Impact of sleep disturbances on health-related quality of life in postmenopausal women: a systematic review

Abstract

Importance:

Sleep disturbances are common during and after the menopause transition, with potential effects on morbidity and quality of life; however, they may be underdiagnosed and undertreated.

Objective:

We carried out a systematic literature review to investigate the prevalence and impact of sleep disturbances associated with menopause on women’s health-related quality of life across the stages of menopause.

Evidence review:

Searches were conducted in PubMed and Excerpta Medica Database to identify articles published between 2013 and 2023 containing evidence for the impact of sleep quality on health-related quality of life and the epidemiology of sleep disturbances in women in menopause.

Findings:

In total, 29 publications focusing on epidemiological outcomes of sleep disturbances and 28 studies focusing on the impact of sleep quality on health-related quality of life were identified. Overall, these studies confirmed the high prevalence of sleep disturbances in postmenopausal women. Risk factors for sleep disturbances included menopausal status, depression, vasomotor symptoms, high glycemic index diets, and age. Notably, sleep disturbances were identified even in the absence of vasomotor symptoms. Sleep disturbances were significantly associated with impaired menopause-specific and general health-related quality of life, including depression, anxiety, and musculoskeletal pain. Sleep disturbances were also associated with reduced work productivity and the ability to perform daily activities.

Conclusions and relevance:

Healthy sleep is important at all life stages, including during menopause. Our review indicates that sleep disturbances are highly prevalent during postmenopausal years, even among women without vasomotor symptoms, and can severely impact women’s well-being and quality of life. This study highlights the importance of promoting increased awareness and developing tailored treatment strategies for sleep disturbances in midlife and beyond.

Key Points

• Question: What is the prevalence of sleep disturbances associated with menopause and their impact on health-related quality of life (HRQoL)?

• Findings: This systematic literature review included 29 studies reporting the epidemiology of sleep disturbances in postmenopausal women and 28 studies reporting their impacts on HRQoL. There was a high prevalence of sleep disturbances among postmenopausal women. In addition, poor sleep was significantly correlated with lower HRQoL, and adversely affecting emotional health and work productivity.

• Meaning: Sleep disturbances are very common among postmenopausal women. There is a significant need for increased awareness and better recognition of sleep problems in this population, as well as effective management strategies to improve women’s sleep and health-related quality of life in midlife and beyond.

During menopause, women undergo physical and psychological alterations that are partly due to hormonal changes, predominantly wide fluctuations and progressive reduction in estrogen levels.¹ Key symptoms of menopause include vasomotor symptoms (VMS; ie, hot flashes and night sweats), sleep disturbances, and mood changes.^1-4 These symptoms are interrelated and can be debilitating, substantially affecting women’s quality of life (QoL).

Sleep disturbances are frequent during the menopause transition,^3-6 with the incidence increasing from 5% before menopause⁷ to 16% to 47% in perimenopause and 35% to 60% after menopause.⁸ Overall, 33% to 52% of women show an increase in sleep disturbances in midlife.^9,10 Sleep disturbances are associated with increased risk for depression, cardiovascular disease, and overall morbidity and mortality.^11-13

Menopause-associated sleep disturbances include night-time awakenings, longer, more frequent periods of wakefulness after sleep onset, poor-quality, insufficient, or nonrestorative sleep, difficulty in sleep initiation, and early waking.¹⁴ The scientific literature uses multiple overlapping terms to describe various facets of disrupted sleep, such as sleep disturbance, self-reported insomnia symptoms, poor sleep quality, and clinically defined sleep disorders like insomnia disorder. These terms may refer to subjective experiences, specific symptoms, or clinically diagnosed disorders, and their usage often depends on the context of the study or clinical assessment.^14-17 Sleep disturbances in menopause may be related to hormonal changes, hot flashes, mood disorders, anxiety, psychosocial factors, and other conditions such as obstructive sleep apnea and restless legs syndrome. Notably, sleep disturbances can also occur independently of VMS,^15,18 probably because of direct and indirect modulatory effects of reduced estrogen and progesterone levels on the central nervous system.^16,19 Given that a bidirectional relationship exists between psychosocial factors and menopause symptoms, including sleep disturbances,²⁰ pharmacological and nonpharmacological treatment strategies should be aimed at improving sleep and QoL in perimenopausal and postmenopausal women.

Systemic estrogen and/or progesterone can improve sleep quality,¹⁹ with estrogen shown to reduce sleep latency and spontaneous waking, and increase sleep time.¹⁶ Although menopause hormone therapies (MHT) may alleviate menopause-related sleep disturbances, a recent review noted that improvements are limited and typically seen in women with comorbid VMS.¹⁴ Furthermore, many women choose not to take MHT, whereas others may have medical conditions that would prevent them from using MHT safely.

Although increasing emphasis is placed on the occurrence and severity of vasomotor symptoms, menopause-associated sleep disturbances are often underdiagnosed and undertreated.¹⁴ This systematic literature review (SLR) investigates the prevalence and impact of menopause-associated sleep disturbances on health-related QoL (HRQoL) across the stages of menopause and among surgically induced menopausal women. We used a targeted approach to study the prevalence and risk factors of sleep disturbances associated with menopause, whereas a systematic approach was used to evaluate the impact of sleep quality on HRQoL. The findings of this review will inform clinicians and policymakers on the epidemiology and burden of sleep disturbances in postmenopausal women.

METHODS

Objectives

Seven consensus questions were developed to determine: (i) the proportion of women with sleep disturbances; (ii) the proportion of women with poor sleep quality who have VMS; (iii) the occurrence of sleep disturbances in women without VMS; (iv) risk factors or protective factors responsible for worsening or improving sleep quality; (v) the impact of depressive symptoms on HRQoL; (vi) the impact of sleep disturbances on HRQoL; and (vii) the impact of sleep disturbances on work productivity.

Protocol and search strategy

Predefined eligibility criteria based on population, intervention, control, outcomes, study design, and timeframe (PICOST; Table 1) were used to identify relevant studies based on the aims and objectives of the review. The protocol was registered in the International Prospective Register of Systematic Reviews (registration number: CRD42023448601)¹⁷ and conducted in line with Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines.²¹

TABLE 1.

Inclusion criteria for the research question for sleep disturbances in menopause, based on PICOST criteria

PICOST	Inclusion criteria	Exclusion criteria
Population	Women with:  • Menopause  • Perimenopause  • Menopause transition   ▪ Midlife women  • Postmenopause  • Women with surgical menopause  • Women with no intervention	• Women without menopause and/or menopausal symptoms • Women with induced menopause  ▪ Caused by endocrine adjuvant therapies for the prevention of breast cancer recurrence. These include gonadotropin-releasing hormone antagonists, aromatase inhibitors, and selective estrogen receptor modulators (eg, tamoxifen)
Intervention/comparator	NA	Women receiving any type of intervention including: • Pharmacological therapies  ▪ Hormonal therapy  ▪ Nonhormone therapies • Nonpharmacological interventions
Outcomes	(I) Epidemiology of sleep disturbances in women with menopause  • Incidence  • Prevalence  • Symptoms/manifestations, including but not limited to:   ▪ Insomnia or other sleep disturbance   ▪ Mood or anxiety disorders   ▪ Hot flashes   ▪ Night sweats  • Comorbidities  • Risk factors  • Sleep disturbance with VMS  • Sleep disturbance without VMS  • New (postmenopausal) onset of sleep disturbances (II) Impact of sleep disturbances in women with menopause  • Health-related quality of life  • Patient-reported outcomes tools (eg, PSQI, MRS, WHQ, BDI)  • Work loss  • Productivity loss  • Pain  • Factors (risk) associated with worsening/improving sleep quality	• Outcomes without sleep quality in women with menopause • Treatment impact on sleep quality in women with menopause  ▪ Efficacy of interventions to improve sleep quality
Study design	• Clinical trials, including randomized controlled trials • Observational studies • Cross-sectional studies • Real-world evidence studies	• Pharmacokinetic studies • Animal/in vitro studies • Case reports
Timeframe	2013-2023	Pre-2013
Publication type	• Primary publications • Recommendations/consensus/ guidelines • Case series (≥10 cases) • Congress abstracts (2021-2023)	• Congress abstracts pre-2021 • Case reports • Editorial, letter, notes, correspondence, erratum, and opinion • Flag for bibliographic references  ▪ Reviews  ▪ Systematic review  ▪ Meta-analysis  ▪ Network meta-analysis
Language	English	Non-English

BDI, Beck Depression Inventory; MRS, Menopause Rating Scale; NA, not applicable; PICOST, population, intervention, control, outcomes, study design, and timeframe; PSQI, Pittsburgh Sleep Quality Index; VMS, vasomotor symptoms; WHQ, Women’s Health Questionnaire.

PubMed (Supplemental Table S1, Supplemental Digital Content 1, http://links.lww.com/MENO/B404) and Excerpta Medica Database (EMBase; Supplemental Table S2, Supplemental Digital Content 1, http://links.lww.com/MENO/B404) were searched to identify English-language articles published between 2013 and 2023 containing evidence for the impact of sleep quality on HRQoL and the epidemiology of sleep disturbances in women with menopause.

Screening and study identification

The publications found through electronic searches were manually screened for eligibility based on the title and abstract using the Systematic review Management and Processing software (SYMPRO, AccuScript Consultancy, Ludhiana, India).²² A positive exclusion approach was used to select records for the next step, and all identified full-text articles were screened and assessed for inclusion and data extraction. In addition, a random 10% of records were assessed by one reviewer to ensure consistent application of the eligibility criteria. Discrepancies were resolved by a senior reviewer. Finally, the reference lists of key articles were reviewed to identify any additional relevant studies.

Data extraction

Data were extracted from full-text articles and conference abstracts. For each study, the design, population characteristics, epidemiological outcomes (incidence, prevalence, and risk factors), and impact of sleep disturbances on HRQoL among postmenopausal women (general QoL, menopause-specific QoL, emotional well-being, pain, and impact of sleep quality on work productivity) were extracted and tabulated. Data extraction was performed by one researcher and validated by a second independent researcher. Any disagreements were resolved by consulting a third reviewer.

Quality assessment

Quality appraisal using a risk of bias (RoB) analysis for all the selected full-text publications on HRQoL was performed using the validated RoB tool, Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I).²³ The ROBINS-I evaluates seven domains of potential bias: (1) bias due to confounding, (2) bias in participant selection, (3) bias in classification of interventions, (4) bias due to deviations from intended interventions, (5) bias due to missing data, (6) bias in outcome measurement, and (7) bias in selection of reported results. For the present study, the term ‘intervention’ was adapted to represent the ‘impact of menopause’ on the outcomes. Each study was assigned an overall RoB rating based on the highest risk level identified across all domains by RoB Master,²⁴ an artificial intelligence-based software used for risk of bias analysis, and the output was manually reviewed by a senior reviewer.

RESULTS

Study identification

From 5,122 records initially identified, 954 were selected for full-text screening (Fig. 1), and 55 publications were finally selected for inclusion, including 27 studies identified through the targeted approach focusing on epidemiological outcomes of sleep disturbances,^25-51 26 studies identified using the systematic approach focusing on the impact of sleep quality on HRQoL outcomes,^52-77 and 2 studies reporting both outcomes.^2,3 All the identified publications were full-text articles. The list of citations excluded during screening and the reason for exclusion are provided in Supplemental file S3, Supplemental Digital Content 2, http://links.lww.com/MENO/B405.

FIG. 1 .

Abbreviated PRISMA flow diagram for selection of relevant studies. HRQoL, health-related quality of life; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Quality assessment

All 28 HRQoL studies were assessed using the ROBINS-I tool. Of these, the majority (64.3%, 18/28) were judged to have a moderate RoB, primarily due to confounding factors (domain 1) or because the participants were not analyzed separately according to the menopause status groups (domain 7). The remaining ten studies (35.7%) exhibited a serious RoB owing to a lack of statistical adjustment for confounders (domain 1) and the lack of menopause status subgroups for the outcomes analyzed (Fig. 2). Detailed assessments of each observational study, along with the checklist used, are provided in Supplemental file S4, Supplemental Digital Content 3, http://links.lww.com/MENO/B406.

FIG. 2 .

ROBINS-I risk of bias assessment of HRQoL studies as (A) traffic light plot and (B) unweighted summary bar plot. HRQoL, health-related quality of life; ROBINS-I, Risk Of Bias In Non-randomized Studies - of Interventions.

Epidemiology of sleep disturbances

Twenty-nine studies (15 cross-sectional,^{2,3,26,28-30,32-35,40,45,48-50} 7 observational,^{25,27,36,38,42,46,51} 3 prospective cohort,^30,31,47 3 survey,^39,43,44 and 1 longitudinal study³⁷) reported epidemiological outcomes for sleep disturbances in postmenopausal women, of which 26 were from 11 different countries,^{2,25,26,28-43,45-51} and 3 were multinational studies^3,27,44 (Supplemental Table S5, Supplemental Digital Content 1, http://links.lww.com/MENO/B404). Overall, there was a high prevalence of menopause-related sleep disturbances (difficulty sleeping, latency, duration, and disruption) across geographical regions (Table 2). The highest prevalence (up to 73%) was reported in Asia,³⁴ the lowest (9%) was found in North America,⁴⁰ with South America (56%) and Europe (24%-69%) showing intermediate numbers. In multinational studies, the overall prevalence of sleep disturbances was 55% in women aged 40 to 65 years, ranging from 39% in Italy to 67% in Canada.^3,27,44

TABLE 2.

Prevalence of sleep disturbances in women in menopause by geographical region

Region/country	Prevalence of sleep disturbances (%)
North America	8.9-67.0
USA2,3,28,29,44	16.1-66.0
Mexico40	Mild/moderate: 49.7 severe: 8.9
Canada44,51	10.8-67.0
Asia	21.6-73.1
China48-50	21.6-67.1
Taiwan34	73.1
South Korea35	27.4-29.5
Japan3	60.0
Europe	39.0-69.0
Spain25	39.0-58.5
Finland41,44	Moderate: 24%, severe: 28%41 52.0-64.044
Great Britain44	64.0
Sweden44	48.0
Denmark44	46.0
Norway44	50.0
France44	53.0
Italy44	39.0
Multinational (France, Germany, Italy, Spain, and UK)27	54-65
Multinational (France, Germany, Italy, Spain, and UK)3	69.0
South America	55.9
Brazil32	55.9
International (USA, Great Britain, Canada, Sweden, Denmark, Norway, Finland, France, and Italy)44	55.0

Only two studies reported the prevalence of sleep disturbances in postmenopausal women without VMS.^32,34 In a Brazilian population-based cross-sectional study (n=525), the percentage of sleep disturbances (insomnia disorder, isolated symptoms of insomnia, and PSG alterations suggestive of insomnia) in women without VMS was higher for premenopausal women than for postmenopausal women (Fig. 3).³² Conversely, in a Taiwanese hospital database study (n=1,088), postmenopausal women without VMS reported a greater prevalence of poor sleep on the Pittsburgh Sleep Quality Index (PSQI) than premenopausal women without VMS (73% vs. 61%, P<0.001).³⁴

FIG. 3 .

Percentage of reported sleep disturbances in premenopausal and menopausal women not experiencing VMS.³² Menopausal includes the sum of peri, early, and late-menopause. PSG, polysomnography; VMS, vasomotor symptoms.

Major risk factors affecting sleep quality were menopausal status,^{34-36,42,43,45,48,49,51} depressive symptoms,^33,50 VMS/menopausal symptoms,^29,33 high glycemic index diets,³¹ and age.^47,49 Other factors included chronic pain,⁴⁶ history of migraine,³⁰ and higher sedentary time (>11 h/day).²⁸ Earlier age at menopause⁴⁷ and greater amount of physical activity²⁸ were significant independent factors for better sleep quality, whereas higher nonjuice fruit and vegetable intakes were protective against both incident and prevalent insomnia.³¹ (Supplemental Table S5, Supplemental Digital Content 1, http://links.lww.com/MENO/B404).

Multiple studies (four cross-sectional^35,45,48,49 and two observational studies^36,42,48) have reported the perimenopause (odds ratio [OR]: 1.50-1.751.50-1.75; P<0.05)^{35,36,42,45,48,49} and postmenopause (OR: 1.23-1.73; P<0.05)^{35,36,42,48,49} as significant risk factors for poor sleep quality including insomnia compared with that in premenopausal women. Furthermore, in a cohort of postmenopausal women aged 45 to 60 years, compared with pre/perimenopause, menopausal status was identified as a risk factor for requiring more than 30 minutes to fall asleep and for possible sleep-onset insomnia disorder (OR [95% CI]: 1.24 [1.00-1.53] and 1.51 [1.07-2.12], [P>0.05 for both], respectively).⁵¹ Peri, early, and late-menopause versus premenopause were significantly associated with nocturnal awakening with headache (OR [95% CI]: 13.9 [4.3-45.2], P<0.01; 3.8 [1.9-7.6], P<0.01; and 4.0 [7.1-26.9], P<0.01, respectively) after adjusting for age, socioeconomic status, years of schooling, and body mass index (BMI).⁴³

The presence of menopause without VMS was positively associated with higher global PSQI scores (β 1.54; 95% CI: 1.14-1.95; P<0.001) and was an independent predictor of poor sleepers (OR [95% CI]: 1.45 [1.03-2.05]; P<0.05) in a multivariate linear and logistic regression analyses, respectively, after adjusting for short sleep duration, BMI, systolic blood pressure (SBP), fasting plasma glucose (FPG), triglycerides, high density lipoprotein-cholesterol, creatinine, alcohol, tea drinking, coffee drinking, smoking, and habitual exercise.³⁴

Two studies reported conflicting results on the impact of age on sleep quality.^47,49 In a prospective study from the United States, higher age at menopause was a significant independent factor for better sleep quality, whereas earlier age at menopause was associated with higher risk of developing insomnia symptoms among those who were older than 50 years.⁴⁷ A one-year increase in the age at menopause was associated with a lower risk of developing trouble falling asleep (OR [95% CI]: 0.97 [0.96-0.99]), night-time awakenings (OR [95% CI]: 0.98 [0.97-0.99]), and feelings of nonrestorative sleep (OR [95% CI]: 0.97 [0.95-0.99]; P<0.05 for all).⁴⁷ A cross-sectional study from China, on the other hand, reported higher age as a risk factor for poor sleep quality (OR [95% CI]: 1.23 [1.09-1.39]; P=0.001), together with marital status and menopause status (in menopause transition or postmenopause).⁴⁹

In a US observational study of postmenopausal women, moderate-to-extreme pain interference and severity were significantly associated with an increased risk of insomnia in veterans (risk ratio 95% CI, 1.64 [1.21-2.22] P=0.001 and 1.52 [1.14-2.02] P=0.004 times, respectively) and nonveterans (1.35 [1.29-1.42] P<0.001 and 1.33 [1.28-1.39], P<0.01 times, respectively) compared with those with less pain interference and severity. These findings were statistically significant after adjusting for multiple confounders (age, ethnicity, marital status, education, family income, smoking history, BMI, physical activity, alcohol intake, hormone therapy use, arthritis, cancer diabetes, hypertension, angina, heart failure, myocardial infarction, and stroke).⁴⁶

Few studies (n=4) were identified that assessed women with surgically induced menopause. The proportion of women with surgical menopause was low and ranged from 5% to 10%.^25,37,58,75 In the two studies where outcomes were compared, there was no difference in insomnia scores between women with natural menopause and women with surgical menopause (40.3 vs. 30.9, P=0.147;²⁵ and 93.3 vs. 6.7, P=0.86).⁵⁸

QoL assessed by menopause-specific tools

In nine cross-sectional studies (five assessed both peri and postmenopausal women^{53,54,56,60,62} and four assessed postmenopausal women^58,61,63,69) reporting the impact of sleep quality on QoL using menopause-specific tools (Supplemental Table S6, Supplemental Digital Content 1, http://links.lww.com/MENO/B404), significant correlations were observed between poor sleep and lower QoL.^{53,54,56,60-63,69} Two studies adjusted the outcomes for confounding factors.^54,56 The association of severe QoL impairment with sleep complaints was adjusted for age, ethnicity, work activity, marital status, sexual partner, wine consumption, hormonal therapy, climacteric state, urinary incontinence, probable anxiety, probable depression, loneliness, QoL, and the 11 menopause-related symptoms evaluated by the Menopause Rating Scale (MRS).⁵⁴ The association of sleep problems with health-related domains of the Women’s Health Questionnaire (WHQ) was adjusted for age, menopause status, and Beck Depression Inventory (BDI) score.⁵⁶

Ali et al⁵³ found that menopause-related symptomatology (measured by total scores on the Menopause-Specific Quality of Life scale) was significantly correlated with difficulty sleeping (β: 0.411; P=0.001). Similarly, mean scores on the MRS (95% CI) were significantly worse in women with sleep complaints (71.1 [61.0-79.8]) than in those without (54.3 [49.8-58.6]; P<0.001).⁵⁴ The unadjusted MRS-based sleep QoL was significant (OR [95% CI]: 2.07 [1.29-3.39]; P<0.001), whereas the adjusted data were nonsignificant (OR [95% CI]: 1.48 [0.57-3.88]; P=0.41).⁵⁴ Separately, in 500 peri and postmenopausal women, sleep problems were significantly correlated with the HRQoL dimensions of the Women’s Health Questionnaire using regression models (socioeconomic adjusted R² [aR²]: 0.030 [P=0.005]; lifestyle aR²: 0.042 [P=0.001]; health-related aR²: 0.037 [P=0.004]).⁵⁶

General QoL

Nine studies (five cross-sectional,^{2,58,64,66,67} three prospective cohort,^71,75,77 and one case-control study⁷⁶) assessed the relationship between sleep disruption and QoL using a wide range of HRQoL tools. Overall, poor sleep was negatively correlated with both physical and mental health components (Supplemental Table S6, Supplemental Digital Content 1, http://links.lww.com/MENO/B404). Frequent sleep disturbances (≥3-4 times per week/2 weeks) were negatively correlated with the Physical Component Score (PCS) and Mental Component Score (MCS) of the Short Form 36-item questionnaire (SF-36)^75,77 (β: −0.67 and β: −0.79, respectively [both P<0.0001]),⁷⁵ and with the MCS of the SF-12 (β: −0.612 [P<0.001]).^66,67 Insomnia was identified as a risk factor for physical, emotional, and mixed impairment on the SF-36,⁷⁷ and also demonstrated a negative impact on humanistic outcomes (HRQoL and work impairment) on the SF-8 (PCS β: -0.391; MCS β: −0.277; activity impairment β: 0.040).² In multivariable regression models, sleep disturbances were not associated with QoL using the EuroQoL 5-Dimension scale (standardized β: −0.16 [P>0.05];⁶⁴ OR [95% CI]: 0.59 [0.17-2.03] [P=0.402]⁷⁶); however, lower mental (SF-12 MCS; β: −0.60; P<0.05) and physical (PCS; β: −0.32; P<0.05) QoL scores correlated with higher sleep disturbance scores.⁶⁷ The presence of insomnia alone was also associated with lower QoL domain scores on the World Health Organization brief form questionnaire (psychological F=8.01 [df=1; P=0.01]; environmental F=5.28 [df=1; P=0.02]).⁵⁸ Finally, in osteoporotic postmenopausal women (n=113), impaired sleep quality (as measured by the PSQI) was significantly correlated with reduced QoL measured using the Quality of Life Questionnaire of the European Foundation for Osteoporosis-41 (r=0.433, P<0.001).⁷¹ Similarly, osteopenic postmenopausal women (n=172) demonstrated significant correlation among impaired sleep quality and QoL (r=0.308, P<0.001).⁷¹

Sleep and emotional status

Eleven studies (10 cross-sectional^{52,54-58,60,65,68,70} and 1 prospective study⁷²) reported the impact of sleep disturbances on emotional status using scales such as the BDI,^52,56 Hospital Anxiety and Depression Scale (HADS),⁵⁵ Hamilton Depression Rating Scale (HAM-D),⁶⁵ Self-rating Depression Scale (SDS),⁷⁰ Generalized Anxiety Disorder 7-item scale (GAD-7),⁷² and the 28-item General Health Questionnaire.⁶⁸ Three studies adjusted the outcomes for confounding factors including age, education, BMI, monthly family income, chronic disease, ethnicity, work activity, marital status, sexual partner, wine consumption, hormonal therapy, climacteric state, urinary incontinence, probable anxiety, probable depression, loneliness, QoL, and the 11 menopause-related symptoms that MRS evaluates (Supplemental Table S7, Supplemental Digital Content 1, http://links.lww.com/MENO/B404).^52,54,70

Overall, the results showed an association between sleep problems and depression or anxiety in postmenopausal women (Supplemental Table S7, Supplemental Digital Content 1, http://links.lww.com/MENO/B404).^{52,54-56,58,65,68,70} Sleep efficiency, quality, latency, and duration were reduced as the degree of depression symptomology (assessed by HAM-D) increased.⁶⁵ Poor sleep increased the risk of depression symptoms on the BDI in postmenopausal women (adjusted OR [95% CI]: 4.65 [1.82-11.88]; P<0.05)⁵² and on the SDS in postmenopausal women (11.5 [5.39-24.66]; P<0.001).⁷⁰ Symptoms of depression, assessed using the BDI, were positively correlated with sleep problems (P=0.001),⁵⁶ whereas depression on the HADS was positively correlated with insomnia (P=0.0001).⁵⁵ More severe sleep disturbances were associated with worse HAM-D scores (r: −0.338, P=0.001), and an increase in depression led to reductions in sleep efficiency (r: −0.333; P=0.001), quality (r: −0.219; P=0.001), latency (r: −0.326; P<0.001), and duration (r: −0.337; P<0.001).⁶⁵ Women with hot flash-associated insomnia disorder had higher anxiety scores (mean (SD) GAD-7 2.7 [3.0]) compared with those without insomnia (1.0 [1.4]; P=0.05).⁷² Women with moderate, severe, or very severe sleep disturbances experienced a higher level of anxiety than those with mild sleep disturbances (3.31-fold increase, 4.69-fold increase, and 16.6-fold increase, respectively).⁶⁸ Regression analyses demonstrated that depressive symptoms^56,70 and anxiety disorders^68,72 correlated with sleep problems (P<0.05), with one study indicating a greater impact among postmenopausal compared with perimenopausal women.⁷⁰

Sleep disturbances and pain

Two cross-sectional studies explored the relationship between pain, sleep disorders, and sleep quality.^57,58 In a study in Turkey, significant correlations were observed between pain (assessed using a visual analog scale) and several components of the PSQI, including sleep quality, sleep latency, sleep disturbance, use of sleeping medication, and daytime dysfunction.⁵⁷ A study in South America found that the presence of insomnia (F=10.31 [df=1; P=0.002]) and musculoskeletal pain (MSP) (F=15.27 [df=1; P<0.001]) were individually and independently associated with higher MSP severity.⁵⁸ In addition, there were significant positive correlations between pain intensity and sleep disturbance measures, including latency, disturbance, use of sleep medication, daytime dysfunction (all P<0.01), and subjective sleep quality (P<0.05).⁵⁷ Insomnia was associated with sleep fragmentation (P=0.02), as well as more severe MSP and reduced QoL (both P<0.001).⁵⁸

Sleep and work productivity

Five studies (four cross-sectional^2,3,59,73 and one observational study⁷⁴) reported an impact of sleep quality on work productivity in postmenopausal women using the Work Productivity and Activity Impairment questionnaire,^2,3,73 the Work Ability Index,⁷⁴ and the Occupational QoL subscale of the Utian Quality of Life scale (UQOL) (Supplemental Table S8, Supplemental Digital Content 1, http://links.lww.com/MENO/B404).⁵⁹ In a real-world population of peri or postmenopausal women, 90.8% of women reported that VMS affected their sleep, and 83.1% reported sleep-related changes in productivity.⁷³ Moreover, menopausal symptoms were significantly associated with lower occupational QoL and higher work impairment compared with women not experiencing these symptoms.^2,3,59,73 In a study in Serbia, insomnia negatively impacted UQOL scores for professional activity (ρ: −0.025) and occupational QoL (ρ: −0.090; P=0.099), suggesting a correlation between insomnia and poorer QoL among working women.⁵⁹ In a global cross-sectional survey, sleep disturbances co-occurring with VMS were found to amplify their negative effects, reducing work productivity and ability to perform daily activities.³

DISCUSSION

The results of this systematic literature review show that sleep disturbances are highly prevalent and represent a significant burden in menopausal women, impacting QoL, emotional health, and work outcomes. Although sleep quality in postmenopausal women can be influenced by the presence and severity of VMS at night, it is now known that a significant proportion of postmenopausal women experience sleep disturbances even in the absence of VMS. This suggests that other aspects may also play a role in disturbed sleep, and endocrinological changes occurring during menopause have been proposed as one of the possible etiologies. Both estrogen and progesterone have modulatory effects on the central nervous system and sleep pathways, and menopause hormone therapy is associated with benefits on sleep, including improved total sleep time and sleep quality, as well as faster sleep-onset latency and less wakefulness after sleep onset.^16,19 Estrogen may also act indirectly through effects on mood, body temperature, and VMS.

Our review confirmed the current understanding of a complex and often bidirectional relationship between sleep and concomitant menopause-related symptoms. In particular, the presence of depression and anxiety symptoms was directly related to sleep problems in postmenopausal women in the examined studies. Women experiencing menopause-related sleep disturbances had lower occupational QoL and overall reduced work productivity, in line with another recent review.¹⁴

Depression is associated with reduced life expectancy and increased years lived with disability as well as increased cardiovascular risk,^78,79 whereas sleep disturbances are associated with increased risk for depression, cardiovascular disease, and overall morbidity and mortality.^11-13,80 Depression and chronic pain are both risk factors for sleep disturbance, but the reverse relationship is also true. Thus, these complex bidirectional interactions between sleep disturbances and depression have implications not only for QoL and work performance but also for morbidity, mortality, and overall life expectancy among postmenopausal women.^11-13 For example, in the model proposed by Ali et al⁵³, sleep difficulties and fatigue were mediators of VMS and weight gain for the manifestation of psychological symptoms, including anxiety, depression, psychological distress, and memory problems. Similarly, in an earlier model of mental health status in postmenopausal women, sleep disturbances played a role in reduced mental health, together with factors such as exercise and quality of life.⁶⁶

The incidence of sleep disorders is known to increase throughout the menopause transition, as this time represents for some a window of vulnerability for physical and emotional symptoms^7,8 Results of the present SLR confirmed this and also demonstrated that poor sleep can have a substantial impact on perimenopausal women as well as on postmenopausal women. For example, sleep disturbances increase the risk of depressive symptoms and cardiovascular risk in both peri and postmenopausal women.^{12,13,52,70,80} The present SLR also highlighted the impact of sleep disturbances on morbidity, with significant correlations between sleep disturbance and reported pain.^57,58 Sleep disturbance was also associated with reduced daytime productivity, affecting work and activities of daily living.^2,3,59,73,74

This SLR provides insights into important aspects of women’s health during menopause that are often affected by sleep disturbances. The study adopted a comprehensive search strategy based on well-defined objectives to answer key consensus questions regarding the impact of sleep disturbances on QoL in menopausal women with or without VMS. Multiple databases were used to ensure extensive coverage of primary publications, and a focus on literature published within the past 10 years and inclusion of recent conference abstracts ensured that insights were relevant and up to date. Wide geographical coverage, including North America, South America, Asia, and Europe, and multinational studies, provided a richer global perspective.

Limitations of the SLR should also be acknowledged. The RoB tool used focuses specifically on bias and does not address problems related to imprecision of results, nor does it evaluate external validity.²³ Variability in study designs, including cross-sectional, longitudinal, and case-control studies, might have led to heterogeneity in findings and inconclusive results. There were also inconsistencies in the definition of sleep disturbances across different publications. Restrictions in the search criteria may have led to publication bias due to a focus on published studies in English-language journals, potentially overlooking relevant unpublished or non-English studies. Despite wide geographic coverage, few studies came from the Global South. Excluding studies involving pharmaceutical interventions for menopause-related symptoms, possibly limited the evidence base that would have otherwise demonstrated a more holistic impact of sleep quality on QoL. No direct head-to-head comparisons involving postmenopausal women with and without sleep disturbances were identified during the SLR. Such comparisons would provide more robust evidence to evaluate cause-and-effect relationships between sleep quality and QoL. Finally, the presence of VMS might have complicated the assessment of the impact of sleep quality on QoL, as there is evidence that the two may be interconnected.⁵³ However, studies have also shown that sleep disturbances occur in the absence of VMS in peri and postmenopausal women.^15,18

CONCLUSIONS

In conclusion, healthy sleep is important during every stage of life, including menopause. Sleep disturbances are highly prevalent during menopause, even in women without VMS, and can severely impact women’s well-being, activities, and QoL. Recognition of postmenopausal sleep disturbances, their risk factors, and comorbidities could improve sleep, functioning, and HRQoL in midlife and beyond.