Optimizing Healthspan in Women: A New Paradigm for Successful Aging through the Menopausal Transition

Abstract

Menopause is a normative midlife transition characterized by profound endocrine remodeling and a high burden of symptoms and functional change. Accumulating epidemiologic and translational evidence links menopausal transition with shifts in cardiometabolic risk, musculoskeletal health, sleep, mood, and perceived cognitive function. However, most data support association rather than definitive causal acceleration of aging independent of chronological time. This narrative review proposes a menopause-centered healthspan framework that integrates biological, neurocognitive, and psychosocial domains and translates evidence into pragmatic clinical pathway tools. To inform topic selection and prioritize higher-level evidence, including guidelines, randomized trials, meta-analyses, and large cohort studies, a structured evidence scan utilizing PubMed and targeted citation tracking was performed. The evidence scan identified 256 citations. After duplicate removal, titles/abstracts of 162 unique records were reviewed, of which 102 citations informed the final narrative synthesis. The results emphasize that menopausal hormone therapy remains the most effective treatment for vasomotor symptoms and an evidence-based option for reducing fracture risk in appropriate candidates. However, it is not indicated for the primary prevention of cardiovascular disease or dementia. Absolute risks and benefits vary by age, time since menopause, and formulation/route. The neurocognitive section distinguishes common, often transient midlife cognitive complaints from long-term neurodegenerative outcomes, highlighting that menopause is not established as an independent dementia risk factor in the general population. Overall, the framework aims to support individualized, equity-informed care during menopausal transition.

Graphical Abstract

INTRODUCTION

Women, on average, live longer than men, yet paradoxically spend a greater proportion of their later years contending with chronic diseases and functional impairments [1]. This gender disparity underscores a critical distinction in modern geroscience – the gap between lifespan, commonly stated as the total length of life, and healthspan, defined as the years of healthy, independent living [2]. Consequently, the paradigm of “successful aging” is shifting from merely extending life to optimizing healthspan, with the menopausal transition emerging as a pivotal focal point [3]. In this review, we operationalize “successful aging” as the preservation of functional ability and quality of life with minimized morbidity across cardiometabolic, musculoskeletal, cognitive, emotional, and social domains. Rather than an inevitable turning point, the menopausal transition is best viewed as a physiologic inflection point during which rapid hormonal change can coincide with multidomain health changes; emerging biomarker studies, including epigenetic age measures, suggest associations with menopausal status and timing, but causality and independence from chronological aging remain uncertain [4,5]. Therefore, this phase represents a clinically actionable therapeutic window, offering opportunities for individualized interventions that may shape a woman’s long-term health trajectory and address the unmet need for forward-looking, healthspan-oriented care (Fig. 1) [6,7].

Fig. 1. The female aging trajectory: a timeline of risks and opportunities centered on the menopausal transition. The schematic depicts menopause as a critical window for intervention, during which symptom burden and risk inflections coincide with high-yield prevention opportunities. FSH: follicle stimulating hormone, VMS: vasomotor symptoms, MHT: menopausal hormone therapy.

Optimizing healthspan during this window requires a biopsychosocial approach that acknowledges the complex interplay between biological, neurocognitive, and psychosocial determinants [6,8]. These domains are inextricably linked; for instance, vasomotor symptoms (VMS) can disrupt sleep, cascading into mood disturbances and cognitive impairment, whereas robust social support can buffer the physiological impact of midlife stress [8,9]. Effective management, therefore, must move beyond isolated symptom treatment to address these intertwined factors simultaneously [8].

In this review, we synthesize evidence from the past two decades to propose a unified menopause-centered healthspan framework. We examine how menopausal endocrine remodeling is associated with changes in cardiometabolic risk, musculoskeletal integrity, neurocognitive function, and psychosocial well-being, while explicitly distinguishing associative evidence from causal inference. We then translate these insights into practical clinical pathway tools to support patient-centered counseling and shared decision-making, aligning with international consensus on midlife health [1,10,11]. Lastly, this work complements and extends prior menopause-healthspan syntheses by integrating Korean and broader Asian population data and by providing structured, domain-spanning clinical pathway figures and tables designed for real-world implementation.

METHODS

Approach

To reinforce this conceptual narrative review with an explicit and transparent evidence base, we conducted a structured evidence scan focusing on the menopausal transition and healthspan-related outcomes. We searched PubMed for English-language articles published from January 2000 to August 2025. The core search strategy combined menopausal transition terms (“menopausal transition,” perimenopause, postmenopause, climacteric) with healthspan/aging terms (healthspan, successful aging, frailty, functional decline) and was extended with domain-specific terms (cardiometabolic, musculoskeletal, urogenital, cognition, mood, sleep, quality of life, and social determinants). A representative PubMed query was: ([menopaus* OR perimenopaus* OR postmenopaus* OR climacteric OR “menopausal transition”] AND [healthspan OR “successful aging” OR “healthy aging” OR frailty OR “functional decline” OR cognition OR dementia OR depression OR anxiety OR sleep OR insomnia OR “cardiometabolic” OR cardiovascular OR metabolic OR osteoporosis OR fracture OR sarcopenia OR “quality of life” OR psychosocial OR “social determinants”]).

Because the primary aim was a clinically oriented, cross-domain synthesis rather than a comprehensive systematic review, we did not register a protocol or conduct formal study-level risk-of-bias assessment or evidence grading. Instead, to avoid overstating certainty, we prioritized higher-level evidence such as clinical guidelines/position statements, meta-analyses, randomized trials, and large prospective cohorts when drawing clinical inferences, and we explicitly moderated causal language when the evidence was associative. The database search was complemented by targeted literature discovery, including forward and backward citation tracking of key guidelines and landmark cohort studies. The evidence-scan workflow is summarized in Figure 2, stating 256 citations were initially retrieved; after removal of 94 duplicates, 162 unique citations underwent title/abstract review; 60 items were set aside after title/abstract review primarily due to lack of menopausal context, non-relevant outcomes, non-human designs, or non-peer-reviewed formats; and 102 citations informed the final qualitative synthesis (Supplementary Table 1, available online). The included evidence comprised clinical guidelines/position statements, systematic reviews/meta-analyses, randomized trials, prospective cohort studies, population-based registry/claims analyses, cross-sectional studies, and selected translational/mechanistic reports. For the main text and clinical tools (Figs. 3, 4, 5, Tables 1 and 2), citations were selected based on methodological rigor, clinical relevance, and applicability to Asian populations, including Korean cohorts, to enhance regional validity.

Fig. 2. Structured evidence scan workflow for literature identification, deduplication, title/abstract review, and qualitative synthesis. The flow diagram summarizes key steps of the evidence scan and is provided to enhance transparency regarding how representative evidence was identified for this conceptual narrative review. The complete list of studies included in the qualitative synthesis is provided in Supplementary Table 1 (available online).

Fig. 3. “Menopause healthspan check” pathway. The pathway starts with a rapid multidomain screen (VMS and sleep, mood/distress, cardiometabolic risk, bone risk, and contextual constraints), followed by burden–risk stratification. Layered interventions combine a base lifestyle package for all, symptom-targeted therapy (including menopausal hormone therapy when appropriate and evidence-based non-hormonal options), and psychosocial/cognitive supports. Short-term (8–12 weeks) and longer-term (6–12 months) monitoring anchors care to patient-centered outcomes and objective risk markers. VMS: vasomotor symptoms, MHT: menopausal hormone therapy, GSM: genitourinary syndrome of menopause, BP: blood pressure, BMD: bone mineral density, CBT-I: cognitive behavioral therapy for insomnia, QoL: quality of life.

Fig. 4. Cross-domain feedback loops connecting menopausal symptoms to healthspan outcomes. Vasomotor symptoms can contribute to sleep disruption and mood distress, which may reduce activity and adherence to healthy behaviors. These shifts can worsen cardiometabolic risk and reinforce overall symptom burden during the menopausal transition. Converging pathways may impair function and QoL, underscoring the rationale for integrated care targeting symptoms, sleep, mood, and lifestyle simultaneously. VMS: vasomotor symptoms, QoL: quality of life.

Fig. 5. Conceptual map of intervention domains and expected targets across healthspan outcomes. Checkmarks indicate plausible direct or indirect targets for integrated care (symptom relief, sleep, mood, cardiometabolic risk, bone health, and function/QoL) and are not intended to grade strength of evidence. The schematic illustrates how lifestyle optimization, sleep-focused care, psychosocial support, menopausal hormone therapy when appropriate, and evidence-based non-hormonal options for VMS can be combined as complementary layers. Evidence strength varies substantially by intervention–domain pairing; check marks indicate plausible targets rather than equivalence of evidence, and key areas with the strongest support are highlighted in the text. For example: MHT for VMS and bone protection; CBT-I for insomnia; and established cardiometabolic prevention strategies. VMS: vasomotor symptoms, QoL: quality of life, CBT-I: cognitive behavioral therapy for insomnia, SSRI/SNRI: selective serotonin reuptake inhibitor/serotonin–norepinephrine reuptake inhibitor.

Table 1. Key systemic and functional consequences of estrogen decline relevant to women’s healthspan.

System/domain	Key change linked to estrogen decline	Primary healthspan-relevant clinical implication
Cardiometabolic/vascular	Atherogenic lipid profile (↑LDL, ↓HDL), visceral adiposity, endothelial dysfunction, insulin resistance	Higher risk of CVD, hypertension, and metabolic syndrome; risk inflection around the menopausal transition
Body composition/muscle	↓ Lean mass and strength, sarcopenic obesity, pro-inflammatory milieu (e.g., ↑CRP)	Frailty trajectory, reduced physical function, falls risk; worsened insulin resistance and cardiometabolic resilience
Skeletal	Uncoupled remodeling and accelerated bone resorption	Osteoporosis and fragility fractures, loss of independence and disability risk
Urogenital/sexual	Atrophy of estrogen-dependent tissues, changes in vaginal/urinary epithelium	GSM (dryness, dyspareunia, urinary symptoms), recurrent UTIs; impaired sexual function and QoL
Thermoregulatory/sleep	Hypothalamic thermoregulatory dysregulation, VMS and night sweats	Sleep fragmentation, fatigue, impaired daytime functioning; symptom-driven care opportunity window
Neurocognitive	Altered neurotransmitter function, reduced neuroprotection in hippocampal/prefrontal circuits	Subjective cognitive complaints (“brain fog”) and subtle domain-specific deficits, potential modifier of later-life cognitive vulnerability
Mood/behavioral health	Increased susceptibility to depressive symptoms and anxiety, stress reactivity, bidirectional links with sleep/VMS	Distress and reduced adherence to health behaviors, compounded impact on function and QoL
Ocular health (emerging)	Associations between menopausal estrogen milieu/MHT exposure and ocular outcomes (e.g., glaucoma, age-related eye disease)	Under-recognized domain that may warrant risk-aware screening and interdisciplinary care in susceptible women

LDL: low density lipoprotein cholesterol, HDL: high density lipoprotein cholesterol, CVD: cardiovascular diseases, CRP: C-reactive protein, GSM: genitourinary syndrome of menopause, QoL: quality of life, VMS: vasomotor symptoms.

Table 2. Integrated framework of actionable strategies to optimize healthspan across the menopausal transition.

Domain/care layer	Target goal	Primary intervention	Adjunctive/delivery support	Key rationale/anchor evidence
Lifestyle foundation	Improve cardiometabolic fitness, preserve muscle and bone, support sleep and mood, enhance QoL	Physical activity + resistance training, diet quality (e.g., Mediterranean-style), weight trajectory management, smoking/alcohol risk reduction	Goal-setting and self-monitoring, group- or digital-delivered programs, address caregiving/work constraints	Wide-ranging benefits with low risk, improves function and supports multiple symptom and risk pathways
Symptom-targeted menopause care	Relieve VMS and related sleep disruption, address GSM, improve daily function	MHT when appropriate after individualized risk–benefit assessment, GSM-directed therapy (local options)	Evidence-based non-hormonal VMS options (e.g., SSRI/SNRI, gabapentin) when MHT is not suitable	MHT remains the most effective therapy for VMS, symptom relief can enable adherence to lifestyle change and reduce downstream burden
Sleep-focused care	Restore sleep quality, reduce fatigue, mitigate cognitive and mood consequences	Sleep hygiene + CBT-I principles, evaluate/treat comorbid sleep disorders when suspected	Combine with symptom control (VMS) and stress-management skills, scalable CBT-I formats	Sleep disturbance mediates cognitive complaints and functional decline, actionable target during the menopausal window
Neurocognitive resilience	Enhance cognitive reserve, improve perceived cognition (“brain fog”), maintain executive function	Cognitively stimulating activities, regular aerobic + resistance exercise	Screen and treat contributors (sleep, mood, and medications), patient education to reduce unnecessary dementia-focused anxiety	Midlife cognitive complaints often reflect modifiable sleep/mood pathways, proactive screening yields high clinical yield
Psychosocial context and implementation	Reduce distress, strengthen resilience, improve QoL and sustained engagement with care	Build social connection and purposeful activity, brief CBT/mindfulness-based strategies for coping	Tailor to SES, access, caregiving/work constraints; leverage group/digital delivery to reduce barriers	Psychosocial milieu shapes symptom perception and care access, scalable delivery supports equity and feasibility
Monitoring and follow-up	Anchor care to outcomes and risk markers, adjust intensity over time	8–12 weeks: symptom and behavioral outcomes (VMS, sleep, mood, adherence); 6–12 months: objective markers (BP, lipids, glucose, weight, BMD/fracture risk), function/QoL	Shared decision-making, coordinate with primary care and relevant specialties	Iterative follow-up sustains gains and links symptom management to long-term prevention goals

QoL: quality of life, VMS: vasomotor symptoms, GSM: genitourinary syndrome of menopause, MHT: menopausal hormone therapy, SSRI: selective serotonin reuptake inhibitor, SNRI: serotonin–norepinephrine reuptake inhibitor, CBT-I: cognitive-behavioral therapy for insomnia, SES: socioeconomic status, BP: blood pressure, BMD: bone mineral density.

Eligibility and evidence synthesis strategy

We restricted our literature search to English-language peer-reviewed articles published between 2000 and 2025, focusing on women aged 40 to 70 years. The primary scope was the menopausal transition – ranging from perimenopause to postmenopause – in relation to successful aging, healthspan, or domain-specific outcomes. We prioritized high-level evidence, including clinical guidelines, systematic reviews, large cohorts, and randomized trials, while excluding non-human studies, case reports, and research lacking a clear menopausal context. To ensure regional relevance and external validity, we intentionally incorporated Asian studies, specifically Korean guideline publications and population-based data.

For the narrative synthesis, we organized the selected evidence into three primary domains rather than mutually exclusive categories. First, we assessed biological and somatic health, covering cardiometabolic, musculoskeletal, and urogenital outcomes. Second, we examined neurocognitive and behavioral health, specifically focusing on cognition, mood, and sleep. Third, we analyzed psychosocial health, including quality of life and social determinants. Consequently, we provide a flow diagram of record identification and a complete list of included studies in Supplementary Table 1 (available online) to enhance evidence transparency. Our synthesis highlights evidence from major longitudinal cohorts, such as the Study of Women’s Health Across the Nation, Nurses’ Health Study, and UK Biobank, alongside emerging Asian administrative data, including studies based on the Korean National Health Insurance Service (NHIS), to facilitate clinical translation.

RESULTS

To provide a comprehensive overview of the findings, Table 1 summarizes the major physiologic changes associated with estrogen withdrawal and their primary clinical implications across organ systems. Table 2 presents an integrated, layered strategy framework for menopause-centered healthspan care. Furthermore, Figures 1 and 3, 4, 5 translate this evidence into a visual timeline of risks and opportunities, outlining a practical care pathway that illustrates cross-domain symptom-outcome loops and specific intervention targets.

The biological domain: mechanisms and systemic consequences

The interplay of cellular aging and estrogen decline

The menopausal transition is associated with shifts in cardiometabolic and inflammatory pathways that may contribute to later-life morbidity, although these relationships are intertwined with chronological aging and midlife health behaviors [2,12]. Epidemiologic studies suggest that earlier age at menopause is associated with increased risks of cardiovascular disease and mortality, but residual confounding and reverse causality cannot be fully excluded [2,3]. Biomarker-based studies, such as DNA methylation clocks, have reported associations between menopause-related exposures and measures of biological aging, yet mechanistic causality remains an active area of investigation [12,13,14].

Rapid endocrine change during the menopausal transition is associated with unfavorable changes in body fat distribution such as increased visceral adiposity, lipid profiles, insulin sensitivity, and vascular function, which collectively may raise cardiometabolic risk in susceptible individuals [15,16,17,18,19]. Symptom burden and sleep disruption may further amplify metabolic vulnerability, highlighting the need for integrated, individualized risk assessment and counseling rather than a one-size-fits-all narrative [19,20,21].

Emerging dimensions

Beyond the classical biological domains, aging women are particularly susceptible to a range of ophthalmological conditions that can significantly impair their vision and quality of life [22]. Cataracts, characterized by a clouding of the eye’s natural lens, are a leading cause of visual impairment in older adults, and women tend to develop them earlier than men, possibly due to hormonal factors; glaucoma, a group of eye diseases that damage the optic nerve, is another prevalent cause of vision loss, with certain types, such as primary open-angle glaucoma, being more common in women [22]. Dry eye syndrome, where the eyes do not produce enough tears or the tears evaporate too quickly, is also more prevalent in women, particularly after menopause, often exacerbated by hormonal changes and medications [23].

Additionally, dysregulation of hypothalamic thermoregulation manifests as VMS, and while often perceived as transient, severe VMS can significantly disrupt sleep and impair quality of life [24,25]. Because VMS-related insomnia acts as a “gateway symptom” amplifying mood and cognitive complaints, current protocols increasingly advocate for combined approaches – such as hormone therapy alongside cognitive-behavioral therapy (CBT) – to address perimenopausal insomnia effectively [26].

Neurocognitive and behavioral shifts: implications for the aging brain

The menopausal transition is commonly accompanied by subjective cognitive complaints which are commonly stated as “brain fog,” fluctuating attention, and reduced processing speed, which are frequently transient and strongly influenced by sleep quality, mood symptoms, and vasomotor symptom burden [9,27,28]. Neuroimaging and biomarker studies suggest that midlife endocrine change may be associated with functional and metabolic alterations in brain networks, but such findings do not establish inevitable neurodegenerative progression [27,29,30].

Estrogen is implicated in synaptic plasticity, cerebral glucose metabolism, and neurovascular coupling, providing biologic plausibility for short-term cognitive variability around menopause [27,29,31,32]. At the same time, long-term dementia risk is multifactorial and shaped by vascular risk, education, genetics such as apolipoprotein E status, and life-course exposures [33]. In the general population, menopause itself is not established as an independent dementia risk factor, and evidence linking menopausal timing or symptoms to later neurodegeneration remains heterogeneous [29,34].

Critically, it is essential to distinguish between transient midlife cognitive symptoms and late-life neurodegenerative diseases. Whereas menopausal cognitive complaints are common and often improve with stabilization of symptoms, the indication for menopausal hormone therapy (MHT) is symptom relief, especially VMS, and not dementia prevention. Existing randomized trial data do not support initiation of MHT in older postmenopausal women for the purpose of preventing cognitive decline or dementia, and late initiation may confer harm in certain contexts [35]. Accordingly, neurocognitive care in menopause should focus on modifiable contributors including sleep, mood, cardiometabolic risk, and symptom control, while maintaining conceptual humility regarding long-term neurodegenerative outcomes [33,34,36]. This balanced framing supports patient-centered counseling: validating cognitive concerns, addressing reversible drivers, and avoiding deterministic language that may unintentionally medicalize normal midlife variability [37,38,39,40,41].

The psychosocial milieu and quality of life

The biological and neurocognitive shifts inherent to the menopausal transition do not occur in a vacuum; rather, they are inextricably embedded within a complex psychosocial context [42]. While physiological parameters are critical, the impact of these changes on a woman’s overall quality of life is often determined by her psychosocial milieu. This period frequently converges with significant midlife stressors, creating a “cumulative burden” that challenges a woman’s adaptive capacity [6,43]. Common life events – such as the “empty nest” syndrome, retirement from long-term careers, or the assumption of demanding caregiving roles for aging parents – can amplify the perceived severity of menopausal symptoms [44]. Consequently, successful aging cannot be defined by physical health alone, requiring psychosocial well-being, which serves as the lens through which biological aging is experienced [45,46].

Psychological resilience

Central to navigating this landscape is psychological resilience – defined not merely as the absence of distress, but as the active ability to adapt and thrive in the face of adversity [47]. Resilience acts as a potent modulator of the menopausal experience; women who employ positive coping strategies and maintain an optimistic outlook are significantly better equipped to manage the multifaceted challenges of aging [43,48]. This internal capacity for adaptation is fundamental, serving as a buffer that mitigates the psychological impact of physiological symptoms and preserves a positive sense of self during this transitional phase [49].

Social determinants and support systems

Complementing internal resilience are external support systems. Robust social networks – comprising family, friends, and community connections – emerge as critical protective factors that reduce feelings of isolation and buffer the physiological effects of stress [6,44]. Beyond emotional support, continued social engagement through meaningful work, volunteering, or community activities fosters a profound sense of purpose and belonging, factors that are strongly correlated with higher life satisfaction and better health outcomes [44]. Furthermore, these dynamics are influenced by socioeconomic status (SES), including financial security and educational attainment; higher SES provides essential resources that empower women to maintain independent lifestyles, access quality healthcare, and proactively manage environmental stressors [6,44,47].

Beyond SES, structural inequities that shape menopausal healthspan include differential access to preventive care and symptom treatment, health literacy and language barriers, rural-urban care gaps, workplace and caregiving burdens, cultural stigma around menopause and mental health, exposure to discrimination, and the digital divide that affects access to telehealth and self-management tools [45,47]. These factors can modify both symptom recognition and downstream risk trajectories; therefore, an equity-informed menopause framework should explicitly incorporate context-specific barriers and facilitators when translating evidence into care pathways [44,45,47].

DISCUSSION

An integrated framework for optimizing healthspan: evidence-based strategies

Optimizing healthspan through the menopausal transition and beyond necessitates a fundamental paradigm shift: moving from reactive disease management to a proactive, integrated model of care, as suggested by Figure 6. [6,41]. A truly effective strategy requires addressing the multidimensional architecture of women’s health, simultaneously targeting biological, cognitive, and psychosocial domains [6,7]. To this end, Figure 3 describes an evidence-based framework of actionable strategies designed to empower women and guide clinicians, with specific cross-domain symptom-outcome loops and intervention targets, illustrated in Figures 4 and 5. Crucially, this framework acknowledges that healthspan is shaped by structural determinants – such as education, SES, caregiving burden, and workplace context. These factors modulate not only the subjective experience of symptoms but also access to evidence-based care, thereby contributing to inequities in aging outcomes [5,6]. Therefore, combining skills-based approaches, such as CBT for insomnia or VMS-related distress, with social connection and physical activity can yield multiplicative gains [41,44,45]. Delivering these through scalable group or digital formats offers a pragmatic pathway to reduce barriers to care and democratize access to successful aging strategies [45].

Fig. 6. Menopausal transition. The model illustrates that successful aging, defined by optimized healthspan and QoL, is determined by the interplay of four key domains: biological factors, cognitive and behavioral factors, psychosocial factors, and lifestyle and environmental factors. The menopausal transition is positioned as a central event that critically influences all domains, highlighting its pivotal role in women’s aging trajectories. QoL: quality of life.

Lifestyle modifications: the foundation of healthspan

Lifestyle interventions are not merely adjunctive measures; they constitute the cornerstone of any strategy to promote successful aging, offering wide-ranging physiological benefits with minimal risk [1,10,11]. Mainly, dietary strategies serve as primary modulators of biological aging; nutrient-dense patterns and adequate protein intake are essential for maintaining cardiometabolic health and potentially influencing aging trajectories at the molecular level [13,46,47]. Emerging research links specific nutrient exposures to epigenetic aging clocks, suggesting that diet may directly decelerate biological aging, although precise causal pathways remain an active area of investigation [13]. In the context of musculoskeletal integrity, adequate calcium and vitamin D intake remain foundational. Furthermore, combined supplementation strategies, such as vitamin D and K, are being explored as potential adjuncts to preserve bone density in postmenopausal populations [46].

Regular physical activity acts as the other potent facilitator, supporting cardiovascular health, preserving lean mass, and enhancing mood and sleep quality [14,15,25,45]. A synergistic combination of aerobic exercise and resistance training is strictly recommended to counter the dual threat of sarcopenia and sarcopenic obesity [14,25]. This is particularly relevant for Asian populations; population-based evidence from Korea indicates that premature natural menopause and metabolic risk factors, such as smoking, diabetes, are associated with more rapid declines in muscle mass and physical function [19,20]. This reinforces the critical value of initiating resistance training and cardiometabolic risk reduction early in the perimenopausal window.

Therapeutic precision: the role of menopausal hormone therapy

While lifestyle modification forms the foundation of healthspan, MHT remains the most effective therapy for VMS and an evidence-based option for preventing bone loss and reducing fracture risk in appropriately selected candidates [1,10,11]. Contemporary guidance emphasizes individualized prescribing based on symptom burden, age, time since menopause, baseline cardiovascular and venous thromboembolism risk, and the need for endometrial protection [1,10,11]. Absolute risks are heterogeneous and depend on formulation, dose, and route; for example, transdermal estrogen and lower doses may be associated with lower thrombotic risk than oral regimens in some populations [8,48,49]. Therefore, any statement of “net benefit” should be bounded to symptomatic women who are generally younger, typically younger than 60 years of age, and/or within 10 years of menopause onset, after shared decision-making that explicitly addresses absolute risk differences and patient priorities [11,40,41].

Importantly, MHT is not indicated for the primary prevention of cardiovascular disease or dementia, and initiation in older postmenopausal women warrants caution due to a less favorable risk profile [1,10,11]. From a healthspan perspective, the clinical goal is to relieve symptoms that impair function, preserve musculoskeletal health when indicated, and support adherence to broader preventive strategies including diet, activity, sleep, and cardiometabolic risk management, rather than to frame MHT as a universal anti-aging intervention [42,43].

The relationship between MHT and cognition remains rather complex; while MHT may alleviate brain fog secondary to sleep deprivation or severe VMS, it is not recommended for the primary prevention of dementia [33,50,51]. For women with contraindications or those who prefer non-hormonal approaches, evidence-based alternatives such as selective serotonin reuptake inhibitors offer viable pathways to reduce VMS burden and improve quality of life [10,24]. Clinicians are encouraged to review the historical evolution of these guidelines to contextualize current recommendations against past controversies [52].

Future directions

While the cross-domain framework presented in this review aims to translate complex evidence into feasible healthspan strategies, current literature remains constrained by limitations such as heterogeneity in definitions and outcome measures, a predominance of observational designs, and the limited representation of non-Western populations. To bridge these gaps and refine equitable menopause care models, future research should prioritize standardized, multidomain definitions of successful aging that capture function, resilience, and lived experience [6,13]. Concurrently, the validation of female-specific aging biomarkers, including biological age metrics tailored to the menopausal transition, is essential across diverse populations [5]. Finally, moving beyond single-component analyses, the field would benefit from advancing toward pragmatic trials that test integrated intervention packages, leveraging implementation science to scale these models effectively in both primary and specialty settings.

CONCLUSION

Clinically, menopause-centered healthspan care can be framed as a preventive package rather than a symptom-only visit: identify cardiometabolic and bone risk early, treat vasomotor and sleep symptoms effectively to protect day-to-day functioning, and address mood, cognition, and social determinants that shape adherence and resilience. When implemented through shared decision-making and periodic reassessment, this approach supports both individualized care and scalable population impact. Successful aging in women is not a passive outcome but a modifiable trajectory shaped by endocrine, vascular-metabolic, neurocognitive, and psychosocial processes that converge during the menopausal transition. A menopause-centered, multidomain approach – combining lifestyle optimization, symptom-focused therapies including individualized MHT, and psychosocial support – offers a realistic pathway to extend healthspan and reduce inequities. Future work should harmonize multidomain definitions of successful aging and test pragmatic, scalable care models that translate evidence into routine practice.