ, Vickers MR, Kim J, Ford D, Lawton BA, MacLennan AH, et al. Health related quality of life after combined hormone replacement therapy: Randomised controlled trial. BMJ 2008;337:a1190.

  393. Genazzani AR, Nicolucci A, Campagnoli C, Crosignani P, Nappi C, Serra GB, et al. Assessment of the QoL in Italian menopausal women: Comparison between HRT users and non-users. Maturitas 2002;42:267-80.

  394. Limpaphayom KK, Darmasetiawan MS, Hussain RI, Burriss SW, Holinka CF, Ausmanas MK. Differential prevalence of quality-of-life categories (domains) in Asian women and changes after therapy with three doses of conjugated estrogens/medroxyprogesterone acetate: The Pan-Asia Menopause (PAM) study. Climacteric 2006;9:204-14.

  395. Hlatky MA, Boothroyd D, Vittinghoff E, Sharp P, Whooley MA, For the HERS Research Group. Quality-of-life and depressive symptoms in postmenopausal women after receiving hormone therapy. JAMA 2002;287:591.

  396. Hays J, Ockene JK, Brunner RL, Kotchen JM, Manson JE, Patterson RE, et al. Effects of estrogen plus progestin on health-related quality of life. N Engl J Med 2003;348:1839-54.

  397. Bhattacharya SM. Effects of tibolone on health-related quality of life in menopausal women. Int J Gynaecol Obstet 2007;99:43-5.

SECTION 3: BIDIRECTIONAL INTERPLAY BETWEEN MENOPAUSE AND SYSTEMIC HEALTH

1. Noncommunicable diseases are multifactorial, and menopause represents a biologically systemic phase during which declining ovarian hormones influence metabolic, vascular, immune, musculoskeletal, and neurocognitive function. Conversely, preexisting systemic disorders and their treatments may modify the timing of menopause, pattern of symptom expression, and long-term health outcomes of menopause.[1-3]

2. This bidirectional relationship underscores menopause as both a marker and a modulator of overall systemic health, warranting integrative, targeted screening and management across organ systems.

NERVOUS SYSTEM

3. Menopause is associated with changes in mood, sleep, migraine pattern, and cognitive complaints, but it does not cause the onset of major neurological or psychiatric disorders. Preexisting neurological conditions such as migraine with aura (MA) and epilepsy require specific consideration when selecting a menopause hormone therapy (MHT) regimen (Grade B).[1-3]

4. Neuropsychiatric symptoms: Refer to Section 2.

5. Sleep: Refer to Section 2.

6. Migraine without Aura (MO): It is more sensitive to estrogen fluctuations, may worsen during perimenopause, and is not associated with an increased risk of ischemic stroke or vascular events.

7. MO does not independently contraindicate MHT use. The decision to give MHT is guided by vascular risk assessment based on comorbidities rather than migraine status itself. Transdermal and low-dose continuous regimens are preferred to minimize hormonal fluctuations at menopause transition (MT).[2,4,5]

8. MA is a strong independent risk factor for ischemic stroke, and systemic estrogen therapy should be used with caution or avoided.

9. When MHT is considered in women with MA, best practice includes a thorough vascular risk assessment, use of lower-dose estrogen preference for transdermal delivery, a continuous regimen to minimize hormonal fluctuations, and close follow-up in the initial months of therapy (Grade C).[4,6,7]

10. Epilepsy: Estrogen has proconvulsant effects, while progesterone has anticonvulsant effects. Hormonal fluctuations at MT can alter seizure thresholds, with variable improvement or worsening postmenopause (Grade B).[8,9] Women with epilepsy are at increased risk of early menopause (EM) and osteoporosis.[10,11]

11. Antiepileptic drugs (AEDs): enzyme inducers such as carbamazepine, phenytoin, phenobarbital, primidone, topiramate, and oxcarbazepine accelerate Vitamin D and sex steroid metabolism, increasing bone loss and fracture risk in postmenopausal women (Grade A).[10-13] Noninducing AEDs such as levetiracetam, lamotrigine, and gabapentin have a safer bone profile.

12. MHT: Oral conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) therapy has been associated with increased seizure frequency in postmenopausal women with epilepsy (Grade C).[14,15] Modern regimens using low-dose transdermal estradiol and micronized progesterone are preferred for their anticonvulsant and favorable neuroprofile (Grade B).[14,15]

13. Multiple sclerosis (MS): Menopause may accelerate MS progression and neurodegeneration, with symptoms such as fatigue and cognitive dysfunction worsening postmenopause (Grade C).[16] MHT can be used safely for symptom management, with preliminary but inconclusive evidence for disease modification (Grade C).[17]

14. Parkinson’s Disease (PD): Estrogen decline after premenopausal oophorectomy has been linked to an increased risk of Parkinsonism. The physiological changes and pathological mechanisms involved in PD neurodegeneration may differ at different stages of the menopausal process; further research is needed to clarify the association.[18,19] Evidence on whether MHT modifies outcomes in established PD remains sparse and inconsistent (Grade C).[20-22]

15. Chronic pain syndrome: Estrogen and progesterone modulate pain processing via neuroendocrine pathways, and at menopause, there is an increased prevalence and severity of fibromyalgia, temporomandibular pain, migraine, and musculoskeletal pain (Grade B).[23-25] Evidence does not support prescribing MHT for the treatment or prevention of chronic musculoskeletal, fibromyalgia-type, or neuropathic pain.[26-28]

16. Dementia: Although the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, uses the term “major neurocognitive disorder,” the evidence regarding menopause and MHT relates specifically to dementia as traditionally defined in clinical and research settings. Therefore, we use the term “dementia” for clarity and consistency with the literature.[29]

17. India currently has an estimated 8.8–9.5 million people living with dementia in 2025, projected to rise to nearly 16 million by 2050. Community-based studies report dementia prevalence ranging from 1.5% to 5% in individuals aged >60 years.[30-34]

18. Alzheimer’s disease (AD): In India, AD is the leading cause of dementia (50%–60%), followed by vascular dementia (15%–25%), often as mixed dementia. Lewy body and frontotemporal dementias account for a smaller proportion (5%–10%). Reversible causes such as Vitamin B12 deficiency, hypothyroidism, and postinfective sequelae remain relevant in the Indian context.[30,35,36]

19. Prevalence is consistently higher in women than in men, partly attributable to longer life expectancy and hormonal influences.[30,35,36] The total societal cost of dementia is approximately rupees 14,700 crore and is expected to more than triple by 2030.[37,38]

20. Menopause: Dementia develops only when multiple risk factors interact over decades. Estrogen decline may affect vulnerability windows, but genetics, especially APOE ε4, vascular risk, education, lifestyle, and aging biology play a far larger role. Thus, most postmenopausal women do not develop dementia despite universal estrogen decline.[39,40]

21. Women with prodromal cognitive impairment or APOE4 genotype report worse sleep, mood instability, and vasomotor symptoms (VMSs), which amplify menopausal distress.[41]

22. Diagnosis of AD relies on clinical assessment supported by cognitive testing, neuroimaging, and biomarkers.[42]

23. Biomarker testing for AD is now available in India at approximately Rs. 12,000–15,000, primarily through cerebrospinal fluid assays (amyloid beta 42 [Aβ42], total tau, and phosphorylated tau). Emerging blood-based biomarkers (plasma p-tau, Aβ42/40 ratio, neurofilament light, and glial fibrillary acidic protein) are not yet routinely available in clinical practice.[43,44]

24. Biomarker testing should be considered in cases of early-onset dementia, atypical or mixed presentations, and mild cognitive impairment where confirmation of AD pathology would influence management or trial eligibility. Still, it is not recommended for population screening.[45]

25. Aggressive cardiovascular risk control, adoption of a healthy lifestyle, and engagement in cognitive stimulation are associated with reduced risk of dementia and should be emphasized as preventive strategies (Grade A).[46,47]

26. Introduction of accessible diagnostic and early-stage dementia care services, including memory clinics, is recommended in India to reduce the diagnostic gap and enable timely management (Grade B).[48,49]

27. MHT is not recommended for the prevention of dementia at any age or for slowing the progression of established AD (Grade A).[50] Initiating CEE with or without MPA in women aged ≥65 years was associated with an increased risk of dementia and did not improve cognitive outcomes (Grade A).[50-55]

SKELETOMUSCULAR SYSTEM

Postmenopausal osteoporosis and fragility fractures

28. Postmenopausal osteoporosis (PMO) is often termed a “silent” disease and carries a high lifetime risk of fragility fractures. Such fractures are associated with significant mortality, loss of independence, and substantial social and economic burden.[56]

29. Global estimates suggest that up to 1 in 2 women over the age of 50 may experience an osteoporosis-related fracture during their remaining lifetime, with India reporting the highest disability-adjusted life years rates.[57]

30. Indian data consistently demonstrate that fragility fractures, particularly hip fractures (HFs), occur about a decade earlier (mean age 65–71 years) than in Western populations (>75–80 years). However, most available datasets included both men and women; hence, these studies provide robust evidence of earlier fracture onset in the Indian population, but they may underestimate the sex-specific burden and predictors of PMO.[58-60]

31. In a tertiary-care hospital-based study of perimenopausal women (40–49 years), nearly one in five had vertebral fractures, and these women had lower anti-müllerian hormone levels, suggesting that declining ovarian reserve may parallel skeletal fragility.[61]

32. This earlier onset aligns with epidemiological evidence showing that approximately 1 in 3 postmenopausal women has osteoporosis and nearly 1 in 2 has osteopenia, often manifesting in the 50s–60s (Grade A).[62-66]

33. The burden of fragility fractures is rising steeply due to demographic aging and nutritional factors. In particular, hypovitaminosis D and low dietary calcium intake beginning in childhood contribute to reduced peak bone mass (PBM) and the earlier onset of osteoporosis (Grade B).[62,66,67]

34. Hospital and community-based studies further implicate low body mass index (BMI), poor sleep, elevated triglycerides, increased C-reactive protein (CRP), and EM as significant risk factors (Grade B).[65,68-71]

35. Nutritional deficits are widespread: about 3 in 4 women consume less calcium than the recommended dietary allowance (RDA) and 2 in 3 women are Vitamin D deficient. These “twin nutrient deficiencies,” compounded by demographic aging and lifestyle risk factors, contribute to the earlier onset of osteoporosis and fragility fractures in Indian women.[72-74]

36. Over 70% of Indian women and many clinicians have poor awareness of PMO, significantly limiting prevention and treatment efforts (Grade C).[75-77]

37. The Indian Menopause Society (IMS) 2020 clinical practice guidelines on PMO recognize PMO as a significant national concern and urge early screening, lifestyle counselling, and timely preventive strategies tailored to Indian women.[78]

38. Gynecologists are the first line of defense for skeletal and musculoskeletal health in midlife women. Routine gynecological visits should integrate bone health assessment, lifestyle counseling, and timely preventive or therapeutic interventions.[79]

Definitions and types of osteoporosis

39. Osteoporosis: It is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in increased fragility and fracture risk as measured by dual-energy X-ray absorptiometry (DXA) black.[80] Bone mass is calculated as bone mineral density (BMD) from DXA, and microarchitectural deterioration of bone tissue is quantified indirectly using trabecular bone score (TBS) derived from DXA, and more precisely by high-resolution peripheral quantitative computed tomography or histomorphometry.[81,82]

40. Primary osteoporosis type I (PMO): It occurs in women after menopause due to estrogen deficiency. It predominantly affects trabecular bone, with accelerated bone loss of 1%–2% (up to 5%) annually in the first 5–7 years postmenopause.

41. Primary osteoporosis type II (senile osteoporosis): Age-related bone loss at 1% per year, affecting both cortical and trabecular bone in men and women.[78]

42. Secondary osteoporosis: It results from identifiable secondary causes, such as endocrine disorders (e.g., hyperthyroidism, hyperparathyroidism, Cushing’s), medication use (especially glucocorticoids), chronic systemic illnesses, and malabsorption syndromes that impair bone metabolism or limit PBM acquisition.[83,84]

43. Premenopausal osteoporosis: It is defined by a low BMD (Z-score < −2.0) with or without fragility fractures in women before menopause (Grade A).[85-87] The majority of cases are secondary linked to gynecologic, endocrine, metabolic, or systemic causes and therefore warrant thorough evaluation before pharmacologic treatment. Drug therapy is considered only for women with recurrent fractures, progressive bone loss, or irreversible secondary causes (Grade A).[85-87]

44. Idiopathic premenopausal osteoporosis: It is a rare diagnosis, established only when no secondary cause of low bone mass or fragility fracture can be identified after comprehensive evaluation. Its pathogenesis remains incompletely understood, likely reflecting heterogeneous mechanisms, including genetic predisposition, impaired bone formation, altered bone microarchitecture, and intrinsic skeletal factors (Grade C).[88-90]

45. Fragility fractures: Fragility fractures most commonly involve the hip, vertebrae, and distal radius, though other sites such as the humerus, pelvis, ribs, and pubic rami may also be affected following minimal trauma (Grade A).[56,91]

46. Causes of fragility fractures: Fragility fractures are caused by both BMD-related and non-BMD-related factors, resulting from a complex interplay of osteoporosis, sarcopenia, frailty, nutritional deficits, comorbidities, and falls (Grade A).[92,93]

47. Osteomalacia: It is defined as a condition in which there is impaired mineralization of the bone matrix (osteoid) in mature skeletons, most commonly due to Vitamin D deficiency or disordered phosphate metabolism, leading to bone pain, muscle weakness, and increased fracture risk, particularly Looser’s zones (pseudo fractures).

Risk factors for postmenopausal osteoporosis and fragility fractures

48. Major risk factors: defined by the World Health Organization (WHO) (Grade A): Advancing age, Low BMI, history of a fracture, parental history of HF, smoking, alcohol, use of glucocorticoids, and rheumatoid arthritis.[94]

49. Environmental factors: nutrition (calcium intake using the quick dietary calculator and protein), physical activity, sunlight exposure, and risk of falling are important modifiable risk factors (Grade B).[94,95]

50. PBM: It is the highest level of bone mass achieved as result of normal growth. It is an important predictor of the onset of primary osteoporosis. It is influenced by genetic, hormonal, racial, nutritional, and lifestyle factors as well as physical activity. Environmental factors modulate the genetic potential in achieving PBM.[96,97]

51. Age, sex, and genetics are key nonmodifiable risk factors for osteoporosis. PBM is attained by 25–30 years, with 40%–50% achieved by age 18. Women reach skeletal maturity with 10%–15% lower bone mass than men. Asian Indians have significantly lower PBM compared to some other races.[98-101]

52. Barker’s theory: Barker’s developmental origins of health and disease (DOHaD) framework is relevant to postmenopausal outcomes,highlighting that prevention begins before conception and continues across the life course.[102]

Diagnosis of postmenopausal osteoporosis

53. Table 1 shows the WHO classification of osteoporosis for BMD-based categories with and without fractures.[103]

Table 1.

Diagnosis of postmenopausal osteoporosis with and without fractures (World Health Organization categories for diagnosis of osteoporosis)

Diagnosis T-score (SD)
Normal Equal to −1.0 or higher
Low bone mass (osteopenia) Between −1.0 and −2.5
Osteoporosis Equal to −2.5 or lower
Severe osteoporosis Equal to −2.5 or lower with fracture
Open in a new tab

SD: Standard deviation

54. BMD: The current gold standard for BMD assessment is DXA. BMD values are expressed as T-scores (standard deviation [SD] difference from young adult mean) or Z-scores (SD difference from age- and sex-matched mean).[103]

55. The reference range for calculating the T-score in postmenopausal women is based on the NHANES III Caucasian female reference database (age 20–29 years).[103]

56. Global organizations,including the World Health Organization (WHO), the International Osteoporosis Foundation (IOF), the International Society for Clinical Densitometry (ISCD), and the National Osteoporosis Foundation (NOF), as well as Indian professional bodies such as the Indian Menopause Society (IMS) and the Indian Society for Bone and Mineral Research (ISBMR), currently recommend using the NHANES III Caucasian female reference database for T-score calculation.[56,78,91,103-105]

57. However, this reference standard may overestimate the prevalence of osteoporosis in Indian women. The ETHNICA 2025 study demonstrated that when Indian normative (Indian Council of Medical Research [ICMR]) reference data were applied instead of Caucasian values, the estimated prevalence of osteoporosis declined from 26.6% to 18%, highlighting substantial ethnic calibration bias.[106]

58. This finding underscores the urgent need for nationally validated BMD reference standards correlated with fracture outcomes, to serve as the scientific basis for diagnostic thresholds and treatment eligibility criteria in Indian women (Grade B).[56,78,91,103,105,107]

59. Diagnosis and categorization of osteoporosis by IOF and WHO: In postmenopausal women, osteoporosis is diagnosed by the presence of a fragility fracture (clinical or radiological), irrespective of BMD, and/or by a BMD T-score ≤−2.5 measured at the lumbar spine, total hip, or femoral neck. For diagnostic purposes, the lowest valid T-score among these skeletal sites should be used (Grade A).[103]

60. The ISCD diagnostic criteria for osteoporosis in postmenopausal women and in men aged 50 and older are if the T-score of the lumbar spine, total hip, or femoral neck is −2.5 or less. In certain circumstances (hyperparathyroidism, gross obesity, or degenerative spine disease, when hip/spine are not interpretable), the 33% radius (also called 1/3 radius) may be utilized.[108]

61. Z-score: This indicates how many SDs an individual’s BMD differs from the mean for age and sex. Primarily used in children, adolescents, and premenopausal women. A Z-score <−2 is considered “low for age.”[108]

62. Diagnosis of fragility fractures: Clinical recognition is essential since many patients first present with fracture rather than low BMD.

Screening of postmenopausal osteoporosis (for women without fragility fractures) from ≥40 years of age

63. Principle: Primary osteoporosis is a silent disease, often undetected until a fracture occurs (Grade A).[78,91]

64. Early detection is vital to prevent morbidity and mortality and reduce the economic and societal burden (Grade A).[109]

65. In India, population-wide DXA-based screening is not cost-effective, instead a targeted case-finding approach using risk factors with DXA where available is recommended (Grade B).[78,91]

66. Rationale: Risk factors are derived from history and clinical examination. Distinguish between factors that reduce bone mass and those that increase fracture risk independent of BMD (e.g., falls risk).

67. Fracture risk should be calculated ideally using BMD together with clinical risk factors, not T-scores alone (Grade A).[56]

Fracture risk assessment: Risk-assessment tools for Indian women

World Health Organization Fracture Risk Assessment Tool (FRAX®)

68. Fracture Risk Assessment Tool (FRAX) integrates key clinical risk factors with or without BMD to estimate the 10-year probability of HF and major osteoporotic fractures (MOF). The absolute risk of fracture depends upon age, life expectancy, and the current relative risk. FRAX is an internationally validated model used in over 100 countries, offering population-specific calibration and valuable fracture-probability estimates.

69. It has an online and offline format. FRAX is the preferred first-line tool for assessing fracture risk and provides the interventional threshold (IT) and very high-risk thresholds to guide treatment decisions, with and without BMD (Grade A).[56,110,111]

70. FRAX is country-specific, and an Indian FRAX model is available online (www.shef.ac.uk/FRAX).[112] The Indian FRAX® model, derived from a small North-Indian cohort, lacks nationwide calibration and likely underestimates true fracture risk; it omits falls risk, lumbar-spine BMD, and regional skeletal variation and requires online access, limiting applicability in rural settings (Grade C).[58,113]

71. After calculating the 10-year probabilities of MOF and HP risk using FRAX without BMD, the woman is categorized into low-risk, high-risk, and very high-risk categories.

72. FRAXplus: an upgrade to the widely used FRAX, developed to address several limitations of the original model (https://www.fraxplus.org/frax-plus).

The osteoporosis self-assessment tool for Asians

73. The osteoporosis self-assessment tool for Asians (OSTA) is a simple, non-BMD screening tool that uses only age and weight. It stratifies women into low, moderate, and high-risk categories; it has been validated in Indian and other Asian populations [Figure 1].

Figure 1.

Figure 1

Open in a new tab

Osteoporosis self-assessment tool for Asians[114]

74. OSTA is practical for community and primary-care screening where DXA is unavailable and has a high negative predictive value (NPV) for excluding severe osteoporosis (Grade B).[114]

75. As OSTA cannot estimate fracture probability or guide precise treatment thresholds, it should be used for an initial triage.[114]

76. Proposed Strategy for using OSTA and FRAX India: A stepwise, resource-sensitive framework combining OSTA and FRAX enables rational, tiered risk assessment in Indian practice

77. Screening at primary care centers - OSTA: It is a low-cost community screening tool, easily applied by paramedical staff or frontline health workers in primary-care and outreach settings to identify women at potential risk. It requires only age and weight, making it practical where DXA or Internet access is unavailable and suitable for busy clinical environments with limited physician time.

78. Screening at secondary or tertiary care centers - FRAX without BMD: Categorizes women as low, high, or very high risk for fracture. However, detailed data requirements may limit use in high-volume practices.

79. Definitive risk quantification - FRAX with BMD using DXA: Remains the definitive risk quantifier for individualized treatment planning and establishing pharmacologic intervention thresholds, ideally performed in secondary or tertiary care centers with standardized DXA facilities.

80. Assess BMD and TBS for fracture risk by DXA (Gold standard)

Dual X-ray absorptiometry

81. Indications for Dual-Energy X-ray Absorptiometry (DXA) (Grade B)[78]

a. All postmenopausal women >5 years since menopause

b. Postmenopausal women <5 years since menopause who have additional clinical risk factors for osteoporosis

c. Women in the menopausal transition with secondary causes of bone loss (e.g., endocrine, metabolic, or medication related)

d. Presence of radiological osteopenia or vertebral compression fracture

e. Women with fragility fractures confirmed by radiology or DXA

f. To establish a diagnostic and therapeutic baseline, before initiating pharmacotherapy for osteoporosis

g. Emerging indication: Assessment of total body composition (fat and lean mass) for metabolic and sarcopenic risk evaluation.

82. The Indian-specific basis for these recommendations is discussed in Clinical Practice Guidelines on Postmenopausal Osteoporosis: An Executive Summary and Recommendations. J Midlife Health. 2020.[78]

83. For each SD decrease in BMD, there is a doubling of fracture risk. For monitoring treatment and comparing DXA results, accurate comparisons can only be made when the scans have been done using the same machine and when comparing the values generated from the same sites.

84. To monitor therapy, the interval to the next DXA should depend on the calculated individual risk and would mostly be scheduled between 1 and 5 years later (Grade B).[108]

Categorizing women into risks for fracture based on fracture risk assessment tool/osteoporosis self-assessment tool for Asians/DXA

85. Based on FRAX with and without BMD, the chart gives a 10-year probability of MOF and suggests an IT to guide treatment decisions. (NOGG-UK clinical guideline for the prevention and treatment of osteoporosis/Celia L. Gregson et al/ Archives of Osteoporosis (2022) 17: 58/https://doi. org/10.1007/s11657-022-01061-5/CC BY).

86. OSTA: The risk of osteoporosis in the high-, medium-, and low-risk categories was found to be 61%, 15% and 3%, respectively.

High-risk patients: to measure BMD, if possible, and consider drug treatment even if BMD is not available (About 61% of individuals in the high-risk group have osteoporosis)

Moderate-risk patients: to measure BMD and consider drug treatment if BMD is low (About 15% of individuals in the moderate-risk group have osteoporosis)

Low-risk patients: not to measure BMD unless other risk factors are present.

87. Precautions: Calculation assumes no other risk factors for osteoporosis. Significantly increased risks are associated with rheumatoid arthritis, fracture of the wrist, hip, or rib after age 45, and other risks such as low-trauma related fractures or long-term corticosteroids.[115-117]

88. Categorizing PMO for fracture risk based on FRAX/OSTA/DXA [Table 2].

Table 2.

Categorizing fracture risk based on results from the fracture risk assessment tool/osteoporosis self-assessment tool for Asians and bone mineral density by dual-energy X-ray absorptiometry

Classification t-score (SD) FRAX/OSTA Fracture risk
Normal Equal to −1.0 or higher FRAX-low OSTA-low Low risk
Low bone mass (osteopenia) Between −1.0 and −2.5 FRAX - <20% MOF or <3% HPF OSTA-Moderate Upper or lower percentile of low risk
Low bone mass Between −1.0 and−2.5 FRAX>20% MOF or >3% HPF OSTA-High High risk
Osteoporosis Equal to −2.5 or lower FRAX >20% MOF or >3% HPF OSTA-High High risk
Severe osteoporosis Equal to −3 or lower, with fracture FRAX - >30% MOF or >4.5% HPF Very high risk
Open in a new tab

MOF: Major osteoporotic fracture, HPF: Hip fracture, FRAX: Fracture risk assessment tool, OSTA: Osteoporosis self-assessment tool for Asians, SD: Standard deviation

Clinical evaluation

89. Women without fractures: Categorize as captured in the clinical risk factor assessment and DXA [Table 2].

Women with fractures: Typical presentations include sudden severe pain following low-energy trauma, groin/lateral hip pain with inability to bear weight, and possible limb shortening (hip). Distal forearm pain with swelling and deformity after falling on an outstretched hand (wrist). Sudden severe mid-back pain after minimal trauma or insidious chronic mid-back discomfort that may radiate around the abdomen should prompt spine imaging.

90. Related symptoms: Generalized bone pain should raise suspicion of osteomalacia or skeletal metastasis (Grade B).[115,116]

91. Vitamin D deficiency symptoms: proximal muscle weakness, difficulty with squatting, climbing stairs, and rising from low chairs. Tenderness may be elicited on the pretibial region and sternum.[78,117]

92. Calcium deficiency symptoms: Muscle spasms, twitches, cramps, numbness, or tingling in the fingers, toes, or around the mouth.[78]

93. Sarcopenia and frailty share many symptoms, most notably muscle weakness, slowness, fatigue, and weight loss, but frailty also encompasses broader issues such as exhaustion, cognitive decline, and increased vulnerability to stressors. Early recognition of these symptoms is crucial for intervention and prevention of further decline.[118]

94. Fall risk assessment: a multifactorial evaluation is recommended.[119]

95. Physical examination: Annual height and weight measurement, assessment of balance and gait (including the Get-Up-and-Go test), and routine dental evaluation.

96. A prospective height loss of ≥ 4 cm from peak adult height, or a current–previous height difference of ≥ 2 cm accompanied by other risk factors (such as kyphosis, back pain, or glucocorticoid use), should prompt evaluation for vertebral fracture or underlying osteoporosis (Grade B).[78,120]

97. Inability to touch the occiput to the wall while standing (thoracic fracture); inability to insinuate the four fingers between the lowest rib and iliac crest (lumbar fracture); kyphosis and Dowager’s hump are seen in the late stage of osteoporosis (Grade A).[78,120]

Investigations

98. Laboratory tests: to rule out secondary causes. Complete blood picture, erythrocyte sedimentation rate, CRP, blood sugar, serum calcium, serum creatinine, serum albumin, alkaline phosphatase, thyroid-stimulating hormone (TSH), 25-hydroxy Vitamin D, preferably fasting serum phosphorus, parathyroid hormone (PTH) (based on clinical judgment).[78,121]

99. TBS: The TBS derived from lumbar spine DXA images is an adjunct tool for evaluating bone microarchitecture and fracture risk independent of BMD in postmenopausal women with discordance between BMD and clinical fracture risk, type 2 diabetes, glucocorticoid use, or secondary osteoporosis (Grade B).[81,122]

• TBS >1.310: normal microarchitecture, low fracture risk

• TBS 1.23–1.31: partially degraded microarchitecture

• TBS <1.230: degraded microarchitecture, high fracture risk.

100. Peripheral DXA (X-ray based): May be used as a mass screening tool because of its high NPV (Grade C).[123]

101. Quantitative ultrasound (QUS): Is a portable, inexpensive, and radiation-free tool with utility in community and rural India for preliminary osteoporosis screening, cannot be used for diagnosis or monitoring therapy (Grade B).[124,125] In Taiwanese postmenopausal women, QUS outperformed OSTA in those aged 45–65, while OSTA outperformed QUS in those aged 66–80 years.[126]

102. X-ray thoracolumbar spine: X-ray abnormalities usually indicate advanced bone disease; hence, plain X-rays are recommended in all diagnostic protocols for osteoporosis. The lateral view of the thoracolumbar spine is the preferred position for detecting altered vertebral architecture.[78]

103. Bone turnover markers (BTMs) are not recommended as part of routine tests for the clinical diagnosis of osteoporosis (Grade B).[78,121] Their primary role is in monitoring therapy to assess compliance and efficacy of therapy (Grade B).[78,121]

Management of postmenopausal osteoporosis

104. Osteoporosis is a long-term condition for which there is currently no cure; therefore, lifelong treatment and monitoring to prevent fractures are often required.

105. Table 3 gives a comprehensive management plan based on the outcomes of the assessment of BMD/FRAX/OSTA.

Table 3.

Treatment recommendation based on bone mineral density/fracture risk assessment tool/osteoporosis self-assessment tool for Asians

BMD Fracture risk BMD + CRF/CRF by FRAX and or OSTA Treatment decision Choice of therapy
Low bone mass Low TLM/reassess after 5 years TLM
Low bone mass Upper percentile of low risk Treat if risk with or without BMD is above IT Early PM-MHT, BP Late PM-BP
Osteoporosis High Treat Early PM-MHT, BP, DU Late PM-BP, DU, TER, RZ
Severe osteoporosis Very high risk Refer to specialist Early PM-BP, DU, TER, RZ Late PM-BP, DU, TER, RZ
Open in a new tab

BMD: Bone mineral density, CRF: Clinical risk factors, TLM: Therapeutic lifestyle management, PM: Postmenopause, MHT: Menopause hormone therapy, BP: Bisphosphonates, DU: Denosumab, TER: Teriparatide, RZ: Romosozumab, IT: Interventional threshold, FRAX: Fracture Risk Assessment Tool, OSTA: Osteoporosis self-assessment tool for Asians

Universal recommendations

106. Therapeutic lifestyle management (TLM): It includes a balanced diet, adequate physical activity, exposure to sunlight, and avoidance of bone-depleting agents. Balanced diet: Daily salt intake should not exceed 5 g (1 tsp). Protein should be 1 g/kg body weight. Decrease caffeine intake (<3 cups/day), limit alcohol, and avoid tobacco use. Maintain good oral hygiene and receive routine dental checkups (Grade B).[78]

107. Calcium: Assess total calcium intake from dietary sources using the NOF. Calcium Calculator. Washington, DC: NOF; c2020–2024. Available from: https://www.nof.org/patients/treatment/calcium-calculator [Table 4].

Table 4.

Adapted and an approximate quick dietary calcium assessment chart

Source Calcium (mg)* Number of servings Total calcium (mg)
Dairy source 300–525/1 glass x
300/1 katori curds x
Non dairy 200–300 x
Open in a new tab

*Approximate estimates. Total intake of calcium in mg. Calculate the total daily dietary intake by entering the sources and the number of servings from dairy and nondairy sources before supplementation

108. Encourage achieving the recommended calcium intake primarily through daily foods [Table 2], emphasizing that this is an achievable target for every Indian through simple, locally available options.[127]

109. Adequate calcium intake (>800 mg/day) can be achieved through culturally appropriate, affordable Indian diets without routine supplementation.

110. Aim for 3–4 calcium sources daily, for example, 1 glass milk + 1 Katori greens + 1 tbsp sesame + 1 dal = 800 mg calcium. Add sesame/curry leaf/mint/coriander/chutney. Dairy foods also add 6–8 g of protein per serving, supporting bone and muscle strength

111. Enhance calcium intake: Resource-limited diets with ragi, pulses, leafy greens, and sesame/curry leaves chutney can meet daily needs (Grade B).[128] Mixed diets with milk, curd, greens, dal, peanuts, and small fish (sardines with bones) yield similar adequacy (Grade B).[128] Affluent/health-conscious diets that include fortified milk, paneer, sesame, nuts, and diverse greens easily meet RDA goals (Grade A).[128,129] Table 5 for Indian foods with calcium-rich contents.

Table 5.

Indian foods with calcium-rich contents

Dietary product Serving Calcium (mg)
Milk/curd (buffalo) 1 glass (250 mL) 520
Milk/curd (cow) 1 glass (250 mL) 300
Milk/curd (low fat) 1 glass (250 mL) 300
Khoa 100 g 600
Paneer 100 g 320
Cheese slice 20 g 160
Ragi 100 g 360
Horse gram whole/Rajma 100 g 280
Soyabean 100 g 240
Moth bean/Bengal gram (whole) 100 g 200
Red/Green/Black gram/chickpeas 100 g (whole) 100–120
Drumstick leaves 100 g 300
Radish leaves/Methi leaves 100 g 270
Mint/parsley 100 g 200
Okra (BHINDI) 100 gas 85
Cabbage 100 g 60
Dried figs 5 whole 95
Almonds 1 handful 25 g 60
Sesmae seeds (til) 15 g, 1 tablespoon 90
Cumin 6 g 0.4 tablespoon 60
Orange 1 medium size 50
Fish Rohu 25 g 160
Open in a new tab

Adapted from Longvah T, Ananthan R, Bhaskarachary K, Venkaiah K. Indian Food Composition. Hyderabad: National Institute of Nutrition, Indian Council of Medical Research; 2017

Calcium requirements in Indian postmenopausal women: Discrepancies and evolving guidelines, recommended dietary allowance of calcium

112. The ICMR RDA (2010): Recommended 600 mg/day of calcium for postmenopausal women. This value was based on a sound factorial approach: obligatory urinary/fecal/dermal losses, balance studies, limited Indian absorption data, and adaptation of FAO/WHO/UNU norms with adjustments for Indian dietary bioavailability. This aligned with global practice, in which calcium RDAs are derived from balance studies rather than fracture outcome data (Grade B).[130-133]

113. Importantly, calcium requirements vary with ethnicity, habitual protein intake, Vitamin D status, and other confounders, underscoring the need for population-specific recommendations (Grade C).[130]

114. Average intake in India remains around 400 mg/day, which is well below both global and Indian targets.

115. The ICMR 2020 expert group revised the RDA upward to 1200 mg/day for women >50 years, using updated factorial modelling and population distribution (estimated average requirement + RDA framework). While biologically reasonable, this threshold would necessitate near-universal supplementation, which may not be practical or cost-effective in the Indian setting (Grade C).[134]

116. IMS 2020 guideline: Adopted ≥800 mg/day as a pragmatic recommendation achievable through food-based sources with selective supplementation (Grade B)[78,127] [Table 2].

Vitamin D

117. The recommended daily intake of Vitamin D for Indian adults is 1000–2000 IU, aligning with Endocrine Society and Indian (ICMR, ESI, IMS) guidance, which target serum 25-hydroxyvitamin D (25(OH)D) ≥30 ng/mL; lower institute of medicine values (600–800 IU/day) may be inadequate in India due to widespread deficiency and limited sunlight exposure (Grade A).[78,134-138]

118. Individuals with obesity, HIV infection, or those receiving glucocorticoids, anticonvulsants, antifungal, or antiviral therapy may require higher doses to achieve sufficiency. A desirable serum 25(OH)D range is 30–60 ng/mL. Levels up to 100 ng/mL are generally considered safe and unlikely to cause toxicity.

119. In contrast, in conditions such as granulomatous disorders (e.g., sarcoidosis and tuberculosis), it is prudent to maintain serum 25(OH)D just above 30 ng/mL, avoiding higher levels due to an increased risk of hypercalcemia.[137]

120. Sunlight is the preferred natural source of Vitamin D. Exposure of 15%–30% of body surface area (face, neck, arms, and forearms) without sunscreen for about 30 min between 10 am and 3 pm, depending on season, latitude, altitude, air pollution, and skin pigmentation, can maintain adequate Vitamin D synthesis. This exposure is roughly equivalent to an oral intake of 340–490 IU/day, given that 100 IU increases serum 25(OH)D by 1 ng/mL (Grade A).[73,139,140]

Physical activity/exercise

121. Appropriate resistance, weight-bearing aerobics, and core-stabilizing exercises are needed to maintain bone health (Grade A).[141,142]

122. Brisk walking 4–5 times/week for 30 min is healthy but on its own not sufficient for bone health (Grade A).[143,144]

123. Patients with severe osteoporosis should avoid forward flexion exercises, heavy weightlifting, and side-bending exercises, as these activities exert compressive forces on the spine that may lead to fractures (Grade A).[145-147]

124. Prevention of falls: Balance exercises are essential. A multifactorial risk assessment and intervention is the most consistently effective strategy to prevent falls (Grade A).[148,149]

NUTRITIONAL PHARMACOLOGICAL MANAGEMENT

125. Nutritional supplementation: Combined calcium + Vitamin D supplementation (1000–1200 mg Ca + 800–1000 IU D3/day) reduces hip and total fracture risk in older adults (Grade A).[150-153]

126. Calcium: Supplements are used to correct calcium and Vitamin D deficiency and form an integral part of established osteoporosis management to achieve a total of 1000–1200 mg/day (Grade A).[154] The risk of cardiovascular events, including calculi, is not observed with the recommended doses of calcium (Grade A).[155,156]

127. Calcium supplements should be individualized, limited to ≤500 mg per dose, 800–1200 mg/day total, and spaced from interfering nutrients or drugs. Dietary restriction is not advised, and excessive intake (>2500 mg/day) should be avoided (Grade A).[56,150]

128. Vitamin D: Vitamin D deficiency is widespread across India, with prevalence estimates around 20%–100%, higher among women and residents of northern and eastern zones due to limited sun exposure and cultural clothing practices (Grade A).[157,158]

129. Vitamin D is obtained from sunlight, fortified foods, and supplements, but most Indians receive inadequate sun exposure, and current food fortification levels are insufficient to meet the RDA.

130. According to ICMR-NIN (2024) and Food Safety and Standards Authority of India standards, fortified edible oil provides approximately 110–160 IU/day, while fortified milk provides 200 IU/day, assuming average adult intake of 25–30 g oil + 250 mL milk/day, together covering only about two-thirds of the RDA.[157,159,160] Hence, supplementation is advisable in high-risk groups (indoor workers, elderly, obese, or malabsorptive states).

131. Gupta’s review underlines that even apparently healthy Indians show low serum 25(OH)D levels, supporting universal supplementation, initial correction followed by maintenance dosing until widespread and effective food fortification becomes a reality (Grade B).[157,161]

132. Measurement of serum 25(OH)D is recommended in individuals at risk of Vitamin D deficiency, including those with osteoporosis, fragility fractures, malabsorption, chronic kidney or liver disease, obesity, or limited sun exposure. Routine screening of the general population is not recommended (Grade A).[134,135]

133. Cholecalciferol is preferred for the correction and maintenance of Vitamin D deficiency; aim for a serum 25(OH)D level of 40–60 ng/mL. Doses ≤4000 IU/day are safe; toxicity occurs with >10,000 IU/day (Grade B).[162,163]

134. Cholecalciferol (Vitamin D3) is available in oral tablets, capsules, granules, nanoemulsions, and spray forms, typically in doses of 1000 IU, 2000 IU, and 60,000 IU.

135. Intramuscular preparations (300,000–600,000 IU per ampoule) are cost-effective and particularly useful in patients with malabsorption, poor adherence, or intolerance to oral therapy. However, they may cause injection-site discomfort and yield variable serum 25(OH)D levels.

136. The choice between daily and bolus dosing remains debated. The Endocrine Society (USA) recommends daily dosing for physiological mimicry, yet adherence challenges are common with long-term daily use.[135]

137. Bolus regimens, weekly or monthly, are supported by Vitamin D’s long half-life and comparable ability to sustain 25(OH)D and PTH levels over time, as excess Vitamin D is stored in adipose tissue and released gradually.

138. Thus, daily, weekly, or monthly schedules may be selected based on patient preference, likelihood of adherence, and clinical context, provided the cumulative dose remains within recommended limits.[135,137,164]

Management

139. Vitamin D deficiency (<20 ng/ml/<50 nmol/L): cholecalciferol (Vitamin D3), 60,000 IU/orally once a week for 12 weeks, preferably with milk or 2000 IU/day.

140. Vitamin D insufficiency (20–30 ng/ml/50–75 nmol/L): cholecalciferol (Vitamin D3), 60,000 IU/orally once a week for 8 weeks, preferably with milk or 2000 IU/day.

141. One IM injection of 600,000 IU is given to correct the deficiency (not to be repeated for 3 months and may be given after confirmation of persistent low Vitamin D levels).

142. Caution: Always combine with adequate calcium intake (dietary or supplemental) for bone benefits. Higher doses may be required in obesity, malabsorption, and chronic kidney disease.

143. All regimes are to be followed by maintenance therapy.

144. Maintenance therapy: Cholecalciferol 60,000 IU once a month in summer or twice a month in winter. Vitamin D supplements of 2000 IU/day, or Injection of Cholecalciferol 300,000 IU IM, twice a year or 600,000 IU IM once a year,[78,136,165] or exposure to sunlight in the recommended time and duration.

145. Calcitriol (0.25–0.5 μg/day) and Alfacalcidol are indicated only in chronic renal or hepatic disease with impaired Vitamin D activation. Their use mandates monitoring of calcium and renal function due to the risk of hypercalcemia, hypercalciuria, and nephrocalcinosis (Grade A).[166,167]

146. Vitamin K supplementation: 180–350 μg/day of Vitamin K2-7 may be considered along with calcium, magnesium, Vitamin D, and a balanced diet. The current RDA (WHO/FAO) of 65–80 μg/day is considered inadequate. Suggested intake is ≥100 μg/day throughout life, with higher doses when indicated. Vitamin K supports both bone health and cardiovascular health in women with osteoporosis (Grade C).[168]

Pharmacological management of postmenopausal osteoporosis: Prevention versus treatment

147. Prevention refers to interventions aimed at halting or slowing bone loss in postmenopausal women with low bone mass (T-score between −1.0 and −2.5) and increased fracture risk. Treatment refers to the use of pharmacological agents to reduce fracture risk in women with established osteoporosis (T-score <−2.5 or presence of a fragility fracture).[78]

Indications for pharmacotherapy

The clear indications for pharmacotherapy are a history of fragility fractures, osteoporosis defined by DXA, and low bone mass with 10-year HF probability >3% OR a 10-year major OP fracture probability >20% (FRAX).

148. Categorization according to risk of fracture: Management is based on the concept of stratifying women into low, intermediate, high, or very high-risk categories according to BMD and clinical risk factors [Table 3].

149. In the absence of DXA: Treatment decisions are based on the outcomes of FRAX and OSTA [Table 3].

150. Choice of medication: depends on fracture risk level, drug-related (risk-benefit), patient profile (age, years since menopause, symptoms, and comorbidities), and environment-related factors (economics and social).

151. Patients should be educated about PMO and its treatment and empowered to participate in shared decision-making to improve adherence. Oral health and the warning signs of atypical femoral fractures are discussed.

152. Calcium and Vitamin D cotherapy is mandatory to optimize outcomes (Grade A).[78,169]

153. There are no direct head-to-head randomized trials comparing the fracture-reduction efficacy of different osteoporosis drugs; available evidence is derived primarily from placebo-controlled studies and indirect comparisons. Details of individual drug efficacy, safety, and indications are summarized in the accompanying tables (Grade B).[121]

154. Refer to endocrinologist/specialist: Special groups such as the premenopausal woman, breast cancer survivors on endocrine therapy, those with secondary causes of osteoporosis, very high risk for fracture, and nonresponders to treatment.

Options of pharmacotherapy

155. Very high risk for fracture: specialist referral should be considered. The indications are the presence of single but essential clinical risk factors, such as a recent vertebral fracture (within the last 2 years), ≥2 vertebral fractures (whenever they have occurred), BMD T-score ≤−3.5, and treatment with high-dose glucocorticoids (≥7.5 mg/day of prednisolone or equivalent over 3 months).

156. Refer urgently given rapid loss in bone post initiation of glucocorticoids; while waiting, offer intravenous zoledronate as a first-line treatment option following a HF (Grade A).[169,170]

157. Teriparatide, abaloparatide, or romosozumab are first-line treatment options in postmenopausal women at very high fracture risk, particularly in those with vertebral fractures (Grade A).[121,133,171,172]

158. High risk for fracture: In EM (within 10 years of menopause) – first line of management is MHT/or bisphosphonates/denosumab. The second line includes teriparatide, abaloparatide, or romosozumab, particularly in those at risk for vertebral fractures. In late menopause (>10 years postmenopause), the first-line management is bisphosphonates/denosumab. The second line includes teriparatide, abaloparatide, or romosozumab, particularly in those at risk for vertebral fractures.

159. Intermediate risk for fracture: In EM (within 10 years of menopause) – first line of management is MHT/or bisphosphonates. In case of contraindications, intolerance, or patient preference for ease and compliance, denosumab may be offered. In late menopause (>10 years postmenopause), bisphosphonates is preferred. In cases of contraindications, intolerance/treatment failure, or patient preference for ease and compliance, denosumab may be offered.

160. Low risk of fracture: TLM

Follow-up, monitoring, and duration

161. Follow-up: Patients should be monitored every 3–6 months initially for 2–3 visits, and thereafter annually for clinical assessment, evaluation of adherence, and monitoring of adverse effects.

162. Monitoring should include symptom review, assessment of compliance, health status, and fall risk, secondary causes, maintain calcium and Vitamin D status/drug-specific laboratory investigations, and periodic BMD measurement every 1–2 years where feasible (Grade A).[133]

163. During bisphosphonate or denosumab therapy report any oral symptoms such as dental mobility, pain, or swelling any unexplained thigh, groin, or hip pain, and if such symptoms develop, the femur should be imaged.

164. Investigations during therapy

  • Teriparatide: Serum calcium and creatinine at 1 month and every 6 months

  • Denosumab: Serum calcium and 25-hydroxy-Vitamin D before each 6-monthly injection

  • Zoledronic acid: Renal function and calcium before each annual infusion

  • Alendronate: Symptom review and adherence every 6–12 months.[121]

165. Bone turnover markers: In selected clinical situations and research settings, markers of bone turnover may be used to monitor treatment response and adherence. Recommended markers include serum C-terminal telopeptide (CTX) for bone resorption and serum procollagen type I N-terminal propeptide (PINP) for bone formation.[133]

Use markers for bone resorption when on antiresorptives and use bone formation markers when on anabolic agents.

After baseline, for resorption markers repeat at three or 6 months and for formation markers at 6 months after treatment has been initiated.

Timing of sample: morning (before 9 am) after an overnight fast for CTX and anytime for PINP.

166. We suggest that DXA should be repeated on the same machine to monitor the response to osteoporosis therapy. Interpretation of serial BMD results must account for measurement precision and least significant change (LSC) to distinguish true change from random variation (Grade B).[173]

167. The lumbar spine (L1–L4) is the preferred primary site for BMD monitoring, with the hip (total hip and femoral neck) serving as the secondary site. Both sides should be measured routinely for comprehensive treatment monitoring.[173]

168. Most established osteoporosis therapies produce only modest increases in BMD, and their antifracture efficacy is only partly explained by these changes. Stabilization of BMD without further decline is a marker of effective treatment and reflects reduced bone turnover and fracture risk (Grade A).[133]

169. Nonresponse to osteoporosis therapy may result from poor adherence, inadequate calcium or Vitamin D status, unrecognized secondary osteoporosis, interfering medications, or suboptimal drug selection and monitoring strategies. Identification and correction of these factors are essential before changing therapy (Grade C).[133]

170. Duration of therapy has to be individualized depending on the patient’s profile, drug used, and response to treatment. Oral bisphosphonates (alendronate, ibandronate, and risedronate) for at least 5 years, zoledronate for at least 3 years, and then reassess fracture risk. Longer durations of treatment, for at least 10 years with oral and 6 years with zoledronate, in special situations. Teriparatide for 24 months (can be given only once in a lifetime), abaloparatide for 18 months, and romosozumab for 12 months.

Denosumab safety and efficacy have been established for 10 years. For MHT: shared decision-making for an extended period of use.

Sequential osteoporosis therapies

171. Sequential therapy in osteoporosis involves strategically transitioning between different classes of medications to optimize bone health outcomes throughout a patient’s treatment journey.

172. The optimal sequential therapy approach requires individualized assessment based on fracture risk, prior treatment history, patient factors, and long-term treatment goals, with anabolic-first strategies providing the strongest evidence base for maximizing bone health outcomes.[174]

173. Anabolic to antiresorptive sequences (preferred): an anabolic agent (teriparatide or romosozumab) followed by an antiresorptive (bisphosphonate or denosumab) to maintain BMD gains and ensure long-term fracture protection (Grade B).[121,175]

174. Antiresorptive to antiresorptive sequences: Bisphosphonate to denosumab transition

175. Denosumab discontinuation is most critical: requires mandatory sequential therapy due to rapid bone loss, delay/lack of an alternate treatment 6 months after the last denosumab dose, and rebound fracture risk. Denosumab must always be followed by a bisphosphonate, either zoledronate or alendronate, in patients with adequate renal function.[176-178]

176. Hormone-based sequential approaches: Estrogen/MHT/raloxifene-to-bisphosphonate transitions when HRT is discontinued due to age or contraindications.

177. Between-anabolic agent transitions: Recent evidence suggests superior efficacy with the teriparatide to romosozumab sequence.

178. Combination regimens are typically reserved for very high-risk patients (e.g., multiple prior fractures, extremely low BMD, and imminent fracture risk).

179. Duration of concurrent therapy varies; anabolic agents are limited to 12–24 months, while antiresorptives continue per standard maintenance protocols. Monitor for hypercalcemia, orthostatic hypotension (with PTH analogues), and ensure strict adherence to dosing intervals.

180. Tailoring combination therapy requires multidisciplinary assessment, balancing fracture risk reduction with cost, safety, and patient preferences.[179] Teriparatide + Denosumab Combination.[180] Hormone Replacement + Bisphosphonate Combinations.[181]

Menopause hormone therapy

181. MHT may be considered as a first-line treatment in younger postmenopausal women (<60 years or within 10 years of menopause) who are at intermediate and high fracture risk after full risk assessment, provided there are no contraindications (Grade A).[182-188]

182. Continued use after 60 years is a shared decision based on an individual risk–benefit analysis.[182-188]

183. Tibolone may be preferable to MHT in symptomatic menopausal women with mammographically dense breast tissue (Grade A).[189,190]

184. MHT should not be started solely for bone protection after 10 years of menopause (Grade B).[191,192]

185. Raloxifene is a selective estrogen receptor modulator approved for the prevention and treatment of PMO, mainly with evidence for vertebral fracture and/or breast cancer, especially where bisphosphonates or other agents are unsuitable. No benefit for HF reduction.[193]

186. Primary ovarian insufficiency (POI) and EM: HT should be offered to women with POI and EM, and it can be recommended until the age of natural menopause (Grade B).[194-196]

Menopause hormone therapy versus bisphosphonates

187. Both MHT and bisphosphonates effectively reduce osteoporotic fracture risk, but their clinical roles differ according to menopausal stage, risk category, and symptom profile (Grade A).[133,184,186,197,198]

188. Bisphosphonates do not confer the systemic short- or long-term health benefits of MHT in eligible women, particularly regarding cardiometabolic, urogenital, cognitive, and overall quality-of-life outcomes (Grade B).[133,184,186,197,198]

189. Bisphosphonates demonstrate additional systemic benefits, including reduced postfracture mortality, lower risk of bone metastases and recurrence in postmenopausal breast cancer, anti-inflammatory effects, and possible cardiovascular and survival advantages in older adults. These effects are most consistent in postmenopausal women and fracture survivors.[170,199-202]

Refer to Flowcharts 1 and 2 for assessing and managing bone health.

Flowchart 1.

Flowchart 1

Open in a new tab

Algorithm for assessing and managing bone health

Flowchart 2.

Flowchart 2

Open in a new tab

Management after fracture

SARCOPAENIA

190. Sarcopenia: It is a progressive and generalized skeletal-muscle disorder characterized by low muscle strength and low muscle quantity or quality, with or without impaired physical performance. It is associated with increased risk of falls, fractures, disability, and mortality.[118,203,204]

191. According to the South-West Asia Group for Sarcopenia (SWAG-SARCO) definition, developed specifically for South Asia, sarcopenia is identified by a reduction in any two of the following: muscle function, strength, or mass.[205,206]

192. In India, the prevalence of sarcopenia in older adults is 39%–44% and 19% can have severe sarcopenia.[207,208]

Screening tools

193. Calf Circumference (CC) and SARC-F questionnaire are the initial tools.

194. Primary: Measure CC as a part of the initial clinical evaluation. CC is a validated, simple, noninvasive, cost-effective anthropometric measure with high sensitivity and specificity for sarcopenia screening and correlates well with muscle mass (Grade B).[209-211]

195. CC has been validated as a screening tool in Indian studies, with ≤32 cm (women) as key thresholds for identifying sarcopenia risk (sensitivity 100%, specificity 60%, NPV 100%, accuracy 80%).[212]

196. CC should be interpreted with caution in individuals with high or low BMI, as adiposity can affect measurements. Adjusted cut-offs or correction factors may be used.

197. Protocol: Measure right calf, standing position, noncompressing tape, largest circumference; note edema/obesity[209] (consider + 1 cm threshold in obese adults as per Thai data).[211]

198. India-specific (CC ≤32 cm (women) is a strong screen (Sn 100%, NPV 100%); confirm positives with strength/mass tests.[212]

199. The Asian Working Group for Sarcopenia and the SWAG-SARCO recommend calf-circumference cut-offs of 34 cm for men and 33 cm for women. The European Working Group on Sarcopenia in Older People-2 uses 31 cm as a universal proxy measure.[118,203,205] Thai community cohorts: validate 33 cm (women) and suggest + 1 cm for obese adults to improve accuracy.[211]

200. SARC-F questionnaire: It is a self-administered questionnaire, which has five components, including strength, assistance in walking, rising from a chair, climbing stairs, and falls. It is a simple, inexpensive, and convenient method for screening for sarcopenia risk. It has low-to-moderate sensitivity and very high specificity for predicting low muscle strength. SARC-F score: A 3-level score range of 0–2 points for each item. The total score range is 0–10, with scores ≥4 indicating sarcopenia risk.[213]

201. SARC-CalF: SARC-CalF adds a calf measurement to the SARC-F questionnaire to make screening more reliable. A score of 11 or above indicates probable sarcopenia. In women, a calf circumference of 33 cm or less adds 10 points to the score. This combined tool detects sarcopenia better than SARC-F alone, both in the community and in clinics.[214,215]

202. Diagnosis: AEWGSOP recommends the use of grip strength or a chair stand to measure muscle function with specific cutoff points for each test.

203. Grip strength: Handgrip strength is the most widely used method for measuring muscle strength. This test requires 5 min and a well-calibrated handheld dynamometer. Method-six measures should be taken, three with each arm. Ideally, patients should be encouraged to squeeze as hard as possible for 3–5 s during the measure; the highest of the six measurements is reported as the final result.[216]

204. Chair stand test: It is also known as Chair Rise Test. It assesses lower extremity muscle function. This test requires 1–2 min and uses only a straight-back chair without armrests and a stopwatch. Method - The subject is first asked to stand from a sitting position without using their arms. If they can perform the task, they are then asked to stand up and sit down five times, as quickly as possible, with arms folded across their chests. The time taken to complete five stands is recorded. A chair-stand time >15 s for five rises or low handgrip strength (<16 kg in women; <27 kg in men) indicates reduced muscle strength or possible sarcopenia.[118]

Other diagnostic methods

205. Assessment of physical performance includes gait speed measurement and the Short Physical Performance Battery (SPPB), incorporating the timed up-and-go test, 400-m walk, or long-distance corridor walk for endurance evaluation. A gait speed of 0.8 m/s suggests poor physical performance in adults aged over 60 years.

206. Assessment of muscle mass by DXA/Bioelectrical Impedance Analysis. BIA, where feasible. Appendicular skeletal muscle index cutoff used in Indian women is <5.0 kg/m2.[217,218]

207. Case-finding strategy: Suspect sarcopenia in all women in the geriatric age group.Screening: SARC-F or SARC-CalF may be used for initial screening. A positive screen should prompt an objective assessment. Muscle strength assessment: Handgrip strength (preferred) or the Chair Stand Test may be used.Severity assessment: Gait speed, Short Physical Performance Battery (SPPB), Timed Up and Go Test (TUGT), and 400-m walk test.Muscle mass assessment: DXA orBioelectrical Impedance Analysis.[205]

208. Balance: In postmenopausal women, impaired balance and postural instability arise from age-related neuromuscular decline (vision, proprioception, reaction time, and muscle strength). Estrogen deficiency may affect muscle coordination and proprioceptive control, and there is limited data on its effects on vestibular signaling (Grade B).[219]

209. These factors collectively increase fall risk, a major determinant of forearm, hip, and other fragility fractures (Grade B).[220]

210. Preventive strategies should emphasize strength, balance training, and fall-risk screening, with MHT reserved for bone protection rather than balance improvement.[221,222]

211. Screening for balance impairment in postmenopausal women should include simple functional assessments, such as the Timed Up and Go test, Functional Reach Test, and one-leg stand, combined with a structured evaluation of fall risk factors (Grade A).[222-225]

212. Frailty: Prevalence ranged from 14.5% in Uttarakhand to 41.3% in Arunachal Pradesh.[226]

213. Frailty is a multicausal clinical syndrome characterized by a decrease in strength, endurance, and reduction in physiological processes, increasing an individual’s susceptibility to the development of dependency and/or death.[227]

214. Diagnosis: The Fried’s frailty phenotype tool includes five items: unintentional weight loss (4.5 kg or more over the past year), exhaustion (self-reported), low physical activity, weakness (low grip strength), and walking speed. Individuals with two deficits are considered prefrail, and those with three or more deficits are classified as frail.[228]

215. Management: Sarcopenia and frailty are reversible with early multimodal intervention. The most robust evidence supports progressive resistance training, adequate dietary protein (1.0–1.5 g/kg/day), and Vitamin D sufficiency. Pharmacologic options play only an adjunct role (Grade B).[229,230]

216. Management of postmenopausal women with balance impairment should incorporate a multifactorial fall prevention approach combining individualized exercise therapy, medication review, vision correction, and footwear optimization consistent with global evidence-based recommendations.[231,232]

CARDIOVASCULAR DISEASE

217. In women experiencing menopause at the expected age, the MT, along with aging, is associated with metabolic changes that elevate cardiovascular disease (CVD) risk. MT may be considered a window of opportunity to screen and promote preventive measures to reduce the risk of CVD.

Risk factors for cardiovascular disease in women can be divided into three categories:

218. Well-established risk factors such as hypertension, dyslipidemia, diabetes, obesity, unhealthy diet, sedentary lifestyle, and smoking or tobacco use.[233] A family history of premature CVD (men <55 years, women <65 years) is a strong risk factor and accounts for a major share of Atherosclerotic CVDs (ASCVD) globally, while CKD and chronic inflammatory states further increase risk.[234]

219. Under-recognized or under-rated risk factors include psychosocial (depression and anxiety); abuse and intimate partner violence (inducing chronic stress); socioeconomic and cultural status, race, and poverty; poor health literacy; and environmental risk factors (air pollution).[233]

220. Female-specific risk factors such as POI and EM, history of polycystic ovaries (PCO), functional hypothalamic amenorrhea, radiation and chemotherapy for breast cancer, and complications of pregnancy, including preeclampsia, gestational diabetes mellitus, gestational hypertension, preterm delivery, and low-for-estimated-gestational-age birth weight. Other conditions that are not necessarily sex-specific but are female predominant, like certain autoimmune disorders, including, but not limited to, rheumatoid arthritis, systemic lupus erythematosus, and scleroderma.[233,235-237]

Screening for women aged ≥35 years

221. Promote awareness and education: Educate clinicians and women that CVD is the leading cause of death in women, exceeding breast cancer mortality.[238,239]

222. Integrating menopause counselling with CVD risk screening enhances early detection and preventive intervention.[240]

Risk assessment tools for the prediction of cardiovascular disease

223. The Globorisk and Reynolds risk scores are designed for CVD-naïve women.

Globorisk-India estimates the 10-year probability of a first fatal or nonfatal myocardial infarction (MI) or stroke, not procedure-based events.[241]

224. The Reynolds risk score estimates the risk of major cardiovascular events (ischaemic stroke, MI, need for coronary revascularizations, or cardiovascular death) in women over 45 years of age.[242,243]

225. The Framingham Risk Score and ACC/AHA risk calculators are widely used tools; however, they have not been specifically validated or stratified for the Indian population. The QRISK3 score, used in the NHS, incorporates additional factors such as mental illness, autoimmune diseases, and CKD. It has also been applied to South Asian populations living in the United Kingdom.

Globorisk-India (primary recommendation)

226. We recommend using Globorisk-India (laboratory or nonlaboratory version) as the first-line tool for women aged a35 years. After estimating baseline risk, reclassify upward if any female-specific risk enhancer is present. Manage according to the revised risk category.[241,244-252]

227. Advantages of Globorisk-India (2023): Include its calibration specifically for the Indian population, availability of both laboratory-based and nonlaboratory versions suitable for urban and rural settings, ease of use via mobile or paper-based tools, and its ability to provide more accurate, context-appropriate risk estimates than Western models. It is also cost-effective, scalable, and well-suited for integration into national women’s health and NCD screening programs.[240,241,245,246]

228. How to calculate Globorisk-India tool

  • Access: Use the web calculator at www.globorisk.org or the validated desk/pocket chart

  • Collect core data: Age, sex (female), systolic blood pressure (mmHg), BMI or total cholesterol, diabetes (yes/no), and smoking (yes/no)

  • Select version: Nonlaboratory for PHC/outreach use. Laboratory-based for hospitals or specialist clinics.

Interpret risk

  • <10% = Low → Lifestyle optimization

  • 10%–20% = Moderate → Intensified lifestyle ± pharmacotherapy.

  • 20% = High → Comprehensive medical management (blood pressure [BP], lipids, glycaemia).

Integrate female-specific modifiers into clinical judgement: Premature or EM (<45 years) history of gestational diabetes, preeclampsia, or polycystic ovary syndrome (PCOS), autoimmune disease, hypothyroidism, or chronic inflammatory disorders.

Upgrade risk category: If any one modifier → move up one tier (Low → Moderate; Moderate → High).

If two or more modifiers or modifier + diabetes/dyslipidemia → move up two tiers.

Document: Globorisk-India = %; upgraded due to-modifier.

229. Reynolds risk score (secondary recommendation)

Reserve for women 45–80 years with no prior CVD but ambiguous results on standard scores. It incorporates hs-CRP to account for inflammation as a risk factor. Also includes familial (parental MI) factor for greater precision in borderline-risk cases.[242,243] However, the derivation cohort consisted predominantly of white, middle- to upper-socioeconomic status women, which may limit its generalizability.

230. How to calculate the Reynolds risk score

Available online on these two links: https://www.mdcalc.com/calc/3932/reynolds-risk-score-cardiovascular-risk-women?utm_

https://reference.medscape.com/calculator/192/reynolds-cad-risk?utm_

Reassess every 3–5 years or when major risk factors change.

231. Atypical clinical presentation: Women often present without classic exertional chest pain. Instead, symptoms may include fatigue, breathlessness, palpitations, epigastric discomfort, nausea, dizziness, or jaw and back pain rather than retrosternal heaviness. Silent or unrecognized MI is also more common in women, particularly among the elderly and those with diabetes.[247,253]

Diagnostic and management challenges

232. CVD in women is often under-recognized and under-treated. Standard diagnostic tools, electrocardiogram (ECG), stress testing, and troponin thresholds, may show lower specificity due to sex-based physiological differences.[254,255]

233. Women more frequently present with nonobstructive or microvascular coronary disease, resulting in normal angiograms despite ischemic symptoms. They have a higher prevalence of endothelial dysfunction and thrombosis, with or without plaque formation, as underlying mechanisms of acute MI. These processes contribute to microvascular ischemia.[256]

234. Hence, women experience delays in diagnosis, fewer referrals for angiography, and reduced use of guideline-directed therapy, contributing to higher short-term mortality and recurrent angina, mainly from heart failure with preserved ejection fraction.[257,258]

Early recognition of cardiovascular disease in women

235. Maintain high clinical suspicion: CVD should be considered in all women of 35 years presenting with fatigue, dyspnea, palpitations, or epigastric pain, especially with risk factors such as diabetes, hypertension, dyslipidemia, obesity, EM, or family history.[238,247,253]

236. Absence of classic angina does not exclude ischemia, particularly in women with microvascular dysfunction.[247,257]

237. Identify early symptoms: Women may experience unusual fatigue, poor sleep, anxiety, or exertional breathlessness weeks before acute coronary events, often dismissed as stress or menopause related.[247,253,259]

238. Early evaluation: These prodromal symptoms warrant prompt clinical evaluation and risk screening, rather than attributing these to “stress” or “age.”[247,253,259]

Optimize diagnostic strategy

239. Use high-sensitivity troponins with sex-specific cutoffs and functional test (stress echo) when ECG or treadmill tests are inconclusive.[247,257,260]

240. Coronary computed tomography angiography is to be used in false positive cases and is not a screening test. Coronary flow reserve is done during coronary angiography to assess borderline lesions.[247,257,260]

241. Computed tomography (CT) coronary artery calcification (CAC) is used to assess the extent of the calcified plaque in the coronary arteries. A higher CAC score indicates a higher risk of a coronary event. It is an established tool for stratifying cardiovascular events. It is recommended for use in patients with intermediate ASCVD risk scores or uncertain profiles to more precisely evaluate risks.[261]

242. Microvascular angina (MVA) is often grouped under the broader ischemia with non-obstructive coronary arteries category, which includes both MVA and vasospastic angina.

243. INOCA: If a woman has typical angina symptoms but normal coronary angiography, consider MVA, ischemia caused by dysfunction of small coronary vessels rather than major blockages.[257,262]

244. Positive stress test, objective ischemia (ST depression, reversible perfusion defect, or stress-induced wall motion change) despite nonobstructive coronaries (<50%) on angiography or CT suggests INOCA.[257,262]

Prevention and management of cardiovascular disease

245. TLM: Robust evidence supports the effectiveness of lifestyle interventions – particularly multifactorial programs that combine dietary modification, regular physical activity, and behavioral counselling in reducing intermediate cardiovascular risk factors in both high-risk individuals and the general population. These interventions consistently demonstrate improvements in BP, lipid profiles, body weight, and glycemic parameters, thereby contributing to both primary and secondary prevention of CVD.[263-266]

246. Lifestyle and risk factor: Smoking cessation remains the single most effective strategy. Behavioral counseling, nicotine-replacement therapy, and pharmacologic support (e.g., varenicline, bupropion) may be considered where appropriate.[267,268]

247. Body weight: Maintain or achieve an ideal body weight. A family-based, structured lifestyle modification program yields a net gain in quality of life and is cost-effective at a three-times gross domestic product per capita threshold.[269-271]

248. Physical activity: Engage in 150 min/week of moderate-intensity aerobic activity (e.g., brisk walking and cycling) or 75 min/week of vigorous-intensity activity, or an equivalent combination.[272]

249. Digital and behavioral support tools: Apps, telecoaching, and wearables can enhance adherence and behavioral outcomes; however, their long-term clinical impact remains uncertain.[273]

250. Lipid optimization: For Indian midlife women, optimal lipid targets should aim for low-density lipoprotein cholesterol (LDL-C) <130 mg/dL in low-risk and <100 mg/dL (preferably <70 mg/dL) in higher-risk groups. Triglycerides <150 mg/dL and high-density lipoprotein cholesterol (HDL-C) >50 mg/dL are desirable. Early initiation of statin therapy is recommended when LDL-C exceeds these thresholds, particularly in the presence of South Asian ethnicity or other female-specific risk enhancers (e.g., premature menopause and gestational diabetes).[274-277]

251. Blood pressure optimization: Midlife women should be counselled on achieving and maintaining BP <120/80 mm Hg through diet, physical activity, weight control, and stress reduction. Pharmacotherapy is indicated for persistent BP >140/90 mm Hg (or >130/80 mm Hg in diabetes).[278,279]

252. Dietary approaches to stop hypertension diet: Limit sodium (<2 g/day), maintain a healthy weight, and engage in 150 min/week of moderate physical activity. These measures lower systolic BP by an average of 4–11 mmHg.[280,281]

253. Antihypertensives: Thiazide diuretics (e.g., chlorthalidone and indapamide) are the preferred first-line antihypertensive agents unless contraindicated. Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, and calcium-channel blockers may be added or substituted as required to achieve optimal BP control.[282]

254. Glycemic optimization: For Indian midlife women with diabetes, aim for hemoglobin A1c (HbA1C) <7% through lifestyle optimization with early pharmacologic intensification when needed. This threshold is associated with a substantial reduction in microvascular complications and improvement in overall cardiovascular outcomes (Grade A).[283-285]

255. Low-dose aspirin for primary prevention: Primary prevention in women without risk factors is not recommended at any age. Indian guidelines emphasize that, given the high burden of CVD, low-dose aspirin may be considered only in high-risk women aged 40–60 years (≥two risk factors: diabetes, hypertension, CKD, family history, high LDL/Lp(a), CAC >100) with low bleeding risk, after shared decision-making and risk assessment.[274,286,287]

256. Antioxidant, vitamin, and folate supplementation: Do not use Vitamin E, Vitamin C, multivitamin, folic acid, or B-Vitamin supplements (alone or in combination) for CVD prevention.[288]

257. Omega-3 Fatty Acids and Prescription Icosapent Ethyl (eicosapentaenoic acid 4 g/day): Do not recommend routine omega-3 supplements for CVD prevention; consider prescription-strength icosapent ethyl in statin-treated, high-risk women with triglycerides t150 mg/dL. Grade A (for icosapent ethyl) and Grade C (for routine omega-3 use).[289,290]

258. MHT is not indicated solely for primary or secondary cardioprotection (Grade A).[291-293]

259. MHT initiated early among healthy women with premature or surgical menopause may reduce the adverse consequences of prolonged estrogen deficiency on cardiometabolic health.[291,294,295]

ENDOCRINE AND METABOLIC HEALTH AT MENOPAUSE

Obesity

260. Prevalence: In India, 40% of women are abdominally obese. Among women aged 30–49 years, 5–6 in 10 are affected. Prevalence is higher in older, urban, wealthier, and nonvegetarian women.[296]

261. In the ICMR – INDIAB study, the prevalence of abdominal obesity was 39.5%, with a higher prevalence in women (49.6%) than in men (28.8%). Among women, prevalence rose with age, from 28.0% at 20–29 years to 46.0%, 55.2%, and 57.9% in the 30–39, 40–49, and 50–59-year groups, before slightly declining to 52.4% among those aged 60 years and above.[297]

262. Weight gain and central adiposity: During the MT, women experience progressive weight gain (0.7 kg/year) and redistribution of fat toward visceral depots, largely due to estrogen decline and related metabolic changes. Aging remains the dominant factor, but dietary excess, physical inactivity, sleep disturbances, and genetic susceptibility further contribute to central adiposity and metabolic risk (Grade A).[298-303]

Health impact of obesity

263. Obesity and changes in body composition after menopause are major drivers of cardiometabolic diseases such as type 2 diabetes mellitus, dyslipidemia, hypertension, nonalcoholic fatty liver disease, and metabolic syndrome (Grade A).[304,305]

264. Central and visceral fat accumulation also heightens the risk of gynecologic (endometrial, breast, and ovarian) and nongynecologic malignancies (colorectal, esophageal, kidney, gallbladder, pancreatic, liver, stomach, and thyroid) (Grade A).[306,307]

265. Obesity is associated with an increased risk of cervical cancer, particularly adenocarcinoma, and with lower detection rates of precancerous lesions, and the association is consistent but less robust than that for endometrial or breast cancer (Grade B).[308]

267. Beyond cardiometabolic and oncologic consequences, obesity contributes to osteoarthritis, obstructive sleep apnea, gastroesophageal reflux disease, anxiety, depression, urinary incontinence, and dementia, while adversely affecting bone health and health-related quality of life (Grade A).[309-312]

268. Obesity and breast cancer risk: Obesity has opposite effects on breast cancer risk before and after menopause. Before menopause, higher body weight is generally linked to a lower risk of breast cancer (mainly in European women). After menopause, obesity increases breast cancer risk in women from Asia, Europe, North America, and Africa, mainly because fat tissue produces more estrogen through peripheral aromatization (Grade A).[313-316]

269. Based on body fat percentage and morbidity data, normal BMI thresholds are lower and narrower in Asian Indians than in Western populations. Obesity should be identified and managed earlier due to the higher metabolic risk at lower BMI levels[317] [Table 6].

Table 6.

Body mass index in kg/m2 category and management

Category WHO Indian Intervention
Underweight <18.5 <18 Encourage balanced diet and exercise
Healthy 18.5–24.9 18.0–22.9 Encourage balanced diet and exercise
Overweight 25.0–29.9 23.0–24.9 TLM
Obese Grade I 30.0–34.9 >25 TLM plus drug therapy if comorbidities exist*
Obese Grade II 35.0–39.9 TLM plus drug therapy: If comorbidities exist, bariatric surgery*
Obese Grade III >40 TLM, drug therapy, and bariatric surgery
Open in a new tab

*Comorbidities: Hypertension, diabetes, and hyperlipidemia. WHO: World Health Organization, TLM: Therapeutic lifestyle management

270. Waist circumference is a simple, reproducible, and robust predictor of cardiometabolic risk and should be routinely measured in clinical practice to monitor the impact of lifestyle and pharmacologic interventions[317-319] [Table 7].

Table 7.

Obesity is defined by waist circumference

WHO (cm) Indian (cm) Management
>80 >72 Action line 1 - avoid weight gain or lose weight
>88 >80 Action line 2 - supervised weight management
Open in a new tab

WHO: World Health Organization

Management

271. Management should involve primary physicians, dietitians, exercise physiologists, mental health professionals, endocrinologists, and gynecologists.

Healthcare providers should be trained in midlife obesity management and menopausal counselling.

272. TLM remains the cornerstone of obesity management in midlife and postmenopausal women (Grade A).[319-321] Refer to Section 6.

273. Behavioral Techniques: Use goal setting, motivational interviewing, and digital self-monitoring to enhance adherence. Apply problem-solving and cognitive restructuring to manage negative thoughts, with ongoing feedback and relapse prevention for sustained success (Grade A).[319]

274. Weight Loss Goals: Target a BMI ≤23 kg/m2 with gradual weight loss of 0.5 kg/week, aiming for a 5%–10% reduction over 6 months, by decreasing calories, particularly carbohydrates, and increasing physical activity. Sustained success requires family and social support to maintain motivation and adherence (Grade C).[319]

275. Monitoring and follow-up: intervention phase I: Provide intensive counseling with bimonthly progressing to monthly follow-ups (in-person or telehealth) (Grade A).[319]

Maintenance phase: Ensure lifelong engagement with 3-monthly in-person and monthly digital reviews.

276. Encourage self-monitoring of weight, diet, physical activity, and metabolic or menopausal parameters using digital or app-based tools.[319-321]

Pharmacologic and surgical management of obesity

277. If f5% weight loss is not achieved after 6 months of intensive lifestyle therapy, initiate anti-obesity medication for women with a BMI≥27 kg/m2 alongside ongoing lifestyle measures.[320-323]

278. First line: Glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide 2.4 mg weekly, liraglutide 3.0 mg daily, or tirzepatide 2.5 mg, starting with smaller doses and gradually increasing the dose to prevent GI side effects. They are most effective for sustained weight loss and cardiometabolic benefits (Grade A).[324]

279. Second line: When GLP-1 receptor agonists are contraindicated, unavailable, or unaffordable, use phentermine/topiramate, bupropion/naltrexone, or orlistat, selected based on tolerance and comorbidities.

280. Metformin: Not classified as an anti-obesity drug. Recommended only in obese women with insulin resistance, prediabetes, or PCOS, where it improves insulin sensitivity and may modestly reduce weight (Grade B).[325]

Diabetes mellitus

281. Approximately one in five adults aged ≥45 years in India, equating to about 50.4 million people, have diabetes, and 43% remain undiagnosed, underscoring a major public health challenge. Driven by urbanization, central obesity, sedentary lifestyles, and genetic predisposition (Grade A).[326,327]

282. Among postmenopausal Indian women, the prevalence of diabetes is approximately 12% based on the multicentric hospital-based study by the IMS.[68] Among rural peri- and postmenopausal women, the prevalence was higher at 25%.[327] The ICMR-INDIAB study (unpublished data) estimates a prevalence of about 18% in postmenopausal women in India.

283. Opportunistic screening for diabetes mellitus should be initiated in all women above the age of 30 years, and every 3 years in younger women with risk factors such as obesity, family history, gestational diabetes, PCO, or hypertension (Grade C).[68,328]

284. Use of the Indian diabetes risk score (IDRS) provides a no-cost, non-invasive, simple, and easily applicable tool for diabetes screening in mass screening programmes. IDRS consists of four components – age, abdominal obesity, family history of diabetes, and physical activity, with a maximum score of 100.[329,330]

285. The preferred laboratory tests for screening are fasting plasma glucose (FPG) or nonfasting HbA1c (Grade A).[328]

  • If FPG <100 mg/dL or HbA1c <5.7%, repeat testing every 3 years is recommended

  • If FPG 100–125 mg/dL or HbA1c 5.7%–6.4%, repeat testing at 1–3-year intervals is advised.

286. Prediabetes is defined as FPG 100–125 mg/dL or HbA1c 5.7%–6.4%.[328]

287. Midlife women with diabetes require preventive strategies for cardiovascular health, osteoporosis, and cancer screening, addressing sex-specific risks (Grade B).[331]

288. All women with diabetes should undergo annual screening for hypertension, dyslipidemia, and microalbuminuria, and have a comprehensive eye examination to detect retinopathy and other microvascular complications (Grade A).[328]

289. Maintain HbA1c <7% with strict control of BP, lipids, and weight to reduce cardiovascular and microvascular risk (Grade A).[328]

290. MHT in women with Type 2 diabetes: Use MHT for symptomatic relief of VMS and genitourinary syndrome of menopause, with secondary improvement in sleep and quality of life and a potential metabolic benefit (Grade B).[296,332-334] MHT is not indicated for glycemic control.

291. Oral MHT on accepted indications exerts a more substantial favourable effect on glucose metabolism and insulin sensitivity and may reduce the incidence of type 2 diabetes in women without prior disease (Grade A).[295,332,333] MHT is not to be prescribed for the prevention of diabetes.

292. Transdermal MHT is preferred in women with obesity, metabolic syndrome, or established type 2 diabetes who are at higher risk of thrombosis, hypertension, or hypertriglyceridemia, as it bypasses hepatic first-pass metabolism and has neutral effects on triglycerides and CRP (Grade A).[295,332,333]

293. MHT in women with type 1 diabetes: In type 1 diabetes, data on MHT are sparse and inconclusive; MHT should be used only for usual menopausal indications and not for glycaemic or metabolic benefit (Grade C).[333-335]

Thyroid disease

294. The prevalence of hypothyroidism among postmenopausal Indian women ranges from 3% to 7% in hospital-based studies MHT is not containdicated in thyroid disorders.[336]

295. Hypothyroidism is significantly more common in older women compared with younger individuals and may be influenced by age at natural menopause and autoimmune susceptibility (Grade A).[337]

296. Clinical features include lethargy, constipation, dry skin, alopecia, memory impairment, and depression; affected women are often overweight or obese and may have elevated cholesterol and low HDL.[338]

297. Early recognition is essential, as thyroid dysfunction can exacerbate menopausal symptoms, increase cardiovascular risk, and mimic cognitive or affective disorders in midlife women (Grade A).[339,340]

298. Routine screening for thyroid dysfunction has been recommended by the IMS 2019–2020 as part of midlife health evaluation (Grade C).[341] The initial test should be serum TSH, with free thyroxine (FT4) estimation only if TSH is abnormal or when clinical suspicion is high (Grade C).[341]

299. Screening is particularly relevant in symptomatic women, those with autoimmune disease, dyslipidemia, obesity, or early/late menopause, as thyroid dysfunction may mimic menopausal symptoms and exacerbate cardiovascular or metabolic risk (Grade B).[340]

300. Subclinical hypothyroidism: Routine L-thyroxine therapy is not recommended for asymptomatic postmenopausal women with TSH <10 mIU/L. Periodic TSH monitoring every 6–12 months is advised (Grade A).[342,343]

301. Treatment should be considered if TSH ≥10 mIU/L, symptoms persist, or if there is positive thyroid peroxidase antibody, cardiovascular risk, or MHT initiation planned (Grade A).[344]

302. In elderly women and those with CVD or risk factors, therapy should begin with a low starting dose (typically 25–50 µg daily), with dose increments every 2–4 weeks until optimal TSH and FT4 levels are achieved (Grade A).[344] Gradual titration minimizes the risk of precipitating angina, arrhythmias, or cardiac ischemia in susceptible individuals.

303. TSH should be monitored every 6–8 weeks after dose adjustment, then annually once stable (Grade A).[345]

304. Overtreatment with L-thyroxine resulting in suppressed TSH (<0.1 mIU/L) is associated with a significantly increased risk of atrial fibrillation, coronary heart disease events, and bone loss leading to osteoporotic fractures in postmenopausal women (Grade A).[340,346,347]

MULTISYSTEM HEALTH AT MENOPAUSE

305. Liver hemangiomas: Clinical reviews and observational data report that hormone exposure, such as estrogen therapy and pregnancy, has been associated with accelerated growth of hepatic hemangiomas, although clinically significant progression is uncommon.[348]

306. MHT may be considered with caution when a valid indication exists, provided the hemangioma is well characterized and not symptomatic or at risk for complications such as compression or rupture.[327] Use of low-dose, transdermal estrogen (less hepatic first pass) is preferred. Routine ultrasonographic surveillance is recommended, particularly in women with larger lesions or multiple hemangiomas.[349]

307. Anemia remains highly prevalent among older Indian adults, with pooled estimates ranging from 52% to 73% and a consolidated meta-estimate of 68.3% (95% confidence interval [CI]: 60.7%–75.9%).[350] Nutritional deficiency remains a major contributor (iron, B12, folate), but a substantial proportion is due to chronic diseases/inflammation/multifactorial etiologies in older adults.[351,352]

308. Anaemia aggravates menopausal symptoms, contributing to fatigue, cognitive decline, and mood disturbance.[353] Screening for anaemia and its nutritional causes should be part of the baseline menopause workup and the periodic health evaluation after 40 years (Grade B).[354]

309. Ocular health: Visual impairment and blindness increase with age, female sex, and low socioeconomic status, with most causes being preventable or treatable. Hormonal changes after menopause may accelerate degenerative ocular conditions such as glaucoma, age-related macular degeneration, and cataracts through oxidative stress, vascular dysregulation, and loss of estrogen-mediated neuroprotection.[355-358] However, MHT should not be prescribed solely for ocular symptoms; the decision must be individualized based on systemic benefits and risks. Collaborative management between menopause specialists and ophthalmologists is advised (Grade B).[359,360]

310. Prevention and screening: Baseline vision and ocular evaluation (visual acuity, refraction, and fundus) should be part of the menopause workup; in asymptomatic women over 40, a routine eye examination every 2–3 years is reasonable. Annual screening is advised in those with diabetes, hypertension, autoimmune disease, or long-term MHT or corticosteroid use (Grade B).[361]

311. Oral health: Periodontal disease, tooth loss, and xerostomia increase after menopause due to estrogen deficiency, which accelerates alveolar bone resorption and alters oral microbiota.[362]

312. Auditory health: May decline after menopause due to estrogen-related vascular and cochlear changes, contributing to impaired hearing acuity, tinnitus, and reduced sound discrimination.[363] Routine oral and hearing assessments should be part of a comprehensive midlife health evaluation (Grade B).[364]

313. Skin: Estrogen decline during menopause leads to a 2% loss of dermal collagen per postmenopausal year, reduced elastin, sebum, and glycosaminoglycans, resulting in thinning, dryness, and reduced skin tensile strength.[365]

314. Although systemic MHT provides documented secondary benefits for skin collagen, elasticity, and hydration, it is not primarily prescribed for cutaneous or aesthetic indications; these dermatologic benefits are more pronounced with early initiation.[366,367]

MICROBIOTA AND MENOPAUSE

315. Estrogen decline during menopause leads to alterations in the gut, vaginal, and urinary microbiota, which disrupts mucosal immunity, epithelial integrity, and microbial diversity (Grade A).[368]

316. Diets rich in fibre, fermented foods, and probiotics may support microbial diversity and estrogen metabolism (Grade B).[369-372] Local estrogen therapy helps restore vaginal Lactobacillus dominance (Grade A).[373]

REFERENCES

  1. Rocca WA, Grossardt BR, Shuster LT. Oophorectomy, menopause, estrogen treatment, and cognitive aging: Clinical evidence for a window of opportunity. Brain Res 2011;1379:188-98.

  2. Waliszewska-Prosół M, Grandi G, Ornello R, Raffaelli B, Straburzyński M, Tana C, et al. Menopause, perimenopause, and migraine: Understanding the intersections and implications for treatment. Neurol Ther 2025;14:665-80.

  3. Wang Y, Mishra A, Brinton RD. Transitions in metabolic and immune systems from pre-menopause to post-menopause: Implications for age-associated neurodegenerative diseases. F1000Res 2020;9: F1000 Faculty Rev-68.

  4. Khandelwal S, Meeta M, Tanvir T. Menopause hormone therapy, migraines, and thromboembolism. Best Pract Res Clin Obstet Gynaecol 2022;81:31-44.

  5. Ripa P, Ornello R, Degan D, Tiseo C, Stewart J, Pistoia F, et al. Migraine in menopausal women: A systematic review. Int J Womens Health 2015;7:773-82.

  6. MacGregor EA. Migraine, menopause and hormone replacement therapy. Post Reprod Health 2018;24:11-8.

  7. Sacco S, Ornello R, Ripa P, Tiseo C, Degan D, Pistoia F, et al. Migraine and risk of ischaemic heart disease: A systematic review and meta-analysis of observational studies. Eur J Neurol 2015;22:1001-11.

  8. Harden CL, Pulver MC, Ravdin L, Jacobs AR. The effect of menopause and perimenopause on the course of epilepsy. Epilepsia 1999;40:1402-7.

  9. Harden CL, Koppel BS, Herzog AG, Nikolov BG, Hauser WA. Seizure frequency is associated with age at menopause in women with epilepsy. Neurology 2003;61:451-5.

  10. Andersen NB, Jørgensen NR. Impaired bone health as a co-morbidity of epilepsy. Best Pract Res Clin Rheumatol 2022;36:101755.

  11. Pack AM, Morrell MJ. Epilepsy and bone health in adults. Epilepsy Behav 2004;5 Suppl 2: S24-9.

  12. Voinsecu P, Smith K, Pegg E, Bromley R, Latt T, Norton A. The intersection of menopause and epilepsy: A review of current knowledge and gaps. EMJ Neurol 2025;13:102-11.

  13. Singla S, Kaushal S, Arora S, Singh G. Bone health in patients with epilepsy: A community-based pilot nested case-control study. Ann Indian Acad Neurol 2017;20:367-71.

  14. Harden CL. Hormone replacement therapy: Will it affect seizure control and AED levels? Seizure 2008;17:176-80.

  15. Herzog AG, Fowler KM, Smithson SD, Kalayjian LA, Heck CN, Sperling MR, et al. Progesterone versus placebo therapy for women with epilepsy: A randomized clinical trial. Neurology 2012;78:1959-66.

  16. Bove R, Okai A, Houtchens M, Elias-Hamp B, Lugaresi A, Hellwig K, et al. Effects of menopause in women with multiple sclerosis: An evidence-based review. Front Neurol 2021;12:554375.

  17. Hsu S, Bove R. Hormonal therapies in multiple sclerosis: A review of clinical data. Curr Neurol Neurosci Rep 2024;24:1-15.

  18. Rocca WA, Smith CY, Gazzuola Rocca L, Savica R, Mielke MM. Association of premenopausal bilateral oophorectomy with parkinsonism and Parkinson disease. JAMA Netw Open 2022;5:e2238663.

  19. Ali A, Tabassum SA, Rehman Z, Ramani M, Ali K, Siddiqui AM, et al. Association of bilateral oophorectomy with incidence of Parkinson’s disease: A systematic review and meta-analysis. Parkinsonism Relat Disord 2024;121:106025.

  20. Yuk JS, Jeong SH. Association between menopausal hormone therapy and risk for Parkinson’s disease. J Parkinsons Dis 2023;13:1357-67.

  21. Unda SR, Marciano S, Milner TA, Marongiu R. State-of-the-art review of the clinical research on menopause and hormone replacement therapy association with Parkinson’s disease: What meta-analysis studies cannot tell us. Front Aging Neurosci 2022;14:971007.

  22. Wang P, Li J, Qiu S, Wen H, Du J. Hormone replacement therapy and Parkinson’s disease risk in women: A meta-analysis of 14 observational studies. Neuropsychiatr Dis Treat 2015;11:59-66.

  23. Vidal-Neira LF, Neyro JL, Maldonado G, Messina OD, Moreno-Alvarez M, Ríos C. Climacteric and fibromyalgia: A review. Climacteric 2024;27:458-65.

  24. Gulati M, Dursun E, Vincent K, Watt FE. The influence of sex hormones on musculoskeletal pain and osteoarthritis. Lancet Rheumatol 2023;5:e225-38.

  25. Dias RC, Costa EH, Chrisostomo KR, Junior JK, Paiva ES, Azevedo PM, et al. Fibromyalgia and menopause: An open study on postmenopausal hormone therapy. Minerva Obstet Gynecol 2023;75:424-31.

  26. Sasaki H, Sakihama M, Karakida N, Miyazaki T, Kobayashi H, Taniguchi N. Menopausal hormone therapy shows superior efficacy to complementary and alternative medicine in treating symptomatic hand osteoarthritis in Japanese women during perimenopause. Womens Health (Lond) 2025;21:17455057251359384.

  27. Chlebowski RT, Cirillo DJ, Eaton CB, Stefanick ML, Pettinger M, Carbone LD, et al. Estrogen alone and joint symptoms in the women’s health initiative randomized trial. Menopause 2013;20:600-8.

  28. Williams JA, Chester-Jones M, Minns Lowe C, Goff MV, Francis A, Brewer G, et al. Hormone replacement therapy (conjugated oestrogens plus bazedoxifene) for post-menopausal women with symptomatic hand osteoarthritis: Primary report from the HOPE-e randomised, placebo-controlled, feasibility study. Lancet Rheumatol 2022;4:e725-37.

  29. American Psychiatric Association, DSM-5 Task Force. Diagnostic and Statistical Manual of Mental Disorders: DSM-5™. 5th ed. American Psychiatric Publishing, Inc.; 2013. Available from: https://doi.org/10.1176/appi.books.9780890425596.

  30. Lee J, Meijer E, Langa KM, Ganguli M, Varghese M, Banerjee J, et al. Prevalence of dementia in India: National and state estimates from a nationwide study. Alzheimers Dement 2023;19:2898-912.

  31. Choudhary A, Ranjan JK, Asthana HS. Prevalence of dementia in India: A systematic review and meta-analysis. Indian J Public Health 2021;65:152-8.

  32. Ravindranath V, Sundarakumar JS. Changing demography and the challenge of dementia in India. Nat Rev Neurol 2021;17:747-58.

  33. Vas CJ, Pinto C, Panikker D, Noronha S, Deshpande N, Kulkarni L, et al. Prevalence of dementia in an urban Indian population. Int Psychogeriatr 2001;13:439-50.

  34. Raina SK, Raina S, Chander V, Grover A, Singh S, Bhardwaj A. Is dementia differentially distributed? A study on the prevalence of dementia in migrant, urban, rural, and tribal elderly population of Himalayan region in Northern India. N Am J Med Sci 2014;6:172-7.

  35. Alladi S, Rajagopalan J, Hurzuk S, Pattabiraman M, Narendhar R, Thomas PT, et al. The dementia care landscape in India: context, systems, policies and services. STRiDE Desk Review. London: CPEC, London School of Economics and Political Science; 2022.

  36. Kumar CT, Shaji KS, Varghese M, Nair MK, editors. Dementia in India 2020. Cochin: Alzheimer’s and Related Disorders Society of India (ARDSI), Cochin Chapter; 2019. Available from: https://dementiacarenotes.in/dcnfiles/Dementia-in-India-2020.pdf. [Last accessed on 2025 Oct 20].

  37. Ray S, Kumar A, Kapil S, Sharma R, Gayathri J. Early detection and management of Alzheimer’s disease and dementia in India: A policy perspective CSIR-NIScPR Policy Bulletin/February-2023/01. Available from: https://niscpr.res.in › bulletin › bulletin-2023-03-15. [Last acessed on 2025 Nov 10].

  38. Rao GN, Bharath S. Cost of dementia care in India: Delusion or reality? Indian J Public Health 2013;57:71-7.

  39. Villa A, Vegeto E, Poletti A, Maggi A. Estrogens, neuroinflammation, and neurodegeneration. Endocr Rev 2016;37:372-402.

  40. Rocca WA, Grossardt BR, Shuster LT. Oophorectomy, estrogen, and dementia: A 2014 update. Mol Cell Endocrinol 2014;389:7-12.

  41. Thurston RC, Maki P, Chang Y, Wu M, Aizenstein HJ, Derby CA, et al. Menopausal vasomotor symptoms and plasma Alzheimer disease biomarkers. Am J Obstet Gynecol 2024;230:342.e1-8.

  42. Jack CR Jr., Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA research framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement 2018;14:535-62.

  43. Roche diagnostics launches India’s first automated CSF based test for Alzheimer’s disease. Alzheimers Dement 2022;18:700-89. https://diagnostics.roche.com/in/en/news-listing/2022/automated-cerebrospinal-fluid-based-test-for-alzheimers-disease.html. [Last accesed on 2025 Nov 28].

  44. Alzheimer’s Disease Screening Profile (CSF). Metropolis Healthcare; 2025. Available from: https://www.metropolisindia.com. [Last accessed 2025 Oct 01].

  45. Dubois B, von Arnim CA, Burnie N, Bozeat S, Cummings J. Biomarkers in Alzheimer’s disease: Role in early and differential diagnosis and recognition of atypical variants. Alzheimers Res Ther 2023;15:175.

  46. Livingston G, Huntley J, Sommerlad A, Ames D, Ballard C, Banerjee S, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet 2020;396:413-46.

  47. Juul Rasmussen I, Frikke-Schmidt R. Modifiable cardiovascular risk factors and genetics for targeted prevention of dementia. Eur Heart J 2023;44:2526-43.

  48. Varghese B, Abraham M, Kumar CS. Memory clinics- a model for dementia care. IP Indian J Neurosci 2020;4:48-51.

  49. Thrivikraman SK, Dev G. Role of community health workers as trans-disciplinary models for decreasing the impact of dementia on care partners of persons suffering from dementia: A scoping review. J Geriatr Care Res 2022;9:47-56.

  50. Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: The women’s health initiative memory study: A randomized controlled trial. JAMA 2003;289:2651-62.

  51. Espeland MA, Rapp SR, Shumaker SA, Brunner R, Manson JE, Sherwin BB, et al. Conjugated equine estrogens and global cognitive function in postmenopausal women: Women’s health initiative memory study. JAMA 2004;291:2959-68.

  52. Saleh RN, Hornberger M, Ritchie CW, Minihane AM. Hormone replacement therapy is associated with improved cognition and larger brain volumes in at-risk APOE4 women: Results from the European Prevention of Alzheimer’s Disease (EPAD) cohort. Alzheimers Res Ther 2023;15:10.

  53. Gleason CE, Dowling NM, Kara F, James TT, Salazar H, Ferrer Simo CA, et al. Long-term cognitive effects of menopausal hormone therapy: Findings from the KEEPS continuation study. PLoS Med 2024;21:e1004435.

  54. Nerattini M, Jett S, Andy C, Carlton C, Zarate C, Boneu C, et al. Systematic review and meta-analysis of the effects of menopause hormone therapy on risk of Alzheimer’s disease and dementia. Front Aging Neurosci 2023;15:1260427.

  55. Mosconi L, Nerattini M, Williams S, Fink M. New horizons in menopause, menopausal hormone therapy, and Alzheimer’s disease: Current insights and future directions. J Clin Endocrinol Metab 2025;110:911-21.

  56. Kanis JA, Cooper C, Rizzoli R, Reginster JY, Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO) and the Committees of Scientific Advisors and National Societies of the International Osteoporosis Foundation (IOF). European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 2019;30:3-44.

  57. Liang H, Chen S, Shi M, Xu J, Zhao C, Yang B, et al. Global epidemiology and burden of osteoporosis among postmenopausal women: Insights from the Global Burden of Disease Study 2021. NPJ Aging 2025;11:78.

  58. Dhanwal DK, Dennison EM, Harvey NC, Cooper C. Epidemiology of hip fracture: Worldwide geographic variation. Indian J Orthop 2011;45:15-22.

  59. Dash SK, Panigrahi R, Palo N, Priyadarshi A, Biswal M. Fragility hip fractures in elderly patients in Bhubaneswar, India (2012-2014): A prospective multicenter study of 1031 elderly patients. Geriatr Orthop Surg Rehabil 2015;6:11-5.

  60. Dhibar DP, Gogate Y, Aggarwal S, Garg S, Bhansali A, Bhadada SK. Predictors and outcome of fragility hip fracture: A prospective study from North India. Indian J Endocrinol Metab 2019;23:282-8.

  61. Kuriakose C, Cherian KE, Jebasingh F, Kapoor N, Asha HS, Jose A, et al. The prevalence of vertebral fractures among Indian perimenopausal women and its association with ovarian biomarkers. J Bone Miner Metab 2022;40:142-9.

  62. Shatrugna V, Kulkarni B, Kumar PA, Rani KU, Balakrishna N. Bone status of Indian women from a low-income group and its relationship to the nutritional status. Osteoporos Int 2005;16:1827-35.

  63. Anupama DS, Noronha JA, Acharya KK, Prabhu MM, Shetty J, Shankar R, et al. Burden of osteopenia and osteoporosis among postmenopausal women in India: A systematic review and meta-analysis. J Midlife Health 2022;13:107-14.

  64. Babhulkar S, Seth S. Prevalence of osteoporosis in India: An observation of 31238 adults. Int J Res Orthop 2021;7:362-8.

  65. Khinda R, Valecha S, Kumar N, Walia JP, Singh K, Sethi S, et al. Prevalence and predictors of osteoporosis and osteopenia in postmenopausal women of Punjab, India. Int J Environ Res Public Health 2022;19:2999.

  66. Bhatia M, Mishra A, Sukla P. Post-menopausal osteoporosis: Prevalence of risk factors and probable symptoms. Int J Community Med Public Health 2018;5:5253.

  67. Harinarayan CV, Akhila H. Modern India and the tale of twin nutrient deficiency-calcium and Vitamin D-nutrition trend data 50 years-retrospect, introspect, and prospect. Front Endocrinol (Lausanne) 2019;10:493.

  68. Singh M. Early age of natural menopause in India, a biological marker for early preventive health programs. Climacteric 2012;15:581-6.

  69. Gupta A. Osteoporosis in India – The nutritional hypothesis. Natl Med J India 1996;9:268-74.

  70. Agrawal AC, Garg AK. Epidemiology of osteoporosis. Indian J Orthop 2023;57:45-8.

  71. Imran M, Singh A, Bhardwaj A, Agrawal D. Prevalence of osteoporosis and associated risk factors among postmenopausal women: A cross-sectional study from Northern India. J Midlife Health 2022;13:206-12.

  72. Harinarayan C, Ramalakshmi T. Patterns of dietary calcium intake in South Indian rural, urban and Metropolitan city subjects. J Clin Sci Res 2015;4:143.

  73. Harinarayan CV, Ramalakshmi T, Prasad UV, Sudhakar D. Vitamin D status in Andhra Pradesh: A population based study. Indian J Med Res 2008;127:211-8.

  74. Sreenivasulu K, Banerjee M, Tomo S, Shukla K, Selvi MK, Garg MK, et al. Seasonal variation and Vitamin-D status in ostensibly healthy Indian population: An experience from a tertiary care institute. Metabol Open 2024;23:100298.

  75. Thakur P, Kuriakose C, Cherian KE, Asha HS, Kapoor N, Paul TV. Knowledge gap regarding osteoporosis among medical professionals in Southern India. J Eval Clin Pract 2020;26:272-80.

  76. Kale A, Khandelwal N, Sirohi B, Shaki O, Rai S. Knowledge, attitudes, practices, and awareness levels among Indian postmenopausal women about osteoporosis and its relationship with sociodemographic factors: A cross-sectional study from Northern India. Cureus 2024;16:e59606.

  77. Kadam N, Chiplonkar S, Khadilkar A, Khadilkar V. Low knowledge of osteoporosis and its risk factors in urban Indian adults from Pune city, India. Public Health Nutr 2019;22:1292-9.

  78. Meeta M, Harinarayan CV, Marwah R, Sahay R, Kalra S, Babhulkar S. Clinical practice guidelines on postmenopausal osteoporosis: An executive summary and recommendations – Update 2019-2020. J Midlife Health 2020;11:96-112.

  79. Yordanov A, Vasileva-Slaveva M, Tsoneva E, Kostov S, Yanachkova V. Bone health for gynaecologists. Medicina (Kaunas) 2025;61:530.

  80. Consensus development conference: Prophylaxis and treatment of osteoporosis. Am J Med 1991;90:107-10.

  81. Silva BC, Leslie WD, Resch H, Lamy O, Lesnyak O, Binkley N, et al. Trabecular bone score: A noninvasive analytical method based upon the DXA image. J Bone Miner Res 2014;29:518-30.

  82. Boutroy S, Bouxsein ML, Munoz F, Delmas PD. In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography. J Clin Endocrinol Metab 2005;90:6508-15.

  83. Mirza F, Canalis E. Management of endocrine disease: Secondary osteoporosis: Pathophysiology and management. Eur J Endocrinol 2015;173: R131-51.

  84. Briot K, Roux C. Glucocorticoid-induced osteoporosis. RMD Open 2015;1:e000014.

  85. Pepe J, Body JJ, Hadji P, McCloskey E, Meier C, Obermayer-Pietsch B, et al. Osteoporosis in premenopausal women: A clinical narrative review by the ECTS and the IOF. J Clin Endocrinol Metab 2020;105:dgaa306.

  86. Baim S, Binkley N, Bilezikian JP, Kendler DL, Hans DB, Lewiecki EM, et al. Official positions of the international society for clinical densitometry and executive summary of the 2007 ISCD position development conference. J Clin Densitom 2008;11:75-91.

  87. Cohen A. Premenopausal osteoporosis. Endocrinol Metab Clin North Am 2017;46:117-33.

  88. Gourlay ML, Brown SA. Clinical considerations in premenopausal osteoporosis. Arch Intern Med 2004;164:603-14.

  89. Rubin MR, Schussheim DH, Kulak CA, Kurland ES, Rosen CJ, Bilezikian JP, et al. Idiopathic osteoporosis in premenopausal women. Osteoporos Int 2005;16:526-33.

  90. Seeman E. Bone quality: The material and structural basis of bone strength. J Bone Miner Metab 2008;26:1-8.

  91. Bhadada SK, Chadha M, Sriram U, Pal R, Paul TV, Khadgawat R, et al. The Indian Society for Bone and Mineral Research (ISBMR) position statement for the diagnosis and treatment of osteoporosis in adults. Arch Osteoporos 2021;16:102.

  92. Shilpa K, Norman G. Prevalence of frailty and its association with lifestyle factors among elderly in rural Bengaluru. J Family Med Prim Care 2022;11:2083-9.

  93. Shilpa SR, Lanjewar S, Narlawar UW, Narlawar UW, Thungamithirai P, Akash GU, et al. Prevalence of frailty among rural community-dwelling elderly: A cross-sectional study in central India. Int J Community Med Public Health 2024;12:298-303.

  94. Kanis JA. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int 1994;4:368-81.

  95. Vaishya R, Iyengar KP, Jain VK, Vaish A. Demystifying the risk factors and preventive measures for osteoporosis. Indian J Orthop 2023;57:94-104.

  96. Chevalley T, Rizzoli R. Acquisition of peak bone mass. Best Pract Res Clin Endocrinol Metab 2022;36:101616.

  97. Akhiiarova K, Khusainova R, Minniakhmetov I, Mokrysheva N, Tyurin A. Peak bone mass formation: Modern view of the problem. Biomedicines 2023;11:2982.

  98. Hereford T, Kellish A, Samora JB, Reid Nichols L. Understanding the importance of peak bone mass. J Pediatr Soc North Am 2024;7:100031.

  99. Marwaha RK, Tandon N, Shivaprasad C, Kanwar R, Mani K, Aggarwal R, et al. Peak bone mineral density of physically active healthy Indian men with adequate nutrition and no known current constraints to bone mineralization. J Clin Densitom 2009;12:314-21.

  100. Marwaha RK, Puri S, Tandon N, Dhir S, Agarwal N, Bhadra K, et al. Effects of sports training & nutrition on bone mineral density in young Indian healthy females. Indian J Med Res 2011;134:307-13.

  101. Mittal R, Mukherjee A, Kumar N, Indian Council of Medical Research. Population-Based Reference Standards of Peak Bone Mineral Density of Indian Males and Females: An ICMR Multi-Centre Task Force Study. New Delhi: ICMR; 2023.

  102. Barker DJ. The fetal and infant origins of adult disease. BMJ 1990;301:1111.

  103. World Health Organisation. Guidelines for Preclinical Evaluation and Clinical Trials in Osteoporosis. Geneva: World Health Organisation; 1998. Available from: https://iris.who.int. [Last accessed on 2025 Oct 14].

  104. The International Society for Clinical Densitometry OFFICIAL POSITIONS 2019; 2019. Available from: https://www.iscd.org. [Last accessed on 2025 Aug 19].

  105. Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, et al. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int 2014;25:2359-81.

  106. Kandasamy N, Karjala SL, Jayakumar D, Machiraju PK, Kalathur HK, Balakrishnan L. Estimation of T scores with Hologic using NatIve versus Caucasian data in IndiAns (ETHNICA): A single center retrospective study. BMC Musculoskelet Disord 2025;26:448.

  107. Krueger D, Tanner SB, Szalat A, Malabanan A, Prout T, Lau A, et al. DXA reporting updates: 2023 official positions of the international society for clinical densitometry. J Clin Densitom 2024;27:101437.

  108. Shuhart C, Cheung A, Gill R, Gani L, Goel H, Szalat A. Executive summary of the 2023 adult position development conference of the international society for clinical densitometry: DXA reporting, follow-up BMD testing and trabecular bone score application and reporting. J Clin Densitom 2024;27:101435.

  109. Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 2006;17:1726-33.

  110. Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E. FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int 2008;19:385-97.

  111. Vandenput L, Johansson H, McCloskey EV, Liu E, Åkesson KE, Anderson FA, et al. Update of the fracture risk prediction tool FRAX: A systematic review of potential cohorts and analysis plan. Osteoporos Int 2022;33:2103-36.

  112. Rajan R, Paul J, Cherian KE, Asha HS, Kapoor N, Paul TV. FRAX® with or without BMD and TBS predicts fragility fractures in community-dwelling rural Southern Indian postmenopausal women. Arch Osteoporos 2020;15:82.

  113. Dhanwal DK, Siwach R, Dixit V, Mithal A, Jameson K, Cooper C. Incidence of hip fracture in Rohtak district, North India. Arch Osteoporos 2013;8:135.

  114. Koh LK, Sedrine WB, Torralba TP, Kung A, Fujiwara S, Chan SP, et al. A simple tool to identify Asian women at increased risk of osteoporosis. Osteoporos Int 2001;12:699-705.

  115. Bhan A, Rao AD, Rao DS. Osteomalacia as a result of Vitamin D deficiency. Endocrinol Metab Clin North Am 2010;39:321-31.

  116. Coleman RE. Metastatic bone disease: Clinical features, pathophysiology and treatment strategies. Cancer Treat Rev 2001;27:165-76.

  117. Beaudart C, Buckinx F, Rabenda V, Gillain S, Cavalier E, Slomian J, et al. The effects of Vitamin D on skeletal muscle strength, muscle mass, and muscle power: A systematic review and meta-analysis of randomized controlled trials. J Clin Endocrinol Metab 2014;99:4336-45.

  118. Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, et al. Sarcopenia: Revised European consensus on definition and diagnosis. Age Ageing 2019;48:16-31.

  119. US Preventive Services Task Force, Nicholson WK, Silverstein M, Wong JB, Barry MJ, Chelmow D, et al. Interventions to prevent falls in community-dwelling older adults: US preventive services task force recommendation statement. JAMA 2024;332:51-7.

  120. Siminoski K, Jiang G, Adachi JD, Hanley DA, Cline G, Ioannidis G, et al. Accuracy of height loss during prospective monitoring for detection of incident vertebral fractures. Osteoporos Int 2005;16:403-10.

  121. Eastell R, Rosen CJ, Black DM, Cheung AM, Murad MH, Shoback D. Pharmacological management of osteoporosis in postmenopausal women: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2019;104:1595-622.

  122. Aggarwal T, Shah R, Pal R, Rastogi A, Singla V, Bhadada SK. Trabecular bone score in Asian-Indian post-menopausal women across the spectrum of hyperglycaemia: Insights from a cross-sectional study. Indian J Endocrinol Metab 2025;29:43-8.

  123. Hans D, Downs RW Jr., Duboeuf F, Greenspan S, Jankowski LG, Kiebzak GM, et al. Skeletal sites for osteoporosis diagnosis: The 2005 ISCD official positions. J Clin Densitom 2006;9:15-21.

  124. Hans D, Métrailler A, Gonzalez Rodriguez E, Lamy O, Shevroja E. Quantitative ultrasound (QUS) in the management of osteoporosis and assessment of fracture risk: An update. In: Laugier P, Grimal Q, editors. Bone Quantitative Ultrasound: New Horizons. Cham: Springer International Publishing; 2022. p. 7-34.

  125. Bala S, Prabha MLS, Krishna TP. Prevalence and risk factors of low bone mineral density with quantitative ultrasonography among south Indian postmenopausal women. Int J Community Med Public Health [Internet]. 2016;3:1735-40. Available from: https://www.ijcmph.com/index.php/ijcmph/article/view/291. [Last accessed on 2026 Jan 19].

  126. Liu DH, Lin CS, Wu PC. Osteoporosis self-assessment tool for Asians and calcaneal quantitative ultrasound for identifying primary osteoporosis in Taiwanese postmenopausal women. Front Endocrinol (Lausanne) 2025;16:1639176.

  127. Meeta M. How much calcium does an Indian postmenopausal woman need? J Midlife Health 2022;13:9-14.

  128. Gopalan C, Sastri BR, Balasubramanian SC. Nutritive Value of Indian Foods. New Delhi: ICMR; 1976. Available from: https://library.wur.nl. [Last accessed on 2025 Oct 15].

  129. Longvah T, Ananthan R, Bhaskarachary K, Venkaiah K. Indian Food Composition Tables; 2017. Available from: https://www.ninindia.org. [Last accessed on 2025 Oct 15].

  130. Allowances RD. Nutrient Requirements and Recommended Dietary Allowances for Indians. Hyderabad, India: ICMR-National Institute of Nutrition; 2009. Available from: https://www.nin.res.in/downloads/DietaryGuidelinesforNINwebsite.pdf. [Last accessed on 2025 Oct 15].

  131. Vitamin and Mineral Requirements in Human Nutrition: Report of a Joint FAO/WHO Expert Consultation, Bangkok, Thailand. 1998. WHO. FAO; 1998. Available from: https://www.fao.org/ag/humannutrition/36659-04427f866c8b2539d8e47d408cad5f3f9.pdf. [Last accessed on 2025 Oct 05].

  132. Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium; Ross AC, Taylor CL, Yaktine AL, Del Valle HB, editors. Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press (US); 2011. Available from: https://www.ncbi.nlm.nih.gov/books/NBK56070/. [Last accessed on 2025 Sep 12].

  133. Gregson CL, Armstrong DJ, Avgerinou C, Bowden J, Cooper C, Douglas L, et al. The 2024 UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos 2025;20:119.

  134. ICMR-NIN IN. Expert Group on Nutrient Requirement for Indians, Recommended Dietary Allowances (RDA) and Estimated Average Requirements (EAR). Hyderabad: ICMR-National Institute of Nutrition; 2020. Available from: https://www.nin.res.in. [Last accessed on 2025 Nov 14].

  135. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of Vitamin D deficiency: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2011;96:1911-30.

  136. Kalra S, Zargar AH, Das AK, Baidya A, Dasgupta A, Selvan C, et al. Prevention and treatment of Vitamin D deficiency in India: An expert group consensus. Indian J Endocrinol Metab 2025;29:13-26.

  137. Demay MB, Pittas AG, Bikle DD, Diab DL, Kiely ME, Lazaretti-Castro M, et al. Vitamin D for the prevention of disease: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2024;109:1907-47.

  138. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report on dietary reference intakes for calcium and Vitamin D from the institute of medicine: What clinicians need to know. J Clin Endocrinol Metab 2011;96:53-8.

  139. Holick MF. Environmental factors that influence the cutaneous production of Vitamin D. Am J Clin Nutr 1995;61:638S-45S.

  140. Babu US, Calvo MS. Modern India and the Vitamin D dilemma: Evidence for the need of a national food fortification program. Mol Nutr Food Res 2010;54:1134-47.

  141. Zhang W, Li X, He Q, Wang X. Effects of exercise on bone metabolism in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials. Front Endocrinol (Lausanne) 2025;16:1597046.

  142. Granacher U, Gollhofer A, Hortobágyi T, Kressig RW, Muehlbauer T. The importance of trunk muscle strength for balance, functional performance, and fall prevention in seniors: A systematic review. Sports Med 2013;43:627-41.

  143. Cheng L, Chang S, He B, Yan Y. Effects of Tai Chi and brisk walking on the bone mineral density of perimenopausal women: A randomized controlled trial. Front Public Health 2022;10:948890.

  144. Martyn-St James M, Carroll S. Meta-analysis of walking for preservation of bone mineral density in postmenopausal women. Bone 2008;43:521-31.

  145. Giangregorio LM, Papaioannou A, Macintyre NJ, Ashe MC, Heinonen A, Shipp K, et al. Too fit to fracture: Exercise recommendations for individuals with osteoporosis or osteoporotic vertebral fracture. Osteoporos Int 2014;25:821-35.

  146. Sinaki M. Exercise for patients with osteoporosis: Management of vertebral compression fractures and trunk strengthening for fall prevention. PM R 2012;4:882-8.

  147. Sinaki M, Itoi E, Wahner HW, Wollan P, Gelzcer R, Mullan BP, et al. Stronger back muscles reduce the incidence of vertebral fractures: A prospective 10 year follow-up of postmenopausal women. Bone 2002;30:836-41.

  148. Sherrington C, Fairhall N, Wallbank G, Tiedemann A, Michaleff ZA, Howard K, et al. Exercise for preventing falls in older people living in the community: An abridged Cochrane systematic review. Br J Sports Med 2020;54:885-91.

  149. Panel on Prevention of Falls in Older Persons, American Geriatrics Society and British Geriatrics Society. Summary of the updated American Geriatrics Society/British Geriatrics Society clinical practice guideline for prevention of falls in older persons. J Am Geriatr Soc 2011;59:148-57.

  150. Yao P, Bennett D, Mafham M, Lin X, Chen Z, Armitage J, et al. Vitamin D and calcium for the prevention of fracture: A systematic review and meta-analysis. JAMA Netw Open 2019;2:e1917789.

  151. Yakabe M, Hosoi T, Matsumoto S, Fujimori K, Tamaki J, Nakatoh S, et al. Prescription of Vitamin D was associated with a lower incidence of hip fractures. Sci Rep 2023;13:12889.

  152. Dawson-Hughes B. Effect of Vitamin D on risk of falls and fractures – The contribution of recent mega-trials. Metabol Open 2024;23:100300.

  153. Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, et al. Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med 1992;327:1637-42.

  154. Weaver CM, Alexander DD, Boushey CJ, Dawson-Hughes B, Lappe JM, LeBoff MS, et al. Calcium plus Vitamin D supplementation and risk of fractures: An updated meta-analysis from the national osteoporosis foundation. Osteoporos Int 2016;27:367-76.

  155. Bolland MJ, Grey A, Reid IR. Calcium supplements and cardiovascular risk: 5 years on. Ther Adv Drug Saf 2013;4:199-210.

  156. Lewis JR, Zhu K, Prince RL. Adverse events from calcium supplementation: Relationship to errors in myocardial infarction self-reporting in randomized controlled trials of calcium supplementation. J Bone Miner Res 2012;27:719-22.

  157. Ritu G, Gupta A. Vitamin D deficiency in India: Prevalence, causalities and interventions. Nutrients 2014;6:729-75.

  158. Harinarayan CV. Prevalence of Vitamin D insufficiency in postmenopausal South Indian women. Osteoporos Int 2005;16:397-402.

  159. Food Safety and Standards (Fortification of Foods) Regulations, 2018. Available from: https://www.fssai.gov.in/upload/uploadfiles/files/Compendium_Food_Fortification_Regulations_30_09_2021.pdf. [Last accessed on 2025 Nov 10].

  160. Marwaha RK, Dabas A, Puri S, Kalaivani M, Dabas V, Yadav S, et al. Efficacy of daily supplementation of milk fortified with Vitamin D2 for three months in healthy school children: A randomized placebo controlled trial. Indian Pediatr 2021;58:820-5.

  161. Goswami R, Gupta N, Ray D, Singh N, Tomar N. Pattern of 25-hydroxy Vitamin D response at short (2 month) and long (1 year) interval after 8 weeks of oral supplementation with cholecalciferol in Asian Indians with chronic hypovitaminosis D. Br J Nutr 2008;100:526-9.

  162. Ortiz-Prado E, Vasconez-Gonzalez J, Izquierdo-Condoy JS, Suárez-Sangucho IA, Prieto-Marín JG, Villarreal-Burbano KB, et al. Cholecalciferol (Vitamin D3): Efficacy, safety, and implications in public health. Front Nutr 2025;12:1579957.

  163. Marwaha RK, Dabas A. Interventions for prevention and control of epidemic of Vitamin D deficiency. Indian J Pediatr 2019;86:532-7.

  164. Zhuang Y, Zhu Z, Chi P, Zhou H, Peng Z, Cheng H, et al. Efficacy of intermittent versus daily Vitamin D supplementation on improving circulating 25(OH)D concentration: A Bayesian network meta-analysis of randomized controlled trials. Front Nutr 2023;10:1168115.

  165. Giustina A, Bilezikian JP, Adler RA, Banfi G, Bikle DD, Binkley NC, et al. Consensus statement on Vitamin D status assessment and supplementation: Whys, whens, and hows. Endocr Rev 2024;45:625-54.

  166. Vieth R. Vitamin D toxicity, policy, and science. J Bone Miner Res 2007;22 Suppl 2: V64-8.

  167. Norman AW. From Vitamin D to hormone D: Fundamentals of the Vitamin D endocrine system essential for good health. Am J Clin Nutr 2008;88:491S-9S.

  168. Emaus N, Gjesdal CG, Almås B, Christensen M, Grimsgaard AS, Berntsen GK, et al. Vitamin K2 supplementation does not influence bone loss in early menopausal women: A randomised double-blind placebo-controlled trial. Osteoporos Int 2010;21:1731-40.

  169. Kanis JA, Harvey NC, McCloskey E, Bruyère O, Veronese N, Lorentzon M, et al. Algorithm for the management of patients at low, high and very high risk of osteoporotic fractures. Osteoporos Int 2020;31:1-12.

  170. Lyles KW, Colón-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C, et al. HORIZON Recurrent Fracture Trial. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med 2007;357:1799-809.

  171. Cosman F, Lewiecki EM, Eastell R, Ebeling PR, Jan De Beur S, Langdahl B, et al. Goal-directed osteoporosis treatment: ASBMR/BHOF task force position statement 2024. J Bone Miner Res 2024;39:1393-405.

  172. Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, et al. Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med 2017;377:1417-27.

  173. Shepherd JA. Positions of the international society for clinical densitometry and their etiology: A scoping review. J Clin Densitom 2023;26:101369.

  174. Fassio A, Gatti D, Biffi A, Ronco R, Porcu G, Adami G, et al. The sequential antifracturative treatment: A meta-analysis of randomized clinical trials. Ther Adv Musculoskelet Dis 2024;16:1759720X241234584.

  175. Cosman F, Oates M, Betah D, Timoshanko J, Wang Z, Ferrari S, et al. Romosozumab followed by denosumab versus denosumab only: A post hoc analysis of FRAME and FRAME extension. J Bone Miner Res 2024;39:1268-77.

  176. Cruchelow KR, Peter ME, Chakrabarti A, Gipson HM, Gregory WT, DeClercq J, et al. Denosumab treatment lapses, discontinuation, and off-treatment fracture risk: A retrospective study of patients with osteoporosis in a real-world clinical setting. Bone 2023;177:116925.

  177. Burckhardt P, Faouzi M, Buclin T, Lamy O, The Swiss Denosumab Study Group. Fractures after denosumab discontinuation: A retrospective study of 797 cases. J Bone Miner Res 2021;36:1717-28.

  178. Sølling AS, Harsløf T, Langdahl B. Treatment with zoledronate subsequent to denosumab in osteoporosis: A 2-year randomized study. J Bone Miner Res 2021;36:1245-54.

  179. Zhang C, Song C. Combination therapy of PTH and antiresorptive drugs on osteoporosis: A review of treatment alternatives. Front Pharmacol 2020;11:607017.

  180. Sun Y, Li Y, Li J, Xie X, Gu F, Sui Z, et al. Efficacy of the combination of teriparatide and denosumab in the treatment of postmenopausal osteoporosis: A meta-analysis. Front Pharmacol 2022;13:888208.

  181. Harris ST, Eriksen EF, Davidson M, Ettinger MP, Moffett AH Jr., Baylink DJ, et al. Effect of combined risedronate and hormone replacement therapies on bone mineral density in postmenopausal women. J Clin Endocrinol Metab 2001;86:1890-7.

  182. Ettinger B, Ensrud KE, Wallace R, Johnson KC, Cummings SR, Yankov V, et al. Effects of ultralow-dose transdermal estradiol on bone mineral density: A randomized clinical trial. Obstet Gynecol 2004;104:443-51.

  183. Kiel DP, Felson DT, Anderson JJ, Wilson PW, Moskowitz MA. Hip fracture and the use of estrogens in postmenopausal women. The Framingham study. N Engl J Med 1987;317:1169-74.

  184. Cauley JA, Robbins J, Chen Z, Cummings SR, Jackson RD, LaCroix AZ, et al. Effects of estrogen plus progestin on risk of fracture and bone mineral density: The women’s health initiative randomized trial. JAMA 2003;290:1729-38.

  185. Effects of hormone therapy on bone mineral density: Results from the postmenopausal estrogen/progestin interventions (PEPI) trial. The writing group for the PEPI. JAMA 1996;276:1389-96.

  186. Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The women’s health initiative randomized controlled trial. JAMA 2004;291:1701-12.

  187. Torgerson DJ, Bell-Syer SE. Hormone replacement therapy and prevention of nonvertebral fractures: A meta-analysis of randomized trials. JAMA 2001;285:2891-7.

  188. Lorentzon M, Johansson H, Harvey NC, Liu E, Vandenput L, Crandall CJ, et al. Menopausal hormone therapy reduces the risk of fracture regardless of falls risk or baseline FRAX probability-results from the women’s health initiative hormone therapy trials. Osteoporos Int 2022;33:2297-305.

  189. Cummings SR, Ettinger B, Delmas PD, Kenemans P, Stathopoulos V, Verweij P, Mol-Arts M, et al.; for the LIFT Trial Investigators. The effects of tibolone in older postmenopausal women. N Engl J Med 2008;359:697-708.

  190. Kenemans P, Speroff L, International Tibolone Consensus Group. Tibolone: Clinical recommendations and practical guidelines. A report of the international tibolone consensus group. Maturitas 2005;51:21-8.

  191. Rozenberg S, Al-Daghri N, Aubertin-Leheudre M, Brandi ML, Cano A, Collins P, et al. Is there a role for menopausal hormone therapy in the management of postmenopausal osteoporosis? Osteoporos Int 2020;31:2271-86.

  192. Trémollieres FA, Chabbert-Buffet N, Plu-Bureau G, Rousset-Jablonski C, Lecerf JM, Duclos M, et al. Management of postmenopausal women: Collège National des Gynécologues et Obstétriciens Français (CNGOF) and Groupe d’Etude sur la Ménopause et le Vieillissement (GEMVi) clinical practice guidelines. Maturitas 2022;163:62-81.

  193. Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: Results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) investigators. JAMA 1999;282:637-45.

  194. Gonçalves CR, Vasconcellos AS, Rodrigues TR, Comin FV, Reis FM. Hormone therapy in women with premature ovarian insufficiency: A systematic review and meta-analysis. Reprod Biomed Online 2022;44:1143-57.

  195. Sullivan SD, Sarrel PM, Nelson LM. Hormone replacement therapy in young women with primary ovarian insufficiency and early menopause. Fertil Steril 2016;106:1588-99.

  196. Ishizuka B. Current understanding of the etiology, symptomatology, and treatment options in premature ovarian insufficiency (POI). Front Endocrinol (Lausanne) 2021;12:626924.

  197. Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, et al. HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 2007;356:1809-22.

  198. Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture intervention trial research group. Lancet 1996;348:1535-41.

  199. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Adjuvant bisphosphonate treatment in early breast cancer: Meta-analyses of individual patient data from randomised trials. Lancet 2015;386:1353-61.

  200. Hewitt RE, Lissina A, Green AE, Slay ES, Price DA, Sewell AK. The bisphosphonate acute phase response: Rapid and copious production of proinflammatory cytokines by peripheral blood gd T cells in response to aminobisphosphonates is inhibited by statins. Clin Exp Immunol 2005;139:101-11.

  201. Kunzmann V, Bauer E, Feurle J, Weissinger F, Tony HP, Wilhelm M. Stimulation of gammadelta T cells by aminobisphosphonates and induction of antiplasma cell activity in multiple myeloma. Blood 2000;96:384-92.

  202. Peris P, Monegal A, Guañabens N. Bisphosphonates in inflammatory rheumatic diseases. Bone 2021;146:115887.

  203. Chen LK, Woo J, Assantachai P, Auyeung TW, Chou MY, Iijima K, et al. Asian working group for sarcopenia: 2019 Consensus update on sarcopenia diagnosis and treatment. J Am Med Dir Assoc 2020;21:300-7.e2.

  204. Pal R, Aggarwal A, Singh T, Sharma S, Khandelwal N, Garg A, et al. Diagnostic cut-offs, prevalence, and biochemical predictors of sarcopenia in healthy Indian adults: The Sarcopenia-Chandigarh Urban Bone Epidemiological Study (Sarco-CUBES). Eur Geriatr Med 2020;11:725-36.

  205. Dhar M, Kapoor N, Suastika K, Khamseh ME, Selim S, Kumar V, et al. South Asian Working Action Group on SARCOpenia (SWAG-SARCO) – A consensus document. Osteoporos Sarcopenia 2022;8:35-57.

  206. Kalra S, Shaikh IA, Shende S, Kapoor N, Unnikrishnan AG, Sharma OP, et al. An Indian consensus on sarcopenia: Epidemiology, etiology, clinical impact, screening, and therapeutic approaches. Int J Gen Med 2025;18:1731-45.

  207. Rao AR, Bhagwasia M, Singh V, Bajpai S, Singhal S, Chatterjee P, et al. Prevalence and determinants of sarcopenia among older adults in India: Insights from the longitudinal aging study in India. J Am Geriatr Soc 2025;73:1429-40.

  208. Rahman R, Wilson BP, Paul TV, Yadav B, Kango Gopal G, Viggeswarpu S. Prevalence and factors contributing to primary sarcopenia in relatively healthy older Indians attending the outpatient department in a tertiary care hospital: A cross-sectional study. Aging Med (Milton) 2021;4:257-65.

  209. Kim S, Kim M, Lee Y, Kim B, Yoon TY, Won CW. Calf circumference as a simple screening marker for diagnosing sarcopenia in older Korean adults: The Korean frailty and aging cohort study (KFACS). J Korean Med Sci 2018;33:e151.

  210. Kawakami R, Miyachi M, Sawada SS, Torii S, Midorikawa T, Tanisawa K, et al. Cut-offs for calf circumference as a screening tool for low muscle mass: WASEDA’S health study. Geriatr Gerontol Int 2020;20:943-50.

  211. Champaiboon J, Petchlorlian A, Manasvanich BA, Ubonsutvanich N, Jitpugdee W, Kittiskulnam P, et al. Calf circumference as a screening tool for low skeletal muscle mass: Cut-off values in independent Thai older adults. BMC Geriatr 2023;23:826.

  212. Malik R, Goel H. Clinical validation of calf circumference with DEXA scans as a measure of muscle mass to assess sarcopenia in community settings in Indian postmenopausal women. J Midlife Health 2024;15:99-103.

  213. Malmstrom TK, Morley JE. SARC-F: A simple questionnaire to rapidly diagnose sarcopenia. J Am Med Dir Assoc 2013;14:531-2.

  214. Lim WS, Chew J, Lim JP, Tay L, Hafizah N, Ding YY. Case for validated instead of standard cut-offs for SARC-CalF. J Nutr Health Aging 2019; 23:393-5.

  215. Yang M, Hu X, Xie L, Zhang L, Zhou J, Lin J, et al. Screening sarcopenia in community-dwelling older adults: SARC-F versus SARC-F combined with calf circumference (SARC-CalF). J Am Med Dir Assoc 2018;19:277.e1-8.

  216. Roberts HC, Denison HJ, Martin HJ, Patel HP, Syddall H, Cooper C, et al. A review of the measurement of grip strength in clinical and epidemiological studies: Towards a standardised approach. Age Ageing 2011;40:423-9.

  217. Baumgartner RN, Koehler KM, Gallagher D, Romero L, Heymsfield SB, Ross RR, et al. Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol 1998;147:755-63.

  218. Marwaha RK, Garg MK, Bhadra K, Mithal A, Tandon N. Assessment of lean (muscle) mass and its distribution by dual energy X-ray absorptiometry in healthy Indian females. Arch Osteoporos 2014;9:186.

  219. El Khiati R, Tighilet B, Besnard S, Chabbert C. Vestibular disorders and hormonal dysregulations: State of the art and clinical perspectives. Cells 2023;12:656.

  220. Tinetti ME, Speechley M, Ginter SF. Risk factors for falls among elderly persons living in the community. N Engl J Med 1988;319:1701-7.

  221. Greising SM, Baltgalvis KA, Lowe DA, Warren GL. Hormone therapy and skeletal muscle strength: A meta-analysis. J Gerontol A 2009;64:1071-81.

  222. Howe TE, Rochester L, Neil F, Skelton DA, Ballinger C. Exercise for improving balance in older people. Cochrane Database Syst Rev 2011;2011: CD004963.

  223. Podsiadlo D, Richardson S. The timed “up & go”: A test of basic functional mobility for frail elderly persons. J Am Geriatr Soc 1991;39:142-8.

  224. Duncan PW, Weiner DK, Chandler J, Studenski S. Functional reach: A new clinical measure of balance. J Gerontol 1990;45: M192-7.

  225. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, Orav JE, Stuck AE, Theiler R, et al. Fall prevention with supplemental and active forms of Vitamin D: A meta-analysis of randomised controlled trials. BMJ 2009;339:b3692.

  226. Nagarkar A, Kulkarni AS. Regional variation in prevalence of frailty in India: Evidence from longitudinal ageing study in India (LASI) wave-1. Indian J Med Res 2024;159:441-8.

  227. Morley JE, Vellas B, van Kan GA, Anker SD, Bauer JM, Bernabei R, et al. Frailty consensus: A call to action. J Am Med Dir Assoc 2013;14:392-7.

  228. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: Evidence for a phenotype. J Gerontol A 2001;56: M146-57.

  229. WHO Clinical Consortium on Healthy Ageing Topic Focus: Frailty and Intrinsic Capacity. Available from: https://iris.who.int/server/api/core/bitstreams/b8cc03c9-07e4-4bb1-ba21-3ccb0f030ec2/content. [Last accessed on 2025 Oct 22].

  230. World Health Organization. WHO Clinical Consortium on Healthy Ageing 2019: Report of Consortium Meeting Held 21-22 November 2019. Geneva, Switzerland: World Health Organization; 2020. Available from: https://www.esceo.org/sites/esceo/files/pdf/WHO%20CCHA2019%20-%20FINAL%20REPORT.pdf. [Last accessed on 2025 Oct 22].

  231. Montero-Odasso M, van der Velde N, Martin FC, Petrovic M, Tan MP, Ryg J, et al. World guidelines for falls prevention and management for older adults: A global initiative. Age Ageing 2022;51:afac205.

  232. Hopewell S, Adedire O, Copsey BJ, Boniface GJ, Sherrington C, Clemson L, et al. Multifactorial and multiple component interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev 2018;7: CD012221.

  233. Vogel B, Acevedo M, Appelman Y, Bairey Merz CN, Chieffo A, Figtree GA, et al. The Lancet women and cardiovascular disease commission: Reducing the global burden by 2030. Lancet 2021;397:2385-438.

  234. Wong ND, Budoff MJ, Ferdinand K, Graham IM, Michos ED, Reddy T, et al. Atherosclerotic cardiovascular disease risk assessment: An American Society for Preventive Cardiology clinical practice statement. Am J Prev Cardiol 2022;10:100335.

  235. Jansen G, de Rooy A, Janssen E, Altintas S, van’t Hof A, Mihl C, et al. Atherosclerosis after pre-eclampsia: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2026;67:15-26. [doi: 10.1002/uog.70014].

  236. Visseren FL, Mach F, Smulders YM, Carballo D, Koskinas KC, Bäck M, et al. 2021 ESC guidelines on cardiovascular disease prevention in clinical practice: Developed by the task force for cardiovascular disease prevention in clinical practice with representatives of the European Society of Cardiology and 12 medical societies With the special contribution of the European Association of Preventive Cardiology (EAPC). Eur Heart J 2021;42:3227-337.

  237. Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: Executive summary: A report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Circulation 2019;140:e563-95.

  238. Prabhakaran D, Jeemon P, Roy A. Cardiovascular diseases in India. Circulation 2016;133:1605-20.

  239. Arora S, Stouffer GA, Kucharska-Newton AM, Qamar A, Vaduganathan M, Pandey A, et al. Twenty year trends and sex differences in young adults hospitalized with acute myocardial infarction. Circulation 2019;139:1047-56.

  240. World Health Organization. Prevention of Cardiovascular Disease. Pocket Guidelines for Assessment and Management of Cardiovascular Risk. Africa: WHO/ISH Cardiovascular Risk Prediction Charts for the African Region. World Health Organization; 2007. Available from: https://books.google.com. [Last accessed on 2025 Oct 12].

  241. Ueda P, Woodward M, Lu Y, Hajifathalian K, Al-Wotayan R, Aguilar-Salinas CA, et al. Laboratory-based and office-based risk scores and charts to predict 10-year risk of cardiovascular disease in 182 countries: A pooled analysis of prospective cohorts and health surveys. Lancet Diabetes Endocrinol 2017;5:196-213.

  242. Ridker PM, Buring JE, Rifai N, Cook NR. Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: The Reynolds risk score. JAMA 2007;297:611-9.

  243. Cook NR, Paynter NP, Eaton CB, Manson JE, Martin LW, Robinson JG, et al. Comparison of the Framingham and Reynolds risk scores for global cardiovascular risk prediction in the multiethnic women’s health initiative. Circulation 2012;125:1748-56, S1-11.

  244. Hajifathalian K, Ueda P, Lu Y, Woodward M, Ahmadvand A, Aguilar-Salinas CA, et al. A novel risk score to predict cardiovascular disease risk in national populations (Globorisk): A pooled analysis of prospective cohorts and health examination surveys. Lancet Diabetes Endocrinol 2015;3:339-55.

  245. Birhanu MM, Zengin A, Evans RG, Joshi R, Kalyanram K, Kartik K, et al. Comparison of the performance of cardiovascular risk prediction tools in rural India: The Rishi Valley prospective cohort study. Eur J Prev Cardiol 2024;31:723-31.

  246. Kar SS, Kannusamy S, Rehman T, Murali S, Laxminarayanan S, Balachander J. Cardiovascular risk profiling using the globorisk calculator among noncommunicable disease patients attending primary health centers of a tertiary care teaching hospital in South India: A cross-sectional analytical study. Indian J Community Med 2024;49:290-5.

  247. Mehta LS, Beckie TM, DeVon HA, Grines CL, Krumholz HM, Johnson MN, et al. Acute myocardial infarction in women. Circulation 2016;133:916-47.

  248. Zhu D, Chung HF, Dobson AJ, Pandeya N, Giles GG, Bruinsma F, et al. Age at natural menopause and risk of incident cardiovascular disease: A pooled analysis of individual patient data. Lancet Public Health 2019;4:e553-64.

  249. Kramer CK, Campbell S, Retnakaran R. Gestational diabetes and the risk of cardiovascular disease in women: A systematic review and meta-analysis. Diabetologia 2019;62:905-14.

  250. Brown MC, Best KE, Pearce MS, Waugh J, Robson SC, Bell R. Cardiovascular disease risk in women with pre-eclampsia: Systematic review and meta-analysis. Eur J Epidemiol 2013;28:1-19.

  251. Schoenfeld SR, Kasturi S, Costenbader KH. The epidemiology of atherosclerotic cardiovascular disease among patients with SLE: A systematic review. Semin Arthritis Rheum 2013;43:77-95.

  252. Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet 2017;390:1550-62.

  253. EUGenMed Cardiovascular Clinical Study Group, Regitz-Zagrosek V, Oertelt-Prigione S, Prescott E, Franconi F, Gerdts E, et al. Gender in cardiovascular diseases: Impact on clinical manifestations, management, and outcomes. Eur Heart J 2016;37:24-34.

  254. Fitzgerald BT, Scalia WM, Scalia GM. Female false positive exercise stress ECG testing – Fact versus fiction. Heart Lung Circ 2019;28:735-41.

  255. Aldiwani H, Mahdai S, Alhatemi G, Merz CN. Microvascular angina: Diagnosis and management. Eur Cardiol Rev 2021;16:e46.

  256. Alonso-Herranz L, Albarrán-Juárez J, Bentzon JF. Mechanisms of fibrous cap formation in atherosclerosis. Front Cardiovasc Med 2023;10:1254114.

  257. Pepine CJ, Ferdinand KC, Shaw LJ, Light-McGroary KA, Shah RU, et al. ACC CVD in Women Committee. Emergence of nonobstructive coronary artery disease: A woman’s problem and need for change in definition on angiography. J Am Coll Cardiol 2015;66:1918-33.

  258. Taqueti VR, Shaw LJ, Cook NR, Murthy VL, Shah NR, Foster CR, et al. Excess cardiovascular risk in women relative to men referred for coronary angiography is associated with severely impaired coronary flow reserve, not obstructive disease. Circulation 2017;135:566-77.

  259. McSweeney JC, Cleves MA, Zhao W, Lefler LL, Yang S. Cluster analysis of women’s prodromal and acute myocardial infarction symptoms by race and other characteristics. J Cardiovasc Nurs 2010;25:311-22.

  260. Chapman AR, Adamson PD, Shah AS, Anand A, Strachan FE, Ferry AV, et al. High-sensitivity cardiac troponin and the universal definition of myocardial infarction. Circulation 2020;141:161-71.

  261. Parikh P, Shah N, Ahmed H, Schoenhagen P, Fares M. Coronary artery calcium scoring: Its practicality and clinical utility in primary care. Cleve Clin J Med 2018;85:707-16.

  262. Bairey Merz CN, Pepine CJ, Walsh MN, Fleg JL, Camici PG, Chilian WM, et al. Ischemia and no obstructive coronary artery disease (INOCA). Circulation 2017;135:1075-92.

  263. Slater K, Colyvas K, Taylor R, Collins CE, Hutchesson M. Primary and secondary cardiovascular disease prevention interventions targeting lifestyle risk factors in women: A systematic review and meta-analysis. Frontiers Cardiovasc Med 2022;9:1010528.

  264. Limbachia J, Ajmeri M, Keating BJ, de Souza RJ, Anand SS. Effects of lifestyle interventions on cardiovascular risk factors in South Asians: A systematic review and meta-analysis. BMJ Open 2022;12:e059666.

  265. Lloyd-Jones DM, Allen NB, Anderson CA, Black T, Brewer LC, Foraker RE, et al. Life’s essential 8: Updating and enhancing the American Heart Association’s construct of cardiovascular health: A presidential advisory from the American Heart Association. Circulation 2022;146:e18-43.

  266. Zhang YB, Pan XF, Chen J, Cao A, Xia L, Zhang Y, et al. Combined lifestyle factors, all-cause mortality and cardiovascular disease: A systematic review and meta-analysis of prospective cohort studies. J Epidemiol Community Health 2021;75:92-9.

  267. Critchley JA, Capewell S. Mortality risk reduction associated with smoking cessation in patients with coronary heart disease: A systematic review. JAMA 2003;290:86-97.

  268. Pahwa V, Pimple SA, Bhattacharjee A, Kuberkar D, Mishra GA, Chaturvedi P. Behavioural interventions for tobacco cessation in India: A systematic review and meta-analysis. J Family Med Prim Care 2023;12:2542-51.

  269. John AS, Ganapathi S, Harikrishnan S, Lekha TR, Stanley A, Soman B, et al. Within-trial cost-effectiveness analysis of a family-based structured lifestyle modification intervention program for cardiovascular risk reduction: Results from the PROLIFIC trial. Glob Heart 2025;20:65.

  270. Jeemon P, Harikrishnan S, Ganapathi S, Sivasankaran S, Binukumar B, Padmanabhan S, et al. Efficacy of a family-based cardiovascular risk reduction intervention in individuals with a family history of premature coronary heart disease in India (PROLIFIC): An open-label, single-centre, cluster randomised controlled trial. Lancet Glob Health 2021;9:e1442-50.

  271. Unick JL, Beavers D, Bond DS, Clark JM, Jakicic JM, Kitabchi AE, et al. The long-term effectiveness of a lifestyle intervention in severely obese individuals. Am J Med 2013;126:236-42.e2.

  272. Lee IM, Shiroma EJ, Lobelo F, Puska P, Blair SN, Katzmarzyk PT, et al. Effect of physical inactivity on major non-communicable diseases worldwide: An analysis of burden of disease and life expectancy. Lancet 2012;380:219-29.

  273. Akinosun AS, Polson R, Diaz-Skeete Y, De Kock JH, Carragher L, Leslie S, et al. Digital technology interventions for risk factor modification in patients with cardiovascular disease: Systematic review and meta-analysis. JMIR Mhealth Uhealth 2021;9:e21061.

  274. Puri R, Bansal M, Mehta V, Duell PB, Wong ND, Iyengar SS, et al. Lipid association of India 2023 update on cardiovascular risk assessment and lipid management in Indian patients: Consensus statement IV. J Clin Lipidol 2024;18:e351-73.

  275. Agarwala A, Michos ED, Samad Z, Ballantyne CM, Virani SS. The use of sex-specific factors in the assessment of women’s cardiovascular risk. Circulation 2020;141:592-9.

  276. Shufelt CL. Statin therapy in midlife women. Menopause 2021;28:1067-9.

  277. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2019;73:3168-209.

  278. Unger T, Borghi C, Charchar F, Khan NA, Poulter NR, Prabhakaran D, et al. 2020 international society of hypertension global hypertension practice guidelines. Hypertension 2020;75:1334-57.

  279. Fu J, Liu Y, Zhang L, Zhou L, Li D, Quan H, et al. Nonpharmacologic interventions for reducing blood pressure in adults with prehypertension to established hypertension. J Am Heart Assoc 2020;9:e016804.

  280. Siervo M, Lara J, Chowdhury S, Ashor A, Oggioni C, Mathers JC. Effects of the dietary approach to stop hypertension (DASH) diet on cardiovascular risk factors: A systematic review and meta-analysis. Br J Nutr 2015;113:1-15.

  281. Hashemi R, Rahimlou M, Baghdadian S, Manafi M. Investigating the effect of DASH diet on blood pressure of patients with type 2 diabetes and prehypertension: Randomized clinical trial. Diabetes Metab Syndr 2019;13:1-4.

  282. Maheshwari A, Gupta R, Verma N, Narasingan SN, Singh RB, Saboo B, et al. Position statement on hypertension by Indian Society of Hypertension, 2023. J Hum Hypertens 2024;38:736-44.

  283. RSSDI Clinical Practice Recommendations for the Management of Type 2 Diabetes Mellitus 2022. Int J Diabetes Dev Ctries 2022;42(Suppl 1):1-143.

  284. Anjana RM, Unnikrishnan R, Deepa M, Venkatesan U, Pradeepa R, Joshi S, et al. Achievement of guideline recommended diabetes treatment targets and health habits in people with self-reported diabetes in India (ICMR-INDIAB-13): A national cross-sectional study. Lancet Diabetes Endocrinol 2022;10:430-41.

  285. Hu H, Hori A, Nishiura C, Sasaki N, Okazaki H, Nakagawa T, et al. Hba1c, blood pressure, and lipid control in people with diabetes: Japan epidemiology collaboration on occupational health study. PLoS One 2016;11:e0159071.

  286. US Preventive Services Task Force, Davidson KW, Barry MJ, Mangione CM, Cabana M, Chelmow D, et al. Aspirin use to prevent cardiovascular disease: US preventive services task force recommendation statement. JAMA 2022;327:1577-84.

  287. Patrono C. Low-dose aspirin for the prevention of atherosclerotic cardiovascular disease. Eur Heart J 2024;45:2362-76.

  288. US Preventive Services Task Force, Mangione CM, Barry MJ, Nicholson WK, Cabana M, Chelmow D, et al. Vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer: US preventive services task force recommendation statement. JAMA 2022;327:2326-33.

  289. Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, et al. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev 2020;3: CD003177.

  290. Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med 2019;380:11-22.

  291. Boardman HM, Hartley L, Eisinga A, Main C, Roqué i Figuls M, Bonfill Cosp X, et al. Hormone therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database Syst Rev 2015;2015: CD002229.

  292. Kim JE, Chang JH, Jeong MJ, Choi J, Park J, Baek C, et al. A systematic review and meta-analysis of effects of menopausal hormone therapy on cardiovascular diseases. Sci Rep 2020;10:20631.

  293. Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) research group. JAMA 1998;280:605-13.

  294. Cho L, Kaunitz AM, Faubion SS, Hayes SN, Lau ES, Pristera N, et al. Rethinking menopausal hormone therapy: For whom, what, when, and how long? Circulation 2023;147:597-610.

  295. Manson JE, Chlebowski RT, Stefanick ML, Aragaki AK, Rossouw JE, Prentice RL, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the women’s health initiative randomized trials. JAMA 2013;310:1353-68.

  296. Chaudhary M, Sharma P. Abdominal obesity in India: Analysis of the National Family Health Survey-5 (2019-2021) data. Lancet Reg Health Southeast Asia 2023;14:100208.

  297. Anjana RM, Unnikrishnan R, Deepa M, Pradeepa R, Tandon N, Das AK, et al. Metabolic non-communicable disease health report of India: The ICMR-INDIAB national cross-sectional study (ICMR-INDIAB-17). Lancet Diabetes Endocrinol 2023;11:474-89.

  298. Opoku AA, Abushama M, Konje JC. Obesity and menopause. Best Pract Res Clin Obstet Gynaecol 2023;88:102348.

  299. Palacios S, Chedraui P, Sánchez-Borrego R, Coronado P, Nappi RE. Obesity and menopause. Gynecol Endocrinol 2024;40:2312885.

  300. Simpson SJ, Raubenheimer D, Black KI, Conigrave AD. Weight gain during the menopause transition: Evidence for a mechanism dependent on protein leverage. BJOG 2023;130:4-10.

  301. Karvonen-Gutierrez C, Kim C. Association of mid-life changes in body size, body composition and obesity status with the menopausal transition. Healthcare (Basel) 2016;4:42.

  302. Greendale GA, Han W, Finkelstein JS, Burnett-Bowie SM, Huang M, Martin D, et al. Changes in regional fat distribution and anthropometric measures across the menopause transition. J Clin Endocrinol Metab 2021;106:2520-34.

  303. Sternfeld B, Wang H, Quesenberry CP Jr., Abrams B, Everson-Rose SA, Greendale GA, et al. Physical activity and changes in weight and waist circumference in midlife women: Findings from the study of women’s health across the nation. Am J Epidemiol 2004;160:912-22.

  304. Hurtado MD, Saadedine M, Kapoor E, Shufelt CL, Faubion SS. Weight gain in midlife women. Curr Obes Rep 2024;13:352-63.

  305. Misra A, Soares MJ, Mohan V, Anoop S, Abhishek V, Vaidya R, et al. Body fat, metabolic syndrome and hyperglycemia in South Asians. J Diabetes Complications 2018;32:1068-75.

  306. Pati S, Irfan W, Jameel A, Ahmed S, Shahid RK. Obesity and cancer: A current overview of epidemiology, pathogenesis, outcomes, and management. Cancers (Basel) 2023;15:485.

  307. Davoodi SH, Malek-Shahabi T, Malekshahi-Moghadam A, Shahbazi R, Esmaeili S. Obesity as an important risk factor for certain types of cancer. Iranian J Cancer Prevention 2013;6:186.

  308. Urbute A, Frederiksen K, Thomsen LT, Kesmodel US, Kjaer SK. Overweight and obesity as risk factors for cervical cancer and detection of precancers among screened women: A nationwide, population-based cohort study. Gynecol Oncol 2024;181:20-7.

  309. Zheng H, Chen C. Body mass index and risk of knee osteoarthritis: Systematic review and meta-analysis of prospective studies. BMJ Open 2015;5:e007568.

  310. Esmaeili N, Gell L, Imler T, Hajipour M, Taranto-Montemurro L, Messineo L, et al. The relationship between obesity and obstructive sleep apnea in four community-based cohorts: An individual participant data meta-analysis of 12,860 adults. EClinicalMedicine 2025;83:103221.

  311. Shang X, Fu Y, Jin X, Wang C, Wang P, Guo P, et al. Association of overweight, obesity and risk of urinary incontinence in middle-aged and older women: A meta epidemiology study. Front Endocrinol (Lausanne) 2023;14:1220551.

  312. Jokela M, Laakasuo M. Obesity as a causal risk factor for depression: Systematic review and meta-analysis of Mendelian randomization studies and implications for population mental health. J Psychiatr Res 2023;163:86-92.

  313. Dehesh T, Fadaghi S, Seyedi M, Abolhadi E, Ilaghi M, Shams P, et al. The relation between obesity and breast cancer risk in women by considering menstruation status and geographical variations: A systematic review and meta-analysis. BMC Womens Health 2023;23:392.

  314. García-Estévez L, Cortés J, Pérez S, Calvo I, Gallegos I, Moreno-Bueno G. Obesity and breast cancer: A paradoxical and controversial relationship influenced by menopausal status. Front Oncol 2021;11:705911.

  315. Chan DS, Vieira AR, Aune D, Bandera EV, Greenwood DC, McTiernan A, et al. Body mass index and survival in women with breast cancer-systematic literature review and meta-analysis of 82 follow-up studies. Ann Oncol 2014;25:1901-14.

  316. Bhaskaran K, Douglas I, Forbes H, dos-Santos-Silva I, Leon DA, Smeeth L. Body-mass index and risk of 22 specific cancers: A population-based cohort study of 5·24 million UK adults. Lancet 2014;384:755-65.

  317. Misra A, Chowbey P, Makkar BM, Vikram NK, Wasir JS, Chadha D, et al. Consensus statement for diagnosis of obesity, abdominal obesity and the metabolic syndrome for Asian Indians and recommendations for physical activity, medical and surgical management. J Assoc Physicians India 2009;57:163-70.

  318. Ross R, Neeland IJ, Yamashita S, Shai I, Seidell J, Magni P, et al. Waist circumference as a vital sign in clinical practice: A consensus statement from the IAS and ICCR working group on visceral obesity. Nat Rev Endocrinol 2020;16:177-89.

  319. Ranjan P, Vikram NK, Choranur A, Pradeep Y, Ahuja M, Meeta M, et al. Executive summary of evidence and consensus-based clinical practice guidelines for management of obesity and overweight in midlife women: An AIIMS-DST initiative. Diabetes Metab Syndr 2022;16:102426.

  320. Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults. Circulation 2014;129 25 Suppl 2: S102-38.

  321. Bull FC, Al-Ansari SS, Biddle S, Borodulin K, Buman MP, Cardon G, et al. World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br J Sports Med 2020;54:1451-62.

  322. Palshetkar N, Pai H, Patel M, Patki A, Tandulwadkar S, Purandare A, et al. Optimizing obesity management for women in an Indian Obstetrics and Gynecology setting: A consensus approach by the Indian Society of Assisted Reproduction (ISAR). Indian J Obstet Gynecol Res 2024;11:330-44.

  323. Apovian CM, Aronne LJ, Bessesen DH, McDonnell ME, Murad MH, Pagotto U, et al. Pharmacological management of obesity: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2015;100:342-62.

  324. Wilding JP, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med 2021;384:989-1002.

  325. Pasquali R, Casanueva F, Haluzik M, van Hulsteijn L, Ledoux S, Monteiro MP, et al. European society of endocrinology clinical practice guideline: Endocrine work-up in obesity. Eur J Endocrinol 2020;182: G1-32.

  326. Sekher TV, Flood D, Green H, Hu P, Ali MK, Shete A, et al. Prevalence, awareness, treatment, and control of diabetes in India: A nationally representative survey of adults aged 45 years and older. Lancet Glob Health 2025;13:e1543-52.

  327. Shah D, Yadav V, Singh UP, Sinha A, Dumka N, Banerjee R, et al. Prevalence of non-communicable chronic diseases in rural India amongst peri- and post-menopausal women: Can artificial intelligence help in early identification? Maturitas 2024;186:108029.

  328. ICMR Guidelines for Management of Type 2 Diabetes 2018. Available from: https://www.icmr.gov.in/icmrobject/custom_data/pdf/resource-guidelines/ICMR_GuidelinesType2diabetes2018_0.pdf. [Last accessed on 2025 Oct 14].

  329. Mohan V, Deepa R, Deepa M, Somannavar S, Datta M. A simplified Indian diabetes risk score for screening for undiagnosed diabetic subjects. J Assoc Physicians India 2005;53:759-63.

  330. Mohan V, Anbalagan VP. Expanding role of the Madras diabetes research foundation – Indian diabetes risk score in clinical practice. Indian J Endocrinol Metab 2013;17:31-6.

  331. American Diabetes Association Professional Practice Committee. 4. Comprehensive medical evaluation and assessment of comorbidities: Standards of care in diabetes-2024. Diabetes Care 2024;47: S52-76.

  332. Salpeter SR, Walsh JM, Ormiston TM, Greyber E, Buckley NS, Salpeter EE. Meta-analysis: Effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women. Diabetes Obes Metab 2006;8:538-54.

  333. Santen RJ, Allred DC, Ardoin SP, Archer DF, Boyd N, Braunstein GD, et al. Postmenopausal hormone therapy: An endocrine society scientific statement. J Clin Endocrinol Metab 2010;95:s1-66.

  334. Speksnijder EM, Ten Noever de Brauw GV, Malekzadeh A, Bisschop PH, Stenvers DJ, Siegelaar SE. Effect of postmenopausal hormone therapy on glucose regulation in women with type 1 or type 2 diabetes: A systematic review and meta-analysis. Diabetes Care 2023;46:1866-75.

  335. Holt RI, DeVries JH, Hess-Fischl A, Hirsch IB, Kirkman MS, Klupa T, et al. The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2021;64:2609-52.

  336. Shringi MS, Vaidya RA, Joshi JV. Subclinical hypothyroidism in perimenopausal-a study of 648 women in Maitreyi’s healthcare programme. Obstet Gynecol Today 2004;9:671.

  337. Kesibi D, Rotondi M, Edgell H, Tamim H. Associations between age at natural menopause and risk of hypothyroidism among postmenopausal women from the Canadian Longitudinal Study on Aging (CLSA). PLoS One 2025;20:e0324635.

  338. Vanderpump MP. The epidemiology of thyroid disease. Br Med Bull 2011;99:39-51.

  339. Jabbar A, Pingitore A, Pearce SH, Zaman A, Iervasi G, Razvi S. Thyroid hormones and cardiovascular disease. Nat Rev Cardiol 2017;14:39-55.

  340. Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endocr Rev 2008;29:76-131.

  341. Meeta M, Digumarti L, Agarwal N, Vaze N, Shah R, Malik S. Clinical practice guidelines on menopause: An executive summary and recommendations: Indian menopause society 2019-2020. J Midlife Health 2020;11:55-95.

  342. Villar HC, Saconato H, Valente O, Atallah AN. Thyroid hormone replacement for subclinical hypothyroidism. Cochrane Database Syst Rev 2007;2007: CD003419.

  343. Feller M, Snel M, Moutzouri E, Bauer DC, de Montmollin M, Aujesky D, et al. Association of thyroid hormone therapy with quality of life and thyroid-related symptoms in patients with subclinical hypothyroidism: A systematic review and meta-analysis. JAMA 2018;320:1349-59.

  344. Stott DJ, Rodondi N, Kearney PM, Ford I, Westendorp RGJ, Mooijaart SP, et al.; TRUST Study Group. Thyroid hormone therapy for older adults with subclinical hypothyroidism. N Engl J Med 2017;376:2534-44.

  345. Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, et al. Clinical practice guidelines for hypothyroidism in adults: Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract 2012;18:988-1028.

  346. Flynn RW, Bonellie SR, Jung RT, MacDonald TM, Morris AD, Leese GP. Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy. J Clin Endocrinol Metab 2010;95:186-93.

  347. Gharib H, Tuttle RM, Baskin HJ, Fish LH, Singer PA, McDermott MT. Subclinical thyroid dysfunction: A joint statement on management from the American Association of Clinical Endocrinologists, the American Thyroid Association, and the endocrine society. J Clin Endocrinol Metab 2005;90:581-5.

  348. Glinkova V, Shevah O, Boaz M, Levine A, Shirin H. Hepatic haemangiomas: Possible association with female sex hormones. Gut 2004;53:1352-5.

  349. Leon M, Chavez L, Surani S. Hepatic hemangioma: What internists need to know. World J Gastroenterol 2020;26:11-20.

  350. Daniel RA, Ahamed F, Mandal S, Lognathan V, Ghosh T, Ramaswamy G. Prevalence of anemia among the elderly in India: Evidence from a systematic review and meta-analysis of cross-sectional studies. Cureus 2023;15:e42333.

  351. Bhasin A, Rao MY. Characteristics of anemia in elderly: A hospital based study in South India. Indian J Hematol Blood Transfus 2011;27:26-32.

  352. Alwar V, Reethi K, Rameshkumar K. Geriatric anemia: An Indian perspective. Indian J Hematol Blood Transfus 2013;29:126-7.

  353. Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: Evidence for a high rate of unexplained anemia. Blood 2004;104:2263-8.

  354. World Health Organization. Nutritional Anaemias: Tools for Effective Prevention and Control Nutritional Anaemias: Tools for Effective Prevention and Control; 2017. Available from: https://www.who.int. [Last accessed on 2025 Oct 10].

  355. Vajaranant TS, Pasquale LR. Estrogen deficiency accelerates aging of the optic nerve. Menopause 2012;19:942-7.

  356. Freeman EE, Muñoz B, Bressler SB, West SK. Hormone replacement therapy, reproductive factors, and age-related macular degeneration: The Salisbury eye evaluation project. Ophthalmic Epidemiol 2005;12:37-45.

  357. Youngblood H, Schoenlein PV, Pasquale LR, Stamer WD, Liu Y. Estrogen dysregulation, intraocular pressure, and glaucoma risk. Exp Eye Res 2023;237:109725.

  358. Prokai-Tatrai K, Zaman K, Kapic A, Hogan K, Sanchez-Rodriguez G, Silverio AE, et al. Retina-targeted 17β-estradiol by the DHED prodrug rescues visual function and actuates neuroprotective protein networks after optic nerve crush in a rat model of surgical menopause. Int J Mol Sci 2025;26:1846.

  359. Lee HJ, Yu EH, Jeong YH, Joo JK. Impact of hormone therapy on ocular disease risk in postmenopausal women: Evidence from the Korean national health insurance service database. J Menopausal Med 2025;31:120-9.

  360. Hao Y, Xiaodan J, Jiarui Y, Xuemin L. The effect of hormone therapy on the ocular surface and intraocular pressure for postmenopausal women: A systematic review and meta-analysis of randomized controlled trials. Menopause 2020;27:929-40.

  361. American Optometric Association. Evidence-Based Clinical Practice Guideline Comprehensive Adult Eye and Vision Examination. St. Louis: American Optometric Association; 2015. Available from: https://www.aoa.org/sites/default/files/documents/CPG-1.pdf. [Last accessed on 2025 Oct 19].

  362. Shrivastava S. Menopause and oral health: Clinical implications and preventive strategies. J Midlife Health 2024;15:135-41.

  363. Curhan SG, Eliassen AH, Eavey RD, Wang M, Lin BM, Curhan GC. Menopause and postmenopausal hormone therapy and risk of hearing loss. Menopause 2017;24:1049-56.

  364. World Health Organization. World Report on Ageing and Health. Geneva: World Health Organization; 2015. Available from: https://www.who.int/publications/i/item/9789241565042. [Last accessed on 2025 Oct 10].

  365. Affinito P, Palomba S, Sorrentino C, Di Carlo C, Bifulco G, Arienzo MP, et al. Effects of postmenopausal hypoestrogenism on skin collagen. Maturitas 1999;33:239-47.

  366. Stevenson S, Thornton J. Effect of Estrogens on Skin Aging and the Potential Role of SERMs Estrogens and Skin Biology; 2007. Available from: https://www.dovepress.com/. [Last accessed on 2025 Dec 14].

  367. Brincat M, Moniz CJ, Studd JW, Darby A, Magos A, Emburey G, et al. Long-term effects of the menopause and sex hormones on skin thickness. Br J Obstet Gynaecol 1985;92:256-9.

  368. Zhou Z, Feng Y, Xie L, Ma S, Cai Z, Ma Y. Alterations in gut and genital microbiota associated with gynecological diseases: A systematic review and meta-analysis. Reprod Biol Endocrinol 2024;22:13.

  369. Honda S, Tominaga Y, Espadaler-Mazo J, Huedo P, Aguiló M, Perez M, et al. Supplementation with a probiotic formula having β-glucuronidase activity modulates serum estrogen levels in healthy peri- and postmenopausal women. J Med Food 2024;27:720-7.

  370. Ayubi E, Abdoli S, Mehrpooya M, Karami Z, Jenabi E, Ghaleiha A, et al. The effect of probiotic administration on the severity of menopausal symptoms and mental health of postmenopausal women: A triple-blind randomized controlled trial in the West of Iran. Menopause 2025;32:166-73.

  371. Han AL, Ryu MS, Yang HJ, Jeong DY, Choi KH. The efficacy of cheonggukjang in alleviating menopausal syndrome and its effects on the gut microbiome: A randomized, double-blind trial. Nutrients 2025;17:505.

  372. Wang F, Wei W, Liu PJ. Effects of probiotic supplementation on bone health in postmenopausal women: A systematic review and meta-analysis. Front Endocrinol (Lausanne) 2024;15:1487998.

  373. Thomas-White K, Taege S, Limeira R, Brincat C, Joyce C, Hilt EE, et al. Vaginal estrogen therapy is associated with increased Lactobacillus in the urine of postmenopausal women with overactive bladder symptoms. Am J Obstet Gynecol 2020;223:727.e1-11.

SECTION 4: GYNECOLOGICAL SYSTEMS AND MENOPAUSE

Endometriosis

1. Women with endometriosis face a higher risk of earlier menopause (1–3 years), with a 7-fold increase in surgical menopause occurring approximately 19 months earlier and natural menopause occurring about 5 months earlier. This is due to repeated ovarian inflammation, surgeries such as endometrioma excision, and decreased ovarian reserve (Grade B).[1-3]

2. Postmenopausal active endometriosis is rare, representing about 2%–5% of all endometriosis cases. It may persist or reactivate due to stimulation of residual endometrial implants by exogenous estrogen therapy or obesity-related peripheral aromatization (Grade C).[4] Endometriosis can also arise de novo from local estrogen biosynthesis within ectopic lesions through celomic metaplasia or activation of pluripotent stem cells (Grade C).[5-7]

3. Postmenopausal endometriosis may show a higher tendency to infiltrate, affecting extragonadal areas such as the bowel, bladder, ureter, or surgical scars (Grade B).[8,9] It also carries a small but clinically important risk of turning malignant, most commonly endometrioid or clear cell carcinoma originating from ovarian or extragonadal sites (Grade B).[8,9]

4. The likelihood of malignant transformation increases with prolonged exposure to unopposed estrogen or persistent residual endometriotic disease. Malignancy should be considered if endometriotic lesions enlarge, become nodular, or present with new-onset postmenopausal bleeding or pelvic pain (Grade C).[10]

5. Vigilant clinical follow-up and histopathological assessment of any enlarging or symptomatic lesion are crucial (Grade C).[9,10] Magnetic resonance imaging (MRI) is the preferred imaging modality for evaluation (Grade B).[10]

6. Surgery should be the initial treatment choice for postmenopausal endometriosis to rule out cancer and ensure complete removal, ideally through total laparoscopic hysterectomy with bilateral salpingo-oophorectomy (TLH BSO) and removal of all visible implants (Grade C).[11]

7. If surgery is not an option, continuous progestogens or an aromatase inhibitor (AI), possibly combined with add-back therapy, can be used to manage the symptoms of postmenopausal endometriosis (Grade C).[11]

8. In women with surgical menopause and a history of endometriosis, continuous combined menopausal hormone therapy (ccMHT) or tibolone is preferred for vasomotor symptoms (VMS) and bone protection and to gain the benefits of avoiding disease recurrence after complete excision (Grade B).[11,12] The benefits of ccMHT versus estrogen alone in endometriosis are not well established (Grade B);[1,13] however, it is preferable to avoid unopposed estrogen, as it can stimulate the remaining endometriotic tissue or elevate the risk of cancerous changes.[1,10,14]

9. For women with a history of endometriosis and intact uterus and ovaries, low-dose oral estrogen and LNG-IUS may be used to manage VMS (Grade B).[1] Cyclic regimens should be avoided to prevent reactivation of lesions (Grade C).[1]

10. Regular monitoring includes baseline and periodic pelvic examinations, targeted ultrasound or MRI for new pelvic pain or bleeding, and bone mineral density (BMD) monitoring during AI therapy (Grade B).[11,12]

Adenomyosis

11. Adenomyosis is an estrogen-dependent condition that usually becomes clinically inactive or less active after natural or surgical menopause; symptomatic postmenopausal adenomyosis is rare (Grade C).[15,16] If indicated, MHT is administered as ccMHT or tibolone, and continued clinical vigilance for recurrence, abnormal bleeding, or uterine enlargement is suggested (Grade C).[16]

Fibroid

12. Uterine fibroids are benign smooth muscle tumors that respond to hormones with high levels of estrogen receptor (ER) and progesterone receptor (PR). They usually shrink after menopause when ovarian steroid hormone levels decline (Grade B).[17]

13. Persistent or enlarging uterine fibroids in postmenopausal women, especially in the setting of continuous estrogen exposure, such as obesity or exogenous MHT, require thorough evaluation to exclude uterine sarcoma, although this remains a rare occurrence (Grade B).[17-21]

14. Management: At menopausal transition (MT) – Refer to Section 2. In postmenopausal women with fibroids, ccMHT is preferred over sequential therapy because it causes little or no significant change in fibroid volume (Grade B)[22] and results in fewer bleeding episodes. The reported effects of MHT on fibroid size are variable (Grade C).[23]

15. Tibolone (2.5 mg/day) effectively relieves menopausal symptoms without significantly increasing the uterine or fibroid size over 1–3 years. Randomized controlled trials (RCTs) indicate that, unlike standard MHT, tibolone is largely neutral toward fibroids (Grade B).[22,24,25]

16. Clinical follow-up with pelvic examination and targeted imaging is recommended only if new bleeding, pelvic pain, or uterine enlargement occurs. Routine imaging surveillance is not advised for asymptomatic women (Grade B).[22,23]

Polycystic ovarian syndrome

17. Women with polycystic ovarian syndrome (PCOS) tend to experience delayed menopause, usually by 2–4 years, due to chronic anovulation and preservation of the follicular pool (Grade B).[26,27]

18. In PCOS, increased androgen secretion by ovarian theca cells (functional ovarian hyperandrogenism) is a key defect.[28]

19. MT does not seem to worsen the cardiometabolic profile in most women with PCOS; the phenotypic subtypes, hyperandrogenic versus normoandrogenic, obese versus lean, largely determine long-term cardiometabolic risk and the need for individualized follow-up and management (Grade B).[29-32]

20. The nonhyperandrogenic phenotype exhibits limited long-term metabolic risk after reproductive hormone stabilization, and routine midlife screening is sufficient (Grade C).[31,32]

21. Women with current or past hyperandrogenic PCOS, especially those with persistent androgen excess or metabolic syndrome, are at risk of developing cardiometabolic disease, endometrial hyperplasia or carcinoma during and after menopause (Grade B).[33,34] They require ongoing cardiometabolic monitoring, lifestyle adjustments, and careful and personalized use of MHT (Grade B).[35,36]

Adnexa

22. Age-related decline of estrogen at menopause results in atrophic and fibrotic changes in the ovaries and fallopian tubes, which reduce follicular reserve, vascularity, and mucosal immunity.[37]

23. After menopause, hydrosalpinx and paratubal cysts are usually residual benign consequences of previous inflammation or surgery rather than newly developed lesions. The decrease in estrogen diminishes tubal activity and cyst formation.

24. No intervention is necessary unless the lesions are symptomatic, large, or exhibit imaging features indicative of malignancy (Grade B).[38,39]

25. Prophylactic salpingectomy during hysterctomy (recommended) or salpingectomy (suggested in high risk with counselling) is recommended to lower the risk of epithelial ovarian cancer by removing the tubal origin of cancer (Grade A).[40-42]

26. Simple cysts and paraovarian cysts are common benign findings after menopause, and most represent retention or inclusion cysts caused by surface invagination rather than neoplasia. Many of these cysts resolve spontaneously, remain stable, or decrease in size over time (Grade A).[43]

27. A CA-125 test followed by an initial 3–6 months and then annual transvaginal sonography is sufficient for postmenopausal simple cysts (<5 cm, unilocular, thin-walled, and without septations or solid components) (Grade A).[44-46] Doppler evaluation is not routinely recommended in these cases but should be performed when complex morphology or vascularized solid areas are detected (Grade A).[44-46]

28. In postmenopausal women, complex or enlarging adnexal cysts, mural nodularity, or raised CA-125 levels indicate increased malignant potential (particularly serous or mucinous cystadenomas or borderline epithelial tumors) and require surgical evaluation and histopathological confirmation (Grade A).[47,48]

29. The use of transvaginal descriptors, such as the Ovarian of transvaginal descriptors, such (O-RADS) or International Ovarian Tumor Analysis (IOTA) systems, provides standardized, evidence-based frameworks for evaluating adnexal masses in postmenopausal women.[46,49]

30. Indian studies confirm that IOTA Simple Rules, ADNEX, and O-RADS are accurate and practical tools for the evaluation of adnexal masses in routine practice (Grade B).[50-53]

31. Hormone replacement therapy (HRT) is not recommended for adnexal atrophy. However, ccMHT or tibolone may be utilized in perimenopausal or surgically menopausal women with residual pelvic endometriosis or pelvic adhesion-related pain under close monitoring to prevent reactivation (Grade B).[54-56]

Vulva

32. Menopause is a physiological transition characterized by declining estrogen and androgen levels, resulting in reduced vulvovaginal tissue elasticity and resilience and is part of genitourinary syndrome.

33. Reduced dermal collagen, decreased sebaceous and sweat gland activity, and weakened mucosal immunity lead to impaired epithelial repair, dysbiosis of the vulval microbiota, and increased pH, making the vulval epithelium more vulnerable to chronic irritation, recurrent infections, and inflammatory dermatoses.[57,58]

34. Benign vulval dermatoses such as lichen sclerosus, lichen planus, lichen simplex chronicus, and nonhuman papillomavirus-related vulvar intraepithelial neoplasia are more commonly seen after menopause. Chronic inflammation, tissue fragility, and pruritus are typical features.[57,58]

35. MHT has no curative role in these disorders; symptom management and disease remission rely on topical high-potency corticosteroids, bland emollients, avoidance of irritants, and long-term monitoring to detect malignant transformation (Grade B).[57,58] Interdisciplinary care involving gynecologists and dermatologists enhances diagnostic accuracy and quality of life.[57,58]

ABNORMAL MENOPAUSE

Delayed menopause/late-onset menopause: Definition and health consequences – Refer to Section 1

36. Twin and genomic studies indicate strong heritability, while longitudinal cohort data emphasize the roles of endocrine, environmental, and life-course factors, including family history, parity, nutrition, and lifestyle determinants.[59-63]

37. Screening and management: Robust data are lacking, and the protocols remain similar to those with the natural age at menopause. The absolute risk of endometrial carcinoma in asymptomatic women remains low; therefore, routine endometrial evaluation is not recommended based solely on delayed menopause. Evaluation should be triggered by symptoms such as bleeding and tailored to individual risk factors (Grade B).[64]

Premature ovarian insufficiency: Definition and diagnosis – Refer to Section 1

38. A common issue in premature ovarian insufficiency (POI) is diagnostic delay, often spanning 2–5 years. Although direct causal data are limited, strong evidence indicates that untreated POI accelerates bone loss and raises the risk of cardiometabolic and other health issues, emphasizing the importance of prompt diagnosis and hormone therapy (HT) initiation (Grade B).[65-68]

39. Comprehensive and personalized management, including informed counseling, assessment of fertility goals, optimization of general health, lifestyle modification, and HT, forms the foundation of care for women with POI.[69]

40. Systemic HRT should be initiated early after diagnosis and continued until the expected age of natural menopause (ANM) to reduce skeletal, cardiovascular, and neurocognitive sequelae and preserve quality of life (Grade B).[70-72]

41. Screening and pre-MHT workup protocols are primarily similar to those for natural menopause, with a particular focus on bone health assessment.[73] DXA should be performed at diagnosis to assess both BMD and body composition, given the high prevalence of early bone loss and sarcopenia.[73,74]

42. Although women with POI are often beyond the age of peak bone mass, their bone loss results from reversible hypoestrogenism rather than from senile bone remodeling. Therefore, Z-scores (age-matched comparisons) are preferred for diagnosis, reserving T-scores for long-term postmenopausal follow-up.[73-76]

43. Current RCT evidence supports the use of HRT versus OCP, and final comparative results are expected from the Premature Ovarian Insufficiency Study of Effectiveness of Hormonal Therapy.[77-79]

44. In asymptomatic women with POI, high-quality randomized data are limited; however, current evidence and international guidelines consistently recommend HRT to improve the quality of life and reduce the risks of bone loss, cardiovascular disease, and cognitive decline associated with prolonged hypoestrogenism until the usual ANM (Grade B).[73,80-84]

45. Androgen therapy should only be considered for select, estrogen-replete women with persistent sexual symptoms; transdermal testosterone is preferred where available, but currently, no licensed preparation for women exists in India (Grade B).[85]

EARLY MENOPAUSE

46. Early menopause (EM) is not classified as POI but signifies the physiological end of the continuum of the pathological state of accelerated ovarian aging. Both conditions share pathophysiological pathways and long-term health consequences, differing only in age threshold and severity of health outcomes.[83,84,86]

47. Women experiencing EM should be offered appropriate-dose systemic HT. While robust data are limited, observational studies and biological reasoning support HT to preserve bone health and potentially decrease the risk of cardiometabolic and neurocognitive complications associated with prolonged hypoestrogenism.

48. Therapy should be continued until the ANM, at which point the risks and benefits should be re-assessed.[80,86-88]

IATROGENIC (SURGICAL AND INDUCED) MENOPAUSE

49. Iatrogenic menopause refers to the loss of ovarian function caused by medical or surgical interventions, such as indicated or prophylactic bilateral oophorectomy, pelvic radiotherapy, chemotherapy, or ovarian ablation for malignancy.[81,84]

50. Systematic reviews suggest that hysterectomy for benign reasons, even with ovarian preservation, leads to earlier ovarian failure and menopause onset compared to women who retain their uterus (Grade B).[89-92]

51. The primary reasons for surgical menopause include both clinical and nonclinical indications. Heavy menstrual bleeding, often caused by fibroids or adenomyosis, and uterine prolapse are the most common reasons for hysterectomy in India.[93,94]

52. Nonclinical factors include lower education, poorer households, a concentration of procedures within the private sector, and limited access to conservative or minimally invasive alternatives.[95]

53. The Indian Council of Medical Research strongly warns against performing hysterectomy and surgical castration without medical indication. Every clinician must ensure a clear medical justification, document informed consent, preserve the ovaries whenever possible, and advise women on the lifelong health effects of premature estrogen loss.[96-100]

54. Women experiencing iatrogenic menopause should receive multidisciplinary care involving gynecologists, oncologists, and endocrinologists. In the absence of contraindications, physiologic-dose MHT should be initiated soon after surgery or the completion of oncologic therapy and continued until the expected ANM.

55. Early counseling, personalized risk assessment, and preventive lifestyle advice should be incorporated into all treatment pathways where ovarian failure is expected, ensuring that women receive timely information and access to fertility preservation options before gonadotoxic therapy or surgery. Ovarian tissue or oocyte cryopreservation before significant follicular depletion is the only proven method to preserve reproductive potential and endocrine function.[101-103]

REFERENCES

  1. Erel CT, Nigdelis MP, Ozcivit Erkan IB, Goulis DG, Chedraui P, Giannini A, et al. Endometriosis and menopausal health: An EMAS clinical guide. Maturitas 2025;202:108715.

  2. Chung HF, Hayashi K, Dobson AJ, Sandin S, Ideno Y, Hardy R, et al. Association between endometriosis and type and age of menopause: A pooled analysis of 279 948 women from five cohort studies. Hum Reprod 2025;40:1210-9.

  3. Thombre Kulkarni M, Shafrir A, Farland LV, Terry KL, Whitcomb BW, Eliassen AH, et al. Association between laparoscopically confirmed endometriosis and risk of early natural menopause. JAMA Netw Open 2022;5:e2144391.

  4. Tan DA, Almaria MJ. Postmenopausal endometriosis: Drawing a clearer clinical picture. Climacteric 2018;21:249-55.

  5. Cassani C, Tedeschi S, Cucinella L, Morteo V, Camnasio CA, Tiranini L, et al. Menopause and endometriosis. Maturitas 2024;190:108129.

  6. Kajiyama H, Suzuki S, Yoshihara M, Tamauchi S, Yoshikawa N, Niimi K, et al. Endometriosis and cancer. Free Radic Biol Med 2019;133:186-92.

  7. Bulun SE. Aromatase and estrogen receptor α deficiency. N Engl J Med 2023;389:1712-25.

  8. Ladanyi C, Boyd S, Sticco P, Mohling S. Postmenopausal endometriosis, where are we now? Curr Opin Obstet Gynecol 2019;31:267-78.

  9. Kalaitzopoulos DR, Mitsopoulou A, Iliopoulou SM, Daniilidis A, Samartzis EP, Economopoulos KP. Association between endometriosis and gynecological cancers: A critical review of the literature. Arch Gynecol Obstet 2020;301:355-67.

  10. Giannella L, La Marca A, Setti T, Cerami LB, Bergamini E, Boselli F, et al. Malignant transformation of postmenopausal endometriosis: A systematic review of the literature. Cancers (Basel) 2021;13:4026.

  11. Becker CM, Bokor A, Heikinheimo O, Horne A, Jansen F, Kiesel L, et al. ESHRE guideline: Endometriosis. Hum Reprod Open 2022;2022:hoac009.

  12. Polyzos NP, Fatemi HM, Zavos A, Grimbizis G, Kyrou D, Velasco JG, et al. Aromatase inhibitors in post-menopausal endometriosis. Reprod Biol Endocrinol 2011;9:90.

  13. Gemmell LC, Webster KE, Kirtley S, Vincent K, Zondervan KT, Becker CM. The management of menopause in women with a history of endometriosis: A systematic review. Hum Reprod Update 2017;23:481-500.

  14. Ioannidou A, Vrachnis N, Thomakos N, Siristatidis C, Kassanos D, Daskalakis G. Malignant transformation of endometriosis and associated risk factors: A systematic review. Int J Environ Res Public Health 2025;22:1507.

  15. Upreti P, Godara P. Adenomyosis in a postmenopausal woman: A rare entity. Indian J Obstet Gynecol Res 2022;9:432-4. Available from: https://doi.org/10.18231/j.ijogr.2022.083. [Last accessed on 2025 Nov 12].

  16. Kitawaki J. Adenomyosis: The pathophysiology of an oestrogen-dependent disease. Best Pract Res Clin Obstet Gynaecol 2006;20:493-502.

  17. Chill HH, Safrai M, Reuveni Salzman A, Shushan A. The rising phoenix-progesterone as the main target of the medical therapy for leiomyoma. Biomed Res Int 2017;2017:4705164.

  18. Pritts EA, Vanness DJ, Berek JS, Parker W, Feinberg R, Feinberg J, et al. The prevalence of occult leiomyosarcoma at surgery for presumed uterine fibroids: A meta-analysis. Gynecol Surg 2015;12:165-77.

  19. Jiang D, Liu H, Huang K, Chen Y, Liu Q, Shu C, et al. The prevalence of occult malignancy in women undergoing hysterectomy or myomectomy for benign indications and the impact of morcellation on survival outcomes: A meta-analysis. Gynecol Obstet Invest 2025;90:328-41.

  20. Templeman C, Marshall SF, Clarke CA, DeLellis Henderson K, Largent J, Neuhausen S, et al. Risk factors for surgically removed fibroids in a large cohort of teachers. Fertil Steril 2009;92:1436-46.

  21. Stewart EA, Laughlin-Tommaso SK, Catherino WH, Lalitkumar S, Gupta D, Vollenhoven B. Uterine fibroids. Nat Rev Dis Primers 2016;2:16043.

  22. Moro E, Degli Esposti E, Borghese G, Manzara F, Zanello M, Raimondo D, et al. The impact of hormonal replacement treatment in postmenopausal women with uterine fibroids: A state-of-the-art review of the literature. Medicina (Kaunas) 2019;55:549.

  23. Ang WC, Farrell E, Vollenhoven B. Effect of hormone replacement therapies and selective estrogen receptor modulators in postmenopausal women with uterine leiomyomas: A literature review. Climacteric 2001;4:284-92.

  24. Gregoriou O, Vitoratos N, Papadias C, Konidaris S, Costomenos D, Chryssikopoulos A. Effect of tibolone on postmenopausal women with myomas. Maturitas 1997;27:187-92.

  25. Fedele L, Bianchi S, Raffaelli R, Zanconato G. A randomized study of the effects of tibolone and transdermal estrogen replacement therapy in postmenopausal women with uterine myomas. Eur J Obstet Gynecol Reprod Biol 2000;88:91-4.

  26. Owens LA, Franks S. Polycystic ovary syndrome: Origins and implications: The impact of polycystic ovary syndrome on reproductive health: A narrative review. Reproduction 2025;169:e240485.

  27. Minooee S, Ramezani Tehrani F, Rahmati M, Mansournia MA, Azizi F. Prediction of age at menopause in women with polycystic ovary syndrome. Climacteric 2018;21:29-34.

  28. Nelson VL, Legro RS, Strauss JF 3rd, McAllister JM. Augmented androgen production is a stable steroidogenic phenotype of propagated theca cells from polycystic ovaries. Mol Endocrinol 1999;13:946-57.

  29. Shah D, Rasool S. Polycystic ovary syndrome (PCOS) transition at menopause. J Midlife Health 2021;12:30-2.

  30. Helvaci N, Yildiz BO. The impact of ageing and menopause in women with polycystic ovary syndrome. Clin Endocrinol (Oxf) 2022;97:371-82.

  31. Lindén Hirschberg A. Approach to investigation of hyperandrogenism in a postmenopausal woman. J Clin Endocrinol Metab 2023;108:1243-53. doi:10.1210/clinem/dgac673.

  32. Pililis S, Lampsas S, Kountouri A, Pliouta L, Korakas E, Livadas S, et al. The cardiometabolic risk in women with polycystic ovarian syndrome (PCOS): From pathophysiology to diagnosis and treatment. Medicina (Kaunas) 2024;60:1656.

  33. Millán-de-Meer M, Luque-Ramírez M, Nattero-Chávez L, Escobar-Morreale HF. PCOS during the menopausal transition and after menopause: A systematic review and meta-analysis. Hum Reprod Update 2023;29:741-72.

  34. Çelik Ö, Köse MF. An overview of polycystic ovary syndrome in aging women. J Turk Ger Gynecol Assoc 2021;22:326-33.

  35. Fauser BC, Tarlatzis BC, Rebar RW, Legro RS, Balen AH, Lobo R, et al. Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): The Amsterdam ESHRE/ASRM-sponsored 3rd PCOS consensus workshop group. Fertil Steril 2012;97:28-38.e25.

  36. Teede HJ, Tay CT, Laven JJ, Dokras A, Moran LJ, Piltonen TT, et al. Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome. J Clin Endocrinol Metab 2023;108:2447-69.

  37. Jin C, Wang X, Yang J, Kim S, Hudgins AD, Gamliel A, et al. Molecular and genetic insights into human ovarian aging from single-nuclei multi-omics analyses. Nat Aging 2025;5:275-90.

  38. Savelli L, Ghi T, De Iaco P, Ceccaroni M, Venturoli S, Cacciatore B. Paraovarian/paratubal cysts: Comparison of transvaginal sonographic and pathological findings to establish diagnostic criteria. Ultrasound Obstet Gynecol 2006;28:330-4.

  39. Levine D, Brown DL, Andreotti RF, Benacerraf B, Benson CB, Brewster WR, et al. Management of asymptomatic ovarian and other adnexal cysts imaged at US: Society of Radiologists in Ultrasound Consensus Conference Statement. Radiology 2010;256:943-54.

  40. Kurman RJ, Shih IM. Origin and pathogenesis of tubal and ovarian serous carcinomas: Recent insights. Mod Pathol 2016;29 Suppl 1: S24-37.

  41. Nezhat FR, Apostol R, Nezhat C, Pejovic T. New insights in the pathophysiology of ovarian cancer and implications for screening and prevention. Am J Obstet Gynecol 2015;213:262-7.

  42. Falconer H, Yin L, Grönberg H, Altman D. Ovarian cancer risk after salpingectomy: A nationwide population-based study. J Natl Cancer Inst 2015;107:dju410.

  43. Greenlee RT, Kessel B, Williams CR, Riley TL, Ragard LR, Hartge P, et al. Prevalence, incidence, and natural history of simple ovarian cysts among women >55 years old in a large cancer screening trial. Am J Obstet Gynecol 2010;202:373.e1-9.

  44. van Nagell JR, DePriest PD. Management of adnexal masses in postmenopausal women. Am J Obstet Gynecol 2005;193:30-5.

  45. Timmerman D, Planchamp F, Bourne T, Landolfo C, du Bois A, Chiva L, et al. ESGO/ISUOG/IOTA/ESGE consensus statement on pre-operative diagnosis of ovarian tumors. Int J Gynecol Cancer 2021;31:961-82.

  46. Timmerman D, Testa AC, Bourne T, Ameye L, Jurkovic D, Van Holsbeke C, et al. Simple ultrasound-based rules for the diagnosis of ovarian cancer. Ultrasound Obstet Gynecol 2008;31:681-90.

  47. Rauh-Hain JA, Melamed A, Buskwofie A, Schorge JO. Adnexal mass in the postmenopausal patient. Clin Obstet Gynecol 2015;58:53-65.

  48. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins–Gynecology. Practice bulletin no. 174: Evaluation and management of adnexal masses. Obstet Gynecol 2016;128:e210-26.

  49. Andreotti RF, Timmerman D, Strachowski LM, Froyman W, Benacerraf BR, Bennett GL, et al. O-RADS US risk stratification and management system: A consensus guideline from the ACR ovarian-adnexal reporting and data system committee. Radiology 2020;294:168-85.

  50. Basha MA, Metwally MI, Gamil SA, Khater HM, Aly SA, El Sammak AA, et al. Comparison of O-RADS, GI-RADS, and IOTA simple rules regarding malignancy rate, validity, and reliability for diagnosis of adnexal masses. Eur Radiol 2021;31:674-84.

  51. Borges AL, Brito M, Ambrósio P, Condeço R, Pinto P, Ambrósio B, et al. Prospective external validation of IOTA methods for classifying adnexal masses and retrospective assessment of two-step strategy using benign descriptors and ADNEX model: Portuguese multicenter study. Ultrasound Obstet Gynecol 2024;64:538-49.

  52. Landolfo C, Bourne T, Froyman W, Van Calster B, Ceusters J, Testa AC, et al. Benign descriptors and ADNEX in two-step strategy to estimate risk of malignancy in ovarian tumors: Retrospective validation in IOTA5 multicenter cohort. Ultrasound Obstet Gynecol 2023;61:231-42.

  53. Solanki V, Singh P, Sharma C, Ghuman N, Sureka B, Shekhar S, et al. Predicting malignancy in adnexal masses by the International Ovarian Tumor Analysis – Simple rules. J Midlife Health 2020;11:217-23.

  54. Fedele L, Bianchi S, Raffaelli R, Zanconato G. Treatment of symptomatic postmenopausal endometriosis with tibolone. Obstet Gynecol 1999;94:758-61.

  55. Vercellini P, Viganò P, Somigliana E, Fedele L. Endometriosis: Pathogenesis and treatment. Nat Rev Endocrinol 2014;10:261-75.

  56. Zanello M, Borghese G, Manzara F, Degli Esposti E, Moro E, Raimondo D, et al. Hormonal replacement therapy in menopausal women with history of endometriosis: A review of literature. Medicina (Kaunas) 2019;55:477.

  57. Fuller AE, Dunsmoor-Su R. Complex vulvar and vaginal disease in menopause. Curr Opin Obstet Gynecol 2023;35:164-8.

  58. Musbahi E, Kamp E, Ashraf M, DeGiovanni C. Menopause, skin and common dermatosis. Part 3: Genital disorders. Clin Exp Dermatol 2022;47:2123-9.

  59. Snieder H, MacGregor AJ, Spector TD. Genes control the cessation of a woman’s reproductive life: A twin study of hysterectomy and age at menopause. J Clin Endocrinol Metab 1998;83:1875-80.

  60. van Asselt KM, Kok HS, Pearson PL, Dubas JS, Peeters PH, Te Velde ER, et al. Heritability of menopausal age in mothers and daughters. Fertil Steril 2004;82:1348-51.

  61. Morris DH, Jones ME, Schoemaker MJ, Ashworth A, Swerdlow AJ. Familial concordance for age at natural menopause: Results from the breakthrough generations study. Menopause 2011;18:956-61.

  62. Zhang X, Huangfu Z, Wang S. Review of Mendelian randomization studies on age at natural menopause. Front Endocrinol (Lausanne) 2023;14:1234324.

  63. Gold EB, Crawford SL, Avis NE, Crandall CJ, Matthews KA, Waetjen LE, et al. Factors related to age at natural menopause: Longitudinal analyses from SWAN. Am J Epidemiol 2013;178:70-83.

  64. Abulajiang Y, Liu T, Wang M, Abulai A, Wu Y. The influence of menopause age on gynecologic cancer risk: A comprehensive analysis using NHANES data. Front Oncol 2025;15:1541585.

  65. Meczekalski B, Niwczyk O, Bala G, Szeliga A. Managing early onset osteoporosis: The impact of premature ovarian insufficiency on bone health. J Clin Med 2023;12:4042.

  66. Liu J, Jin X, Liu W, Chen W, Wang L, Feng Z, et al. The risk of long-term cardiometabolic disease in women with premature or early menopause: A systematic review and meta-analysis. Front Cardiovasc Med 2023;10:1131251.

  67. Kapoor E. Premature ovarian insufficiency. Curr Opin Endocr Metab Res 2023;28:100435.

  68. Minis E, Pinero L, Bhatt S, O’Besso V, Douglas NC, Morelli SS. Primary ovarian insufficiency: Time to diagnosis and a review of current literature. Clin Exp Obstet Gynecol 2022;49;129.

  69. Meeta, Digumarti L, Agarwal N, Vaze N, Shah R, Malik S. Clinical practice guidelines on menopause: Indian menopause society.

  70. Popat VB, Calis KA, Kalantaridou SN, Vanderhoof VH, Koziol D, Troendle JF, et al. Bone mineral density in young women with primary ovarian insufficiency: Results of a three-year randomized controlled trial of physiological transdermal estradiol and testosterone replacement. J Clin Endocrinol Metab 2014;99:3418-26.

  71. Rivera CM, Grossardt BR, Rhodes DJ, Brown RD Jr., Roger VL, Melton LJ 3rd, et al. Increased cardiovascular mortality after early bilateral oophorectomy. Menopause 2009;16:15-23.

  72. Rocca WA, Shuster LT, Grossardt BR, Maraganore DM, Gostout BS, Geda YE, et al. Long-term effects of bilateral oophorectomy on brain aging: Unanswered questions from the Mayo Clinic Cohort Study of Oophorectomy and Aging. Womens Health (Lond) 2009;5:39-48.

  73. Panay N, Anderson RA, Bennie A, Cedars M, Davies M, Ee C, et al. Evidence-based guideline: Premature ovarian insufficiency. Hum Reprod Open 2024;2024:hoae065.

  74. Nguyen HH, Milat F, Vincent AJ. New insights into the diagnosis and management of bone health in premature ovarian insufficiency. Climacteric 2021;24:481-90.

  75. Shepherd JA. Positions of the international society for clinical densitometry and their etiology: A scoping review. J Clin Densitom 2023;26:101369.

  76. Kanis JA, Cooper C, Rizzoli R, Reginster JY, Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO) and the Committees of Scientific Advisors and National Societies of the International Osteoporosis Foundation (IOF). European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 2019;30:3-44.

  77. Sullivan SD, Sarrel PM, Nelson LM. Hormone replacement therapy in young women with primary ovarian insufficiency and early menopause. Fertil Steril 2016;106:1588-99.

  78. Gazarra LB, Bonacordi CL, Yela DA, Benetti-Pinto CL. Bone mass in women with premature ovarian insufficiency: A comparative study between hormone therapy and combined oral contraceptives. Menopause 2020;27:1110-6.

  79. Cartwright B, Robinson J, Seed PT, Fogelman I, Rymer J. Hormone replacement therapy versus the combined oral contraceptive pill in premature ovarian failure: A randomized controlled trial of the effects on bone mineral density. J Clin Endocrinol Metab 2016;101:3497-505.

  80. de Villiers TJ, Pines A, Panay N, Gambacciani M, Archer DF, Baber RJ, et al. Updated 2013 International Menopause Society recommendations on menopausal hormone therapy and preventive strategies for midlife health. Climacteric 2013;16:316-37.

  81. Swee DS, Javaid U, Quinton R. Estrogen replacement in young hypogonadal women-transferrable lessons from the literature related to the care of young women with premature ovarian failure and transgender women. Front Endocrinol (Lausanne) 2019;10:685.

  82. Rocca WA, Grossardt BR, Maraganore DM. The long-term effects of oophorectomy on mortality and neurodegenerative disease. Menopause 2008;15:1050-8.

  83. Shuster LT, Rhodes DJ, Gostout BS, Grossardt BR, Rocca WA. Premature menopause or early menopause: Long-term health consequences. Maturitas 2010;65:161-6.

  84. Faubion SS, Kuhle CL, Shuster LT, Rocca WA. Long-term health consequences of premature or early menopause and considerations for management. Climacteric 2015;18:483-91.

  85. Davis SR, Baber R, Panay N, Bitzer J, Cerdas Perez S, Islam RM, et al. Global consensus position statement on the use of testosterone therapy for women. Climacteric 2019;22:429-34.

  86. Mishra GD, Davies MC, Hillman S, Chung HF, Roy S, Maclaran K, et al. Optimising health after early menopause. Lancet 2024;403:958-68.

  87. Rocca WA, Grossardt BR, Shuster LT. Oophorectomy, menopause, estrogen treatment, and cognitive aging: Clinical evidence for a window of opportunity. Brain Res 2011;1379:188-98.

  88. Rocca WA, Bower JH, Maraganore DM, Ahlskog JE, Grossardt BR, de Andrade M, et al. Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Neurology 2007;69:1074-83.

  89. Madueke-Laveaux OS, Elsharoud A, Al-Hendy A. What we know about the long-term risks of hysterectomy for benign indication – A systematic review. J Clin Med 2021;10:5335.

  90. Trabuco EC, Moorman PG, Algeciras-Schimnich A, Weaver AL, Cliby WA. Association of ovary-sparing hysterectomy with ovarian reserve. Obstet Gynecol 2016;127:819-27.

  91. Xu Z, Chung HF, Dobson AJ, Wilson LF, Hickey M, Mishra GD. Menopause, hysterectomy, menopausal hormone therapy and cause-specific mortality: Cohort study of UK Biobank participants. Hum Reprod 2022;37:2175-85.

  92. Laughlin-Tommaso SK, Khan Z, Weaver AL, Smith CY, Rocca WA, Stewart EA. Cardiovascular and metabolic morbidity after hysterectomy with ovarian conservation: A cohort study. Menopause 2018;25:483-92.

  93. Pandey D, Sehgal K, Saxena A, Hebbar S, Nambiar J, Bhat RG. An audit of indications, complications, and justification of hysterectomies at a teaching hospital in India. Int J Reprod Med 2014;2014:279273.

  94. Desai S, Shukla A, Nambiar D, Ved R. Patterns of hysterectomy in India: A national and state-level analysis of the Fourth National Family Health Survey (2015-2016). BJOG 2019;126:72-80.

  95. Shekhar C, Paswan B, Singh A. Prevalence, sociodemographic determinants and self-reported reasons for hysterectomy in India. Reprod Health 2019;16:118.

  96. Indian Council of Medical Research (ICMR). Hysterectomy for Benign Gynaecological Conditions: Task Force Study on the Clinical, Epidemiological and Ethical ASPECTS of hysterectomy in India. New Delhi: ICMR; 2022. Available from: https://www.icmr.gov.in/icmrobject/uploads/STWs/1725952340_obg_hysterectomy.pdf. [Last accessed on 2025 Oct 19].

  97. Ministry of Health & Family Welfare (MoHFW). Advisory on Rational Use of Hysterectomy and Need for Standardized Indications. Government of India; 2019. Available from: https://medicaldialogues.in/pdf_upload/5925201312243332judgement05-apr-2023-208385.pdf. [Last accessed on 2025 Sep 10].

  98. Price SA, Maki PM, El Khoudary SR, Brand A, Islam RM, Domchek SM, et al. What happens after menopause (WHAM)? A progress report of a prospective controlled study of women after pre-menopausal risk-reducing bilateral salpingo-oophorectomy. BJOG 2025; doi: 10.1111/1471-0528.18304. [Epub ahead of print].

  99. Parker WH, Broder MS, Chang E, Feskanich D, Farquhar C, Liu Z, et al. Ovarian conservation at the time of hysterectomy and long-term health outcomes in the nurses’ health study. Obstet Gynecol 2009;113:1027-37.

  100. Rocca WA, Grossardt BR, de Andrade M, Malkasian GD, Melton LJ 3rd. Survival patterns after oophorectomy in premenopausal women: A population-based cohort study. Lancet Oncol 2006;7:821-8.

  101. Chronopoulou E, Raperport C, Sfakianakis A, Srivastava G, Homburg R. Elective oocyte cryopreservation for age-related fertility decline. J Assist Reprod Genet 2021;38:1177-86.

  102. Anderson RA, Wallace WH, Telfer EE. Ovarian tissue cryopreservation for fertility preservation: Clinical and research perspectives. Hum Reprod Open 2017;2017:hox001.

  103. Cobo A, García-Velasco JA, Remohí J, Pellicer A. Oocyte vitrification for fertility preservation for both medical and nonmedical reasons. Fertil Steril 2021;115:1091-101.

SECTION 5: CANCERS

1. India ranks third globally in terms of cancer burden, with a lifetime risk of 1 in 9 individuals and a projected 57% increase in new cases by 2040, highlighting the urgent need for nationwide prevention and early detection strategies (Grade A).[1-3]

Breast cancer

2. Breast cancer (BC) is the most prevalent cancer among Indian women, making up nearly a quarter (27%) of all female cancers and 13.5% of all new cancer cases in 2020 (Grade A),[1-3] with a significantly higher lifetime risk in urban women (1 in 22) compared to rural women (1 in 60) (Grade B).[4]

3. There is an increasing incidence of BC among younger Indian populations. Observational data indicate that 40%–50% of BC patients are under 50 years of age, with 10%–25% possibly younger than 40 years of age.[5] Tumors in younger women are often hormone receptor (HR) negative and biologically more aggressive, leading to higher mortality.[6]

4. Indian women are diagnosed with BC nearly a decade earlier (mean age: 49–53 years vs. 60–62 years in Western populations) and more frequently present with advanced-stage III–IV of the disease (Grade B).[6-9] The curative potential drops from 95% in Stage I to 21% in Stage IV (Grade A).[6,10]

5. This emphasizes the urgent need for early detection, downstaging through organized and opportunistic screening, and equitable access to timely, multidisciplinary care.[4,6,10]

6. Existing Western risk prediction models, such as Gail, are not calibrated for Indian women and often underestimate their risk.[11] They may be used for approximate stratification until validated Indian-specific tools are available (Grade B).[11,12]

7. Most international guidelines from developed countries recommend annual or biennial mammographic screening for women aged 40–74 years at average risk and suggest starting annual mammography or magnetic resonance imaging (MRI) at a younger age for high-risk groups (Grade A).[13]

8. In India, organized population-wide mammography is not yet practical; instead, opportunistic screening through clinical breast examination (CBE), breast self-awareness, and prompt symptom evaluation remains the most feasible and cost-effective approach (Grade B).[14,15] Indian randomized controlled trials show evidence that CBE screening by trained frontline health workers results in earlier detection and a 30% reduction in mortality among women aged ≥50 years, without raising overdiagnosis rates.[14-18]

9. The CBE-based opportunistic screening model is supported by global evidence. Systematic reviews have repeatedly shown notable stage shifts with CBE, although evidence for a mortality benefit remains indirect and of moderate quality (Grade B).[19-21]

10. In India, mammography encounters challenges such as economic constraints, inconsistent quality assurance, and higher false-positive rates, which restrict its feasibility for population-wide use (Grade B).[16,17] Therefore, it is advisable to conduct selective or opportunistic screening every 2–3 years based on individual risk assessments and shared decision-making regarding the benefits and possible harms (Grade B).[9,22-25]

11. Breast MRI is the most sensitive imaging technique for detecting BC and is recommended in addition to mammography for women at high risk (≥20%–25% lifetime risk) due to genetic factors, a strong family history, prior chest irradiation, or BRCA1/2 mutations (Grade A).[26]

12. In India, routine breast MRI screening is not recommended for the general population. It should be reserved for specific cases, such as diagnostic uncertainty, dense breast tissue, inconclusive mammograms, or high-risk patients, because of its high cost, limited availability, and need for specialized expertise (Grade B).[5] When indicated, high-risk women should undergo annual MRI combined with mammography starting 10 years before the age of the youngest affected relative or by age 30, whichever occurs first (Grade A).[9,26]

13. Positron emission computed tomography should not be routinely used for BC screening or staging (Grade A).[27] Instead, its use should be reserved for advanced or unclear cases where it influences management decisions (Grade B).[27]

14. Prevention includes lifestyle changes, such as maintaining a healthy body mass index (BMI), staying active, limiting alcohol intake, avoiding tobacco, and promoting breastfeeding, all of which lower the risk (Grade A).[28,29]

15. High-risk women, including confirmed BRCA1/2 carriers, may consider risk-reducing surgery or chemoprevention options, such as tamoxifen, raloxifene, or anastrozole, following expert counseling (Grade A).[30,31] However, their use is often restricted by barriers such as access, cost, and cultural influences.

16. In India, integrating primary prevention with early detection remains the most cost-effective strategy for reducing mortality rates (Grade B).[26,27]

Breast cancer survivors

17. In survivors of estrogen receptor-positive BC, standard adjuvant endocrine treatments include tamoxifen, ovarian suppression, and aromatase inhibitors (AIs). These therapies lower estrogen levels, potentially exacerbating menopausal, urogenital, and bone health issues (Grade A).[32,33]

18. Personalized management is advised for each peri/postmenopausal woman experiencing a decreased quality of life (QOL) due to menopause symptoms.[34-37] An annual gynecological checkup is recommended to manage general and menopausal symptoms, support bone health, and encourage reporting of any abnormal vaginal bleeding.

19. Vasomotor symptoms (VMSs): Systemic menopause hormone therapy (MHT)/hormone replacement therapy is contraindicated in BC survivors for relief of menopausal symptoms (Grade A).[38,39]

20. Findings from a recent systematic review and meta-analysis suggest that MHT may serve as an off-label treatment option for BC survivors with menopausal symptoms. This could be considered for selected HR-negative survivors experiencing severe, refractory symptoms, especially after nonhormonal therapies have failed, and only following explicit shared decision-making (Grade C).[40,41] Further randomized trials are needed before reconsidering the current advice against offering MHT to BC survivors.[39]

21. For women, including BC survivors who cannot use systemic MHT, nonhormonal options such as cognitive behavior therapy and proven medications such as serotonin–norepinephrine reuptake inhibitors and gabapentin are recommended as the primary treatment for VMSs (Grade A).[42-45] Lifestyle changes and mind–body practices can also be offered alongside to help improve overall symptoms and QOL (Grade B).[42-45]

22. Genitourinary syndrome of menopause: The initial treatment typically involves local nonhormonal therapies (Grade B).[46] Ultra-low-dose and low-dose options, particularly estriol for a limited time, may be considered only after consulting an oncologist and engaging in shared decision-making (Grade C).[46]

23. Bone loss: In premenopausal women on AI, estrogen levels decrease suddenly and significantly, resulting in a 6%–8% reduction in bone mineral density during the first 1–2 years. In contrast, postmenopausal women using AI experience a slower decline of approximately 2%–3% each year.[47-49] Both groups have an increased risk of fractures and should take proactive steps to protect their bones by adequate intake of calcium and Vitamin D, alongside therapeutic lifestyle management and follow-up dual-energy X-ray absorptiometry scans (Grade A).[48,49] Baseline assessment, prevention, and treatment of osteoporosis are integral to essential care (Grade A).[50]

24. It is recommended to begin bone-protective treatment early with bisphosphonates (intravenous zoledronic acid, 4 mg every 3–6 months for about 2–5 years) or denosumab for women at intermediate (Grade B)[51] to high risk on AI (Grade A).[51-53] Sequential therapy with denosumab (60 mg subcutaneously every 6 months), followed by bisphosphonate, is an accepted regimen for AI-associated bone loss (Grade B).[53]

25. Endometrium: Baseline gynecological assessment and transvaginal ultrasound (TVS) are performed.[54] Current evidence does not support routine endometrial screening using TVS or biopsy for asymptomatic women taking tamoxifen (Grade B).[55,56]

26. Endometrial cancer (EC) presents early and is curable; therefore, women presenting with bleeding require evaluation with a hysteroscopic-guided biopsy regardless of estrogen therapy (ET). If hysteroscopy is not available, saline infusion sonography and guided endometrial biopsy (EB) should be performed (Grade A).[57-60]

27. In asymptomatic postmenopausal women on tamoxifen, endometrial thickness alone is an unreliable predictor of malignancy and must always be interpreted in conjunction with clinical presentation (additional risk factors such as obesity and prolonged tamoxifen use) and detailed sonographic features, such as the presence of irregular/cystic morphology and increased vascularity on Doppler. Huang et al. suggest a clinical threshold of 9–10 mm for considering an EB in an asymptomatic woman (Grade B).[56,57]

Cancer cervix

28. Cervical cancer ranks as the fourth most common cancer among women worldwide and the second most common among Indian women.[61]

29. Cervical cancer prevention includes: (1) human papillomavirus (HPV) vaccination for girls, ideally before age 15, and (2) effective screening with HPV DNA tests, to be performed at least twice in a lifetime – at ages 35 and 45 – followed by immediate treatment for women who test positive (screen-and-treat) (Grade A).[62-64]

30. Cervical cancer screening coverage across India is only 2.0%. Urban participants had higher screening rates (3.3%) compared to rural participants (1.4%) (Grade A).[65]

31. Risk factors for cervical cancer encompass persistent infection with high-risk HPV types, early initiation of sexual activity, multiple sexual partners, partners with several previous partners, immune-compromising conditions such as human immunodeficiency virus, and smoking (Grade A).[62,66]

Screening tests available in India

32. The Government of India recommends visual inspection with acetic acid (VIA) as the primary method for cervical cancer screening in population programs. It is advised that women aged 30–65 years should be screened every 5 years based on strong evidence (Grade A).[67,68]

33. VIA is suitable for women aged 30–49 years, but its sensitivity declines in postmenopausal women due to the receding transformation zone (TZ).[62,69]

34. Visual inspection with Lugol’s iodine is always conducted in conjunction with VIA and is not evaluated as an independent screening method in clinical trials (Grade B).[62]

35. Conventional Pap smear and liquid-based cytology (LBC): Cytology screening has seen limited success in developing countries due to a relatively high false-negative rate and the lack of organized screening programs and referral pathways (Grade B).[62]

36. Primary HPV DNA screening: Transition to HPV DNA testing is recommended, where feasible (Grade A).[62,69,70] Primary HPV screening is more effective and cost-efficient than VIA screening in low- and middle-income countries, as demonstrated by multiple studies (Grade A).[71]

37. The World Health Organization (WHO) also recommends using primary HPV DNA testing followed by thermal ablation as part of the “Screen-and-Treat” approach for the general population.[62] HPV DNA testing should be followed by VIA/colposcopy before thermal ablation.

38. Point-of-care HPV testing, followed by thermal ablation when appropriate, is currently being studied as a combined single-visit method.[63]

39. Colposcopy, along with colposcopy-directed biopsy, is the recommended confirmatory test for women who test positive on any screening method regardless of the initial screening outcome (Grade A).[62]

40. Hormonal changes frequently result in unsatisfactory colposcopy in many women after menopause (Grade B).[72]

41. Short-term intravaginal ET administered daily for 2 weeks and then paused for a week before repeat cytology or colposcopy can improve smear quality and enhance visualization of the TZ in postmenopausal women (Grade B).[72-76]

Cervical cancer screening for women at menopause transition and postmenopause

42. Regular cervical screening is recommended for women during the menopause transition (MT) and after menopause (Grade A).[77]

43. In India, since opportunistic screening is widespread, any woman in the specified groups should be advised to undergo screening if she has not had one in the past 3–5 years (Grade B).[78,79] Women who have never undergone screening during their lifetime should be recommended to do so, even at age 65 or older, if they maintain a good QOL (Grade B).[79]

44. VIA screening has limited accuracy because the TZ recedes into the cervical canal due to estrogen deficiency (Grade B).[62] VIA screening is generally not recommended for individuals over 50 years of age.[62]

45. Cytological screening using conventional methods or LBC is recommended every 3 years (Grade A).[62] Transition to HPV DNA testing is recommended where feasible (Grade A).[62,69,70] Co-testing with LBC and HR HPV is recommended over the use of cytology or HPV alone, especially in postmenopausal screening (Grade A).[80] Primary HPV screening: Both provider-collected and self-HPV sampling are recommended (Grade A).[81]

46. For cervical intraepithelial neoplasia Grade 1 (CIN1) and certain CIN2 lesions that meet the WHO eligibility criteria, such as a fully visible TZ, no endocervical extension, and no suspicion of invasion, ablative treatments such as thermal ablation may be considered (Grade A).[82]

47. High-grade squamous intraepithelial lesion (CIN2/3) with endocervical extension or nonvisible squamocolumnar junction should be treated with excisional procedures (large loop excision of the TZ/loop electrosurgical excision procedure or cold-knife cone), not ablation (Grade A).[76,82,83]

48. In postmenopausal women, excisional treatment should ideally be performed by experienced colposcopists because cervical atrophy, stenosis, and Type 3 TZ increase the technical difficulty and the risk of complications (Grade B).[76,82-85]

49. Follow-up: Posttreatment follow-up is identical to that for premenopausal women. HPV-based test of cure at 6, 18, and 30 months, followed by 3-yearly HPV surveillance for at least 25 years (Grade A).[82-85]

Cancer ovary

50. Ovarian cancer is the third most common female cancer in India, accounting for approximately 6% of all female cancers in the country, with 47,333 new cases (GLOBOCAN 2022).[86] It remains a leading cause of gynecological cancer mortality due to late-stage presentation (Grade A).[86-88]

51. There is no proven benefit of routine ovarian cancer screening in women at average risk or asymptomatic women (Grade A).[89-91]

52. The most practical approach is “screening by vigilance,” which involves raising awareness among clinicians and patients of red-flag symptoms, such as persistent bloating, early satiety, or unexplained gastrointestinal discomfort, and ensuring prompt pelvic examinations and TVS in women over 40 years (Grade B).[89-91]

53. Pathogenic BRCA1/2 mutations are present in approximately 3%–28% of Indian women with epithelial ovarian cancer, highlighting the importance of early detection, genetic testing, and family cascade counseling (Grade B).[92-94]

54. A first-degree relative with ovarian cancer or a personal or family history of early-onset BC (<50 years) significantly increases the lifetime risk of ovarian cancer, warranting genetic counseling and consideration of BRCA testing for hereditary breast–ovarian cancer syndromes (Grade A).[95]

55. Risk-reducing bilateral salpingo-oophorectomy (BSO) remains the most effective primary prevention strategy for women with confirmed BRCA1/2 mutations, offering an 80%–96% reduction in ovarian cancer risk and a 70% reduction in overall mortality (Grade A).[96] It targets ovarian, fallopian tube, and peritoneal cancers.[96]

56. For women at average risk undergoing hysterectomy or ovarian surgery for benign reasons, opportunistic bilateral salpingectomy may be considered a practical preventive measure (Grade A).[97-101]

Endometrial cancer

57. In India, uterine corpus cancer remains relatively uncommon, with the national age-standardized incidence historically around 2–3 per 100,000 and more recent National Cancer Registry Programme estimates of approximately 4 per 100,000 women (Grade A).[102] Higher rates, approximately 4–6 per 100,000, have been reported from urban population-based cancer registries (PBCRs) such as Delhi, Bengaluru, and Thiruvananthapuram, reflecting demographic and lifestyle differences (Grade B).[102,103]

58. EC is most frequently diagnosed in postmenopausal women aged 55–65 years (Grade A).[104] The overall morbidity and mortality of EC are low, as most patients (70%–80%) are diagnosed at an early stage due to abnormal bleeding at MT or postmenopausal bleeding (PMB) (Grade A).[105]

59. Obesity is a significant, modifiable risk factor for EC. Large meta-analyses have demonstrated a strong dose–response relationship between increasing BMI and EC risk, ranging from approximately 2–4-fold in women with BMI ≥30 kg/m2 to up to 8–10-fold in those with morbid obesity (BMI ≥40 kg/m2) compared with women of normal weight (Grade A).[106-108] The risk of EC is elevated 2–7-fold in women receiving tamoxifen.[60,109,110]

60. Evidence shows that endometrial intraepithelial neoplasia (EIN) is the main precursor lesion for endometrioid EC. The annual progression rate is 8%, and the cumulative risk over 10–20 years without treatment ranges from 20% to 30% (Grade A).[111,112]

61. Unopposed ET in women with an intact uterus increases the risk of EC by 2–10 times, and this risk increases with longer use (Grade A).[113,114]

62. Women with Lynch syndrome have a markedly increased lifetime risk of EC, which varies by mismatch repair gene mutation: approximately 40%–57% for MSH2, 30%–40% for MLH1 and MSH6, and 10%–15% for PMS2 carriers, compared to 2%–3% in the general population (Grade A).[115]

63. Cyclic or continuous progestin at an appropriate dose administered alongside estrogen reduces or eliminates the increased risk of EC associated with unopposed ET. Continuous combined MHT regimens offer the strongest protection (Grade A).[116]

64. During menopause, women should be advised about the risks and symptoms of EC and strongly encouraged to report any unexpected bleeding or spotting. Routine TVS or EB screening does not reduce EC mortality in asymptomatic women (Grade A).[117,118]

65. Evaluation is only for women with symptoms or for Lynch syndrome carriers. Regular screening for EC in high-risk groups has not been fully assessed (Grade B).[119]

66. Women diagnosed with EC should be managed using a multidisciplinary team approach (Grade B).[120]

Endometrial hyperplasia

67. Endometrial hyperplasia (EH) results from prolonged unopposed estrogen exposure to the endometrium, either through natural production or external estrogen intake. It has been identified as a precursor to EC (Grade A).[121-123]

68. The 2014 WHO EH classification system has two categories based on the presence or absence of cytological atypia: EH without atypia (nonneoplastic) and atypical hyperplasia/EIN (a premalignant condition) (Grade A).[124,125] The EIN system defines two biological entities, benign endometrium and EIN, based on histomorphological and molecular criteria that predict malignant potential (Grade A).[126,127]

69. EH is a histological diagnosis based on the evaluation of an EB, endometrial curettage sample, or hysterectomy specimen (Grade A).[125-127]

70. The risk of EH progressing to carcinoma within 10 years is <5%, and 20%–30% of EINs progress to EC (Grade C).[128] EIN is a precursor lesion to Type I endometrioid adenocarcinoma of the endometrium and often co-occurs with carcinoma at diagnosis (almost 50%) (Grade A).[129,130]

71. Endometrial stripe thickness and age were the most significant predictors of concurrent EC at the time of hysterectomy for EIN. An endometrial stripe of >2 cm was associated with four times the odds of concurrent EC (95% confidence interval: 1.5–10.0), controlling for age (Grade B).[130] Refer to Section 2 under PMB.

72. All management strategies should include the elimination of extrinsic or intrinsic sources of unopposed estrogen, since excess exposure to estrogen is the primary cause of estrogen-dependent endometrial neoplasia (Grade A).[119,121,122]

73. EH can be managed conservatively with continuous progestin (levonorgestrel-releasing intrauterine system preferred) and scheduled follow-up; hysterectomy is reserved for postmenopausal patients, or when the risk is higher, persistent, or relapse occurs, or when surveillance is not feasible (Grade B).[131,132]

74. Conservative management may be offered for EH when the risk of occult carcinoma or progression is low, and the inciting cause of endometrial proliferation has been corrected, such as anovulation that is now controlled. Progestin therapy requires at least 6 months to produce histological regression. Therefore, close surveillance with two consecutive negative endometrial biopsies performed 6 months apart is recommended (Grade B).[131]

75. For EIN, total hysterectomy (TH) offers definitive treatment and allows for the assessment of concurrent carcinoma (Grade A).[123,131] In postmenopausal women, TH with BSO is appropriate (Grade A).[123,131] In premenopausal women, the decision to perform BSO should be made on an individual basis through shared decision-making, considering the cancer risk versus the harms of surgical menopause (Grade B).[130,131] Supracervical hysterectomy, uterine morcellation, and endometrial ablation are unacceptable for EIN because they pose a risk of undertreatment or dispersal of occult carcinoma and presence of overt carcinoma (Grade A).[121,130,131]

Vulval and vaginal cancer

76. Vulvar cancer is rare in India, with an incidence of 0.5–1.0 per 100,000 women, accounting for approximately 4%–5% of gynecological malignancies. Most cases are diagnosed after the age of 60 years (Grade B).[133] Major Indian risk factors include HPV infection, chronic vulvar dermatoses (particularly lichen sclerosus), diabetes, obesity, poor genital hygiene, and tobacco use (Grade B).[133]

77. Vaginal cancer is very rare, accounting for <1% of all gynecological cancers, with an incidence of 0.2–0.4 per 100,000 women in Indian population-based registries (Grade B).[133] Persistent high-risk HPV infection, previous cervical or vulvar intraepithelial neoplasia, prior radiation, long-term pessary use, and poor genital hygiene are the main risk factors in India (Grade B).[134,135]

78. Primary prevention through HPV vaccination in the eligible population (Grade A).[135-139] Regular self and clinical genital examinations, along with prompt biopsy of any chronic, white, ulcerative, or nonhealing vulvar or vaginal lesions, are essential for effective secondary prevention and early detection of malignancy (Grade A).[140-142]

Gastric, liver, and cervical cancers: India’s leading preventable infection-related malignancies

79. Gastric cancer ranks among the top six cancers in India, with approximately 60,000 new cases annually (about 4.5% of all cancers), exhibiting notable regional variation from 11.1 per 100,000 in Chennai to 1.6 per 100,000 in Bhopal, and showing a slight decline in recent PBCR data (Grade B).[143-145]

80. Population-based control strategies, notably Helicobacter pylori eradication, healthy dietary modifications (such as reducing salt and smoked foods), and tobacco cessation, significantly lower gastric cancer risk, as supported by recent global meta-analyses and the International Agency for Research on Cancer guidance (Grade A).[145,146]

81. In India, tobacco-related (both smoked and smokeless) cancers account for approximately 18% of all female cancer deaths, while infection-related cancers, mainly cervical, stomach, and liver cancers, account for nearly 33% of female cancer mortality (Grade A).[147-149]

82. Targeted infection control and vaccination could prevent nearly a third of female cancer deaths in India through integrated strategies, such as HPV and hepatitis B virus vaccination, strict tobacco control measures, and H. pylori eradication, with particular emphasis on rural and underserved populations (Grade A).[145,148,149]

REFERENCES

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209-49.

  2. Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A, et al. Cancer statistics for the year 2020: An overview. Int J Cancer 2021. doi: 10.1002/ijc.33588.

  3. National Cancer Registry Programme Investigator Group, Mathur P, Sathishkumar K, Das P, Santhappan S, Sankarapillai J, et al. Cancer incidence and mortality across 43 cancer registries in India. JAMA Netw Open 2025;8:e2527805.

  4. Kulothungan V, Ramamoorthy T, Sathishkumar K, Mohan R, Tomy N, Miller GJ, et al. Burden of female breast cancer in India: Estimates of YLDs, YLLs, and DALYs at national and subnational levels based on the national cancer registry programme. Breast Cancer Res Treat 2024;205:323-32.

  5. Breast Cancer India. Trends of Breast Cancer in India: Latest Statistics of Breast Cancer in India (2020); 2020. Available from: https://www.breastcancerindia.net/statistics/trends.html. [Last accessed on 2025 Nov 08].

  6. Sharma P, Das D, Khanna D, Budukh A, Khokhar A, Pradhan S, et al. Prevalence and associated factors of mammography uptake among the women aged 45 years and above: Policy implications from the longitudinal ageing study in India wave I survey. BMC Public Health 2025;25:1073.

  7. Parmar V. Rising incidence of breast cancer in the young fertile Indian population-a reality check. Indian J Surg Oncol 2018;9:296-9.

  8. Pawar A, Yalla P, Sharma M, Puj K, Aaron J, Warikoo V, et al. Clinicopathological characteristics and prognostic outcomes of young adult women (aged 18-30 years) with breast cancer in Ahmedabad, India: A single-centre, retrospective observational study. Lancet Reg Health Southeast Asia 2025;40:100643.

  9. Mehrotra R, Yadav K. Breast cancer in India: Present scenario and the challenges ahead. World J Clin Oncol 2022;13:209-18.

  10. Kaul R, Sharma J, Minhas SS, Mardi K. Hormone receptor status of breast cancer in the Himalayan region of Northern India. Indian J Surg 2011;73:9-12.

  11. Gail MH, Brinton LA, Byar DP, Corle DK, Green SB, Schairer C, et al. Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst 1989;81:1879-86.

  12. Kumar N, Singh V, Mehta G. Assessment of common risk factors and validation of the Gail model for breast cancer: A hospital-based study from Western India. Tzu Chi Med J 2020;32:362-6.

  13. Ren W, Chen M, Qiao Y, Zhao F. Global guidelines for breast cancer screening: A systematic review. Breast 2022;64:85-99.

  14. Ramadas K, Basu P, Mathew BS, Muwonge R, Venugopal M, Prakasan AM, et al. Effectiveness of triennial screening with clinical breast examination: 14-years follow-up outcomes of randomized clinical trial in Trivandrum, India. Cancer 2023;129:272-82.

  15. Mittra I, Mishra GA, Dikshit RP, Gupta S, Kulkarni VY, Shaikh HK, et al. Effect of screening by clinical breast examination on breast cancer incidence and mortality after 20 years: Prospective, cluster randomised controlled trial in Mumbai. BMJ 2021;372:n256.

  16. Jagatap MB, Maurya AP, Pandya B, Brahmachari S, Singh RP. Acceptability and determinants of opportunistic screening for breast cancer in Indian women. Asian Pac J Cancer Prev 2025;26:43-7.

  17. Weerarathna IN, Luharia A, Uke A, Mishra G. Challenges and innovations in breast cancer screening in India: A review of epidemiological trends and diagnostic strategies. Int J Breast Cancer 2024;2024:6845966.

  18. Sankaranarayanan R, Ramadas K, Thara S, Muwonge R, Prabhakar J, Augustine P, et al. Clinical breast examination: Preliminary results from a cluster randomized controlled trial in India. J Natl Cancer Inst 2011;103:1476-80.

  19. Tomlinson-Hansen SE, Budh DP, Sapra A. Breast cancer screening in the average-risk patient. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK556050. [Last updated on 2024 Oct 03].

  20. Ngan TT, Nguyen NT, Van Minh H, Donnelly M, O’Neill C. Effectiveness of clinical breast examination as a ‘stand-alone’ screening modality: An overview of systematic reviews. BMC Cancer 2020;20:1070.

  21. Veitch D, Goossens R, Owen H, Veitch J, Molenbroek J, Bochner M. Evaluation of conventional training in clinical breast examination (CBE). Work 2019;62:647-56.

  22. Chaltiel D, Hill C. Estimations of overdiagnosis in breast cancer screening vary between 0% and over 50%: Why? BMJ Open 2021;11:e046353.

  23. Takkar N, Kochhar S, Garg P, Pandey AK, Dalal UR, Handa U. Screening methods (clinical breast examination and mammography) to detect breast cancer in women aged 40-49 years. J Midlife Health 2017;8:2-10.

  24. Klarenbach S, Sims-Jones N, Lewin G, Singh H, Thériault G, Tonelli M, et al. Recommendations on screening for breast cancer in women aged 40-74 years who are not at increased risk for breast cancer. CMAJ 2018;190: E1441-51.

  25. Mathur P, Sathishkumar K, Chaturvedi M, Das P, Sudarshan KL, Santhappan S, et al. Cancer statistics, 2020: Report from national cancer registry programme, India. JCO Glob Oncol 2020;6:1063-75.

  26. Mann RM, Balleyguier C, Baltzer PA, Bick U, Colin C, Cornford E, et al. Breast MRI: EUSOBI recommendations for women’s information. Eur Radiol 2015;25:3669-78.

  27. Hadebe B, Harry L, Ebrahim T, Pillay V, Vorster M. The role of PET/CT in breast cancer. Diagnostics (Basel) 2023;13:597.

  28. Harvie M, Howell A. Energy restriction and the prevention of breast cancer. Proc Nutr Soc 2012;71:263-75.

  29. Bhadoria AS, Kapil U, Sareen N, Singh P. Reproductive factors and breast cancer: A case-control study in tertiary care hospital of North India. Indian J Cancer 2013;50:316-21.

  30. Bertozzi S, Londero AP, Xholli A, Azioni G, Di Vora R, Paudice M, et al. Risk-reducing breast and gynecological surgery for BRCA mutation carriers: A narrative review. J Clin Med 2023;12:1422.

  31. Cuzick J, Sestak I, Forbes JF, Dowsett M, Cawthorn S, Mansel RE, et al. Use of anastrozole for breast cancer prevention (IBIS-II): Long-term results of a randomised controlled trial. Lancet 2020;395:117-22.

  32. Goel B, Virmani T, Jain V, Kumar G, Sharma A, Al Noman A. Unveiling the link between breast cancer treatment and osteoporosis: Implications for anticancer therapy and bone health. Biomed Res Int 2024;2024:5594542.

  33. Hadji P, Aapro M, Al-Dagri N, Alokail M, Biver E, Body JJ, et al. Management of aromatase inhibitor-associated bone loss (AIBL) in women with hormone-sensitive breast cancer: An updated joint position statement of the IOF, CABS, ECTS, IEG, ESCEO, IMS, and SIOG. J Bone Oncol 2025;53:100694.

  34. The 2022 Hormone Therapy Position Statement of The North American Menopause Society Advisory Panel. The 2022 hormone therapy position statement of The North American Menopause Society. Menopause 2022;29:767-94.

  35. Baber RJ, Panay N, Fenton A, IMS Writing Group. 2016 IMS recommendations on women’s midlife health and menopause hormone therapy. Climacteric 2016;19:109-50.

  36. Stuenkel CA, Davis SR, Gompel A, Lumsden MA, Murad MH, Pinkerton JV, et al. Treatment of symptoms of the menopause: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2015;100:3975-4011.

  37. Marsden J, British Menopause Society. British Menopause Society consensus statement: The risks and benefits of HRT before and after a breast cancer diagnosis. Post Reprod Health 2019;25:33-7.

  38. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Type and timing of menopausal hormone therapy and breast cancer risk: Individual participant meta-analysis of the worldwide epidemiological evidence. Lancet 2019;394:1159-68.

  39. Manson JE, Chlebowski RT, Stefanick ML, Aragaki AK, Rossouw JE, Prentice RL, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the women’s health initiative randomized trials. JAMA 2013;310:1353-68.

  40. Coronado PJ, Gómez A, Iglesias E, Fasero M, Baquedano L, Sánchez S, et al. Eligibility criteria for using menopausal hormone therapy in breast cancer survivors: A safety report based on a systematic review and meta-analysis. Menopause 2024;31:234-42.

  41. Glynne S, Simon J, Branson A, Payne S, Newson L, Manyonda I, et al. Menopausal hormone therapy for breast cancer patients: What is the current evidence? Menopause 2026;33:88-117.

  42. Mann E, Smith MJ, Hellier J, Balabanovic JA, Hamed H, Grunfeld EA, et al. Cognitive behavioural treatment for women who have menopausal symptoms after breast cancer treatment (MENOS 1): A randomised controlled trial. Lancet Oncol 2012;13:309-18.

  43. Loprinzi CL, Kugler JW, Sloan JA, Mailliard JA, LaVasseur BI, Barton DL, et al. Venlafaxine in management of hot flashes in survivors of breast cancer: A randomised controlled trial. Lancet 2000;356:2059-63.

  44. Pandya KJ, Morrow GR, Roscoe JA, Zhao H, Hickok JT, Pajon E, et al. Gabapentin for hot flashes in 420 women with breast cancer: A randomised double-blind placebo-controlled trial. Lancet 2005;366:818-24.

  45. Ayers B, Smith M, Hellier J, Mann E, Hunter MS. Effectiveness of group and self-help cognitive behaviour therapy in reducing problematic menopausal hot flushes and night sweats (MENOS 2): A randomised controlled trial. BMJ Open 2012;2:e000948.

  46. Servayge J, Verduyn AC, Page A, Lagaert L, Tjalma WA. Clinical guidelines for managing menopausal symptoms in women with (a history of) breast cancer. Facts Views Vis Obgyn 2023;15:297-308.

  47. Perez EA, Weilbaecher K. Aromatase inhibitors and bone loss. Oncology (Williston Park) 2006;20:1029-39.

  48. Rabaglio M, Sun Z, Price KN, Castiglione-Gertsch M, Hawle H, Thürlimann B, et al. Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial. Ann Oncol 2009;20:1489-98.

  49. Liu PH, Tsai CF, Hsu YC, Wu CY, Yang HY. Aromatase inhibitors therapy and major osteoporotic fracture risk in postmenopausal breast cancer patients: A nationwide real-world cohort study. Breast Cancer Res 2025;27:95.

  50. Reid DM, Doughty J, Eastell R, Heys SD, Howell A, McCloskey EV, et al. Guidance for the management of breast cancer treatment-induced bone loss: A consensus position statement from a UK Expert Group. Cancer Treat Rev 2008;34 Suppl 1: S3-18.

  51. Dhabhar B. Cancer treatment-induced bone loss: Role of Denosumab in non-metastatic breast cancer. Breast Cancer (Dove Med Press) 2022;14:163-73.

  52. Wu W, Zhu Y, Lin H, Liu J, Liu S, Zhang L, et al. Clinical and economic research of bone modifiers as adjuvant therapy for early breast cancer: A systematic literature review. Breast 2025;83:104551.

  53. Eisen A, Somerfield MR, Accordino MK, Blanchette PS, Clemons MJ, Dhesy-Thind S, et al. Use of adjuvant bisphosphonates and other bone-modifying agents in breast cancer: ASCO-OH (CCO) guideline update. J Clin Oncol 2022;40:787-800.

  54. Garuti G, Grossi F, Centinaio G, Sita G, Nalli G, Luerti M. Pretreatment and prospective assessment of endometrium in menopausal women taking tamoxifen for breast cancer. Eur J Obstet Gynecol Reprod Biol 2007;132:101-6.

  55. Kantarcı S, Karabulut A, Kilis S, Dağlı U, Uçar İ, İnan AH. Endometrial pathology in tamoxifen-treated breast cancer patients: Correlation of endometrial thickness on ultrasound, preoperative sampling, and final pathology. Anatol J Gen Med Res 2025;35:178-84.

  56. Salani R, Andersen BL. Gynecologic care for breast cancer survivors: Assisting in the transition to wellness. Am J Obstet Gynecol 2012;206:390-7.

  57. Huang L, Lu Y, Chen Y, Liu H, An J. Determining a treatment threshold value for endometrial thickness in women with breast cancer receiving tamoxifen. Int J Womens Health 2025;17:3189-99.

  58. Cohen I, Shapira J, Zeevi D, Glezerman M. Endometrial pathologies in postmenopausal breast-cancer patients treated with tamoxifen: Correlation between clinical presentation and histopathologic findings. J Clin Oncol 2004;22:4102-6.

  59. Vitale SG, Buzzaccarini G, Riemma G, Pacheco LA, Di Spiezio Sardo A, Carugno J, et al. Endometrial biopsy: Indications, techniques and recommendations. An evidence-based guideline for clinical practice. J Gynecol Obstet Hum Reprod 2023;52:102588.

  60. Cuzick J, Forbes JF, Sestak I, Cawthorn S, Hamed H, Holli K, et al. Long-term results of tamoxifen prophylaxis for breast cancer-96-month follow-up of the randomized IBIS-I trial. J Natl Cancer Inst 2007;99:272-82.

  61. Ramamoorthy T, Kulothungan V, Sathishkumar K, Tomy N, Mohan R, Balan S, et al. Burden of cervical cancer in India: Estimates of years of life lost, years lived with disability and disability adjusted life years at national and subnational levels using the national cancer registry programme data. Reprod Health 2024;21:111.

  62. World Health Organization. WHO Guideline for Screening and Treatment of Cervical Pre-Cancer Lesions for Cervical Cancer Prevention. 2nd ed. Geneva: WHO; 2021. Available from: https://www.who.int/publications/i/item/9789240030824. [Last accessed on 10 Oct 2025].

  63. World Health Organization. Global Strategy to Accelerate the Elimination of Cervical Cancer as a Public Health Problem. Geneva: World Health Organization; 2020. Available from: https://www.who.int/publications-detail-redirect/9789240014107. [Last accessed on 10 Oct 2025].

  64. World Health Organization. WHO Updates Recommendations on HPV Vaccination Schedule; 2022. Available from: https://www.who.int/publications/i/item/9789240030824. [Last accessed on 10 Oct 2025].

  65. Garg P, Krishnamoorthy Y, Halder P, Rajaa S, Verma M, Kankaria A, et al. Urban-rural disparities in cervical cancer screening among Indian women between 30-49 years: A geospatial and decomposition analysis using a nationally representative survey. BMC Cancer 2025;25:67.

  66. Kashyap N, Krishnan N, Kaur S, Ghai S. Risk factors of cervical cancer: A case-control study. Asia Pac J Oncol Nurs 2019;6:308-14.

  67. Sankaranarayanan R, Wesley R, Thara S, Dhakad N, Chandralekha B, Sebastian P, et al. Test characteristics of visual inspection with 4% acetic acid (VIA) and Lugol’s iodine (VILI) in cervical cancer screening in Kerala, India. Int J Cancer 2003;106:404-8.

  68. Poli UR, Bidinger PD, Gowrishankar S. Visual inspection with acetic acid (VIA) screening program: 7 years experience in early detection of cervical cancer and pre-cancers in rural South India. Indian J Community Med 2015;40:203-7.

  69. Murillo R, Almonte M, Pereira A, Ferrer E, Gamboa OA, Jerónimo J, et al. Cervical cancer screening programs in Latin America and the Caribbean. Vaccine 2008;26 Suppl 11: L37-48.

  70. Sankaranarayanan R, Nene BM, Shastri SS, Jayant K, Muwonge R, Budukh AM, et al. HPV screening for cervical cancer in rural India. N Engl J Med 2009;360:1385-94.

  71. Simms KT, Keane A, Nguyen DT, Caruana M, Hall MT, Lui G, et al. Benefits, harms and cost-effectiveness of cervical screening, triage and treatment strategies for women in the general population. Nat Med 2023;29:3050-8.

  72. Richards A, Dalrymple C, Schmid K, Atkinson K. Abnormal cervicovaginal cytology, unsatisfactory colposcopy, and the use of vaginal estrogen cream: An observational study of clinical outcomes for women in low estrogen states. J Low Genit Tract Dis 2015;19:295-300.

  73. Bateson DJ, Weisberg E. An open-label randomized trial to determine the most effective regimen of vaginal estrogen to reduce the prevalence of atrophic changes reported in postmenopausal cervical smears. Menopause 2009;16:765-9.

  74. Jammalamadaka A, Manjula J, Shakuntal BB. Problems and pitfalls of colposcopy in postmenopausal women. J Obstet Gynaecol India 2007;57:525-9.

  75. Redman CW, Kesic V, Cruickshank ME, Gultekin M, Carcopino X, Castro Sanchez M, et al. European consensus statement on essential colposcopy. Eur J Obstet Gynecol Reprod Biol 2021;256:57-62.

  76. Patni R. Colposcopy postmenopause: A challenge in cervical cancer elimination goal! J Midlife Health 2022;13:263-4.

  77. Mittal S, Basu P, Lucas E. Atlas of Visual Inspection of the Cervix with Acetic Acid for Screening, Triage, and Assessment for Treatment: IARC CancerBase No. 16. Lyon, France: International Agency for Research on Cancer; 2020. Available from: https://screening.iarc.fr/atlasvia.php. [Last accessed on 2025 Oct 21].

  78. Bhatla N, Aoki D, Sharma DN, Sankaranarayanan R. Cancer of the cervix uteri: 2021 update. Int J Gynaecol Obstet 2021;155 Suppl 1:28-44.

  79. Çakmak B, Köseoğlu DR. Comparison of cervical cytological screening results between postmenopausal and elderly women. Turk J Pathol 2014;30:38-42.

  80. Zhou Q, Li T, Zhu L, Chang Y, Yang J, Chen W, et al. The clinical performance of different cervical cancer screening strategies in premenopausal and postmenopausal women. Menopause 2025;32:640-7.

  81. Helenius G, Lillsunde-Larsson G, Karlsson MG, Kaliff M, Bergengren L. Cervical screening with self-sampling for postmenopausal women with molecular triage using extended genotyping and methylation. Eur J Obstet Gynecol Reprod Biol 2025;305:404-9.

  82. World Health Organization. WHO Guidelines for the Use of Thermal Ablation for Cervical Pre-Cancer Lesions. Geneva: WHO; 2019.

  83. Jordan J, Martin-Hirsch P, Arbyn M, Schenck U, Baldauf JJ, Da Silva D, et al. European guidelines for clinical management of abnormal cervical cytology, part 2. Cytopathology 2009;20:5-16.

  84. Perkins RB, Guido RS, Castle PE, Chelmow D, Einstein MH, Garcia F, et al. 2019 ASCCP risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract Dis 2020;24:102-31.

  85. Gustafson LW, Petersen LK, Bor P, Andersen B, Hammer A. Cervical cancer prevention among older women - challenges in screening, diagnostic workup and treatment. Acta Obstet Gynecol Scand 2021;100:1364-8.

  86. International Agency for Research on Cancer. GLOBOCAN 2022: India Fact Sheet. Ovarian (C56) - India. Global Cancer Observatory (GCO). Lyon: IARC. Available from: https://gco.iarc.who.int/media/factsheets/cancers/25-ovary-fact-sheet.pdf. [Last accessed on 2024 Feb 08].

  87. Gangane NM, Patil BU, Ghongade PV. Ovarian cancer: A report from population-based cancer registry at central rural India. J Cancer Res Ther 2023;19: S857-62.

  88. Indian Council of Medical Research-National Centre for Disease Informatics and Research (ICMR–NCDIR). Consensus Document for Management of Epithelial Ovarian Cancer. Bengaluru: ICMR-NCDIR; 2019.

  89. US Preventive Services Task Force, Grossman DC, Curry SJ, Owens DK, Barry MJ, Davidson KW, et al. Screening for ovarian cancer: US preventive services task force recommendation statement. JAMA 2018;319:588-94.

  90. Jacobs IJ, Menon U, Ryan A, Gentry-Maharaj A, Burnell M, Kalsi JK, et al. Ovarian cancer screening and mortality in the UK collaborative trial of ovarian cancer screening (UKCTOCS): A randomised controlled trial. Lancet 2016;387:945-56.

  91. AOGIN India Consensus Panel. Screening for gynecologic cancers: Current evidence and Indian perspective. J Obstet Gynaecol India 2023;73 Suppl 1:45-53.Available from: https://www.aoginindia.in/AOGIN-India-Conf-2023.pdf. [Last accessed on 2025 Oct 28].

  92. Elias K, Smyczynska U, Stawiski K, Nowicka Z, Webber J, Kaplan J, et al. Identification of BRCA1/2 mutation female carriers using circulating microRNA profiles. Nat Commun 2023;14:3350.

  93. Gupta S, Rajappa S, Advani S, Agarwal A, Aggarwal S, Goswami C, et al. Prevalence of BRCA1 and BRCA2 mutations among patients with ovarian, primary peritoneal, and fallopian tube cancer in India: A multicenter cross-sectional study. JCO Glob Oncol 2021;7:849-61.

  94. John AO, Singh A, Yadav P, Joel A, Thumaty DB, Fibi Ninan K, et al. The BRCA mutation spectrum among breast and ovarian cancers in India: Highlighting the need to screen BRCA1 185delAG among South Indians. Eur J Hum Genet 2024;32:1319-26.

  95. Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: A combined analysis of 22 studies. Am J Hum Genet 2003;72:1117-30.

  96. Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Clin Oncol 2009;27:e98-9.

  97. Kahn RM, Gordhandas S, Godwin K, Stone RL, Worley MJ Jr., Lu KH, et al. Salpingectomy for the primary prevention of ovarian cancer: A systematic review. JAMA Surg 2023;158:1204-11.

  98. Tang Y, Sun H, Fu P, Zhou T, Liu R. Prophylactic salpingectomy as a preventative strategy for ovarian cancer in the general population: A systematic review and meta-analysis. J Gynecol Oncol 2025;36:e8.

  99. Hanley GE, Pearce CL, Talhouk A, Kwon JS, Finlayson SJ, McAlpine JN, et al. Outcomes from opportunistic salpingectomy for ovarian cancer prevention. JAMA Netw Open 2022;5:e2147343.

  100. Gupta V, Agarwal S, Chaudhari P, Saxena N, Nimonkar S. A study to evaluate the effect of opportunistic salpingectomy on ovarian reserve and function. J Obstet Gynaecol India 2023;73:62-8.

  101. Balsarkar G. Opportunistic salpingectomy as an ovarian cancer primary prevention strategy. J Obstet Gynaecol India 2017;67:243-6.

  102. Indian Council of Medical Research. Consensus Document for Management of Uterine Cancer. New Delhi: ICMR; 2019.

  103. Shridhar K, Dey S, Bhan CM, Bumb D, Govil J, Dhillon PK. Cancer detection rates in a population-based, opportunistic screening model, New Delhi, India. Asian Pac J Cancer Prev 2015;16:1953-8.

  104. Prem A, Thekkeveettil M, Mathew RS, Cyriac ME, Sheeja S, Joseph AN. Clinicopathological profile of carcinoma endometrium in a single institution of Kerala, India. J Midlife Health 2025;16:96-102.

  105. Crosbie EJ, Kitson SJ, McAlpine JN, Mukhopadhyay A, Powell ME, Singh N. Endometrial cancer. Lancet 2022;399:1412-28.

  106. Reeves GK, Pirie K, Beral V, Green J, Spencer E, Bull D, et al. Cancer incidence and mortality in relation to body mass index in the million women study: Cohort study. BMJ 2007;335:1134.

  107. Aune D, Navarro Rosenblatt DA, Chan DS, Vatten LJ, Vieira AR, Greenwood DC, et al. Anthropometric factors and endometrial cancer risk: A systematic review and dose-response meta-analysis of prospective studies. Br J Cancer 2015;112:2195-205.

  108. Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K, et al. Body fatness and cancer – Viewpoint of the IARC working group. N Engl J Med 2016;375:794-8.

  109. Morgan RW. Risk of endometrial cancer after tamoxifen treatment. Oncology (Williston Park) 1997;11:25-33.

  110. Kübler K, Nardone A, Anand S, Gurevich D, Gao J, Droog M, et al. Tamoxifen induces PI3K activation in uterine cancer. Nat Genet 2025;57:2192-202.

  111. Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia. A long-term study of “untreated” hyperplasia in 170 patients. Cancer 1985;56:403-12.

  112. Doherty MT, Sanni OB, Coleman HG, Cardwell CR, McCluggage WG, Quinn D, et al. Concurrent and future risk of endometrial cancer in women with endometrial hyperplasia: A systematic review and meta-analysis. PLoS One 2020;15:e0232231.

  113. Herrinton LJ, Weiss NS. Postmenopausal unopposed estrogens. Characteristics of use in relation to the risk of endometrial carcinoma. Ann Epidemiol 1993;3:308-18.

  114. Grady D, Gebretsadik T, Kerlikowske K, Ernster V, Petitti D. Hormone replacement therapy and endometrial cancer risk: A meta-analysis. Obstet Gynecol 1995;85:304-13.

  115. Dominguez-Valentin M, Sampson JR, Seppälä TT, Ten Broeke SW, Plazzer JP, Nakken S, et al. Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: Findings from the prospective lynch syndrome database. Genet Med 2020;22:15-25.

  116. Furness S, Roberts H, Marjoribanks J, Lethaby A. Hormone therapy in postmenopausal women and risk of endometrial hyperplasia. Cochrane Database Syst Rev 2012;2012: CD000402.

  117. Braun MM, Overbeek-Wager EA, Grumbo RJ. Diagnosis and management of endometrial cancer. Am Fam Physician 2016;93:468-74.

  118. U.S. National Cancer Institute. Endometrial Cancer (Uterine Corpus)-Treatment (PDQ®)-Health Professional Version. Bethesda (MD): NCI; 2025. Available from: https://www.cancer.gov/types/uterine/hp/endometrial-treatment-pdq. [Last accessed on 2025 Oct 25].

  119. Lim N, Hickey M, Young GP, Macrae FA, Kelly C. Screening and risk reducing surgery for endometrial or ovarian cancers in Lynch syndrome: A systematic review. Int J Gynecol Cancer 2022;32:646-55.

  120. Concin N, Matias-Guiu X, Vergote I, Cibula D, Mirza MR, Marnitz S, et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Int J Gynecol Cancer 2021;31:12-39.

  121. Management of endometrial intraepithelial neoplasia or atypical endometrial hyperplasia: ACOG clinical consensus no. 5. Obstet Gynecol 2023;142:735-44.

  122. Singh G, Cue L, Puckett Y. Endometrial hyperplasia. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560693/. [Last accessed on 2025 Dec 01, Last updated on 2024 Apr 30].

  123. Henderson I, Black N, Khattak H, UKARCOG Working Group Authors, Gupta JK, Rimmer MP. Diagnosis and management of endometrial hyperplasia: A UK national audit of adherence to national guidance 2012-2020. PLoS Med 2024;21:e1004346.

  124. Emons G, Beckmann MW, Schmidt D, Mallmann P, Uterus Commission of the Gynecological Oncology Working Group (AGO). New WHO classification of endometrial hyperplasias. Geburtshilfe Frauenheilkd 2015;75:135-6.

  125. Sobczuk K, Sobczuk A. New classification system of endometrial hyperplasia WHO 2014 and its clinical implications. Prz Menopauzalny 2017;16:107-11.

  126. Mutter GL. Endometrial intraepithelial neoplasia (EIN): Will it bring order to chaos? The endometrial collaborative group. Gynecol Oncol 2000;76:287-90.

  127. Sanderson PA, Critchley HO, Williams AR, Arends MJ, Saunders PT. New concepts for an old problem: The diagnosis of endometrial hyperplasia. Hum Reprod Update 2017;23:232-54.

  128. Lacey JV Jr., Sherman ME, Rush BB, Ronnett BM, Ioffe OB, Duggan MA, et al. Absolute risk of endometrial carcinoma during 20-year follow-up among women with endometrial hyperplasia. J Clin Oncol 2010;28:788-92.

  129. Nees LK, Heublein S, Steinmacher S, Juhasz-Böss I, Brucker S, Tempfer CB, et al. Endometrial hyperplasia as a risk factor of endometrial cancer. Arch Gynecol Obstet 2022;306:407-21.

  130. Vetter MH, Smith B, Benedict J, Hade EM, Bixel K, Copeland LJ, et al. Preoperative predictors of endometrial cancer at time of hysterectomy for endometrial intraepithelial neoplasia or complex atypical hyperplasia. Am J Obstet Gynecol 2020;222:60.e1-7.

  131. Royal College of Obstetricians and Gynaecologists. Green-Top Guideline No. 67: Management of Endometrial Hyperplasia. Revised edition. London: RCOG; 2016. p. 2–30. Available from: https://www.rcog.org.uk/guidance/browse-all-guidance/green-top-guidelines/management-of-endometrial-hyperplasia-green-top-guideline-no-67/. [Last accessed on 2025 Oct 20].

  132. Gallos ID, Shehmar M, Thangaratinam S, Papapostolou TK, Coomarasamy A, Gupta JK. Oral progestogens versus levonorgestrel-releasing intrauterine system for endometrial hyperplasia: A systematic review and metaanalysis. Am J Obstet Gynecol 2010;203:547.e1-10.

  133. Capria A, Tahir N, Fatehi M. Vulvar Cancer. [Updated 2023 Jan 9]. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK567798/. [Last accessed on 2025 Dec 12, Last updated on 2023 Jan 09].

  134. Sinno AK, Saraiya M, Thompson TD, Hernandez BY, Goodman MT, Steinau M, et al. Human papillomavirus genotype prevalence in invasive vaginal cancer from a registry-based population. Obstet Gynecol 2014;123:817-21.

  135. Qian J, Gracious K, Chen L, Xu S. Primary vaginal cancer after hysterectomy for benign conditions: A systematic review of the literature. Front Oncol 2024;14:1334778.

  136. Gillison ML, Chaturvedi AK, Lowy DR. HPV prophylactic vaccines and the potential prevention of noncervical cancers in both men and women. Cancer 2008;113:3036-46.

  137. Bhatla N, Meena J, Gupta K, Pal B, Divakar H, Bhalerao S, et al. Human papillomavirus vaccination: Good clinical practice recommendations from the federation of obstetric and gynecological societies of India. J Obstet Gynaecol Res 2020;46:1651-60.

  138. Government of India, Ministry of Health and Family Welfare. Operational Guidelines for Introduction of HPV Vaccine Under Universal Immunization Programme. New Delhi: MoHFW; 2024. Available from: https://www.mohfw.gov. [Last accessed on 2025 Nov 19].

  139. Indian Academy of Pediatrics (IAP) Advisory Committee on Vaccines & Immunization Practices. Optimizing Human Papillomavirus (HPV) Vaccination in Adolescents: A Consensus on Closing Practice Gaps for Enhanced Impact; 2025. Available from: https://aha.iapindia.org/introduction/. [Last accessed on 2025 Nov 19].

  140. Sankaranarayanan R, Bhatla N, Basu P. Current global status and impact of human papillomavirus vaccination: Implications for India. Indian J Med Res 2016;144:169-80.

  141. Duong TH, Flowers LC. Vulvo-vaginal cancers: risks, evaluation, prevention and early detection. Obstet Gynecol Clin North Am 2007;34:783-802, x.

  142. Olawaiye AB, Cuello MA, Rogers LJ. Cancer of the vulva: 2021 update. Int J Gynaecol Obstet 2021;155 Suppl 1:7-18.

  143. Servarayan Murugesan C, Manickavasagam K, Chandramohan A, Jebaraj A, Jameel AR, Jain MS, et al. Gastric cancer in India: Epidemiology and standard of treatment. Updates Surg 2018;70:233-9.

  144. Kannusamy S, Oak A, Cheulkar S, Maske K, Dashmukhe E, Patil A, et al. Spectrum of hepatitis B and hepatitis C-related cancers in India. Ecancermedicalscience 2024;18:1760.

  145. Ramamoorthy T, Sathishkumar K, Das P, Sudarshan KL, Mathur P. Epidemiology of human papillomavirus related cancers in India: Findings from the national cancer registry programme. Ecancermedicalscience 2022;16:1444.

  146. Ford AC, Yuan Y, Park JY, Forman D, Moayyedi P. Eradication therapy to prevent gastric cancer in Helicobacter pylori-positive individuals: Systematic review and meta-analysis of randomized controlled trials and observational studies. Gastroenterology 2025;169:261-76.

  147. Dikshit R, Gupta PC, Ramasundarahettige C, Gajalakshmi V, Aleksandrowicz L, Badwe R, et al. Cancer mortality in India: A nationally representative survey. Lancet 2012;379:1807-16.

  148. NCD Alliance. In India, Tobacco-Related Cancers Represent 42% of Male and 18% of Female Cancer Deaths at Ages 30-69 Years; 2024. Available from: https://ncdalliance.org. [Last accessed on 2025 Nov 14].

  149. World Health Organization. Global Hepatitis Report 2024: Action for Access in Low- and Middle-Income Countries. Geneva: WHO; 2024. Available from: https://www.who.int/publications/i/item/9789240091672. [Last accessed on 2025 Nov 14].

SECTION 6 CLINICAL EVALUATION AND MANAGEMENT: CLINICAL EVALUATION

1. Women may present to a menopause clinic with menstrual disturbances, menopausal symptoms, or for a routine health check-up, and may also be identified opportunistically during other healthcare visits.[1] Refer to Figure 1 for an initial assessment.

Figure 1.

Figure 1

Open in a new tab

Physician’s approach to evaluate a woman at 35 years or older. MT: Menopause transition, FMP: Final menstrual period, PM : Post menpopause

2. Clinical examination should follow a holistic, preventative, and diagnostic approach, extending beyond isolated menopausal symptoms to identify both hidden and obvious noncommunicable diseases (NCDs).[2-4]

3. Age-related biological changes, along with lifestyle and socioeconomic factors, require customized risk assessment and long-term management strategies.

Components of clinical evaluation

4. History and physical examination: Take a thorough history, including menstrual, reproductive, sexual, psychosocial, and family history. Perform the general and systemic physical examinations, as well as breast and pelvic examinations. Measure the Body Mass Index (BMI), waist circumference, and calf circumference.

5. Symptom assessment tools: Record menopausal symptoms using a validated scale. Menopause-related symptoms may be documented using the Menopause Rating Scale (MRS).[5,6] Refer to Table 1.

Table 1.

Menopause Rating Scale

graphic file with name JMH-17-12-g005.jpg
Open in a new tab

The percentage of symptoms at each visit is documented to assess the severity of symptoms and to follow up on the effectiveness of treatment. No problems 0%-4%; Mild problems 5%-24%; Moderate problems 25%-49%; Severe problems 50%-95%; Complete problems 95%-100%

The degree of symptoms is documented in the boxes to assess severity and the follow-up for treatment effectiveness.

The total MRS score is calculated, and menopausal symptoms are classified as None: 0–4; Mild: 5–8; Moderate: 9–16; Severe: 17 plus.

6. Based on the MRS outcome, the Female Sexual Function Index [FSFI-6 Refer to Table 2] for sexual health assessment, Insomnia Severity Index [ISI Refer to Table 3] for sleep disturbances, Patient Health Questionnaire [PHQ-4 Refer to Table 4] for psychological health, and s-Moca for dementia screening are documented as needed.[7-10]

Table 2.

Sexual health-Female Sexual Function Index - 6 Form

Description (range) 1 2 3 4 5
1. Desire Very low on (range) l ☐ ☐ ☐ ☐ ☐
2. Arousal No arousal (range) lth-Female ☐ ☐ ☐ ☐ ☐
3. Lubrication None bricationa ☐ ☐ ☐ ☐ ☐
4. Orgasm Never asmationange) lt ☐ ☐ ☐ ☐ ☐
5. Satisfaction Very dissatisfied ) lth-Female Sexu ☐ ☐ ☐ ☐ ☐
6. Pain Always pain sfied ) lt ☐ ☐ ☐ ☐ ☐
Open in a new tab

Total score=30. A score of ≤19 suggests dysfunction

Table 3.

Sleep: Insomnia Severity Index, 7-item questionnaire

Description 1 2 3 4 5
1. Difficulty falling asleep ☐ ☐ ☐ ☐ ☐
2. Difficulty staying asleep ☐ ☐ ☐ ☐ ☐
3. Problems waking up too early ☐ ☐ ☐ ☐ ☐
4. Satisfaction with current sleep ☐ ☐ ☐ ☐ ☐
5. Interference with daily functioning ☐ ☐ ☐ ☐ ☐
6. Noticeability of sleep problems by others ☐ ☐ ☐ ☐ ☐
7. Worry/distress about sleep problem ☐ ☐ ☐ ☐ ☐
Open in a new tab

Total Score: 28 cut-offs: 0–7: No clinically significant insomnia, 8–14: Sub threshold insomnia, 15–21: Moderate insomnia, ≥22: Severe insomnia

Table 4.

Psychological Health, Patient Health Questionnaire-4, past 2 weeks

Description 0 1 2 3
Little interest or pleasure in doing things ☐ ☐ ☐ ☐
Feeling down, depressed, or hopeless ☐ ☐ ☐ ☐
Feeling nervous, anxious, or on edge ☐ ☐ ☐ ☐
Not being able to stop or control worrying ☐ ☐ ☐ ☐
Open in a new tab

Each item scored 0–3; Total Score: 0–12 ≥6 suggests clinically relevant psychological distress

Risk stratification tools for diseases

7. Breast: A woman may be categorized into low, moderate, or high risk according to her risk of developing invasive breast cancer using the Gail Model, the limitation being that it has not been validated in India (https://www.cancer.gov/bcrisktool).

8. Cardiovascular disease (CVD): 10-year probability risk of myocardial infarction/stroke based on the Globorisk India tool (use the web calculator at www.globorisk.org or the validated desk/pocket chart) and/or Reynolds Risk Score (www.mdcalc.com/calc/3932/reynolds-risk-score-cardiovascular-risk-women?utm). Refer to Section 3 CVD.

9. Skeletal health: Risk assessment for osteoporosis may be done by OSTA/FRAX (http://www.shef.ac.uk/FRAX). Refer to Section 3 on osteoporosis.

10. Muscle health is evaluated using the SARC-calf, a 6-item questionnaire. Refer to Section 3 sarcopenia.

11. The results for risk assessment for diseases are documented in Table 5. The risk status is categorized as low, moderate, or high risk for disease.

Table 5.

Comprehensive chart for documenting the risk score for noncommunicable diseases over 5/10 years and lifetime results

Tool 5/10 years risk score Lifetime risk score Risk status
Gail model
WHO/ISH
OSTA/SCORE/FRAX
SARC f-calf
Open in a new tab

WHO: World Health Organization, ISH: International Society of Hypertension, FRAX: Fracture risk assessment tool, SCORE: Simple calculated osteoporosis risk estimation

12. Record the presence of GSM by noting the most bothersome symptoms and the vaginal pH with a narrow range litmus paper.

Recommended laboratory and imaging investigations

13. Baseline tests: Complete blood count, urine routine, fasting glucose/glycated hemoglobin, lipid profile, thyroid-stimulating hormone.

14. Cancer screening: Pap smear, stool for occult blood, mammography/ultrasound of the breast.

15. Reproductive Health: Vaginal pH and TVS.

16. Others: Dental and eye check-up.

17. Investigations should be individualized based on clinical findings. The investigations listed in Table 6 should be chosen judiciously, depending on the woman’s history and examination.

Table 6.

Tests performed solely on indication

Test Indication
FSH Premature ovarian insufficiency, women on contraceptive pills, women who had hysterectomy, doubt as to the cause of secondary amenorrhea or hot flushes, fertility
Estradiol Premature ovarian insufficiency, women on contraceptive pills, women who had hysterectomy, doubt as to the cause of secondary amenorrhea or hot flushes
Tests to assess increased risk of thrombosis Where there is relevant past or family history, women with previous history of unexplained thromoembolic episodes antithrombin III, Tissue factor pathway inhibitor activity, protein C and protein S are to be estimated. Lupus anticoagulant, anticardiolipin antibodies should also be assessed
Endometrial biopsy Postmenopausal bleeding, recent irregular bleeding, previous use of unopposed estrogen in the presence of uterus, endometrial thickness >11 mm; 4–11 mm with risk factors
Bone masdensity For specific indication Refer to Section 3
LFT When relevant as with suspected liver disease or recent history of liver disease, fatty liver on USG
Urodynamic study To diagnose and differentiate on the severity and type of incontinence before planning surgery
ECG, 2D Echo CVD assessment
25, OH Vitamin D Rule out secondary causes of osteoporosis
Open in a new tab

FSH: Follicle-stimulating hormone, OCPs: Oral contraceptive pills, LFT: Liver function tests, ECG: Electrocardiogram, 2D Echo: Two-dimensional echocardiography, CVD: Cardiovascular disease, 25, OH Vitamin D: 25-hydroxy Vitamin D, VMI: Vaginal saturation index, USG: Ultrasonography

Individualized health plan

18. Each woman needs a personalized health management plan for menopause. Management planning is based on the information obtained by history, clinical examination, the use of risk assessment tools, and the results of the investigations. Refer to Tables 7 and 8.

Table 7.

Management plan for women without menopausal symptoms

Characteristics Category Management
<10 years postmeopause, normal and overweight low risk for NCD/no comorbidities Healthy - Low risk Counsel on preventive health care
>10 years postmeopause. Obese women at moderate risk for NCD well controlled comorbidities Moderate risk for breast cancer Moderate risk Counsel on preventive health care/treat the disease
>20 years postmeopause Congenital heart disease/Established CVD/VTE/Stroke/Transient ischemic attack/ myocardial infarction/High risk for breast cancer/breast ca survivor uncontrolled comorbidities High risk Counsel on preventive health care/treat the disease
Open in a new tab

NCD: Noncommunicable disease, CVD: Cardiovascular disease, VTE: Venous thromboembolism

Table 8.

Management plan for women with menopausal symptoms (vasomotor symptoms/genitourinary syndrome of menopause/bone health)

Characteristics Category Management
<10 years postmeopause, normal and overweight Low risk for NCD/No comorbidities Healthy - Low risk Counsel on preventive health care MHT
>10 years postmeopause, obese women at moderate risk for NCD Well-controlled comorbidities Moderate risk for breast cancer Moderate risk Counsel on preventive health care Treat the disease Individualize MHT
>20 years postmeopause Congenital heart disease/Established CVD/VTE/Stroke/Transient ischemic attack/myocardial infarction/High risk for breast cancer/breast ca survivor uncontrolled co-morbidities High risk Counsel on preventive health care/treat the disease Avoid MHT
Open in a new tab

NCD: Noncommunicable disease, MHT: Menopausal hormone therapy, CVD: Cardiovascular disease, VTE: Venous thromboembolism

19. Based on the symptom profile, women can generally be categorized as either symptomatic or asymptomatic.

20. Based on the health profile, they are further classified as low risk, moderate risk, or high risk to personalize care and treatment decisions.

21. Counseling: The aims of counseling include addressing women’s questions and concerns, educating patients, and boosting their confidence in making decisions.[11-13] If a therapy is selected, the patient and clinician should agree on the goals, risks, and benefits, and a tentative duration of use. The skill of medical counseling and translating statistics into simple language is a vital part of consultation.

22. The classification of the frequency of drug reactions as per the WHO and the Council for International Organizations of Medical Sciences is shown in Table 9.[14]

Table 9.

Classification of frequency of drug reactions

Term Number Colloquial
Very common 1/1–1/10 A person in family
Common 1/10–1/100 A person in street
Uncommon 1/100–1/1000 A person in village
Rare 1/1000–1/10,000 A person in a small town
Very rare <1/10,000 A person in a large town
Open in a new tab

Source: RCOG Clinical Governance Advice. RCOG: Royal College of Obstetricians and Gynecologists

Therapeutic lifestyle modification

23. Indian Mantra for Menopausal Health [Figure 2]: The literal meaning of mantra is “tool or instrument of thought.” This word originates from the most ancient Vedic text, the Rigveda.[15]

Figure 2.

Figure 2

Open in a new tab

The Indian Mantra for menopause well-being

24. Dietary therapy: The ICMR, NIN (2024) recommends “My Plate for the Day” for adults with a caloric intake of 2000 Kcal. Emphasize the traditional Indian dietary patterns with a balance of different food groups.[16] Refer to Table 10.

Table 10.

Nutritional plan for a sedentary woman

Food source g/day
Whole grains (millets, brown rice, whole wheat) 270 g
Legumes/pulses/nonvegetarian 60–90 g
Vegetables 400 g
Fruits 100 g
Diary 300g
Fiber 25–40 g
Oil Two level tablespoon
Daily salt/sugar <5 g (1 tsp)/15–25 g (3–5 tsp)
Handful of nuts and 8–10 glasses of water
Open in a new tab

25. Free sugars include all sugars added to foods or drinks, as well as the sugars naturally found in honey, syrups, jaggery, fruit juices, and fruit concentrates. It excludes the sugars naturally present in whole fruits, vegetables, or plain milk.[16,17]

26. Keep “free sugars” to <5% of your daily energy intake, which is about five teaspoons (25 g) of sugar each day. Ideally, aim for under 5% (around three teaspoons or 15 g), as strongly advised to lower adiposity, type 2 diabetes, CVD, and mortality.[16,17]

27. One teaspoon of sugar, honey, or jaggery is equivalent to 4 g. A small glass (200 ml) of sweetened soft drink or packaged fruit juice contains 5–7 teaspoons of sugar. Indian sweets such as gulab jamun and laddoo often contain 8–12 teaspoons of sugar.[16]

28. Prioritize food sources for calcium intake exceeding 800 mg daily and ensure Vitamin D repletion through 1000–2000 IU daily or 60,000 IU monthly, or by daily exposure of arms, legs, or face to sunlight for 20 min between 11 AM and 2 PM to meet the RDA. Refer to Section 3.

29. Complete tobacco cessation and alcohol minimization are among the most effective, evidence-based strategies (Grade A)[18-21] for protecting postmenopausal women against breast, oral, and lung cancers, liver disease, and osteoporosis, endorsed worldwide by major health authorities.[18-21]

30. Exercise therapy: Physical activity and exercise help maintain a healthy weight, enhance bone density, coordination, and balance, and improve muscle strength and joint mobility. It also improves lipid profiles, alleviates genitourinary issues, reduces depression, and encourages better sleep.[22-24]

31. Exercise should incorporate aerobic, muscle-strengthening, breathing, and balance activities. Engage in 30 min of moderate-intensity physical activity, mainly 5 days a week. Muscle-strengthening activities should be included at a minimum of 2 days per week. The duration of physical activity depends on the goal; 30 min per day improves fitness and lowers the risk of chronic diseases; 60 min per day helps prevent weight gain and maintain metabolic health; 60–90 min per day helps prevent weight regain after weight loss.

32. Mind–body exercise therapy is a physical activity combining movement, mental focus, and controlled breathing. It is frequently used to enhance flexibility, strength, and balance while also encouraging relaxation and alleviating stress. 20–30 min daily can support psychological well-being, improve sleep, and help reduce vasomotor symptoms.[25-27]

33. Yoga therapy of ≥8 weeks duration improves vasomotor, psychological, and quality of life outcomes in perimenopausal women (Grade B).[28-34]

34. Sleep therapy: Proper sleep scheduling and maintaining a regular sleep-wake schedule are crucial. Consistently going to bed and waking up at the same times helps synchronize the circadian rhythm.[35,36]

Avoid stimulants: Limiting caffeine, nicotine, and alcohol for at least 4–6 h before bedtime can enhance sleep onset and quality.

Avoid using your bed for activities such as watching television, using smartphones, or reading to reinforce the connection between bed and sleep.

Avoid stimulating activity close to bedtime: Exercise or heavy meals should be avoided within 2 h of sleep onset.

Create a restful environment: Dim lighting, a quiet room, and a cool temperature (18°C–21°C) enhance sleep quality.

Engaging in prayer, meditation, gratitude journaling, or positive thought exercises before sleep reduces cognitive arousal and nighttime repetitive negative thinking (rumination).

Avoid spending too much time in bed: Limiting bedtime to the actual sleep duration helps improve sleep efficiency.[35,36]

35. Therapy to enhance emotional well-being: Emotional well-being during menopause is affected by biological, psychological, and social factors. Strong social connectedness and perceived emotional support are associated with better quality of life and lower anxiety, through their influence on biological, psychological, and social determinants of health.[37-39]

36. Maintaining a healthy BMI: Losing weight and maintaining it were associated with a reduced breast cancer risk for women aged 50 years and older in The Nurses’ Health Study and The Health Professionals Follow-Up Study (Grade B).[40-42]

37. Immunization: For the schedule for adult immunization.[43] Refer to Table 11.

Table 11.

Schedule of vaccines for adults (Association of Physicians of India 2024)

Vaccine Vaccine type Route Dose and schedule Special populations Age>50 years Comments
Hepatitis B Recombinant DNA or plasma-derived inactivated subunit vaccine IM in the deltoids, avoid buttocks 1 mL, 3 doses at 0, 1, 6 months Every 5 years for HCPs and CKD patients or hemodialysis patients. 2 doses for chronic liver disease and alcoholism Recommended with additional risk Contraindicated if allergic to yeast or history of allergic reaction
Influenza Inactivated and live attenuated IM (inactivated) Intranasal (live) 0.5 mL, 1 dose, annually LAIV: Not recommended If other live vaccines are being given, they should be administered on the same day or spaced 28 days apart
Pneumococcal disease PPSV 23, PCV 13 IM/SC (PPSV) IM (PCV) PCV 13: 0.5 mL PPSV - 0.5 mL. 1 dose PCV 13 followed by PPSV23 1 year later Above 50 years: PCV 13 followed by PPSV23, 1 year later At-risk: PCV 13 followed by PPSV23, 1 year later High-risk: PCV 13 followed by PPSV23, 8 weeks later Recommendation
Shingles (Herpes Zoster) Recombinant zoster vaccine IM oral (live) 0.5 mL, booster: 2–3 years 3–7 years in endemic set up Benefit risk ratio During pregnancy, weight the benefit versus risk and do not use live vaccine during pregnancy
Diptheria, pertussis and tetanus (Tdap) Diphtheria and tetanus toxoids and acellular pertussis antigens IM 0.5 mL, 1 dose 10 years lies Td: Recommended Tdap: Benefit ratio risk History of allergic reaction, during each pregnancy, it is recommended to receive one dose of Tdap, preferably between the gestational weeks of 27 and 36
Open in a new tab

PPSV 23: Pneumococcal polysaccharide vaccine 23, PCV 23: Pneumococcal conjugate vaccine 23, IM: Intramuscularly, SC: Subcutaneously, LAIV: Live-attenuated influenza vaccine, HCPs: Healthcare Professionals, CKD: Chronic kidney disease

Nonhormonal therapies

38. Complementary and alternative treatments should be approached cautiously as the evidence remains limited.

39. Awareness should be raised about phytoestrogens and lycopene-rich foods (18–24 mg daily) in the Indian diet (Grade C).[44-47]

40. In the Indian context, it is highly advisable to validate the effects of locally used herbs and phytoestrogen-containing formulations for menopausal symptom management using modern clinical research methods, including RCTs and phytochemical standardization.

41. Herbal remedies such as Shatavari, Ashoka, and Soy isoflavones may show promise in managing menopausal symptoms, but clinical use should remain cautious until validated through rigorous Indian RCTs and regulatory quality controls. In India, herbal and nutraceutical products are not regulated for potency, purity, or quality.[48-50]

Nonprescription-based therapies

42. Cognitive behavioral therapy (CBT): CBT is a structured, goal-focused form of psychotherapy. It helps individuals manage problems by altering unhelpful thoughts and behavior patterns. Emerging evidence supports CBT as a strong recommendation for managing vasomotor symptoms (VMS) (Grade A).[51-57]

43. Hypnosis is a form of mind–body therapy that uses guided relaxation, focused attention, and suggestion to induce a heightened state of awareness. It reduces hot-flash frequency and severity by approximately 60%–70% and improves sleep and quality of life in postmenopausal women. It can be an adjunct or alternative to pharmacological therapy for vasomotor symptoms (Grade B).[58-60]

Nonhormonal prescription therapies

44. Nonhormonal therapies, including SSRIs SNRIs, and certain anticonvulsants, although less effective than menopausal hormone therapy (MHT), can relieve VMS. They are recommended when MHT is contraindicated, not preferred, or used as supplementary treatment (Grade A).[61]

45. Evidence from randomized controlled trials supports the efficacy of SSRIs (paroxetine, escitalopram, fluoxetine, sertraline), SNRIs (venlafaxine, desvenlafaxine, and duloxetine) (Grade A),[61-63] and gabapentinoids (gabapentin and pregabalin) in alleviating vasomotor symptoms (Grade B).[61-63]

46. Clinical trials typically assess SSRIs/SNRIs or gabapentin over a short period (8–12 weeks); further use should be based on individual benefit, tolerability, and preference, with gradual discontinuation.

47. Neurokinin-3 (NK3) receptor antagonists, such as fezolinetant (approved by the Food and Drug Administration [FDA] in 2023) and elinzanetant (approved by the FDA in 2025), represent a nonhormonal therapy for VMS.

48. In a meta-analysis, fezolinetant 45 mg once daily was statistically significantly more effective than other non-HTs in reducing the frequency and severity of moderate-to-severe VMS and showed at least comparable or superior effects on symptom severity versus most nonhormonal agents (Grade A).[64,65]

49. Elinzanetant 120 mg/day, a dual NK-1/NK-3 receptor antagonist, has demonstrated significant reductions in the frequency and severity of moderate-to-severe VMS and related sleep disturbance in postmenopausal women.[66]

50. For women suffering mainly from insomnia, select gabapentin, while for those with primarily mood disorders, opt for fluoxetine and paroxetine. Low-dose venlafaxine was as effective as low-dose estradiol in controlling VMS.[67] In breast cancer patients, fluoxetine and paroxetine should be avoided as they may interfere with the effectiveness of tamoxifen.[68]

Menopause hormone therapy – An overview

51. Most long-term and randomized data on MHT come from international studies. Hence, when interpreting this data in India, one should account for local epidemiological differences, such as an earlier ANM and distinctive patterns of breast cancer, CVD, metabolic risk, and osteoporosis seen in Indian women.[69-76]

52. MHT should be prescribed for accepted indications, in appropriately selected women, with an understanding that secondary benefits alone do not constitute a sufficient indication for therapy.

Types, terminology

53. Hormone therapy (HT) in menopause medicine is an umbrella term that covers various treatment approaches (estrogen alone or in combination with progestogen and androgens).[71-77]

54. Types: Estrogen therapy (ET)- 17 beta estradiol (E2)/conjugated equine estrogen (CEE)/estriol/estradiol valerate (EV)/estetrol. Combined estrogenestradiolini therapy (EPT)- The commonly used progesterones in EPT are micronized progesterone (MP), dydrogesterone (DYD), and the levonorgestrel-releasing intrauterine system (LNG). Selective estrogen receptor modulators (SERMs) -The available SERMS in India are tibolone and raloxifene. Androgen therapy for women is not available in India.

55. Treatment terminology: Based on the pharmacokinetics of HT, as well as the individual’s age and health profile, the following terminology is recommended (Grade C).[71-77]

56. Estrogen replacement therapy/hormone replacement therapy (ERT/HRT): replicates the estrogen environment of premenopausal women as in premature ovarian insufficiency (POI) and early menopause (EM). It has no contraceptive effect.

57. Estrogen additive therapy (EAT/MHT): complements endogenous postmenopausal estrogen with exogenous estrogen, tailored to meet the indication for HT as in the management of menopause within 10 years of menopause.[77]

58. Estrogen maintenance therapy (EMT): which involves continuing the therapy beyond 10 years of menopause.

59. Oral contraceptive pills (OCPs): are hormonal preparations containing either combined estrogen–progestin (usually including ethinyl estradiol, and in some cases, 17 beta estradiol, EV, or estetrol) or progestin alone, used primarily for contraception and for the regulation of menstrual and hormonal disorders.

60. During MT, low-dose combined oral contraceptives (COCs) can ease vasomotor and mood symptoms, may support bone health, and decrease the risk of colorectal cancer (Grade B).[78-82] COCs offer effective contraception, help regulate irregular bleeding, and lower the risk of endometrial and ovarian cancers (Grade A).[81,82]

61. Although no definitive randomized trials to date compare continuous versus cyclic OCP use specifically in women during the MT expert guidance and reviews support shortened or eliminated hormone-free intervals with continuous or extended use to reduce VMS and abnormal bleeding, as learnt from continuous combined HT users.[78,80,83-86]

62. Checklist before prescribing MHT: Before starting MHT, every woman should undergo a comprehensive clinical evaluation and personalized risk assessment (Grade A).[87-90] Counseling must include potential benefits, risks, and alternatives. A documented, written informed consent is highly recommended as part of shared decision-making and medico-legal safety. Refer to Figure 3.

Figure 3.

Figure 3

Open in a new tab

Hormone Therapy Consent Form

63. The concept of precision medicine in prescribing systemic MHT emphasizes individualized therapy, where treatment is tailored to each woman and may change over time as her age, risk profile, symptoms, and health status evolve.

64. The six right principles for prescribing systemic MHT are to select the right woman, right age, right hormone, right regimen, right route, and right dose.

65. Right woman: The classical indications for postmenopausal MHT that have consistently withstood the test of time, supported by evidence from multiple randomized clinical trials and meta-analyses, are the beneficial effects of estrogens on moderate-to-severe VMS and urogenital atrophy.[91-97] In eligible women at risk for fracture, MHT may be considered after full risk assessment (Grade A).[95.96] HT is strongly recommended for women with POI and should be offered to women with EM until they reach ANM (Grade A).[98-102]

66. Right age: MHT has the most favorable benefit-to-risk profile when started within roughly 10 years of menopause. For starting later than 10 years after menopause or in women over 60, the benefit-to-risk ratio becomes less favorable, and shared decision-making is crucial. It is not recommended for women >20 years postmenopause.[77,103-110]

67. Right hormone: Estrogen. Both CEE and 17 β-estradiol effectively relieve vasomotor symptoms (Grade A).[111,112]

68. Oral CEE favorably alters HDL and Lp(a) levels but raises triglycerides, C-reactive protein (CRP), and clotting factors due to hepatic first-pass effects. Use CEE for lean, low-risk women; prefer 17 β-estradiol (oral or transdermal) for those with cardiovascular and metabolic risks (Grade B for selection).[106,107,113-119]

69. EV is a synthetic ester of 17 β-estradiol that is quickly hydrolyzed to estradiol following oral or parenteral administration. Its clinical efficacy and safety are comparable to those of other oral estrogens for symptom relief and bone protection, although large RCTs are lacking.[120-123]

70. Progesterone: The choice of a progestogen to accompany systemic ET should be based on endometrial safety, systemic risk profile, tolerability, route preference, and cost-effectiveness.[124-127]

71. All approved progesterones effectively prevent estrogen-induced endometrial hyperplasia when used at the correct dose and duration, tailored to individual needs based on estrogen potency and route.

72. MP and DYD maintain a neutral metabolic and vascular profile and are considered Venous thromboembolism (VTE) neutral when combined with transdermal ET (Grade A).[127-130]

73. Evidence from extensive cohort studies indicates that estrogen combined with MP or DYD does not seem to increase breast cancer risk during typical usage durations of <5 years and may pose a lower risk than regimens using synthetic progestins such as medroxyprogesterone acetate (MPA) (Grade B).[131-135] Long-term use exceeding 5–7 years requires individualized reassessment, as data beyond this period remains limited.

74. However, the National Institute for Health and Care Excellence (NICE) evidence review states that “it is unclear whether different progestogen types alter breast cancer risk.” It therefore does not currently recommend choosing progestogen solely based on breast cancer risk.[136-139]

75. A large Norwegian cohort study involving over 1.3 million women found that combined oral estrogen–progestin therapy was linked to a two-fold increase in breast cancer risk, with differences depending on the formulation. Vaginal estradiol showed no increased risk. The study did not include MP or DYD regimens, so its findings mainly relate to synthetic progestins.[135]

76. These data emphasize that breast cancer risk from MHT varies with regimen and duration, endorsing personalized treatment and regular review (Grade A).[131-135]

77. MP helps improve sleep in women with insomnia, but it can cause daytime drowsiness in some.[140,141]

78. DYD: The combination formula offers oral bioavailability, minimal sedation, and fixed-dose components, all of which improve patient adherence.[142-144]

79. LNG-IUS, 20 µg/day: offers effective endometrial protection for 5 years. It has a higher initial cost and necessitates procedural insertion.[138,145,146]

80. Right regime: available treatment options include estrogen alone, sequential combined hormone therapy (scMHT), and continuous combined hormone therapy (ccMHT) regimens. The choice of an appropriate regimen should be guided by factors such as menopausal stage, uterine status, symptomatology, and patient preferences. Refer to Figure 4.

Figure 4.

Figure 4

Open in a new tab

Systemic regime depending on the stage of menopause

81. An estrogen-only regimen is recommended for women who have undergone surgical menopause. Estrogen is administered daily without interruption.[103]

82. Exceptional cases: Firm evidence is lacking; we recommend adding progestogen to estrogen in hysterectomized women who have residual endometrial tissue after endometrial ablation or supracervical hysterectomy, a history of endometriosis, and stage I endometrial carcinoma.[147-149]

83. Alternative: Tibolone 2.5 mg/day may also be considered for women without a uterus.[150,151]

84. scMHT Regimen: In women with an intact uterus, adding a progestogen is crucial to counter the proliferative effects of estrogen on the endometrium and prevent hyperplasia or carcinoma. Estrogen daily with progestogen added for 12–14 days each month is indicated for women in late MT or within 1–2 years of the FMP. Predictable withdrawal bleeding occurs at the end of each progestogen cycle. Shorter progestogen phases (<10 days) or use beyond 5 years are linked to an increased risk of endometrial cancer.[152,153]

85. Alternative: Low-dose combined OCPs may be used in early or late MT for both symptom relief and contraceptive protection (Grade A).[83,84,85]

86. ccMHT regimen: involves daily administration of estrogen and progestogen without interruption. This approach maintains consistent hormonal levels and aims to induce endometrial atrophy over time.[86,153]

87. A 2020 review suggests that scMHT with synthetic progestins, as well as either scMHT or ccMHT with MP, may be associated with a modest rise in endometrial cancer risk when progestogen exposure is insufficient.[152] This risk appears especially relevant with shorter progestogen phases, lower doses, or duration exceeding 5 years. Adequate endometrial protection requires administering progestogen for at least 12–14 days per 28-day cycle or providing continuous exposure, depending on the type of progestin, the dose, and the duration of MHT use.[135,152,153] Refer Figure 4 MHT regimes.

88. Right route: oral versus transdermal should be personalized according to cardiovascular/metabolic risk profile, clinical indications, and patient preference.[104,131,154-157]

89. Transdermal estrogen: is the preferred route of administration for postmenopausal women with metabolic or vascular risk factors such as obesity, metabolic syndrome, type 2 diabetes mellitus, hypertriglyceridemia, elevated CRP, and controlled hypertension.[117,128,129,158]

90. It is also recommended for women with migraine with aura, gallbladder disease, bowel disorders (such as irritable bowel syndrome or inflammatory bowel disease), or those who smoke, including women using hepatic enzyme–inducing medications such as phenytoin or carbamazepine.[157,159]

91. Transdermal estradiol may be beneficial for some women experiencing sexual dysfunction, as it better preserves libido and genital blood flow, whereas the oral route may reduce free testosterone and sexual desire in certain users. Evidence from randomized trials supports biological plausibility, although data are limited and the Cochrane review has not specifically investigated differences in route (Grade B).[160,161]

92. Oral estrogen: In women with low HDL, oral estrogen has a greater effect on raising HDL levels than transdermal routes and also reduces lipoprotein(a).[162,163] Oral MHT positively impacts glucose metabolism and insulin sensitivity, potentially reducing the risk of developing type 2 diabetes in women without preexisting diabetes (Grade A).[163,164]

93. Right dose: Use the appropriate, minimum, effective, and adjustable dose for symptom relief or bone protection, with dose tapering as age advances.[165,166] Low-dose and ultra-low-dose therapies effectively alleviate symptoms and help sustain bone mass[92,167,168] [Tables 12 and 13].

Table 12.

Doses of estrogen therapy

Estrogens Ultra low Low Standard High
CEE-oral (mg) 0.15 0.3, 0.45 0.625 1.25
17ß-estradiol (mg) oral 0.25, 0.5 1.2 4
17ß-estradiol (mg) transdermal 0.014 0.025 0.05 0.1
EV (mg) oral 1 2 4
Open in a new tab

CEE: Conjugated equine estrogens, EV: Estradiol valerate

Table 13.

Types of progesterones and the required dose for preventing endometrial hyperplasia

Progesterone (mg) Sequential combined regimen Continuous combined regimen
MP (oral preferable vaginal) Oral E2 – ≤1 mg/CEE - 0.3 mg/TDE ≤0.025–200 mg of MP for 14 days
Oral E2 – 2 mg/CEE – 0.625 mg/TDE – 0.05–300 mg for 14 days		 Oral E2 – 1 mg/CEE – 0.3 mg/TDE – 0.025–100 mg
Oral E2 – 2 mg/CEE – 0.625/TD – 0.05–200 mg
DYD Oral E2 – ≤1 mg/CEE – 0.3 mg/TDE ≤0.025–10 mg for 14 days
Oral E2 – 2 mg/CEE – 0.625 mg/TDE – 0.05–10 mg for 14 days		 E2 1 mg: 5 mg
E2 0.5 mg: 2.5 mg (ultra low dose)
LNG (intrauterine) 52 mg (releases 20 µg/day) 52 mg (releases 20 µg/day)
Open in a new tab

CEE: Conjugated equine estrogens, LNG: Levonorgestrel-releasing intrauterine system, MP: Micronized progesterone, DYD: Dydrogesterone, TDE: Transdermal estradiol

94. It is important to note that the precise optimal dose for each patient remains personalized, and the evidence is continually evolving. The progestogen dose should be proportional to the estrogen dose to suppress the endometrium. The evidence comparing oral and transdermal MHT regarding dose equivalence for progestogens is limited.[124,169-171]

95. Enhanced monitoring and clinical vigilance are recommended in women with persistent endometrial thickening (>5 mm), obesity (higher endogenous estrogen), or those receiving MHT for >5 years.

Indications of menopausal hormone therapy: Refer to Figure 5

Figure 5.

Figure 5

Open in a new tab

Flow chart to prescribe menopausal hormone therapy

96. Vasomotor symptoms: The most effective treatment for VMS is MHT during menopause transition (Grade A).[91,93,172,173]

97. Depression, Mood, and Sleep: Refer to Section 1.

98. Genitourinary syndrome of menopause: Refer to Section 2.

99. Osteoporosis: Refer to Section 3.

100. Absolute contraindications of systemic HT: Undiagnosed abnormal vaginal bleeding; known, current, suspected, or past breast cancer, estrogen-dependent cancers (endometrial, ovarian, and others); active or recent VTE; history of stroke or MI; severe active liver disease with impaired or abnormal liver function; porphyria cutanea tarda; dementia; hypersensitivity; and known or suspected pregnancy (Grade A).[92,136,157,174]

101. Relative contraindications: The presence of latent or established comorbidities requires personalized assessment, shared decision-making, and coordination within a multidisciplinary care team to ensure safe initiation and monitoring of therapy.

102. Drug Interactions: Enzyme-inducing drugs, such as rifampicin, barbiturates, and some antiepileptic drugs like phenytoin or carbamazepine, may accelerate the metabolism of (MHT) and reduce its effectiveness; clinicians should monitor and adjust accordingly (Grade B).[87]

Duration of use

103. POI: HRT should be maintained until the average ANM (Grade A).[175-182]

Continuation beyond the ANM should be a jointly reviewed decision, considering ongoing indications, patient preferences, and an evolving risk profile (Grade C).[98,183,184]

104. Early menopause: Continuation beyond 48–50 years may be considered on an individual basis through shared decision-making when symptomatic or for bone protection.[175-177]

105. Natural menopause: After nearly 20 years of follow-up, Women’s Health Initiative (WHI) trials showed that EPT and ET were not associated with increased all-cause, cardiovascular, or overall cancer mortality when initiated around the MT.[185-187]

106. Extended therapy beyond these durations may be justified through shared decision-making, particularly for women with recurrent VMS or for osteoporosis prevention when other therapies are unsuitable. Management should remain personalized, with an annually documented benefit–risk review and careful attention to the hormone regimen, duration, and route of administration.[135,70,188-191]

107. Local ET continues to be the primary treatment for GSM across all ages, due to its proven effectiveness and safety with minimal systemic absorption, and may need long-term use (Grade A).[190]

108. Follow-up: Review at 1–2 months after initiation to assess compliance, tolerance, and side effects; at 3 months to address unscheduled bleeding or intolerance; and annually thereafter for a comprehensive evaluation, including risk re-evaluation for NCDs and an updated benefit–risk analysis. Modify the dose or route of therapy as appropriate to the changing clinical profile of the aging woman.

109. Situations requiring immediate discontinuation of HT:

  • New or worsening migraine and headache pattern

  • Visual disturbances such as blurring or symptoms indicating vascular occlusion (e.g., retinal thrombosis)

  • Jaundice or indications of liver dysfunction

  • Persistent or significant elevation in blood pressure

  • Furthermore, HT should be stopped 4–6 weeks prior to elective major surgery involving prolonged immobilization to reduce the risk of VTE

  • If new breast symptoms (lump, nipple change) or unexpected bleeding occur during therapy, the appropriate evaluation should be undertaken, and the decision to continue or pause MHT is made on a case-by-case basis.

  • Unscheduled bleeding until a diagnosis is reached

  • Therapy may be reviewed and resumed following full recovery and a comprehensive clinical reassessment of the patient’s risk profile.

110. Common adverse effects of MHT: Fluid retention may occur in the short term. Recommend reducing dietary salt intake, maintaining adequate hydration, encouraging regular physical activity, and reviewing the estrogen dose. Persistent or troublesome edema should prompt dose reduction or a change in route.

Bloating: consider switching to a low-dose transdermal estrogen; reduce the progestogen dose to the level that still protects the uterus; switch to an alternative progesterone.

Breast tenderness is common during the first few months. Consider reducing the estrogen dose, switching to a different form of estrogen, or trying a different progestin.

Headaches: Switching to transdermal estrogen and using the lowest effective dose often improves tolerance; some women benefit from a continuous-combined regimen.

Mood changes: Lower the progestogen dose; switch progestogen; or change from systemic progestin to the LNG-IUS.[151]

Nausea: Advise taking the tablet with food or at bedtime; if it persists, reduce the estrogen dose or switch to a transdermal preparation.

Chloasma: recommend broad-spectrum sunscreen for women prone to it.

Persistent menopausal symptoms: despite seemingly adequate MHT, reassess the diagnosis, adherence, and drug–drug interactions, especially enzyme-inducing antiepileptics and TB drugs. Then, adjust the estrogen dose or change the route, and optimize the progestogen regimen.[151,191]

Bleeding: during HT is common when beginning MHT, especially within the first 3–6 months or within 3 months of adjusting the dose or route.[192] In scMHT, a scheduled withdrawal bleed is expected at the end of the progestogen phase.[192] Unscheduled bleeding, such as spotting, heavy, or persistent bleeding outside the normal phase, bleeding before completing the progestogen phase in sequential regimens, or any new bleeding after 6 months on a continuous-combined regimen, requires investigation.[192]

While TVS of the endometrium is the standard first-line investigation, it may not exclude pathology in women on MHT, and endometrial sampling remains the definitive method to exclude hyperplasia or carcinoma.[192]

Thick endometrium on TVS in women without bleed: After 6 months of amenorrhea, with an ET of <10 mm, and no significant risk factors for endometrial cancer, can be offered adjustments in their progestogen therapy and follow-up instead of immediate biopsy.[192]

Individuals with one major or two minor risk factors for endometrial carcinoma, and with ET >4 mm on ccMHT or >7 mm on sc/ccMHT, should be offered EB. If the endometrium appears inhomogeneous, cystic, or irregular, or if bleeding recurs, EB is recommended regardless of ET measurement (Grade B).[192]

111. Stopping MHT: Discuss both abrupt and gradual taper options, taking into account the woman’s previous VMS burden, age, and tolerance. Ensure follow-up to address potential recurrence of symptoms. Symptoms recur in up to 50% of women, usually within the first few months after stopping therapy. There is no high-quality evidence that tapering the dose reduces recurrence or severity of vasomotor or other menopausal symptoms compared with abrupt cessation.[193-196]

Special clinical situations: Judicious use of menopausal hormone therapy, when benefits clearly outweigh risks

112. Continuing MHT beyond 10 years from menopause or after age 60: MHT may be continued in healthy women already using low-dose transdermal estradiol with MP or DYD, provided the benefits outweigh the risks. An annual review of symptoms, breast and cardiovascular health, and any emerging contraindications is essential.[107,197-201] When risks related to cardiovascular, thrombotic, or cognitive issues emerge, nonhormonal options are preferred (Grade A).[107,187,198]

113. Vasomotor and sexual symptoms may continue into the seventh and eighth decades, and residual GSM symptoms often need ongoing treatment. Symptom-driven, personalized continuation is suitable when benefits outweigh risks.[199-201]

114. Re-starting or initiating systemic MHT beyond 10 years from menopause or after age 60 enters the early hazard window for VTE and stroke: If therapy is clinically indicated for severe symptoms, opt for transdermal 17 β-estradiol (up to 50 µg/day) with MP or DYD, as this combination is linked to lower VTE and stroke risks than oral estrogen–progestin therapy (Grade A).[107,192,202-208] The prolonged use of MHT in appropriately selected women does not raise all-cause or cardiovascular mortality and can improve quality of life.[107,192,202-208]

115. Starting systemic MHT de novo more than 20 years after menopause, usually at age 70 or older, is not recommended, owing to increased risks of coronary events, stroke, venous thrombosis, and dementia as shown in WHI and other studies (Grade A).[203] Nonhormonal options should be preferred in this group.[203]

116. For bone health after 10 years postmenopause: Nonhormonal pharmacological options, such as bisphosphonates, denosumab, or SERMs, are preferred when MHT is generally not recommended for primary osteoporosis prevention (Grade A).[204,208]

117. Systemic lupus erythematosus (SLE): Active SLE or the presence of antiphospholipid antibodies (aCL or lupus anticoagulant) significantly increases the risk of VTE and stroke.[209] Mild or stable SLE without additional thrombophilia can be safely treated with MHT. Randomized data show no significant increase in severe flares among stable SLE patients receiving MHT.[209]

118. MHT and comorbidities: Refer to Section 3.

119. Breast cancer survivors: In patients aged 40–45 years with breast cancer and secondary amenorrhea following chemotherapy, an undetectable anti-Müllerian hormone at 30 months serves as a reliable predictor of permanent menopause.[210] Refer to Section 5.

120. Benign breast diseases: Do not carry a high risk of malignancy and are not a contraindication to HT. MHT may be used with appropriate screening and vigilance (Grade C).[211,212]

121. MHT and Mammograms: Combined estrogen–progestin therapy raises mammographic breast density, resulting in higher recall rates and decreased mammographic sensitivity. About half of the increased risk of hormone-receptor-positive breast cancer associated with MHT seems to be mediated through this change in density.[213] Mammographic density usually decreases within 1–2 years after stopping therapy. Continued personalized breast imaging and monitoring are advised.[214]

122. Breast, MHT, and Cancer Risk: Women with a low and moderate baseline risk of breast cancer may be prescribed MHT based on individual needs after a comprehensive history, breast examination, use of risk assessment tools, and informed counseling. They should receive accurate, evidence-based information about MHT-related breast cancer risk (Grade A).[134,136,185,215,216]

123. In women at high risk of breast cancer and in breast cancer survivors, nonhormonal therapies are preferred for symptom relief. Systemic MHT is contraindicated due to recurrence risk, as shown in HABITS and LIBERATE trials (Grade A).[185,217-219]

124. However, in rare individual cases, HR-negative disease, long disease-free interval, intolerable symptoms, multidisciplinary consent where systemic MHT is being considered, a comprehensive risk–benefit assessment, and shared decision-making between the oncologist and menopause specialist are essential.[220,221]

125. In BRCA1/2 mutation carriers who undergo risk-reducing bilateral salpingo-oophorectomy, short-term systemic HT up to the median age of natural menopause seems safe (Grade B).[222-224] The use of HT in this context aims to prevent the consequences of premature estrogen deprivation.[222-224] Continuing systemic MHT beyond the natural age of menopause (Grade A)[222-224] is discouraged due to limited long-term safety data on breast and vascular outcomes (Grade C).[185]

126. MHT should be avoided in BRCA carriers who have had previous breast cancer and in women with significant baseline risk factors.[220]

Preexisting cancers and menopausal hormone therapy

127. Decisions regarding MHT after cancer should be made through shared decision-making, involving both the patient and the treating oncologist.[225,226] Recommend offering transdermal instead of oral MHT.[227]

128. MHT is neutral: Low-grade, early-stage EC type I, cervical adenocarcinoma, epithelial ovarian cancer, germ cell tumors, hematological malignancies, local cutaneous malignant melanoma, colorectal cancer, hepatocellular cancer, BRCA 1/2 mutation carriers without cancer, most types of ovarian cancer, squamous cell carcinomas of the cervix, vaginal and vulvar squamous cell carcinoma, prolactinoma, kidney cancer, pancreatic cancer, and thyroid cancer.[225,228-231]

129. MHT is relatively contraindicated: leiomyosarcoma, EC type II, advanced metastatic malignant melanoma, gastric cancer, bladder cancer, and lung cancer (Grade B).[152,225,230,232]

130. MHT is contraindicated in women with endometrial stromal sarcoma, uterine carcinosarcoma (Grade A), ovarian cancers such as estrogen-dependent granulosa cell tumors, low-grade serous tumors, and Sertoli–Leydig tumors, as well as endometrioid ovarian tumors, cervical adenocarcinoma, meningioma, glioma, and hormone receptor-positive cancers. Gastric and bladder cancers are also contraindicated due to increased risk of recurrence or tumor stimulation (Grade B).[152,225,226,230,232]

Integrated conclusions on the risks and benefits of systemic hormone therapy within 10 years of menopause, based on evidence from WHI [Refer to Tables 14 and 15], PEPI, KEEPS, ELITE, and DOPS Trials

Table 14.

Based on women’s health initiative, the number of excess events on hormone therapy versus placebo per 10,000 women per year of hormone therapy

Disease E WHO/CIOMS definition of risk E + P
VTE 4 Rare 1/1000–1/10,000 11
Stroke 1 Rare 1/1000–1/10,000 4
Breast cancer NA Rare 1/1000er/10,000 5
CVD NA Rare 1/1000er/10,000 5
Open in a new tab

Use between the age groups of 50 and 59 years. CVD: Caridovascular disease, CIOMS: Council for International Organizations of Medical Sciences, WHO: World Health Organization, VTE: Venous thromboembolism, NA: Not applicable, E + P: Estrogen +progesterone

Table 15.

Based on Women’s Health Initiative: Fewer events on estrogen versus placebo per 10,000 women per year of hormone therapy use between the age group of 50 years and 59 years

Disease Number of less events with ET
Heart disease 12
Breast cancer 8
Disease Number of less events with E/EPT
Overall mortality 10
Fractures 5
Colorectal cancer 6
Open in a new tab

ET: Estrogen therapy, EPT: Estrogen–progestin therapy

131. The risk–benefit balance of MHT varies depending on several factors, including the woman’s age, time since menopause, baseline health status, family history of noncommunicable diseases and cancers, route of administration, and the specific regimen used.

132. Risks are reduced when therapy starts before age 60 or within 10 years of menopause, following a thorough individual risk assessment, with annual reviews to reassess indication, dose, and duration.

133. As with other long-term therapeutic interventions, careful patient selection, judicious use, and regular monitoring are essential to maximize benefits and minimize potential risks.

134. The risk–benefit balance of MHT depends on several factors, including the woman’s age, time since menopause, baseline health status, route of administration, and regimen used. Risks are minimized when therapy is started before the age of 60 or within 10 years of menopause and is reviewed annually.

135. As with other long-term therapeutic interventions, careful selection, judicious use, and regular monitoring of MHT are essential to maximize benefits and minimize potential risks.

Risks of systemic therapy

136. The magnitude and type of MHT-related risks in the 50–59-year age group, including breast cancer, and stroke, are rare, with fewer than 10 cases per 10,000 women with VTE showing 11events. These risks are lower with CEE than with CEE plus MPA and are equal to or lower than those linked to obesity, a much more common and modifiable risk factor.[233-238]

137. Cardiovascular disease: Systemic therapy should not be used for primary or secondary prevention of CVD. At any age, women at high risk of CVD or with established CVD should avoid MHT (Grade A).[239]

138. VTE: MHT increases the absolute risk by 4 in 10,000 women for ERT users and 11 in 10,000 for EPT users, while in OCP users, it ranges from 3 to 15 per 10,000 woman-years (Grade A). The risk peaks during the first 1-2 years of treatment and is influenced by the oral route, obesity, smoking, thrombophilia, and age.[157,208,240,241]

139. The absolute risk of VTE is significantly higher during physiological states such as pregnancy, with 5–20 VTE cases per 10,000 deliveries, and reaches its peak in the postpartum period at 40–65 per 10,000 woman-years.[242]

140. Transdermal ET (Grade A) and natural progesterones (Grade C) may not cause VTE. Population screening for thrombophilia is not recommended before using MHT.[243,244]

141. Stroke: Unlike CVD, the timing hypothesis does not apply to stroke, as the risk appears predominantly thrombotic rather than atherosclerotic in origin.[245]

142. Standard-dose oral estrogen or combined EPT is linked to an absolute increase of 2 additional strokes per 10,000 woman-years among those aged <60 years (Grade B).[206,245] For women aged 50–54 years, the excess absolute risk is 1.5 per 10,000 woman-years, rising to 2.2 at age 59 and 2.8 at ages 60–64.[206,240,243,245-247]

143. The risk increases with estrogen dose, age, and route of administration, reaching its highest during the first 1–2 years of treatment. In contrast, low-dose (≤50 µg/day) transdermal estradiol and nonoral routes do not seem to raise stroke risk compared to nonusers (Grade C).[198] The event rate, therefore, stays very low, particularly in younger, healthy postmenopausal women using low-dose or transdermal formulations.[198]

144. MHT and breast cancer: The impact of MHT on breast cancer risk is complex, influenced by background risk, type of MHT, dose, duration of use, regimen, route of administration, and prior exposure.

145. The incremental risk associated with MHT is minimal, with an estimated increase of fewer than 1 additional case per 1000 women aged 50–59 years annually (Grade A).[185,216,219,248] This level of risk is comparable to or lower than that related to common preventable lifestyle factors such as obesity, alcohol consumption, and physical inactivity (Grade A).[185,216,219,248]

146. The increased breast cancer risk associated with CEE + MPA diminishes after discontinuation, usually returning to nonuser levels within about 3 years, particularly following short-term use. However, some elevated risk may persist after more than 5 years of use or with certain synthetic progestins (Grade A).[185,216,219,248]

147. Tumors in women using MHT are usually ER-positive and of the lobular type (Grade C).[216,248]

148. The Collaborative Group Lancet 2019 meta-analysis synthesized only observational data. These findings suggest a slight absolute increase in breast cancer risk, mainly with combined estrogen–progestin therapy, and a lower risk with estrogen-only therapy.[38]

149. According to this analysis, adopted by NICE Guidance 2020 (NG23) as a patient discussion aid for women starting MHT at around age 50 and assessed for risk between ages 50–69 years, the estimated excess breast cancer cases after 5 years of use are:[136]

Continuous combined MHT: one additional case per 50 users.

Sequential combined MHT: one additional case for every 70 users.

Estrogen-only MHT: one additional case per 200 users.

All estimates are based on observational data, mainly using oral 17 β-estradiol and synthetic progestins in older women aged 50–69 years.[137] The findings generally align with the Norwegian EBBA-Life cohort and both the studies found no increased risk with vaginal estrogen.[135]

150. In contrast, DOPS, a randomized trial in younger postmenopausal women using 17 β-estradiol ± norethisterone acetate, found no increase in breast cancer incidence or mortality and reported an overall reduction in mortality after 16 years.[131]

151. Similarly, in the WHI trial, women receiving CEE 0.625 mg experienced a statistically lower incidence of breast cancer compared with placebo, and this benefit persisted for over 20 years of extended follow-up. The combined estrogen plus progestin arm showed a modest increase in incidence, mainly limited to the duration of treatment, but no significant difference in breast cancer-specific mortality was observed (Grade A).[185]

152. When counseling women, the focus should be on absolute risks quantified in RCTs, as observational data are susceptible to residual confounding and selection bias.[249,250] Therefore, counseling should primarily depend on RCT-derived absolute risk estimates from WHI and DOPS, while recognizing supportive observational trends. This approach encourages shared decision-making and personalized risk stratification based on age, time since menopause, comorbidities, and treatment goals.

153. MHT and ovarian cancer: In absolute terms, ovarian cancer risk is a rare event with estrogen alone (CEE), the increase is by approximately 0.2 per 1000 women, 0.1 in CEE plus MPA regime, and about 1 per 1000 women with estradiol alone (Grade A).[136,187]

154. MHT and endometrial cancer: Unopposed systemic estrogen (CEE or E2 alone) in women with an intact uterus carries an absolute risk of 1–3 cases per 1000 women.[251] Continuous combined estrogen–progestin therapy (CEE + MPA) lowers endometrial cancer incidence by approximately 3–4 cases per 10,000 women-years compared to placebo.[251,252]

155. Combined oral contraceptives provide significant and lasting protection against both ovarian and endometrial cancers and should be recognized as protective factors in women’s lifetime risk assessments (Grade A).[253,254]

156. MHT and gallbladder: The use of oral estrogen-alone or combined MHT is linked to a higher risk of gallstones, cholecystitis, and cholecystectomy (Grade A).[92] Observational evidence suggests that transdermal estrogen has a lower risk of gallbladder disease compared to oral preparations, and that oral estradiol may pose a reduced risk relative to CEE. However, these differences have not been confirmed in randomized controlled trials (Grade C).[255,256]

Benefits of systemic therapy

157. When initiated near menopause, systemic HT offers significant benefits beyond vasomotor relief, positively impacting metabolic health, bone density, mood, and sleep while also potentially lowering the risk of diabetes and colorectal cancer.[257-260]

158. MHT enhances QOL by providing consistent relief from vasomotor and urogenital symptoms, as well as improving sleep quality, mood, and cognitive well-being (Grade A).[261,262] Reductions in coronary events and all-cause mortality with low absolute risks of serious adverse events were noted in the WHI in the younger women.[263]

159. Androgens: Available data are of low quality and conflicting regarding the risk of breast cancer associated with androgen use.

Tissue-selective hormone modulators

160. Tibolone: Tibolone is a selective tissue estrogen receptor modulator. It is a synthetic steroid compound with estrogenic, progestogenic, and androgenic properties. It exerts an estrogenic effect on bone, inhibiting bone resorption by reducing osteoclastic activity.

161. Tibolone is effective in treating VMS and improves urogenital atrophy. It improves mood and libido (Grade B).[150] It is prescribed in a single daily dose of 2.5 mg orally. A lower dose of 1.25 mg is equally effective for most indications, including osteoporosis (Grade A).[264]

162. Raloxifene is a selective estrogen receptor modulator (SERM) indicated for the prevention and treatment of postmenopausal osteoporosis, particularly in women at increased risk of breast cancer. It acts as an estrogen agonist in bone and lipid metabolism, and as an antagonist in breast and endometrial tissue.[265,266]

163. Raloxifene lowers the risk of invasive estrogen receptor–positive breast cancer by approximately 60%–70% in postmenopausal women, without stimulating the endometrium (Grade A). The recommended dose is 60 mg once daily.[264,265]

164. Bazedoxifene: a third-generation SERM, acts as an estrogen agonist on bone and lipid metabolism and as an antagonist on breast and endometrium. When combined with conjugated estrogens (CE), it forms a tissue-selective estrogen complex (TSEC) that provides symptom relief and bone protection without the need for a progestogen (Grade A).[267,268]

165. TSEC (CE + BZA) provides an effective alternative to traditional MHT for postmenopausal women with a uterus, particularly those at increased risk of breast cancer or intolerant to progestogens. However, it has a slightly increased risk of VTE and is contraindicated in women with previous VTE, breast or uterine cancer, or liver disease (Grade A).[267,268]

Digital tools, artificial intelligence, and machine–learning approaches in menopause care

166. Postmenopausal women may use digital platforms (such as mobile applications, websites, search engines, and podcasts) solely for education, awareness, and symptom monitoring.[268,269]

167. These platforms should not be used to initiate, modify, or cease therapeutic interventions without a clinician’s supervision. Clinician-guided interpretation remains crucial to ensure safety, accuracy, and personalized care.[269,270]

Economics of menopause management

168. Menopause imposes a measurable economic burden on women and society through decreased workplace productivity, increased healthcare utilization, and the ongoing costs of untreated chronic diseases developing in midlife. Untreated vasomotor and sleep symptoms alone have been shown to significantly reduce quality of life and work performance, leading to substantial indirect costs (Grade B).[271]

169. The Indian healthcare system remains one of the most privatized globally, characterized by low public health expenditure and substantial out-of-pocket spending, which creates significant barriers to equitable access for midlife women. Gender and socioeconomic disparities further exacerbate this burden, especially among older women with multimorbidity.[272]

170. Expanding insurance coverage for women in midlife, particularly beyond age 65, and subsidizing evidence-based preventive interventions such as bone-protective agents and cardiovascular screening would enhance equity and reduce catastrophic household expenditure in the long term.[273]

171. Integrating menopause management into national NCD and women’s health programs can lead to downstream cost savings by preventing osteoporosis, cardiovascular disease, and mental health issues through early detection and intervention.[274,275]

172. Economic evaluations and modeling studies support that targeted lifestyle counselling and risk-based preventive screening in midlife/around the menopausal transition can be cost-effective, particularly when compared with the substantial downstream costs of osteoporotic fractures and cardiometabolic events (Grade B).[276-279]

173. Setting up dedicated menopause clinics and integrating midlife health services into primary and district-level care are cost-effective, high-impact approaches to support healthy aging and reduce the long-term strain on India’s health system (Grade B).[280]

REFERENCES

  1. Lakshmi RM, Kusumalatha K, Shraddha S. Analysis of 200 Perimenopausal Women: A Prospective Study, Abstract presented at 12th National Indian Menopause Society Meeting. Rajkot: Souvenir; 2007. p. 25. 45.

  2. Bipasa S. First Time Detection of Medical Disorders in Forty-Plus Women in Health Camps. Abstract presented at 15th National Indian Menopause Society Meeting Chennai: Souvenir; 2010. p. 68.

  3. Santhakumar K, Nivedita Bharati K, Jaishree Gajraj A. Routine Investigations in Women 40 Years and Above. Abstract presented at 15th National Indian Menopause Society Meeting. Chennai: Souvenir; 2010. p. 69.

  4. Hina K, Manju T, Mehandale SS. Midlife Management Clinic for Screening of Metabolic Disorders and Osteoporosis in Women Aged Above 35 Years. Abstract presented at 17th National Indian Menopause Society. Faridabad: Souvenir; 2012. p. 45.

  5. Hauser GA, Huber IC, Keller PJ, Lauritzen C, Schneider HP. Evaluation of climacteric symptoms (Menopause Rating Scale. Zentralbl Gynakol 1994;116:16-23.

  6. Schneider HP, Heinemann LA, Rosemeier HP, Potthoff P, Behre HM. The Menopause Rating Scale (MRS): Reliability of scores of menopausal complaints. Climacteric 2000;3:59-64.

  7. Rosen R, Brown C, Heiman J, Leiblum S, Meston C, Shabsigh R, et al. The female sexual function index (FSFI): A multidimensional self-report instrument for the assessment of female sexual function. J Sex Marital Ther 2000;26:191-208.

  8. Bastien CH, Vallières A, Morin CM. Validation of the insomnia severity index as an outcome measure for insomnia research. Sleep Med 2001;2:297-307.

  9. Kroenke K, Spitzer RL, Williams JB, Löwe B. An ultra-brief screening scale for anxiety and depression: The PHQ-4. Psychosomatics 2009;50:613-21.

  10. Roalf DR, Moore TM, Wolk DA, Arnold SE, Mechanic-Hamilton D, Rick J, et al. Defining and validating a short form Montreal cognitive assessment (s-MoCA) for use in neurodegenerative disease. J Neurol Neurosurg Psychiatry 2016;87:1303-10.

  11. Nimala V. Counselling 12th Women: Is It Worth the Time? Abstract presented at National Indian Menopause Society Meeting. Rajkot: Souvenir; 2007. p. 34.

  12. Shitole AD. Counselling: A Basic Management of Perimenopause and Menopause Period. Abstract presented at 17th National Indian Menopause Society Meeting. Faridabad: Souvenir; 2012. p. 35.

  13. Kakkar V, Arshdeep K, Darshanjot K. Combined effect of drug therapy and counselling in the relief of menopause symptoms. Abstract Presented at 11th National Indian Menopause Society Meeting. Chandigarh: Souvenir; 2003. p. 209.

  14. Calman KC, Royston GH. Risk language and dialects. BMJ 1997;315:939-42.

  15. Jamison SW, Brereton JM, Translators. The Rig Veda: The Earliest Religious Poetry of India. New York: Oxford University Press; 2014. Available from: https://wiswo.org. [Last accessed on 2025 Sep 19].

  16. ICMR-NIN Expert Committee, Dietary Guidelines for Indians; 2024. Available from: https://www.nin.res.in. [Last accessed on 2025 Sep 19].

  17. World Health Organization. Guideline: Sugar Intake for Adults and Children. Geneva: WHO; 2015. Available from: https://www.who.int/publications/i/item/9789241549028. [Last accessed on 2025 Sep 19].

  18. Shapiro CL, Van Poznak C, Lacchetti C, Kirshner J, Eastell R, Gagel R, et al. Management of osteoporosis in survivors of adult cancers with nonmetastatic disease: ASCO clinical practice guideline. J Clin Oncol 2019;37:2916-46.

  19. Loroña NC, Othus M, Malone KE, Linden HM, Tang MC, Li CI. Alcohol, smoking, and risks of breast cancer recurrence and mortality among women with luminal, triple-negative, and HER2-overexpressing breast cancer. Cancer Epidemiol Biomarkers Prev 2024;33:288-97.

  20. Vegunta S, Lester SP, Pruthi S. Effects of major lifestyle factors on breast cancer risk: Impact of weight, nutrition, physical activity, alcohol and tobacco. Breast Cancer Manag 2020;9: BMT33.

  21. Sarkar M, Brady CW, Fleckenstein J, Forde KA, Khungar V, Molleston JP, et al. Reproductive health and liver disease: Practice guidance by the American Association for the study of liver diseases. Hepatology 2021;73:318-65.

  22. Bull FC, Al-Ansari SS, Biddle S, Borodulin K, Buman MP, Cardon G, et al. World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br J Sports Med 2020;54:1451-62.

  23. Birge SJ, Dalsky G. The role of exercise in preventing osteoporosis. Public Health Rep 1989;104 :54-8.

  24. Siebers M, Biedermann SV, Bindila L, Lutz B, Fuss J. Exercise-induced euphoria and anxiolysis do not depend on endogenous opioids in humans. Neuropharmacology 2021;191:108560.

  25. Xu H, Liu J, Li P, Liang Y. Effects of mind-body exercise on perimenopausal and postmenopausal women: A systematic review and meta-analysis. Menopause 2024;31:457-67.

  26. Yazdani Aliabadi M, Javadnoori M, Saki Malehi A, Aslani K. A study of mindfulness-based stress-reduction training effects on menopause-specific quality of life in postmenopausal women: A randomized controlled trial. Complement Ther Clin Pract 2021;44:101398.

  27. Chen TL, Chang SC, Huang CY, Wang HH. Effectiveness of mindfulness-based interventions on quality of life and menopausal symptoms in menopausal women: A meta-analysis. J Psychosom Res 2021;147:110515.

  28. Cramer H, Lauche R, Langhorst J, Dobos G. Effectiveness of yoga for menopausal symptoms: A systematic review and meta-analysis of randomized controlled trials. Evid Based Complement Alternat Med 2012;2012:863905.

  29. Chattha R, Raghuram N, Venkatram P, Hongasandra NR. Treating the climacteric symptoms in Indian women with an integrated approach to yoga therapy: A randomized control study. Menopause 2008;15:862-70.

  30. Chattha R, Nagarathna R, Padmalatha V, Nagendra HR. Effect of yoga on cognitive functions in climacteric syndrome: A randomised control study. BJOG 2008;115:991-1000.

  31. Sijna VP, Shobhana MC. Effect of clinical yoga package on quality of life of perimenopausal women (Kerala RCT). Int J Res Ayurveda Pharm 2021;12:25-8.

  32. Nayak G, Kamath A, Kumar PN, Rao A. Effect of yoga therapy on physical and psychological quality of life of perimenopausal women in selected coastal areas of Karnataka, India. J Midlife Health 2014;5:180-5.

  33. Ponde KV, Kanitkar SR. Effect of yoga therapy versus aerobic exercise on climacteric symptoms, perceived stress and quality of life in perimenopausal women. Int J Clin Exp Physiol 2020;7:126-31.

  34. Majumdar V, Manjunath NK, Snigdha A, Chakraborty P, Majumdar R. Study protocol on effectiveness of yoga practice on composite biomarker age predictors (yBioAge) in an elderly Indian cohort- two-armed open label randomized controlled trial. BMC Geriatr 2023;23:864.

  35. Kline CE, Irish LA, Buysse DJ, Kravitz HM, Okun ML, Owens JF, et al. Sleep hygiene behaviors among midlife women with insomnia or sleep-disordered breathing: The SWAN sleep study. J Womens Health (Larchmt) 2014;23:894-903.

  36. Irish LA, Kline CE, Gunn HE, Buysse DJ, Hall MH. The role of sleep hygiene in promoting public health: A review of empirical evidence. Sleep Med Rev 2015;22:23-36.

  37. Yazdkhasti M, Keshavarz M, Khoei EM, Hosseini A, Esmaeilzadeh S, Pebdani MA, et al. The effect of support group method on quality of life in post-menopausal women. Iran J Public Health 2012;41:78-84.

  38. Namazi M, Sadeghi R, Behboodi Moghadam Z. Social determinants of health in menopause: An integrative review. Int J Womens Health 2019;11:637-47.

  39. Woods NF, Mitchell ES. Social, psychological, and environmental determinants of menopause experience. Obstet Gynecol Clin North Am 2022;49:225-41.

  40. Teras LR, Patel AV, Wang M, Yaun SS, Anderson K, Brathwaite R, et al. Sustained weight loss and risk of breast cancer in women 50 years and older: A pooled analysis of prospective data. J Natl Cancer Inst 2020;112:929-37.

  41. Houghton SC, Eliassen H, Tamimi RM, Willett WC, Rosner BA, Hankinson SE. Central adiposity and subsequent risk of breast cancer by menopause status. J Natl Cancer Inst 2021;113:900-8.

  42. Lofterød T, Frydenberg H, Flote V, Eggen AE, McTiernan A, Mortensen ES, et al. Exploring the effects of lifestyle on breast cancer risk, age at diagnosis, and survival: The EBBA-life study. Breast Cancer Res Treat 2020;182:215-27.

  43. Mathur G, Vora A. Indian Consensus Guideline on Adult Immunization. Available from: https://www.emvac.in. [Last accessed on 2025 Oct 10].

  44. Meeta, Raut AA, Agashe SV, Wajahat A, Sarada CV, Vaidya AD, et al. A clinical study of a standardized extract of leaves of Dalbergia sissoo (Roxb ex DC) in postmenopausal osteoporosis. J Midlife Health 2019;10:37-42.

  45. Laxmi S. Clinical Effects of Soya on Menopausal Symptoms. Abstract Presented at 12th National Indian Menopause Society Meeting. Rajkot: Souvenir; 2007.

  46. Franco OH, Chowdhury R, Troup J, Voortman T, Kunutsor S, Kavousi M, et al. Use of plant-based therapies and menopausal symptoms: A systematic review and meta-analysis. JAMA 2016;315:2554-63.

  47. Leach MJ, Moore V. Black cohosh (Cimicifuga spp.) for menopausal symptoms. Cochrane Database Syst Rev Sep 12;2012: CD007244.

  48. Gudise VS, Dasari MP, Kuricheti SS. Efficacy and safety of shatavari root extract for the management of menopausal symptoms: A double-blind, multicenter, randomized controlled trial. Cureus 2024;16:e57879.

  49. Wal P, Singh I, Singh D, Singh MR. Treatment of menopausal symptoms with herbal medicines: A review. Curr Women Health Rev 2025;21:115-29.

  50. Hiremath K, Budihal D, Aravinth TU. Early prediction of estrogen levels for post-hysterectomy menopausal syndrome using machine learning models with an Ayurveda approach – An observational study. J Ayurveda Holist Med 2025;13:1919.

  51. Kim JH, Yu HJ. The effectiveness of cognitive behavioral therapy on depression and sleep problems for climacteric women: A systematic review and meta-analysis. J Clin Med 2024;13:412.

  52. Hardy C, Griffiths A, Norton S, Hunter MS. Self-help cognitive behavior therapy for working women with problematic hot flushes and night sweats (MENOS@Work): A multicenter randomized controlled trial. Menopause 2018;25:508-19.

  53. Ayers B, Smith M, Hellier J, Mann E, Hunter MS. Effectiveness of group and self-help cognitive behavior therapy in reducing problematic menopausal hot flushes and night sweats (MENOS 2): A randomized controlled trial. Menopause 2012;19:749-59.

  54. Spector A, Li Z, He L, Badawy Y, Desai R. The effectiveness of psychosocial interventions on non-physiological symptoms of menopause: A systematic review and meta-analysis. J Affect Disord 2024;352:460-72.

  55. Ayers B, Hunter MS. Health outcomes of psychosocial interventions for menopausal symptoms: Systematic review. Climacteric 2013;16:25-36.

  56. Hunter MS. Cognitive behavioral therapy for menopausal symptoms. Climacteric 2021;24:51-6.

  57. Green SM, Donegan E, McCabe RE, Fedorkow DM, Streiner DL, Frey BN. Objective and subjective vasomotor symptom outcomes in the CBT-Meno randomized controlled trial. Climacteric 2020;23:482-8.

  58. Elkins G, Arring N, Morgan G, Lorenz T, Muniz V, Lafferty C, et al. Self-administered hypnosis versus sham hypnosis for hot flashes: A randomized clinical trial. JAMA Netw Open 2025;8:e2542537.

  59. Elkins G, Marcus J, Stearns V, Perfect M, Rajab MH, Ruud C, et al. Randomized trial of a hypnosis intervention for treatment of hot flashes among breast cancer survivors. J Clin Oncol 2008;26:5022-6.

  60. Muñiz V, Padilla VJ, Alldredge CT, Elkins G. Clinical hypnosis and cognitive behavioral therapy for hot flashes: A scoping review. Womens Health Rep (New Rochelle) 2025;6:1-20.

  61. Huang AJ, Faubion S, Grady D. Nonhormonal treatment of menopausal vasomotor symptoms. JAMA Intern Med 2025;185:874-5.

  62. Rada G, Capurro D, Pantoja T, Corbalán J, Moreno G, Letelier LM, et al. Non-hormonal interventions for hot flushes in women with a history of breast cancer. Cochrane Database Syst Rev 2010;CD004923.

  63. McCormick CA, Brennan A, Hickey M. Managing vasomotor symptoms effectively without hormones. Climacteric 2020;23:532-8.

  64. Morga A, Ajmera M, Gao E, Patterson-Lomba O, Zhao A, Mancuso S, et al. Systematic review and network meta-analysis comparing the efficacy of fezolinetant with hormone and nonhormone therapies for treatment of vasomotor symptoms due to menopause. Menopause 2024;31:68-76.

  65. Lederman S, Ottery FD, Cano A, Santoro N, Shapiro M, Stute P, et al. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): A phase 3 randomised controlled study. Lancet 2023;401:1091-102.

  66. Pinkerton JV, Simon JA, Joffe H, Maki PM, Nappi RE, Panay N, et al. Elinzanetant for the treatment of vasomotor symptoms associated with menopause: OASIS 1 and 2 randomized clinical trials. JAMA 2024;332:1343-54.

  67. Joffe H, Guthrie KA, LaCroix AZ, Reed SD, Ensrud KE, Manson JE, et al. Low-dose estradiol and the serotonin-norepinephrine reuptake inhibitor venlafaxine for vasomotor symptoms: A randomized clinical trial. JAMA Intern Med 2014;174:1058-66.

  68. Haque R, Shi J, Schottinger JE, Ahmed SA, Cheetham TC, Chung J, et al. Tamoxifen and antidepressant drug interaction in a cohort of 16,887 breast cancer survivors. J Natl Cancer Inst 2016;108:djv337.

  69. Khaled E, Godara J, Alrais G. Menopausal hormone therapy and symptom management: A comprehensive review. Int J Sci Res 2024;13:doi: 10.36106/ijsr/3220352.

  70. Mukherjee A, Davis SR. Update on menopause hormone therapy; current indications and unanswered questions. Clin Endocrinol (Oxf) 2025;doi: 10.1111/cen.15211.9.

  71. Genazzani AR, Gambacciani M, Simoncini T. Hormone therapy in the postmenopausal years: Evidence, guidelines and safety. Hum Reprod Update 2022;28:923-42.

  72. Davis SR, Braunstein GD. Efficacy and safety of testosterone in the management of hypoactive sexual desire disorder in postmenopausal women. J Sex Med 2012;9:1134-48.

  73. Komm BS, Mirkin S. Selective estrogen receptor modulators: Mechanism of action and clinical applications. Menopause 2014;21:242-53.

  74. Garefalakis M, Hickey M. Role of androgens, progestins and tibolone in the menopause. J Br Menopause Soc 2008;14:134-9.

  75. Rahn DD, Carberry C, Sanses TV, Mamik MM, Ward RM, Meriwether KV, et al. Vaginal estrogen for genitourinary syndrome of menopause: A systematic review. Obstet Gynecol 2014;124:1147-56.

  76. Gartlehner G, Patel SV, Reddy S, Rains C, Schwimmer M, Kahwati L. Hormone therapy for the primary prevention of chronic conditions in postmenopausal persons: Updated evidence report and systematic review for the US preventive services task force. JAMA 2022;328:1747-65.

  77. “The 2022 Hormone Therapy Position Statement of The North American Menopause Society” Advisory Panel. The 2022 hormone therapy position statement of The North American Menopause Society. Menopause 2022;29:767-94.

  78. Cho MK. Use of combined oral contraceptives in perimenopausal women. Chonnam Med J 2018;54:153-8.

  79. Kim SM, Shin W, Kim HJ, Lee JS, Min YK, Yoon BK. Effects of combination oral contraceptives on bone mineral density and metabolism in perimenopausal Korean women. J Menopausal Med 2022;28:25-32.

  80. Grandi G, Di Vinci P, Sgandurra A, Feliciello L, Monari F, Facchinetti F. Contraception during perimenopause: Practical guidance. Int J Womens Health 2022;14:913-29.

  81. Collaborative Group on Epidemiological Studies on Endometrial Cancer. Endometrial cancer and oral contraceptives: An individual participant meta-analysis of 27 276 women with endometrial cancer from 36 epidemiological studies. Lancet Oncol 2015;16:1061-70.

  82. Abusal F, Aladwan M, Alomari Y, Obeidat S, Abuwardeh S, AlDahdouh H, et al. Oral contraceptives and colorectal cancer risk – A meta-analysis and systematic review. Ann Med Surg (Lond) 2022;83:104254.

  83. Edelman A, Gallo MF, Nichols MD, Jensen JT, Schulz KF, Grimes DA. Continuous versus cyclic use of combined oral contraceptives for contraception: Systematic Cochrane review of randomized controlled trials. Hum Reprod 2006;21:573-8.

  84. FSRH. Contraception for Women Aged Over 40 Years. Faculty of Sexual & Reproductive Healthcare (UK) Guideline; 2017. https://www.cosrh.org/Common/Uploaded%20files/documents/fsrh-guideline-contraception-for-women-aged-over-40-years.pdf. [Last accessed on 2025 Dec 28].

  85. Kaunitz AM, Portman DJ, Hait H, Reape KZ. Adding low-dose estrogen to the hormone-free interval: Impact on bleeding patterns in users of a 91-day extended regimen oral contraceptive. Contraception 2009;79:350-5.

  86. Hickey M, Ameratunga D, Marino JL. Unscheduled bleeding in continuous combined hormone therapy users. Maturitas 2011;70:400-3.

  87. Mendoza N, Ramírez I, de la Viuda E, Coronado P, Baquedano L, Llaneza P, et al. Eligibility criteria for menopausal hormone therapy (MHT): A position statement from a consortium of scientific societies for the use of MHT in women with medical conditions. MHT Eligibility Criteria Group. Maturitas 2022;166:65-85.

  88. Chaikittisilpa S, Orprayoon N, Vallibhakara O, Vallibhakara SA, Tanmahasamut P, Somboonporn W, et al. Summary of the 2023 Thai Menopause Society clinical practice guideline on menopausal hormone therapy. J Menopausal Med 2024;30:24-36.

  89. Academic Committee of the Korean Society of Menopause, Lee SR, Cho MK, Cho YJ, Chun S, Hong SH, et al. The 2020 menopausal hormone therapy guidelines. J Menopausal Med 2020;26:69-98.

  90. Gosset A, Pouillès JM, Trémollieres F. Menopausal hormone therapy for the management of osteoporosis. Best Pract Res Clin Endocrinol Metab 2021;35:101551.

  91. Maclennan AH, Broadbent JL, Lester S, Moore V. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database Syst Rev 2004;;2004: CD002978.

  92. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002;288:321-33.

  93. Lobo RA, Kaunitz AM. Menopausal hormone therapy and health outcomes during the menopause transition. Lancet Diabetes Endocrinol 2022;10:332-42.

  94. Nachtigall LE. Comparative study: Effectiveness of vaginal and oral estrogen therapy in postmenopausal women with atrophic vaginitis. Am J Obstet Gynecol 1992;166:945-52.

  95. Zhu L, Jiang X, Sun Y, Shu W. Effect of hormone therapy on the risk of bone fractures: A systematic review and meta-analysis of randomized controlled trials. Menopause 2016;23:461-70.

  96. Cauley JA, Robbins J, Chen Z, Cummings SR, Jackson RD, LaCroix AZ, et al. Effects of estrogen plus progestin on risk of fracture and bone mineral density: The Women’s health initiative randomized trial. JAMA 2003;290:1729-38.

  97. Price SA, Maki PM, El Khoudary SR, Brand A, Islam RM, Domchek SM, et al. What happens after menopause (WHAM)? A progress report of a prospective controlled study of women after pre-menopausal risk-reducing bilateral salpingo-oophorectomy. BJOG 2025;doi: 10.1111/1471-0528.18304.

  98. Panay N, Anderson RA, Nappi RE, Vincent AJ, Vujovic S, Webber L, et al. Premature ovarian insufficiency: An international menopause society white paper. Climacteric 2020;23:426-46.

  99. Popat VB, Calis KA, Vanderhoof VH. Bone mineral density in women with primary ovarian insufficiency receiving physiologic transdermal estradiol and testosterone replacement: A randomized controlled trial. J Clin Endocrinol Metab 2014;99:3418-26.

  100. Rocca WA, Gazzuola-Rocca L, Smith CY, Grossardt BR, Faubion SS, Shuster LT, et al. Accelerated accumulation of multimorbidity after bilateral oophorectomy: A population-based cohort study. Mayo Clin Proc 2016;91:1577-89.

  101. Crofton PM, Evans N, Bath LE, Warner P, Whitehead TJ, Critchley HO, et al. Physiological versus standard sex steroid replacement in young women with premature ovarian failure: Effects on bone mass acquisition and turnover. Clin Endocrinol (Oxf) 2010;73:707-14.

  102. Kapoor E. Premature ovarian insufficiency. Curr Opin Endocr Metab Res 2023;28:100435.

  103. Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The Women’s health initiative randomized controlled trial. JAMA 2004;291:1701-12.

  104. Rossouw JE, Aragaki AK, Manson JE, Szmuilowicz ED, Harrington LB, Johnson KC, et al. Menopausal hormone therapy and cardiovascular diseases in women with vasomotor symptoms: A secondary analysis of the Women’s health initiative randomized clinical trials. JAMA Intern Med 2025;185:1330-9.

  105. Lobo RA. Hormone-replacement therapy: Current thinking. Nat Rev Endocrinol 2017;13:220-31.

  106. Harman SM, Brinton EA, Cedars M, Lobo R, Manson JE, Merriam GR, et al. KEEPS: The Kronos Early Estrogen prevention study. Climacteric 2005;8:3-12.

  107. Hodis HN, Mack WJ, Henderson VW, Shoupe D, Budoff MJ, Hwang-Levine J, et al. Vascular effects of early versus late postmenopausal treatment with estradiol. N Engl J Med 2016;374:1221-31.

  108. Manson JE, Chlebowski RT, Stefanick ML, Aragaki AK, Rossouw JE, Prentice RL, et al. Menopausal hormone therapy and health outcomes during WHI follow-up. JAMA 2013; 310:1353-68.

  109. Gu Y, Han F, Xue M, Wang M, Huang Y. The benefits and risks of menopause hormone therapy for the cardiovascular system in postmenopausal women: A systematic review and meta-analysis. BMC Womens Health 2024;24:60.

  110. Andy C, Nerattini M, Jett S, Carlton C, Zarate C, Boneu C, et al. Systematic review and meta-analysis of the effects of menopause hormone therapy on cognition. Front Endocrinol (Lausanne) 2024;15:1350318.

  111. Nelson HD. Commonly used types of postmenopausal estrogen for treatment of hot flashes: scientific review. JAMA 2004;291:1610-20.

  112. Lim SY, Khan B, Syed S. Conjugated equine estradiol and 17β-estradiol both reduce hot flashes to a similar extent in menopausal women. Evid Based Healthc Public Health. 2004;8:310-1.

  113. Dias AR Jr., Melo RN, Gebara OC, D’Amico EA, Nussbacher A, Halbe HW, et al. Effects of conjugated equine estrogens or raloxifene on lipid profile, coagulation and fibrinolysis factors in postmenopausal women. Climacteric 2005;8:63-70.

  114. Walsh BW, Schiff I, Rosner B, Greenberg L, Ravnikar V, Sacks FM. Effects of postmenopausal estrogen replacement on the concentrations and metabolism of plasma lipoproteins. N Engl J Med 1991;325:1196-204.

  115. Karim R, Stanczyk FZ, Hodis HN, Cushman M, Lobo RA, Hwang J, et al. Associations between markers of inflammation and physiological and pharmacological levels of circulating sex hormones in postmenopausal women. Menopause 2010;17:785-90.

  116. Reuben DB, Palla SL, Hu P, Reboussin BA, Crandall C, Herrington DM, et al. Progestins affect mechanism of estrogen-induced C-reactive protein stimulation. Am J Med 2006;119:167.e1-8.

  117. Stevenson JC, Hodis HN, Pickar JH. HRT and cardiovascular risk: Importance of formulation and route. Climacteric 2021;24:19-28.

  118. Graham S, Archer DF, Simon JA, Ohleth KM, Bernick B. Review of menopausal hormone therapy with estradiol and progesterone versus other estrogens and progestins. Gynecol Endocrinol 2022;38:891-910.

  119. Lazzeroni M, Macis D, Decensi A, Gandini S, Sandri MT, Serrano D, et al. The effect of transdermal estradiol or oral conjugated oestrogen and fenretinide versus placebo on haemostasis and cardiovascular risk biomarkers in a randomized breast cancer chemoprevention trial. Ecancermedicalscience 2008;2:67.

  120. O’Connell MB. Pharmacokinetic and pharmacologic variation between different estrogen products. J Clin Pharmacol 1995;35:18S-24S.

  121. Endrikat J, Graeser T, Mellinger U, Ertan K, Holz C. A multicenter, prospective, randomized, double-blind, placebo-controlled study to investigate the efficacy of a continuous-combined hormone therapy preparation containing 1mg estradiol valerate/2mg dienogest on hot flushes in postmenopausal women. Maturitas 2007;58:201-7.

  122. Vatrasresth J, Suwan A, Panyakhamlerd K. Effects of early estradiol valerate administration on bone turnover markers in surgically induced menopausal women. BMC Womens Health 2021;21:363.

  123. Gräser T, Koytchev R, Müller A, Oettel M. Comparison of the efficacy and endometrial safety of two estradiol valerate/dienogest combinations and Kliogest for continuous combined hormone replacement therapy in postmenopausal women. Climacteric 2000;3:109-18.

  124. Stute P, Neulen J, Wildt L. The impact of micronized progesterone on the endometrium: A systematic review. Climacteric 2016;19:316-28.

  125. Bergeron C, Ferenczy A. Endometrial safety of continuous combined hormone replacement therapy with 17β-oestradiol (1 or 2 mg) and dydrogesterone. Maturitas 2001;38:45-53.

  126. Stanczyk FZ, Hapgood JP, Winer S, Mishell DR Jr. Progestogens used in postmenopausal hormone therapy: Differences in their pharmacological properties, intracellular actions, and clinical effects. Endocr Rev 2013;34:171-208.

  127. Xue W, Deng Y, Wang YF, Sun AJ. Effect of half-dose and standard-dose conjugated equine estrogens combined with natural progesterone or dydrogesterone on components of metabolic syndrome in healthy postmenopausal women: A randomized controlled trial. Chin Med J (Engl) 2016;129:2773-9.

  128. Shifren JL, Rifai N, Desindes S, McIlwain M, Doros G, Mazer NA. A comparison of the short-term effects of oral conjugated equine estrogens versus transdermal estradiol on C-reactive protein, other serum markers of inflammation, and other hepatic proteins in naturally menopausal women. J Clin Endocrinol Metab 2008;93:1702-10.

  129. Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: Nested case-control studies using the QResearch and CPRD databases. BMJ 2019;364:k4810.

  130. Panay N, Nappi RE, Stute P, Palacios S, Paszkowski T, Kagan R, et al. Oral estradiol/micronized progesterone may be associated with lower risk of venous thromboembolism compared with conjugated equine estrogens/medroxyprogesterone acetate in real-world practice. Maturitas 2023;172:23-31.

  131. Asi N, Mohammed K, Haydour Q, Gionfriddo MR, Vargas OL, Prokop LJ, et al. Progesterone versus synthetic progestins and the risk of breast cancer: A systematic review and meta-analysis. Syst Rev 2016;5:121.

  132. Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: Results from the E3N cohort study. Breast Cancer Res Treat 2008;107:103-11.

  133. Espié M, Daures JP, Chevallier T, Mares P, Micheletti MC, De Reilhac P. Breast cancer incidence and hormone replacement therapy: Results from the mission study, prospective phase. Gynecol Endocrinol 2007;23:391-7.

  134. Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of breast cancer: Nested case-control studies using the QResearch and CPRD databases. BMJ 2020;371:m3873.

  135. Støer NC, Vangen S, Singh D, Fortner RT, Hofvind S, Ursin G, et al. Menopausal hormone therapy and breast cancer risk: A population-based cohort study of 1.3 million women in Norway. Br J Cancer 2024;131:126-37.

  136. National Institute for Health and Care Excellence (NICE). Menopause: Identification and Management. NICE Guideline NG23; 2024. Evidence Review D: Breast Cancer. Available from: https://www.nice.org.uk. [Last accessed on 2025 Oct 28].

  137. Collaborative Group on Hormonal Factors in Breast Cancer. Type and timing of menopausal hormone therapy and breast cancer risk: Individual participant meta-analysis of the worldwide epidemiological evidence. Lancet 2019;394:1159-68.

  138. Suhonen SP, Allonen HO, Lähteenmäki P. Sustained-release estradiol implants and a levonorgestrel-releasing intrauterine device in hormone replacement therapy. Am J Obstet Gynecol 1995;172:562-7.

  139. Anderson GL, Chlebowski RT, Aragaki AK, Kuller LH, Manson JE, Gass M, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: Extended follow-up of the women’s health initiative randomised placebo-controlled trial. Lancet Oncol 2012;13:476-86.

  140. Hitchcok CL, Prior JC. Oral micronized progesterone for vasomotor symptoms a placebo-controlled randomized trial in healthy postmenopausal women. Menopause 2001;8:10-6.

  141. Leeangkoonsathian E, Pantasri T, Chaovisitseree S, Morakot N. The effect of different progestogens on sleep in postmenopausal women: A randomized trial. Gynecol Endocrinol 2017;33:933-6.

  142. Gompel A. Progesterone, progestins and the endometrium in perimenopause and in menopausal hormone therapy. Climacteric 2018;21:321-5.

  143. Sjögren LL, Mørch LS, Løkkegaard E. Hormone replacement therapy and the risk of endometrial cancer: A systematic review. Maturitas 2016;91:25-35.

  144. Stevenson JC, Panay N, Pexman-Fieth C. Oral estradiol and dydrogesterone combination therapy in postmenopausal women: Review of efficacy and safety. Maturitas 2013;76:10-21.

  145. Wildemeersch D. Potential health benefits of continuous LNG-IUS combined with parenteral ERT for seamless menopausal transition and beyond – A commentary based on clinical experience. Gynecol Endocrinol 2013;29:569-73.

  146. Vercellini P, Viganò P, Somigliana E. The role of the levonorgestrel-releasing intrauterine device in the management of symptomatic endometriosis. Curr Opin Obstet Gynecol 2005;17:359-65.

  147. Istre O, Holm-Nielsen P, Bourne T, Forman A. Hormone replacement therapy after transcervical resection of the endometrium. Obstet Gynecol 1996;88:767-70.

  148. Giannella L, Marconi C, Di Giuseppe J, Delli Carpini G, Fichera M, Grelloni C, et al. Malignant transformation of postmenopausal endometriosis: A systematic review of the literature. Cancers (Basel) 2021;13:4026.

  149. Gemmell LC, Webster KE, Kirtley S, Vincent K, Zondervan KT, Becker CM. The management of menopause in women with a history of endometriosis: A systematic review. Hum Reprod Update 2017;23:481-500.

  150. Fedele L, Bianchi S, Raffaelli R, Zanconato G. Comparison of transdermal estradiol and tibolone for the treatment of oophorectomized women with deep residual endometriosis. Maturitas 1999;32:189-93.

  151. Kenemans P, Speroff L, International Tibolone Consensus Group. Tibolone: Clinical recommendations and practical guidelines. A report of the international tibolone consensus group. Maturitas 2005;51:21-8.

  152. Stevenson JC, Rozenberg S, Maffei S, Egarter C, Stute P, Römer T. Progestogens as a component of menopausal hormone therapy: The right molecule makes the difference. Drugs Context 2020;9:2020-10-1. [doi: 10.7573/dic.2020-10-1].

  153. Tempfer CB, Hilal Z, Kern P, Juhasz-Boess I, Rezniczek GA. Menopausal hormone therapy and risk of endometrial cancer: A systematic review. Cancers (Basel) 2020;12:2195.

  154. Crandall CJ, Hovey KM, Andrews C, Cauley JA, Stefanick M, Shufelt C, et al. Comparison of clinical outcomes among users of oral and transdermal estrogen therapy in the Women’s health initiative observational study. Menopause 2017;24:1145-53.

  155. Shifren JL, Desindes S, McIlwain M, Doros G, Mazer NA. A randomized, open-label, crossover study comparing the effects of oral versus transdermal estrogen therapy on serum androgens, thyroid hormones, and adrenal hormones in naturally menopausal women. Menopause 2007;14:985-94.

  156. Clarkson TB, Karas RH. Do the cardiovascular disease risks and benefits of oral versus transdermal estrogen therapy differ between perimenopausal and postmenopausal women? Menopause 2007;14:963-7.

  157. Stevenson JC. Type and route of estrogen administration. Climacteric 2009;12 Suppl 1:86-90.

  158. Canonico M, Oger E, Plu-Bureau G, Conard J, Meyer G, Lévesque H. et al. Estrogen and risk of venous thromboembolism: The ESTHER study. Circulation 2007;115:840-5.

  159. Khandelwal S, Meeta M, Tanvir T. Menopause hormone therapy, migraines, and thromboembolism. Best Pract Res Clin Obstet Gynaecol 2022;81:31-44.

  160. Taylor HS, Tal A, Pal L, Li F, Black DM, Brinton EA, et al. Effects of oral versus transdermal estrogen therapy on sexual function in early postmenopause: Ancillary study of the kronos early estrogen prevention study (KEEPS). JAMA Intern Med 2017;177:1471-9.

  161. Lara LA, Cartagena-Ramos D, Figueiredo JB, Rosa-E-Silva AC, Ferriani RA, Martins WP, et al. Hormone therapy for sexual function in perimenopausal and postmenopausal women. Cochrane Database Syst Rev 2023;8: CD009672.

  162. Ho JY, Chen MJ, Sheu WH, Yi YC, Tsai AC, Guu HF, et al. Differential effects of oral conjugated equine estrogen and transdermal estrogen on atherosclerotic vascular disease risk markers and endothelial function in healthy postmenopausal women. Hum Reprod 2006;21:2715-20.

  163. Sumino H, Ichikawa S, Kasama S, Takahashi T, Kumakura H, Takayama Y, et al. Different effects of oral conjugated estrogen and transdermal estradiol on arterial stiffness and vascular inflammatory markers in postmenopausal women. Atherosclerosis 2006;189:436-42.

  164. Mauvais-Jarvis F, Manson JE, Stevenson JC, Fonseca VA. Menopausal hormone therapy and type 2 diabetes prevention: Evidence, mechanisms, and clinical implications. Endocr Rev 2017;38:173-88.

  165. Shufelt CL, Merz CN, Prentice RL, Pettinger MB, Rossouw JE, Aroda VR, et al. Hormone therapy dose, formulation, route of delivery, and risk of cardiovascular events in women: Findings from the Women’s health initiative observational study. Menopause 2014;21:260-6.

  166. Canonico M, Carcaillon L, Plu-Bureau G, Oger E, Singh-Manoux A, Tubert-Bitter P, et al. Postmenopausal hormone therapy and risk of stroke: Impact of the route of estrogen administration and type of progestogen. Stroke 2016;47:1734-41.

  167. Casanova G, Bossardi Ramos R, Ziegelmann P, Spritzer PM. Effects of low-dose versus placebo or conventional-dose postmenopausal hormone therapy on variables related to cardiovascular risk: A systematic review and meta-analyses of randomized clinical trials. J Clin Endocrinol Metab 2015;100:1028-37.

  168. Santoro N, Allshouse A, Neal-Perry G, Pal L, Lobo RA, Naftolin F, et al. Longitudinal changes in menopausal symptoms comparing women randomized to low-dose oral conjugated estrogens or transdermal estradiol plus micronized progesterone versus placebo: The Kronos early estrogen prevention study. Menopause 2017;24:238-46.

  169. Gillet JY, Andre G, Faguer B, Erny R, Buvat-Herbaut M, Domin MA, et al. Induction of amenorrhea during hormone replacement therapy: Optimal micronized progesterone dose. A multicenter study. Maturitas 1994;19:103-15.

  170. Cristina Russu M. Endometrial Histology and Safety on Non-Oral Routes of Hormone Therapy for Perimenopausal/Early Menopausal Women: Transdermal Estrogens and Vaginal Micronized Progesterone. Hormone Therapy and Replacement in Cancer and Aging-related Diseases. IntechOpen; 2020. Available from: http://dx.doi.org/10.5772/intechopen.89046. [Last accessed on 2025 Dec 01].

  171. Raudaskoski T, Tapanainen J, Tomás E, Luotola H, Pekonen F, Ronni-Sivula H, et al. Intrauterine 10 microg and 20 microg levonorgestrel systems in postmenopausal women receiving oral oestrogen replacement therapy: Clinical, endometrial and metabolic response. BJOG 2002;109:136-44.

  172. Wildemeersch D, Janssens D, Weyers S. Continuous combined parenteral estrogen substitution and intrauterine progestogen delivery: The ideal HST combination? Maturitas 2005;51:207-14.

  173. Writing Group for the PEPI Trial. Effects of hormone therapy on vasomotor symptoms in recently menopausal women. JAMA 1995;273:199-208.

  174. Early Breast Cancer Trialists Collaborative Group (EBCTCG). Type and timing of menopausal hormone therapy and breast cancer risk: Individual participant meta-analysis of the worldwide epidemiological evidence. Lancet 2019;394:1159-68.

  175. Muka T, Oliver-Williams C, Kunutsor S, Laven JS, Fauser BC, Chowdhury R, et al. Association of age at onset of menopause and time since onset of menopause with cardiovascular outcomes, intermediate vascular traits, and all-cause mortality: A systematic review and meta-analysis. JAMA Cardiol 2016;1:767-76.

  176. Anagnostis P, Christou K, Artzouchaltzi AM, Gkekas NK, Kosmidou N, Siolos P, et al. Early menopause and premature ovarian insufficiency are associated with increased risk of type 2 diabetes: A systematic review and meta-analysis. Eur J Endocrinol 2019;180:41-50.

  177. Anagnostis P, Siolos P, Gkekas NK, Kosmidou N, Artzouchaltzi AM, Christou K, et al. Association between age at menopause and fracture risk: A systematic review and meta-analysis. Endocrine 2019;63:213-24.

  178. Hong JS, Yi SW, Kang HC, Jee SH, Kang HG, Bayasgalan G, et al. Age at menopause and cause-specific mortality in South Korean women: Kangwha cohort study. Maturitas 2007;56:411-9.

  179. Ossewaarde ME, Bots ML, Verbeek AL, Peeters PH, van der Graaf Y, Grobbee DE, et al. Age at menopause, cause-specific mortality and total life expectancy. Epidemiology 2005;16:556-62.

  180. Jones AR, Anderson RA, Wallace WH. Bone health in women with premature ovarian insufficiency: New insights from longitudinal studies. Hum Reprod 2024;39:1013-23.

  181. Cartwright B, Robinson J, Seed PT, Fogelman I, Rymer J. Hormone replacement therapy versus the combined oral contraceptive pill in premature ovarian failure: A randomized controlled trial of the effects on bone mineral density. J Clin Endocrinol Metab 2016;101:3497-505.

  182. Xu Z, Chung HF, Dobson AJ, Wilson LF, Hickey M, Mishra GD. Menopause, hysterectomy, menopausal hormone therapy and cause-specific mortality: Cohort study of UK Biobank participants. Hum Reprod 2022;37:2175-85.

  183. Webber L, Anderson RA, Davies M, Janse F, Vermeulen N. HRT for women with premature ovarian insufficiency: A comprehensive review. Hum Reprod Open 2017;2017:hox007.

  184. Pines A. No increased death toll for long-term menopausal hormone therapy. Climacteric 2017;20:531-2.

  185. Chlebowski RT, Anderson GL, Aragaki AK, Manson JE, Stefanick ML, Pan K, et al. Association of menopausal hormone therapy with breast cancer incidence and mortality during long-term follow-up of the women’s health initiative randomized clinical trials. JAMA 2020;324:369-80.

  186. Gurney EP, Nachtigall MJ, Nachtigall LE, Naftolin F. The women’s health initiative trial and related studies: 10 years later: A clinician’s view. J Steroid Biochem Mol Biol 2014;142:4-11.

  187. Manson JE, Aragaki AK, Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, et al. Menopausal hormone therapy and long-term all-cause and cause-specific mortality: The Women’s health initiative randomized trials. JAMA 2017;318:927-38.

  188. 1.Hrkać TG, Dinka PB. Menopausal Hormone Therapy and Breast Cancer: Evidence from Randomized Clinical Trials. University Hospital Center of Zagreb; 2024. Available from: https://urn.nsk.hr/urn:nbn:hr:105:565009. [Last accessed on 2025 Sep 19].

  189. Curran M, Vazquez A, Wolde T. Best practices for hormonal contraception and menopause therapy in women at increased breast cancer risk. J Menopausal Health 2024;30:291-304.

  190. Zeleke BM, Davis SR, Fradkin P, Bell RJ. Vasomotor symptoms and urogenital atrophy in older women: A systematic review. Climacteric 2015;18:112-20.

  191. Palacios S, Mejía A. Progestogen safety and tolerance in hormonal replacement therapy. Expert Opin Drug Saf 2016;15:1515-25.

  192. Manley K, Hillard T, Clark J, Kumar G, Morrison J, Hamoda H, et al. Management of unscheduled bleeding on HRT: A joint guideline on behalf of the British Menopause Society, Royal College Obstetricians and Gynaecologists, British Gynaecological Cancer Society, British Society for Gynaecological Endoscopy, Faculty of Sexual and Reproductive Health, Royal College of General practitioners and getting it right first time. Post Reprod Health 2024;30:95-116.

  193. Lindh-Astrand L, Bixo M, Hirschberg AL, Sundström-Poromaa I, Hammar M. A randomized controlled study of taper-down or abrupt discontinuation of hormone therapy in women treated for vasomotor symptoms. Menopause 2010;17:72-9.

  194. Crawford SL. What should women expect after stopping hormone therapy? Menopause 2015;22:367-8.

  195. Haimov-Kochman R, Barak-Glantz E, Arbel R, Leefsma M, Brzezinski A, Milwidsky A, et al. Gradual discontinuation of hormone therapy does not prevent the reappearance of climacteric symptoms: A randomized prospective study. Menopause 2006;13:370-6.

  196. Brunner RL, Aragaki A, Barnabei V, Cochrane BB, Gass M, Hendrix S, et al. Menopausal symptom experience before and after stopping estrogen therapy in the women’s health initiative randomized, placebo-controlled trial. Menopause 2010;17:946-54.

  197. El Khoudary SR, Aggarwal B, Beckie TM, Hodis HN, Johnson AE, Langer RD, et al. Menopause transition and cardiovascular disease risk: Implications for timing of early prevention: A scientific statement from the American Heart Association. Circulation 2020;142:e506-32.

  198. Renoux C, Dell’aniello S, Garbe E, Suissa S. Transdermal and oral hormone replacement therapy and the risk of stroke: A nested case-control study. BMJ 2010;340:c2519.

  199. Gartoulla P, Worsley R, Bell RJ, Davis SR. Moderate to severe vasomotor and sexual symptoms remain problematic for women aged 60 to 65 years. Menopause 2015;22:694-701.

  200. Vikström J, Spetz Holm AC, Sydsjö G, Marcusson J, Wressle E, Hammar M. Hot flushes still occur in a population of 85-year-old Swedish women. Climacteric 2013;16:453-9.

  201. Freeman EW, Sammel MD, Sanders RJ. Risk of long-term hot flashes after natural menopause: Evidence from the Penn ovarian aging study cohort. Menopause 2014;21:924-32.

  202. Baik SH, Baye F, McDonald CJ. Use of menopausal hormone therapy beyond age 65 years and its effects on women’s health outcomes by types, routes, and doses. Menopause 2024;31:363-71.

  203. Manson JE, Crandall CJ, Rossouw JE, Chlebowski RT, Anderson GL, Stefanick ML, et al. The Women’s health initiative randomized trials and clinical practice: A review. JAMA 2024;331:1748-60.

  204. Heller DA, Gold CH, Ahern FM, Pringle KE, Brown TV, Glessner MR. Changes in elderly women’s health-related quality of life following discontinuation of hormone replacement therapy. BMC Womens Health 2005;5:7.

  205. Rossouw JE, Prentice RL, Manson JE, Wu L, Barad D, Barnabei VM, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 2007;297:1465-77.

  206. Wassertheil-Smoller S, Hendrix SL, Limacher M, Heiss G, Kooperberg C, Baird A, et al. Effect of estrogen plus progestin on stroke in postmenopausal women: The Women’s health initiative: A randomized trial. JAMA 2003;289:2673-84.

  207. Cushman M, Kuller LH, Prentice R, Rodabough RJ, Psaty BM, Stafford RS, et al. Estrogen plus progestin and risk of venous thrombosis. JAMA 2004;292:1573-80.

  208. Kaunitz AM. Extended duration use of menopausal hormone therapy. Menopause 2014;21:679-81.

  209. Sánchez-Guerrero J, González-Pérez M, Durand-Carbajal M, Lara-Reyes P, Jiménez-Santana L, Romero-Díaz J, et al. Menopause hormonal therapy in women with systemic lupus erythematosus. Arthritis Rheum 2007;56:3070-9.

  210. Anderson RA, Kelsey TW, Perdrix A, Olympios N, Duhamel O, Lambertini M, et al. Diagnostic and predictive accuracy of anti-Mullerian hormone for ovarian function after chemotherapy in premenopausal women with early breast cancer. Breast Cancer Res Treat 2022;192:273-82.

  211. Sahni SK, Fraker JL, Cornell LF, Klassen CL. Hormone therapy in women with benign breast disease – What little is known and suggestions for clinical implementation. Maturitas 2024;185:107992.

  212. Stachs A, Stubert J, Reimer T, Hartmann S. Benign breast disease in women. Dtsch Arztebl Int 2019;116:565-74.

  213. Fornili M, Perduca V, Fournier A, Jérolon A, Boutron-Ruault MC, Maskarinec G, et al. Association between menopausal hormone therapy, mammographic density and breast cancer risk: Results from the E3N cohort study. Breast Cancer Res 2021;23:47.

  214. Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Gass M, Lane D, et al. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: The women’s health initiative randomized trial. JAMA 2003;289:3243-53.

  215. Siitonen H, Joensuu J, Savolainen-Peltonen H, Gissler M, Ylikorkala O, Mikkola TS. Update of the impact of menopausal hormone therapy on breast cancer risk. Eur J Cancer 2025;220:115340.

  216. Rozenberg S, Di Pietrantonio V, Vandromme J, Gilles C. Menopausal hormone therapy and breast cancer risk. Best Pract Res Clin Endocrinol Metab 2021;35:101577.

  217. Holmberg L, Iversen OE, Rudenstam CM, Hammar M, Kumpulainen E, Jaskiewicz J, et al. Increased risk of recurrence after hormone replacement therapy in breast cancer survivors. J Natl Cancer Inst 2008;100:475-82.

  218. Kenemans P, Bundred NJ, Foidart JM, Kubista E, von Schoultz B, Sismondi P, et al. Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: A double-blind, randomised, non-inferiority trial. Lancet Oncol 2009;10:135-46.

  219. Busund M, Ursin G, Lund E, Chen SL, Rylander C. Menopausal hormone therapy and incidence, mortality, and survival of breast cancer subtypes: A prospective cohort study. Breast Cancer Res 2024;26:151.

  220. Glynne S, Simon J, Branson A, Payne S, Newson L, Manyonda I, et al. Menopausal hormone therapy for breast cancer patients: What is the current evidence? Menopause 2025;doi: 10.1155/2017/5064725].

  221. Culhane R, Zaborowski AM, Hill AD. Menopausal hormone therapy in breast cancer survivors. Cancers (Basel) 2024;16:3267.

  222. Kotsopoulos J, Gronwald J, Karlan BY, Huzarski T, Tung N, Moller P, et al. Hormone replacement therapy after oophorectomy and breast cancer risk among BRCA1 mutation carriers. JAMA Oncol 2018;4:1059-65.

  223. Marchetti C, De Felice F, Boccia S, Sassu C, Di Donato V, Perniola G, et al. Hormone replacement therapy after prophylactic risk-reducing salpingo-oophorectomy and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A meta-analysis. Crit Rev Oncol Hematol 2018;132:111-5.

  224. Rocca WA, Mielke MM, Gazzuola Rocca L, Stewart EA. Premature or early bilateral oophorectomy: A 2021 update. Climacteric 2021;24:466-73.

  225. Hickey M, Basu P, Sassarini J, Stegmann ME, Weiderpass E, Nakawala Chilowa K, et al. Managing menopause after cancer. Lancet 2024;403:984-96.

  226. Brennan A, Hickey M. The use of menopausal hormone therapy after cancer. Best Pract Res Clin Obstet Gynaecol 2022;81:22-30.

  227. Goldštajn MŠ, Mikuš M, Ferrari FA, Bosco M, Uccella S, Noventa M, et al. Effects of transdermal versus oral hormone replacement therapy in postmenopause: A systematic review. Arch Gynecol Obstet 2023;307:1727-45.

  228. Deli T, Orosz M, Jakab A. Hormone replacement therapy in cancer survivors – Review of the literature. Pathol Oncol Res 2020;26:63-78.

  229. Adamyan M, Moiseenko T, Menshenina A. EP1091-Possible influencing the quality of life of patients with endometrial cancer and cervical cancer after radical treatment. Int J Gynecol Cancer 2019;29 Suppl 4: A609.

  230. Fiol G, Lete I, Nieto L, Santaballa A, Pla MJ, Baquedano L, et al. Associations between menopausal hormone therapy and colorectal, lung, or melanoma cancer recurrence and mortality: A narrative review. J Clin Med 2023;12:5263.

  231. Zheng G, Baandrup L, Wang J, Hertzum-Larsen R, Hannibal CG, Faber MT, et al. Ovarian cancer risk factors in relation to family history. J Natl Cancer Inst 2024;116:1767-74.

  232. Chiavarini M, Naldini G, Giampieri E. Exogenous hormone factors and the risk of malignant melanoma in women: A systematic review and meta-analysis. Cancers (Basel) 2020;12:1878.

  233. Hodis HN, Mack WJ. The timing hypothesis and hormone replacement therapy: A paradigm shift in the primary prevention of coronary heart disease in women. Part 2: comparative risks. J Am Geriatr Soc 2013;61:1011-8.

  234. Neuhouser ML, Aragaki AK, Prentice RL, Manson JE, Chlebowski R, Carty CL, et al. Overweight, obesity, and postmenopausal invasive breast cancer risk: A secondary analysis of the women’s health initiative randomized clinical trials. JAMA Oncol 2015;1:611-21.

  235. Guo W, Key TJ, Reeves GK. Adiposity and breast cancer risk in postmenopausal women: Results from the UK biobank prospective cohort. Int J Cancer 2018;143:1037-46.

  236. Pastori D, Cormaci VM, Marucci S, Franchino G, Del Sole F, Capozza A, et al. A comprehensive review of risk factors for venous thromboembolism: From epidemiology to pathophysiology. Int J Mol Sci 2023;24:3169.

  237. Horn JW, Feng T, Mørkedal B, Aune D, Strand LB, Horn J, et al. Body mass index measured repeatedly over 42 years as a risk factor for ischemic stroke: The hunt study. Nutrients 2023;15:1232.

  238. Kurth T, Gaziano JM, Rexrode KM, Kase CS, Cook NR, Manson JE, et al. Prospective study of body mass index and risk of stroke in apparently healthy women. Circulation 2005;111:1992-8.

  239. Boardman HM, Hartley L, Eisinga A, Main C, Roqué i Figuls M, Bonfill Cosp X, et al. Hormone therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database Syst Rev 2015;2015: CD002229.

  240. Cheng YJ, Liu ZH, Yao FJ, Zeng WT, Zheng DD, Dong YG, et al. Current and former smoking and risk for venous thromboembolism: A systematic review and meta-analysis. PLoS Med 2013;10:e1001515.

  241. Dragoman MV, Tepper NK, Fu R, Curtis KM, Chou R, Gaffield ME. A systematic review and meta-analysis of venous thrombosis risk among users of combined oral contraception. Int J Gynaecol Obstet 2018;141:287-94.

  242. Maughan BC, Marin M, Han J, Gibbins KJ, Brixey AG, Caughey AB, et al. Venous thromboembolism during pregnancy and the postpartum period: Risk factors, diagnostic testing, and treatment. Obstet Gynecol Surv 2022;77:433-44.

  243. Rovinski D, Ramos RB, Fighera TM, Casanova GK, Spritzer PM. Risk of venous thromboembolism events in postmenopausal women using oral versus non-oral hormone therapy: A systematic review and meta-analysis. Thromb Res 2018;168:83-95.

  244. Kaemmle LM, Stadler A, Janka H, von Wolff M, Stute P. The impact of micronized progesterone on cardiovascular events – A systematic review. Climacteric 2022;25:327-36.

  245. Henderson VW, Lobo RA. Hormone therapy and the risk of stroke: Perspectives 10 years after the women’s health Initiative trials. Climacteric 2012;15:229-34.

  246. Grodstein F, Manson JE, Stampfer MJ, Rexrode K. Postmenopausal hormone therapy and stroke: Role of time since menopause and age at initiation of hormone therapy. Arch Intern Med 2008;168:861-6.

  247. Schierbeck LL, Rejnmark L, Tofteng CL, Stilgren L, Eiken P, Mosekilde L, et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: Randomised trial. BMJ 2012;345:e6409.

  248. McCart Reed AE, Kalinowski L, Simpson PT, Lakhani SR. Invasive lobular carcinoma of the breast: The increasing importance of this special subtype. Breast Cancer Res 2021;23:6.

  249. Msaouel P, Lee J, Thall PF. Interpreting randomized controlled trials. Cancers (Basel) 2023;15:4674.

  250. Jeffery ND, Budke CM, Chanoit GP. What is the value of statistical testing of observational data? Vet Surg 2022;51:1043-51.

  251. Chlebowski RT, Aragaki AK, Pan K, Haque R, Rohan TE, Song M, et al. Menopausal hormone therapy and ovarian and endometrial cancers: Long-Term follow-up of the women’s health initiative randomized trials. J Clin Oncol 2024;42:3537-49.

  252. Furness S, Roberts H, Marjoribanks J, Lethaby A. Hormone therapy in postmenopausal women and risk of endometrial hyperplasia. Cochrane Database Syst Rev 2012;2012: CD000402.

  253. Chlebowski RT, Anderson GL, Sarto GE, Haque R, Runowicz CD, Aragaki AK, et al. Continuous combined estrogen plus progestin and endometrial cancer: The women’s health initiative randomized trial. J Natl Cancer Inst 2016;108:djv350.

  254. Kamani M, Akgor U, Gültekin M. Review of the literature on combined oral contraceptives and cancer. Ecancermedicalscience 2022;16:1416.

  255. Cirillo DJ, Wallace RB, Rodabough RJ, Greenland P, LaCroix AZ, Limacher MC, et al. Effect of estrogen therapy on gallbladder disease. JAMA 2005;293:330-9.

  256. Zhu L, Jiang X, Sun Y, Shu XO, Li H, Yang G, et al. Hormone replacement therapy and risk of cholecystectomy: A prospective study in Chinese women. Maturitas 2014;79:401-6.

  257. Janssen I, Powell LH, Crawford S, Lasley B, Sutton-Tyrrell K. Menopause and the metabolic syndrome: The study of Women’s Health Across the Nation. Arch Intern Med 2008;168:1568-75.

  258. Stevenson JC, Panay N, Pexman-Fieth C. Hormone replacement therapy in the management of the menopause: An overview of risks and benefits. Br J Obstet Gynaecol 2013;120:13-22.

  259. Roman-Blas JA, Castañeda S, Largo R, Herrero-Beaumont G. Osteoarthritis associated with estrogen deficiency. Arthritis Res Ther 2009;11:241.

  260. Labadie JD, Harrison TA, Banbury B, Amtay EL, Bernd S, Brenner H, et al. Postmenopausal hormone therapy and colorectal cancer risk by molecularly defined subtypes and tumor location. JNCI Cancer Spectr 2020;4:pkaa042.

  261. Lobo RA, Pickar JH, Stevenson JC, Mack WJ, Hodis HN. Back to the future: Hormone replacement therapy as part of a prevention strategy for women at the onset of menopause. Atherosclerosis 2016;254:282-90.

  262. Gava G, Orsili I, Alvisi S, Mancini I, Seracchioli R, Meriggiola MC. Cognition, mood and sleep in menopausal transition: The role of menopause hormone therapy. Medicina (Kaunas) 2019;55:668.

  263. Salpeter SR, Walsh JM, Greyber E, Ormiston TM, Salpeter EE. Mortality associated with hormone replacement therapy in younger and older women: A meta-analysis. J Gen Intern Med 2004;19:791-804.

  264. Cummings SR, Ettinger B, Delmas PD, Kenemans P, Stathopoulos V, Verweij P, et al. The effects of tibolone in older postmenopausal women. N Engl J Med 2008;359:697-708.

  265. Jacobsen DE, Melis RJ, Verhaar HJ, van Eijk JT. Raloxifene and tibolone in elderly women: A randomized, double-blind, double-dummy, placebo-controlled trial. Menopause 2012;19:699-707.

  266. Martino S, Cauley JA, Barrett-Connor E, Powles TJ, Mershon J, Disch D, et al. Continuing outcomes relevant to Evista: Breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst 2004;96:1751-61.

  267. Lello S, Capozzi A, Scambia G. The tissue-selective estrogen complex (Bazedoxifene/Conjugated Estrogens) for the treatment of menopause. Int J Endocrinol 2017;2017:5064725.

  268. Sharifi M, Lewiecki EM. Conjugated estrogens combined with bazedoxifene: The first approved tissue selective estrogen complex therapy. Expert Rev Endocrinol Metab 2014;9:123-32.

  269. Duffecy J, Rehman A, Gorman S, Huang YL, Klumpp H. Evaluating a mobile digital therapeutic for vasomotor and behavioral health symptoms among women in midlife: Randomized controlled trial. JMIR Mhealth Uhealth 2025;13:e58204.

  270. Paripoorani D, Gasteiger N, Hawley-Hague H, Dowding D. A systematic review of menopause apps with an emphasis on osteoporosis. BMC Womens Health 2023;23:518.

  271. Whiteley J, DiBonaventura MD, Wagner JS, Alvir J, Shah S. The impact of menopausal symptoms on quality of life, productivity, and economic outcomes. J Womens Health (Larchmt) 2013;22:983-90.

  272. Perianayagam, A. Gender disparities in health and wellbeing of older population in India. NPJ Womens Health 2024;2:44.

  273. Swargiary M, Lhungdim H, Bharadwaz MP. Multi-layered catastrophic health spending of inpatient women by broad group of diseases in India. J Popul Soc Stud 2022;30:183-206.

  274. Aggarwal N, Meeta M, Chawla N. Menopause management: A manual for primary care practitioners and nurse practitioners. J Midlife Health 2022;13 Suppl 1: S2-51.

  275. Ministry of Health & Family Welfare, Government of India. NP-NCD Operational Guidelines. New Delhi: Ministry of Health & Family Welfare, Government of India; 2017. Available from: https://www.mohfw.gov.in/sites/default/files/NPNCD%20Operational%20guidelines_0.pdf. [Last accessed on 2025 Oct 19].

  276. Win ZM, Mao W, Traill T, Kyaw ZL, Paing PY, Ogbuoji O, et al. Cost-effectiveness and budget impact analysis of screening and preventive interventions for cardiovascular disease in Myanmar: An economic modelling study. Lancet Reg Health Southeast Asia 2024;26:100.

  277. Kolu P, Raitanen J, Nygård CH, Tomás E, Luoto R. Cost-effectiveness of physical activity among women with menopause symptoms: Findings from a randomised controlled trial. PLoS One 2015;10:e0135099.

  278. Bellanger M, Barry K, Rana J, Regnaux JP. Cost-effectiveness of lifestyle-related interventions for the primary prevention of breast cancer: A rapid review. Front Med (Lausanne) 2019;6:325.

  279. Nayak S, Roberts MS, Greenspan SL. Cost-effectiveness of different screening strategies for osteoporosis in postmenopausal women. Ann Intern Med 2011;155:751-61.

  280. Meeta M, Tandon V. Evidence-based clinical practice guidelines on menopause and postmenopausal osteoporosis (2019-2020): A step toward implementation of menopausal medicine. J Midlife Health 2020;11:51-2.

Articles from Journal of Mid-Life Health are provided here courtesy of Wolters Kluwer -- Medknow Publications

RESOURCES