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The symptoms of menopause can be distressing, particularly as they occur at a time when women have important roles in society, within the family and at the workplace. Hormonal changes that begin during the menopausal transition affect many biological systems. Accordingly, the signs and symptoms of menopause include central nervous system-related disorders; metabolic, weight, cardiovascular and musculoskeletal changes; urogenital and skin atrophy; and sexual dysfunction. The physiological basis of these manifestations is emerging as complex and related, but not limited to, oestrogen deprivation. Findings generated mainly from longitudinal population studies have shown that ethnic, geographical and individual factors affect symptom prevalence and severity. Moreover, and of great importance to clinical practice, the latest research has highlighted how certain menopausal symptoms can be associated with the onset of other disorders and might therefore serve as predictors of future health risks in postmenopausal women. The goal of this Review is to describe in a timely manner new research findings on the global prevalence and physiology of menopausal symptoms and their impact on future health.

Vasomotor symptoms (hot flushes and night sweats) and other symptoms, including depression, anxiety and panic attacks, are commonly experienced by menopausal women and have been associated with an unfavourable cardiovascular risk profile. To investigate whether presence of menopausal symptoms is associated with the development of cardiovascular disease (CVD). Five electronic databases (Medline, EMBASE and Web of Science) were search until February 17th, 2015 to identify relevant studies. Observational cohort studies or randomised intervention studies were eligible for inclusion if they followed participants prospectively (at least 1 year of follow-up), and reported relevant estimates on the association of any vasomotor symptoms, or other menopausal symptoms, with risk of CVD, coronary heart disease (CHD), or stroke in perimenopausal, menopausal, or postmenopausal women. Data were extracted by two independent reviewers using a pre-designed data collection form. Separate pooled relative risks (RRs) for age and non-established cardiovascular risk factors (e.g., education, ethnicity) adjusted data and for established cardiovascular risk factors and potential mediators-adjusted data (e.g., smoking, body mass index, and hypertension) were calculated. Out of 9,987 initially identified references, ten studies were selected, including 213,976 women with a total of 10,037 cardiovascular disease outcomes. The age and non-established cardiovascular risk factors adjusted RRs) [95% confidence intervals] for development of CHD, Stroke and CVD comparing women with and without any menopausal symptoms were 1.34 [1.13-1.58], 1.30 [0.99-1.70], 1.48 [1.21-1.80] respectively, and the corresponding RRs adjusted for cardiovascular risk factors and potential mediators were 1.18 [1.03-1.35], 1.08 [0.89-1.32], 1.29 [0.98-1.71]. However, these analyses were limited by potential unmeasured confounding and the small number of studies on this topic. Presence of vasomotor symptoms and other menopausal symptoms are generally associated with an increased risk of cardiovascular disease, which is mainly explained by cardiovascular risk factors.

It is unclear whether risk for major depression during the menopausal transition or immediately thereafter is increased relative to pre-menopause. We aimed to examine whether the odds of experiencing major depression were greater when women were peri- or post-menopausal compared to when they were pre-menopausal, independent of a history of major depression at study entry and annual measures of vasomotor symptoms (VMS), serum levels of, or changes in, estradiol (E2), follicular stimulating hormone (FSH) or testosterone (T) and relevant confounders. Participants included the 221 African American and Caucasian women, aged 42-52 years, who were pre-menopausal at entry into the Pittsburgh site of a community-based study of menopause, the Study of Women's Health Across the Nation (SWAN). We conducted the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) to assess diagnoses of lifetime, annual and current major depression at baseline and at annual follow-ups. Psychosocial and health factors, and blood samples for assay of reproductive hormones, were obtained annually. Women were two to four times more likely to experience a major depressive episode (MDE) when they were peri-menopausal or early post-menopausal. Repeated-measures logistic regression analyses showed that the effect of menopausal status was independent of history of major depression and annually measured upsetting life events, psychotropic medication use, VMS and serum levels of or changes in reproductive hormones. History of major depression was a strong predictor of major depression throughout the study. The risk of major depression is greater for women during and immediately after the menopausal transition than when they are pre-menopausal.

Background Women at middle age are puzzled by a series of menopausal disturbances, can be distressing and considerably affect the personal, social and work lives. We aim to estimate the global prevalence of nineteen menopausal symptoms among middle-aged women by performing a systematic review and meta-analysis. Methods Comprehensive search was performed in multiple databases from January, 2000 to March, 2023 for relevant studies. Random-effect model with double-arcsine transformation was used for data analysis. Results A total of 321 studies comprised of 482,067 middle-aged women were included for further analysis. We found varied prevalence of menopausal symptoms, with the highest prevalence of joint and muscular discomfort (65.43%, 95% CI 62.51–68.29) and lowest of formication (20.5%, 95% CI 13.44–28.60). Notably, South America shared dramatically high prevalence in a sort of menopausal symptoms including depression and urogenital symptoms. Besides, countries with high incomes (49.72%) had a significantly lower prevalence of hot flashes than those with low (65.93%), lower-middle (54.17%), and upper-middle (54.72%, p  < 0.01), while personal factors, such as menopausal stage, had an influence on most menopausal symptoms, particularly in vaginal dryness. Prevalence of vagina dryness in postmenopausal women (44.81%) was 2-fold higher than in premenopausal women (21.16%, p  < 0.01). Furthermore, a remarkable distinction was observed between body mass index (BMI) and prevalence of sleep problems, depression, anxiety and urinary problems. Conclusion The prevalence of menopausal symptoms affected by both social and personal factors which calls for attention from general public.

Many women experience both vasomotor menopausal symptoms (VMS) and depressed mood at midlife, but little is known regarding the prospective bi-directional relationships between VMS and depressed mood and the role of sleep difficulties in both directions. A pooled analysis was conducted using data from 21 312 women (median: 50 years, interquartile range 49-51) in eight studies from the InterLACE consortium. The degree of VMS, sleep difficulties, and depressed mood was self-reported and categorised as never, rarely, sometimes, and often (if reporting frequency) or never, mild, moderate, and severe (if reporting severity). Multivariable logistic regression models were used to examine the bi-directional associations adjusted for within-study correlation. At baseline, the prevalence of VMS (40%, range 13-62%) and depressed mood (26%, 8-41%) varied substantially across studies, and a strong dose-dependent association between VMS and likelihood of depressed mood was found. Over 3 years of follow-up, women with often/severe VMS at baseline were more likely to have subsequent depressed mood compared with those without VMS (odds ratios (OR) 1.56, 1.27-1.92). Women with often/severe depressed mood at baseline were also more likely to have subsequent VMS than those without depressed mood (OR 1.89, 1.47-2.44). With further adjustment for the degree of sleep difficulties at baseline, the OR of having a subsequent depressed mood associated with often/severe VMS was attenuated and no longer significant (OR 1.13, 0.90-1.40). Conversely, often/severe depressed mood remained significantly associated with subsequent VMS (OR 1.80, 1.38-2.34). Difficulty in sleeping largely explained the relationship between VMS and subsequent depressed mood, but it had little impact on the relationship between depressed mood and subsequent VMS.

Purpose We compared trajectories of vasomotor symptoms (VMS) and their risk factors in women with breast cancer (BrCa) to those of cancer-free controls. Methods Data were from 15 nearly annual follow-up visits (1996–2017) of the multi-racial/ethnic cohort of midlife women enrolled in the Study of Women’s Health Across the Nation (SWAN). We compared women with incident BrCa to controls for patterns of VMS, controlling for risk factors identified in bivariate analyses using multivariable longitudinal analyses. Results Characteristics at study entry largely did not differ between cases ( n  = 151) and controls ( n  = 2161). Adjusted prevalence of any VMS increased significantly among cases from diagnosis to 2.75 years post diagnosis [per-year adjusted odds ratio (aOR) = 1.76, 95% confidence interval (CI) 1.39–2.24], peaking at 2.75 years post diagnosis, whereas prevalence was stable among controls in this interval [aOR = 1.04, 95% CI 0.99–1.11]. Beyond 2.75 years post diagnosis, prevalence declined significantly in cases [aOR = 0.72, 95% CI 0.61–0.84] and less in controls [aOR = 0.96, 95% CI 0.92–1.00]. Patterns were similar for frequent VMS. Adjustment for tamoxifen use slightly reduced the per-year OR for any prevalent VMS post diagnosis, partially explaining excess VMS in cases. Other treatments were unassociated with VMS. Conclusions Patterns of prevalent VMS reporting differed significantly between cases and controls, particularly post diagnosis, the latter only partially explained by tamoxifen use among cases. Risk factors for VMS largely did not differ between cases and controls.

Abstract Introduction: Midlife, which encompasses the menopause transition in women, can be a time of disrupted sleep and accelerated atherosclerosis accumulation. Short or poor sleep quality has been associated with cardiovascular disease (CVD) risk; few studies have investigated relations among midlife women. We tested whether shorter actigraphy sleep time or poorer subjective sleep quality was associated with carotid atherosclerosis among midlife women. Aims and Methods: Two hundred fifty-six peri- and postmenopausal women aged 40–60 years completed 3 days of wrist actigraphy, hot flash monitoring, questionnaires (Pittsburgh Sleep Quality Index [PSQI], Berlin), a blood draw, and carotid ultrasound [intima media thickness (IMT), plaque]. Associations of objective (actigraphy) and subjective (PSQI) sleep with IMT/plaque were tested in regression models (covariates: age, race, education, body mass index, blood pressure, lipids, insulin resistance, medications, snoring, depressive symptoms, sleep hot flashes, and estradiol). Results Shorter objective sleep time was associated with higher odds of carotid plaque (for each hour shorter sleep, plaque score ≥ 2, odds ratio (OR) [95% confidence interval, CI] = 1.58 [1.11–2.27], p = .01; plaque score = 1, OR [95% CI] = 0.95 [0.68–1.32], p = .75, vs. no plaque, multivariable). Poorer subjective sleep quality was associated with higher mean IMT [β, b (standard error, SE) = 0.004 (0.002), p = .03], maximal IMT [b (SE) = 0.009 (0.003), p = .005], and plaque [plaque score ≥ 2, OR (95% CI) = 1.23 (1.09–1.40), p = .001; score = 1, OR (95% CI) = 1.06 (0.93–1.21), p = .37, vs. no plaque] in multivariable models. Findings persisted additionally adjusting for sleep hot flashes and estradiol. Conclusions: Shorter actigraphy-assessed sleep time and poorer subjective sleep quality were associated with increased carotid atherosclerosis among midlife women. Associations persisted adjusting for CVD risk factors, hot flashes, and estradiol.

Objectives. We investigated whether vasomotor symptom reporting or patterns of change in symptom reporting over the perimenopausal transition among women enrolled in a national study differed according to race/ethnicity. We also sought to determine whether racial/ethnic differences were explained by sociodemographic, health, or lifestyle factors. Methods. We followed 3198 women enrolled in the Study of Women’s Health Across the Nation during 1996 through 2002. We analyzed frequency of vasomotor symptom reporting using longitudinal multiple logistic regressions. Results. Rates of vasomotor symptom reporting were highest among African Americans (adjusted odds ratio [OR]=1.63; 95% confidence interval [CI]=1.21, 2.20). The transition to late perimenopause exhibited the strongest association with vasomotor symptoms (adjusted OR = 6.64; 95% CI = 4.80, 9.20). Other risk factors were age (adjusted OR=1.17; 95% CI=1.13, 1.21), having less than a college education (adjusted OR = 1.91; 95% CI = 1.40, 2.61), increasing body mass index (adjusted OR=1.03 per unit of increase; 95% CI=1.01, 1.04), smoking (adjusted OR=1.63; 95% CI=1.25, 2.12), and anxiety symptoms at baseline (adjusted OR=3.10; 95% CI=2.33, 4.12). Conclusions. Among the risk factors assessed, vasomotor symptoms were most strongly associated with menopausal status. After adjustment for covariates, symptoms were reported most often in all racial/ethnic groups in late perimenopause and nearly as often in postmenopause.

Abstract Purpose The hallmark menopausal symptom, vasomotor symptoms (VMS), has been linked to adverse health indicators. However, the relationship between VMS and biological aging has not been tested. We examined associations between menopausal VMS and biological aging as assessed by 2 DNA methylation-based epigenetic aging indicators previously linked to poor health outcomes. Methods Participants were members of the Women’s Health Initiative Observational Study integrative genomics substudy (N = 1206) who had both ovaries and were not taking hormone therapy. Relationships between VMS at enrollment (presence, severity) or VMS timing groups (no VMS: not at menopause onset nor at study enrollment; early VMS: at menopause onset but not at enrollment; persistent VMS: at menopause onset and study enrollment; and late VMS: at enrollment but not at menopause onset) and epigenetic clock indicators predictive of physical aging and early death (DNAm PhenoAge, DNAm GrimAge) were tested in linear regression models adjusting for age, race/ethnicity, hysterectomy, education, body mass index, smoking, and, in additional models, sleep disturbance. Results Women were on average 65 years of age at enrollment. Severe hot flashes at enrollment were associated with higher DNAm PhenoAge [relative to no hot flashes: B (SE) = 2.79 (1.27), P = 0.028, multivariable]. Further, late-occurring VMS were associated with both higher DNAm PhenoAge [B (SE) = 2.15 (0.84), P = 0.011] and DNAm GrimAge [B (SE) = 1.09 (0.42), P = 0.010, multivariable] relative to no VMS. Main Conclusions Among postmenopausal women, severe or late-occurring VMS were associated with accelerated epigenetic age, controlling for chronological age. Postmenopausal women with severe or late-occurring VMS may have greater underlying epigenetic aging.

Introduction The objectives of this study were to evaluate the prevalence and impact of moderate to severe vasomotor symptoms (VMS) on quality of life, sleep, work, and daily activities. We also assessed treatment patterns for VMS, lifestyle changes to mitigate VMS, and attitudes toward available treatments and menopause. Material and Methods Women from Denmark, Finland, Norway, and Sweden aged 40–65 years completed an online survey as part of a larger multinational study. The primary outcome, prevalence of moderate to severe VMS, was assessed in postmenopausal women. Secondary outcomes, including the impact of VMS on quality of life (Menopause‐Specific Quality of Life [MENQoL] questionnaire), sleep (Patient‐Reported Outcomes Measurement Information System [PROMIS] Sleep Disturbances‐Short Form 8b), and work and daily activities (Work Productivity and Activity Impairment [WPAI] questionnaire) were assessed in perimenopausal and postmenopausal women experiencing ≥1 moderate to severe hot flush per day in the prior month. Additionally, survey questions evaluated treatment patterns, lifestyle changes, and opinions toward VMS treatment and menopause in perimenopausal and postmenopausal women. Results Among 6383 postmenopausal women (primary analysis population), 739 (11.6%) experienced moderate to severe VMS regardless of whether they were receiving treatment. Among 863 symptomatic perimenopausal and postmenopausal women (secondary analysis population), VMS impaired quality of life and sleep. Work and daily activities were impaired by 24.2% and 30.6%, respectively. Around 35% of women sought advice; however, most women (>60%) reported not taking any treatment for VMS. Among those treating VMS, supplements and nonprescription medications were the most common treatments (19.2%); 12.9% of women reported taking menopausal hormone therapy. As many as 54.3% of women reported taking over‐the‐counter treatments; 77.8% adopted lifestyle changes to mitigate VMS. One in 4 women (25.6%) expressed concerns about menopausal hormone therapy side effects; 49.5% of women who had used nonmenopausal hormone therapy prescription medication stopped for lack of efficacy. Many women strongly agreed that menopause is a natural part of aging. Conclusions Over 10% of postmenopausal Nordic women reported suffering from moderate to severe VMS. VMS impaired the quality of life, sleep, work productivity, and daily activities among perimenopausal and postmenopausal Nordic women, emphasizing the need for effective and well‐tolerated treatments. This international cross‐sectional survey of women aged 40–65 years from Nordic Europe adds to global findings demonstrating that moderate to severe vasomotor symptoms are prevalent and impair quality of life, sleep, work productivity, and daily activities.