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Background: Vasomotor symptoms (VMS) are highly prevalent among midlife women and have been associated with subclinical cardiovascular disease (CVD). However, the association between VMS frequency and risk factors such as hypertension (HTN) remains unclear. Materials and Methods: We examined VMS frequency and blood pressure (BP) among 2839 participants of the Study of Women's Health Across the Nation (SWAN), a multiethnic, prospective, study of women enrolled from seven U.S. sites between November 1995 and October 1997. Women were age 42-52, with no history of CVD, and not postmenopausal at baseline. VMS was defined by the number of days a woman reported VMS over the 2-week period before each annual visit. Frequent VMS was defined as ≥6 days of VMS; less frequent VMS was defined 1-5 days of symptoms with asymptomatic women the reference group. BP was measured at each visit in addition to demographic and clinic factors. Results: At baseline, 298 women reported frequent VMS, 794 less frequent VMS and 1747 no VMS. More frequent baseline VMS was associated with higher BP. Compared to no VMS, baseline VMS was associated with HTN (odds ratio [OR] 1.47, 95% confidence interval [CI]; 1.14-1.88 for infrequent VMS, and OR 1.40, (95% CI; 0.97-2.02 for frequent VMS). Risk for incident pre-HTN or HTN during follow-up was increased among women with frequent VMS (hazard ratio of 1.39, 95% CI; 1.09-1.79) after adjustment for multiple covariates. Conclusion: Women with VMS may be more likely to develop HTN compared to women without VMS. Further research related to VMS including frequency of symptoms is warranted. [ABSTRACT FROM AUTHOR]

The article discusses a study which determined whether mood symptoms increased more for women after hysterectomy with or without bilateral oophorectomy relative to natural menopause. Hysterectomy is a common surgery performed on women in the U.S. accompanied by bilateral oophorectomy. Several factors considered in the study include race, educational attainment, menopausal status the year before final menstrual period or surgery, and annual measurements of body mass index (BMI).

A long-standing, but unproven hypothesis is that menopause symptoms cause cognitive difficulties during the menopause transition. This 6-year longitudinal cohort study of 1,903 midlife US women (2000–2006) asked whether symptoms negatively affect cognitive performance during the menopause transition and whether they are responsible for the negative effect of perimenopause on cognitive processing speed. Major exposures were depressive, anxiety, sleep disturbance, and vasomotor symptoms and menopause transition stages. Outcomes were longitudinal performance in 3 domains: processing speed (Symbol Digit Modalities Test (SDMT)), verbal memory (East Boston Memory Test), and working memory (Digit Span Backward). Adjustment for demographics showed that women with concurrent depressive symptoms scored 1 point lower on the SDMT (P < 0.05). On the East Boston Memory Test, the rate of learning among women with anxiety symptoms tested previously was 0.09 smaller per occasion (P = 0.03), 53% of the mean learning rate. The SDMT learning rate was 1.00 point smaller during late perimenopause than during premenopause (P = 0.04); further adjustment for symptoms did not attenuate this negative effect. Depressive and anxiety symptoms had a small, negative effect on processing speed. The authors found that depressive, anxiety, sleep disturbance, and vasomotor symptoms did not account for the transient decrement in SDMT learning observed during late perimenopause. [ABSTRACT FROM PUBLISHER]

OBJECTIVES: The purpose of this study was to estimate risk factors for the deterioration and improvement of premenstrual mood disturbance with oral contraceptive pill use. STUDY DESIGN: Predictors of the deleterious and beneficial effects of oral contraceptive pill use on premenstrual mood were analyzed with the use of logistic regression in a nested case-control study within a community-based cohort of 976 premenopausal women in Massachusetts. RESULTS: Of 658 women who were using oral contraceptive pills, 16.3% of the women reported oral contraceptive pill-related premenstrual mood deterioration, and 12.3% of the women reported premenstrual mood improvement. In adjusted models, previous depression was the only significant predictor of mood deterioration (odds ratio, 2.0; 95% CI, 1.1-3.8); early-onset premenstrual mood disturbance and dysmenorrhea were significant predictors of oral contraceptive pill-related mood improvement (odds ratio, 3.1 [95% CI, 1.9-5.2] and odds ratio, 2.3 [95% CI, 1.4-3.9], respectively). CONCLUSION: Oral contraceptive pills do not influence premenstrual mood in most women. Premenstrual mood is most likely to deteriorate in women with a history of depression and to improve in women with early-onset premenstrual mood disturbance or dysmenorrhea. Key words: Oral contraceptive pill; depression; premenstrual mood syndrome. [ABSTRACT FROM AUTHOR]

Recent census data indicate that, in the United States, an increasing number of women—almost 1.5 million each year—are reaching menopause. The menopausal transition is marked by intense hormonal fluctuations, and may be accompanied by vasomotor complaints, sleep disturbances, changes in sexual function, and increased risk for osteoporosis and cardiovascular disease. In addition, there is evidence of increased risk for developing depression, even among women who never experienced depressive symptoms before. Thus depression during the perimenopause may have a substantial impact on personal, family, and professional spheres of life. A challenge to clinicians and health professionals lies in the identification of the most tolerable treatments to manage depression and improve quality of life in an aging population. Any treatment strategy should take into account not only the spectrum of side effects that may complicate treatment but also other menopause-related factors (e.g., vasomotor symptoms, psychosocial stressors) that may modulate risk for the development of mood disturbance. This article reviews the current literature on the prevalence and risk factors associated with depression during the menopausal transition. The benefits and risks of using hormonal and nonhormonal strategies for the management of depression and other menopause-related somatic symptoms are critically reviewed. [Copyright &y& Elsevier]

Historically, females have been underrepresented in clinical trials evaluating the safety and efficacy of investigational drugs and devices. We assessed participation by sex in recent clinical trials. We extracted data over a 4-year period (2016–2019) from ClinicalTrials.gov on US-based, pharmaceutical industry or government-funded Phase 1–3 clinical trials of drugs and devices. We included trials with adult cardiovascular, psychiatric, and cancer endpoints whose protocol planned to enroll both sexes. Average proportions of females enrolled per trial were described overall and by disease area. Across 1433 trials including 302,664 participants in our analysis, on average, 41.2% were female. Females were underrepresented compared with their proportion of the disease population in cardiovascular disease trials (41.9% female participants vs. 49% female population with cardiovascular disease). In psychiatry, where females comprise 60% of patients, the mean participation of females in clinical trials was 42.0%. Similarly, for cancer trials, where 51% of patients are female, only 41.0% of cancer clinical trial participants were female. For each therapeutic area analyzed, the participation of females in clinical trials fell short of the benchmark derived from national prevalence data. While the participation of females in clinical trials has improved compared to previous reports, sex-based gaps still persist between trial populations and those expected to use these drugs/devices based on distributions of diseases in the population. Given potential sex-based differences in treatment responses and toxicities, adequate inclusion of females in clinical trials remains critical. [ABSTRACT FROM AUTHOR]

Background: Women may be vulnerable to elevated depressive symptoms during the menopause transition (MT). Studies generally have not considered premenopausal depressive symptom history or examined symptoms in relation to the final menstrual period (FMP)., Objective: To identify specific time points in relation to the FMP when depressive symptoms increase or decrease., Methods: Participants were 1582 multiracial/ethnic women from the longitudinal Study of Women's Health Across the Nation (SWAN). Biological, psychosocial, and depressive symptom data were collected approximately annually. Depressive symptoms were measured by the Center for Epidemiological Studies-Depression (CESD) scale., Results: Women with high baseline depressive symptoms (CES-D ≥ 16) declined in symptoms (M = -1.04/yr., 95 % CI = -1.58, -0.50) until 4 years before the FMP, followed by a smaller decrease (M = -0.50/yr., 95 % CI = -0.72, -0.28) until 18 months after the FMP. Depressive symptoms increased (M = 0.21/yr., 95 % CI = 0.11, 0.30) in those with low baseline symptoms until 1 year before the FMP, and decreased (M = -0.06/yr., 95 % CI = -0.11, -0.008) going forward. Greater social support, higher levels of follicle stimulating hormone and estradiol, and less sleep disturbance contributed to greater decline in depressive symptoms among those with high baseline depressive symptoms. Anxiety, experiencing stressful life events, lower body mass index, and poor role-physical function contributed to an increase in depressive symptoms among those with low baseline symptoms., Limitations: Excluded women had higher baseline CES-D scores. Lacked pre-MT depression for pre/early perimenopausal women at baseline., Conclusion: Accounting for baseline depressive symptom level and focusing on the FMP more precisely characterize depressive symptom change over the MT., Competing Interests: Declaration of competing interest Dr. Joffe is a consultant/advisory board member for Bayer, Merck, and Hello Therapeutics, and has grant/research support from Merck, Sage, and Pfizer., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Depressive symptoms and sleep disturbances disproportionately affect midlife women. While there may be a bidirectional association, few studies have examined whether depressive symptoms are longitudinally associated with subsequent sleep. Sleep is typically considered unidimensional, despite emerging evidence that multidimensional sleep health provides novel information on the sleep-health link., Purpose: The current study examined whether higher depressive symptoms were longitudinally associated with poorer multidimensional sleep health., Method: Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale across six to nine annual assessments in 302 midlife women from the Study of Women's Health Across the Nation. Six months after their last assessment, actigraphy (mean ± standard deviation = 29.3 ± 6.9 days) and self-report were used to assess sleep health components: efficiency, duration, mid-sleep timing, regularity, alertness, and satisfaction, which were dichotomized and summed to create a composite multidimensional sleep health score. Mixed-effects models were used to evaluate the longitudinal associations between depressive symptoms and multidimensional sleep health, as well as individual sleep health components, adjusting for covariates. Exploratory analyses stratified models by race/ethnicity., Results: Higher depressive symptoms were associated with subsequent poorer multidimensional sleep health (p < .0.001) and lower alertness (p < .0001) and satisfaction with sleep (p < .0001)., Conclusions: Our finding that higher average depressive symptoms were associated longitudinally with actigraphy-measured poorer sleep health in midlife women is novel and converges with the larger body of evidence that these two common symptoms are strongly associated. The bidirectional relationship between these two prevalent symptoms needs to be studied in prospective longitudinal studies., (© Society of Behavioral Medicine 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The menopausal transition is characterized by progressive changes in ovarian function and increasing circulating levels of gonadotropins, with some women having irregular menstrual cycles well before their final menstrual period. These observations indicate a progressive breakdown of the hypothalamic-pituitary-ovarian axis often associated with an increase in menopausal symptoms. Relationships between vasomotor symptoms (VMS) and depressed mood and sleep as well as a bidirectional association between VMS and depressed mood in mid-life women have been reported, but the endocrine foundations and hormone profiles associated with these symptoms have not been well described. Our objective was to determine the relationship between daily urinary hormone profiles and daily logs of affect and VMS during the early perimenopausal transition., Study Design: SWAN, the Study of Women's Health Across the Nation, is a large, mutli-ethnic, multisite cohort study of 3302 women aged 42-52 at baseline, designed to examine predictors of health and disease in women as they traversed the menopause. Inclusion criteria were: an intact uterus and at least one ovary present, at least one menstrual period in the previous three months, no use of sex steroid hormones in the previous three months, and not pregnant or lactating. A subset (n = 849) of women aged 43-53 years from all study sites in the first Daily Hormone Study collection were evaluated for this substudy., Outcome Measures: We measured daily VMS, and urinary hormones: follicle stimulating hormone (FSH), luteinizing hormone (LH), pregnanediol glucuronide (PdG) and estradiol (estrone conjugate, E1C)., Results: A variable pattern of LH and negative LH feedback were the hormone patterns most strongly associated with increased VMS. In contrast, no hormone pattern was significantly related to negative mood., Conclusion: Fluctuations of LH associated with low progesterone production were associated with VMS but not negative mood, suggesting different endocrine patterns may be related to increased negative mood than to the occurrence of VMS., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background Cardiovascular disease (CVD) in women has unique features, including associations with reproductive factors that are incompletely understood. Vasomotor symptoms (VMS), the classic menopausal symptom, are linked to CVD risk factors and subclinical CVD. Evidence linking VMS to CVD events is limited. We tested whether frequent and/or persistent VMS were associated with increased risk for fatal and nonfatal CVD events in SWAN (Study of Women's Health Across the Nation). Methods and Results A total of 3083 women, aged 42 to 52 years at baseline, underwent up to 16 in-person visits over 22 years. Assessments included questionnaires on VMS frequency (0, 1-5, or ≥6 days/2 weeks), physical measures, phlebotomy, and reported CVD events (myocardial infarction, stroke, heart failure, and revascularization). A subset of events was adjudicated via medical record. Death certificates were obtained. Relationships between baseline VMS or persistent VMS over the follow-up (proportion of visits with frequent VMS) with combined incident nonfatal and fatal CVD were tested in Cox proportional hazards models adjusted for demographics, medication use, and CVD risk factors. Participants experienced 231 CVD events over the follow-up. Women with frequent baseline VMS had an elevated risk of subsequent CVD events (relative to no VMS; ≥6 days: hazard ratio [HR] [95% CI], 1.51 [1.05-2.17], P =0.03; 1-5 days: HR [95% CI], 1.02 [0.75-1.39], P =0.89, multivariable). Women with frequent VMS that persisted over time also had an increased CVD event risk (>33% versus ≤33% of visits: HR [95% CI], 1.77 [1.33-2.35], P <0.0001, multivariable). Conclusions Frequent and persistent VMS were associated with increased risk of later CVD events. VMS may represent a novel female-specific CVD risk factor.

Objectives: The association between sleep and adiposity (indexed by body mass index or waist-to-hip ratio) has typically been evaluated using a single dimension of self-reported sleep. However, other dimensions and behavioral measures of sleep may also be associated with adiposity. This study evaluated whether multidimensional sleep health calculated from actigraphy and self-report was longitudinally associated with adiposity in a sample of midlife women who have a high prevalence of sleep disturbances and adiposity., Design: Longitudinal study with 11-14 years of follow-up time between the sleep health assessment and body mass index / waist-to-hip ratio measurements., Participants: Two hundred and twenty-one midlife women enrolled in the Study of Women's Health Across the Nation Sleep Study., Measurements: Multidimensional sleep health was quantified using actigraphy (M[SD] = 29.1[7.2] nights) measures of sleep efficiency, midpoint, duration, regularity, and self-report measures of alertness and satisfaction. Each component was dichotomized and summed; higher values indicated better sleep health. Height, body weight, and waist and hip circumference were measured at the sleep study and at follow-up. Linear regression models were used to assess associations between sleep health and adiposity, adjusting for demographic and menopausal covariates., Results: There was no substantial within-person change in adiposity over time. Better sleep health was cross-sectionally and longitudinally associated with lower adiposity in unadjusted, but not in adjusted, models. Individual sleep health components were not associated with adiposity after adjustment., Conclusion: We did not observe cross-sectional or longitudinal associations between multidimensional sleep health and adiposity. The sleep-adiposity link may be weaker in midlife adults than in other age groups., (Copyright © 2020 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Background: A test that helps predict the time to the final menstrual period (FMP) has been sought for many years., Objective: To assess the ability of antimullerian hormone (AMH) measurements to predictions the time to FMP., Design: Prospective longitudinal cohort study., Setting: The Study of Women's Health Across the Nation., Participants and Measurements: AMH and FSH were measured in 1537 pre- or early perimenopausal women, mean age 47.5 ± 2.6 years at baseline, then serially until 12 months of amenorrhea occurred. AMH was measured using a 2-site ELISA with a detection limit of 1.85 pg/mL., Main Outcome Measure: Areas under the receiver operating curves (AUC) for AMH-based and FSH-based predictions of time to FMP, stratified by age. Probabilities that women would undergo their FMP in the next 12, 24, or 36 months across a range of AMH values were assessed., Results: AUCs for predicting that the FMP will occur within the next 24 months were significantly greater for AMH-based than FSH-based models. The probability that a woman with an AMH <10 pg/mL would undergo her FMP within the next 12 months ranged from 51% at h<48 years of age to 79% at ≥51 years. The probability that a woman with an AMH >100 pg/mL would not undergo her FMP within the next 12 months ranged from 97% in women <48 years old to 90% in women ≥51 years old., Conclusions: AMH measurement helps estimate when a woman will undergo her FMP, and, in general, does so better than FSH., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Objectives: To describe racial/ethnic differences in sleep duration, continuity, and perceived sleep quality in postmenopausal women and to identify statistical mediators of differences in sleep characteristics., Methods: Recruited from the observational Study of Women's Health Across the Nation (SWAN), 1,203 (548 white, 303 black, 147 Chinese, 132 Japanese, and 73 Hispanic; mean age 65 years, 97% postmenopausal) women participated in a week-long actigraphy and daily diary study in 2013-2015. Actigraphic measures of sleep duration and wake after sleep onset (WASO), and diary-rated sleep quality were averaged across the week. Candidate mediators included health-related variables; stress; and emotional well-being assessed up to 13 times across 18 years from baseline to sleep study., Results: Whites slept longer than other groups; the significant mediators were concurrent financial hardship and increasing number of stressors for Hispanics or Japanese versus whites. Whites had less WASO than blacks and Hispanics; significant mediators were concurrent number of health problems, physical inactivity, waist circumference, vasomotor symptoms, number of life stressors, and financial hardship, and increasing number of health problems from baseline to sleep study. Whites reported better sleep quality than blacks, Chinese, and Japanese; significant mediators were concurrent physical inactivity, vasomotor symptoms, positive affect, and depressive symptoms., Conclusions: Sleep differences between blacks or Hispanics versus whites were mediated by health problems, number of stressors, and financial hardship, whereas sleep differences between Chinese or Japanese versus whites were mediated by emotional well-being. This is the first study using formal mediational approaches., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Background: Psychosocial and health-related risk factors for depressive symptoms are known. It is unclear if these are associated with depressive symptom patterns over time. We identified trajectories of depressive symptoms and their risk factors among midlife women followed over 15 years., Methods: Participants were 3300 multiracial/ethnic women enrolled in a multisite longitudinal menopause and aging study, Study of Women's Health Across the Nation. Biological, psychosocial, and depressive symptom data were collected approximately annually. Group-based trajectory modeling identified women with similar longitudinal patterns of depressive symptoms. Trajectory groups were compared on time-invariant and varying characteristics using multivariable multinomial analyses and pairwise comparisons., Results: Five symptom trajectories were compared (50% very low; 29% low; 5% increasing; 11% decreasing; 5% high). Relative to whites, blacks were less likely to be in the increasing trajectory and more likely to be in the decreasing symptom trajectory and Hispanics were more likely to have a high symptom trajectory than an increasing trajectory. Psychosocial/health factors varied between groups. A rise in sleep problems was associated with higher odds of having an increasing trajectory and a rise in social support was associated with lower odds. Women with low role functioning for 50% or more visits had three times the odds of being in the increasing symptom group., Conclusions: Changes in psychosocial and health characteristics were related to changing depressive symptom trajectories. Health care providers need to evaluate women's sleep quality, social support, life events, and role functioning repeatedly during midlife to monitor changes in these and depressive symptoms.

Objective: To better understand how to educate patients and providers about study findings relevant to treatment guidelines, we assessed pre- versus post-Women's Health Initiative (WHI) differences in menopausal hormone therapy (MHT) initiation and continuation and their correlates, and in women's reasons for initiation and discontinuation., Methods: We analyzed survey data from up to 14 approximately annual visits over 17 years (1996-2013) from 3,018 participants in the Study of Women's Health Across the Nation, a prospective cohort study. We used logistic regression to compare pre- versus post-WHI associations of covariates with MHT initiation and continuation, and to compare pre- versus post-WHI reasons for initiation and continuation., Results: MHT initiation dropped from 8.6% pre-WHI to 2.8% post-WHI (P < 0.0001), and the corresponding decrease in MHT continuation was 84.0% to 62.0% (P < 0.0001). Decreases in MHT initiation and continuation occurred across a range of participant subgroups, consistent with wide dissemination of post-WHI recommendations. However, contrary to current guidelines, we found large declines in MHT use in subgroups for whom MHT is often recommended, that is, younger women and those with more vasomotor symptoms. Post-WHI, women's reasons for MHT initiation and discontinuation reflected concerns highlighted by WHI results. The largest declines in initiation reasons were for reducing risks of osteoporosis and heart disease, whereas the largest increases in discontinuation reasons were for media reports and provider advice., Conclusions: Immediate post-WHI recommendations for MHT use were widely adopted. MHT risks documented in older women, however, may have led younger symptomatic women to forgo MHT for symptom relief.

Objective: HIV-infected women are burdened by depression and anxiety, which may impact adherence to antiretroviral therapy and overall quality of life. Yet, little is known about the scope of psychological symptoms in the growing number of HIV-infected women reaching menopause, when affective symptoms are more prevalent in the general population. We conducted a longitudinal study to compare affective symptoms between perimenopausal HIV-infected and non-HIV-infected women., Methods: The Center for Epidemiologic Studies Depression Scale (CES-D), and the Generalized Anxiety Disorder scale (GAD-7) were completed at baseline and 12 months among 33 HIV-infected and 33 non-HIV-infected perimenopausal women matched by race, age, menstrual patterns, and BMI. Linear regression models estimated the relationship of baseline GAD-7 and CES-D scores with clinical factors., Results: All women were perimenopausal at baseline, and the vast majority remained perimenopausal throughout follow-up. HIV status was associated with higher baseline CES-D scores (median [interquartile range] 21 [12, 29] vs 10 [5, 14]; P = 0.03) and GAD-7 scores (7 [5, 15] vs 2 [1, 7]; P = 0.01), controlling for smoking, substance use, and antidepressant use. Depressive symptoms and anxiety remained significantly higher in the HIV-infected women at 12 months (P ≤ 0.01). Significant relationships of depressive symptoms (P = 0.048) and anxiety (P = 0.02) with hot flash severity were also observed., Conclusions: Perimenopausal HIV-infected women experienced a disproportionately high level of affective symptom burden over a 12-month observation period. Given the potential for these factors to influence adherence to HIV clinical care and quality of life, careful assessment and referral for treatment of these symptoms is essential.

Objective: The aim of the study was to investigate the heterogeneity of temporal patterns of vasomotor symptoms (VMS) over the menopausal transition and identify factors associated with these patterns in a diverse sample of women., Methods: The Study of Women's Health Across the Nation is a multisite longitudinal study of women from five racial/ethnic groups transitioning through the menopause. The analytic sample included 1,455 women with nonsurgical menopause and a median follow-up of 15.4 years. Temporal patterns of VMS and associations with serum estradiol and follicle-stimulating hormone, race/ethnicity, body mass index, and demographic and psychosocial factors were examined using group-based trajectory modeling., Results: Four distinct trajectories of VMS were found: onset early (11 years before the final menstrual period) with decline after menopause (early onset, 18.4%), onset near the final menstrual period with later decline (late onset, 29.0%), onset early with persistently high frequency (high, 25.6%), and persistently low frequency (low, 27.0%). Relative to women with persistently low frequency of VMS, women with persistently high and early onset VMS had a more adverse psychosocial and health profile. Black women were overrepresented in the late onset and high VMS subgroups relative to white women. Obese women were underrepresented in the late onset subgroup. In multivariable models, the pattern of estradiol over the menopause was significantly associated with the VMS trajectory., Conclusions: These data distinctly demonstrate heterogeneous patterns of menopausal symptoms that are associated with race/ethnicity, reproductive hormones, premenopause body mass index, and psychosocial characteristics. Early targeted intervention may have a meaningful impact on long-term VMS.

Background and Purpose: Emerging work has linked menopausal vasomotor symptoms (VMS) to subclinical cardiovascular disease (CVD) among women. However, VMS are dynamic over time. No studies have considered how temporal patterns of VMS may relate to subclinical CVD. We tested how temporal patterns of VMS assessed over 13 years were related to carotid intima media thickness (IMT) among midlife women., Methods: The Study of Women's Health Across the Nation is a longitudinal cohort study of midlife women. Eight hundred and eleven white, black, Hispanic, and Chinese participants with a well-characterized final menstrual period completed measures of VMS, a blood draw, and physical measures approximately annually for 13 years. Women underwent a carotid artery ultrasound at study visit 12., Results: Four trajectories of VMS were identified by trajectory analysis (consistently high, early-onset, late-onset, persistently low VMS) and tested in relation to carotid indices in linear regression models. Results indicated that women with early-onset VMS had both greater mean IMT (beta, b [standard error, SE]=0.03 [0.01], P=0.03) and greater maximal IMT (b [SE]=0.04 [0.01], P=0.008) than women with consistently low VMS, adjusting for demographics and CVD risk factors., Conclusions: This is the first study to test trajectories of VMS in relation to subclinical CVD. Women with VMS early in the menopause transition had higher mean IMT and maximal IMT than those with consistently low VMS across the transition. Associations were not accounted for by demographic factors nor by CVD risk factors. Results can signal to women in need of early CVD risk reduction., (© 2015 American Heart Association, Inc.)

Importance: The expected duration of menopausal vasomotor symptoms (VMS) is important to women making decisions about possible treatments., Objectives: To determine total duration of frequent VMS (≥ 6 days in the previous 2 weeks) (hereafter total VMS duration) during the menopausal transition, to quantify how long frequent VMS persist after the final menstrual period (FMP) (hereafter post-FMP persistence), and to identify risk factors for longer total VMS duration and longer post-FMP persistence., Design, Setting, and Participants: The Study of Women's Health Across the Nation (SWAN) is a multiracial/multiethnic observational study of the menopausal transition among 3302 women enrolled at 7 US sites. From February 1996 through April 2013, women completed a median of 13 visits. Analyses included 1449 women with frequent VMS., Main Outcomes and Measures: Total VMS duration (in years) (hot flashes or night sweats) and post-FMP persistence (in years) into postmenopause., Results: The median total VMS duration was 7.4 years. Among 881 women who experienced an observable FMP, the median post-FMP persistence was 4.5 years. Women who were premenopausal or early perimenopausal when they first reported frequent VMS had the longest total VMS duration (median, >11.8 years) and post-FMP persistence (median, 9.4 years). Women who were postmenopausal at the onset of VMS had the shortest total VMS duration (median, 3.4 years). Compared with women of other racial/ethnic groups, African American women reported the longest total VMS duration (median, 10.1 years). Additional factors related to longer duration of VMS (total VMS duration or post-FMP persistence) were younger age, lower educational level, greater perceived stress and symptom sensitivity, and higher depressive symptoms and anxiety at first report of VMS., Conclusions and Relevance: Frequent VMS lasted more than 7 years during the menopausal transition for more than half of the women and persisted for 4.5 years after the FMP. Individual characteristics (eg, being premenopausal and having greater negative affective factors when first experiencing VMS) were related to longer-lasting VMS. Health care professionals should counsel women to expect that frequent VMS could last more than 7 years, and they may last longer for African American women.

Context: Emerging research suggests links between menopausal hot flashes and cardiovascular disease risk. The mechanisms underlying these associations are unclear, due to the incomplete understanding of the physiology of hot flashes. OBJECTIVE AND MAIN OUTCOME MEASURES: We examined the associations between hot flashes/night sweats and glucose and insulin resistance over 8 yr, controlling for cardiovascular risk factors and reproductive hormones., Design, Setting, and Participants: Participants in the Study of Women's Health Across the Nation (SWAN) (n=3075), a longitudinal cohort study, were ages 42-52 yr at entry. Women completed questionnaires (hot flashes, night sweats: none, 1-5 d, ≥6 d, past 2 wk), physical measures (blood pressure, height, weight), and a fasting blood draw [serum glucose, insulin, estradiol (E2), FSH] annually for 8 yr. Hot flashes/night sweats were examined in relation to glucose and the homeostasis model assessment (HOMA) in mixed models, adjusting for demographics, cardiovascular risk factors, medications, and E2/FSH., Results: Compared to no flashes, hot flashes were associated with a higher HOMAlog index [vs. none; hot flashes, 1-5 d: % difference (95% confidence interval), 2.37 (0.36-4.43), P=0.02; and ≥6 d: 5.91 (3.17-8.72), P<0.0001] in multivariable models that included body mass index. Findings persisted adjusting for E2 or FSH, and were similar for night sweats. Findings were statistically significant, yet modest in magnitude, for the outcome glucose., Conclusions: Hot flashes were associated with a higher HOMA index, an estimate of insulin resistance, and to a lesser extent higher glucose. Metabolic factors may be relevant to understanding the link between hot flashes and cardiovascular disease risk.

Objective: The aim of this study was to examine the association of a history of major depression (MD) with menstrual problems in a multiethnic sample of midlife women., Methods: Participants were 934 women enrolled in the Study of Women's Health Across the Nation, a multisite study of menopause and aging. The outcomes were menstrual bleeding problems and premenstrual symptoms in the year before study entry. The Structured Clinical Interview for the Diagnosis of DSM-IV Axis I Disorders was conducted to determine recent and past psychiatric diagnoses. Covariates included sociodemographic, behavioral, and gynecologic factors., Results: One third of the participants reported heavy bleeding, 20% reported other abnormal bleeding, and 18% reported premenstrual symptoms. One third had past and 11% had recent MD. Past MD was associated with an increased likelihood of heavy bleeding (odds ratio, 1.89; 95% CI, 1.25-2.85), adjusting for recent MD, menopause status, and other covariates. Past MD was not associated with other abnormal bleeding or premenstrual symptoms in the final analysis that adjusted for recent MD., Conclusions: Midlife women with a history of MD are more likely to report heavy bleeding.

Vasomotor symptoms (VMS), or hot flashes and night sweats, are often considered the cardinal symptoms of menopause. SWAN, one of the largest and most ethnically diverse longitudinal studies of the menopausal transition, has allowed unique insights into VMS. Specifically, SWAN has helped yield important information about the prevalence of, racial/ethnic differences in, risk factors for, and implications of VMS for midlife women's mental and physical health. We have reviewed the literature on VMS, emphasizing findings that have emerged from SWAN and new areas of inquiry in the area of VMS.

Is there evidence for a perimenopausal sleep disorder? We address this question in our presentation of the Study of Women's Health Across the Nation (SWAN) "sleep story," in which we summarize and discuss data addressing sleep quality, objective measures of sleep patterns, and sleep disorders that have been published to date by the SWAN and the ancillary SWAN Sleep Study. We describe what has been learned about sleep during the perimenopause. Analyses exploring racial/ethnic diversity and the role of hot flashes and mood disturbance in sleep-perimenopause associations are described. Implications for clinical practice are considered.

Although most women report vasomotor symptoms (hot flashes, night sweats) during midlife, their etiology and risk factors are incompletely understood. Body fat is positively associated with vasomotor symptoms cross-sectionally, but the longitudinal relation between changes in body fat and vasomotor symptoms is uncharacterized. The study aim was to examine whether gains in body fat were related to vasomotor symptom reporting over time. Measures of bioelectrical impedance for body fat, reproductive hormones, and reported vasomotor symptoms were assessed annually over 4 years from 2002 to 2006 among 1,659 women aged 47-59 years participating in the Study of Women's Health Across the Nation. Body fat change was examined in relation to vasomotor symptoms by using generalized estimating equations. Body fat gains were associated with greater odds of reporting hot flashes in models adjusted for age, site, race/ethnicity, education, smoking, parity, anxiety, and menopausal status (relative to stable body fat, gain: odds ratio = 1.23, 95% confidence interval: 1.02, 1.48; P = 0.03; loss: odds ratio = 1.07, 95% confidence interval: 0.89, 1.29; P = 0.45). Findings persisted controlling for estradiol, the free estradiol index, or follicle-stimulating hormone concentrations. The relations between body fat changes and night sweats were not statistically significant. Body fat gains are associated with greater hot flash reporting during the menopausal transition.

Objective: Most menopausal women report vasomotor symptoms (hot flashes, night sweats). However, not all women with vasomotor symptoms, including frequent symptoms, are bothered by them. The primary aim was to identify correlates of vasomotor symptom bother beyond symptom frequency., Design: The Study of Women's Health Across the Nation participants reporting vasomotor symptoms at annual visit 7 comprised the sample (N = 1,042). Assessments included hot flash and night sweats frequency (number per week) and bother (1, not at all- 4, very much). Negative affect (index of depressive symptoms, anxiety, perceived stress, negative mood), symptom sensitivity, sleep problems, and vasomotor symptom duration (number of years) were examined cross-sectionally in relation to bother in ordinal logistic regression models with symptom frequency and covariates. Hot flashes and night sweats were considered separately., Results: In multivariable models controlling for hot flash frequency, negative affect (odds ratio [OR] = 1.27, 95% CI: 1.08-1.51), symptom sensitivity (OR = 1.18, 95% CI: 1.03-1.37), sleep problems (OR = 1.38, 95% CI: 1.04-1.85), poorer health (OR = 1.24, 95% CI: 1.03-1.48), duration of hot flashes (OR = 1.14, 95% CI: 1.06-1.23), younger age (OR = 0.94, 95% CI: 0.89-0.99), and African American race (vs white, OR = 1.59, 95% CI: 1.12-2.26) were associated with hot flash bother. After controlling for night sweats frequency and covariates, sleep problems (OR = 1.84, 95% CI:1.33-2.55) and night sweats duration (OR = 1.10, 95% CI: 1.02-1.20) were associated with night sweats bother., Conclusions: Beyond frequency, factors associated with bothersome hot flashes include mood, symptom sensitivity, symptom duration, sleep problems, age, and race. Correlates of bothersome night sweats include sleep problems and symptom duration. In addition to reducing frequency, interventions for vasomotor symptoms might consider addressing modifiable factors related to symptom bother.

The associations of urinary pregnanediol-glucuronide (PdG) levels and menstrual bleeding and their modification of associations of other risk factors with vasomotor symptoms (VMS) are examined. Daily urine samples were collected for 1 menstrual cycle or 50 days if no bleeding occurred. Participants (n = 742) were aged 43 to 54 years, not using exogenous hormones, not pregnant, had an intact uterus and > 1 ovary, and menstruated in the prior 3 months. Multivariate analyses were performed of urinary hormone metabolites and within-woman proportion of days reporting VMS. VMS reporting was 4-fold greater (P = .0005) in women whose urine collections ended without bleeding. In collections with PdG levels suggestive of ovulatory activity according to the work of Kassam et al, VMS are significantly associated with obesity, early perimenopause, and increasing PdG levels. In collections with lower PdG concentrations, VMS are significantly increased with no bleeding, smoking, higher age, physical activity, follicle-stimulating hormone, and luteinizing hormone and are significantly reduced with increasing estrogen concentrations.

Objective: Data are scarce regarding the sociodemographic predictors of antenatal and postpartum depression. This study investigated whether race/ethnicity, age, finances, and partnership status were associated with antenatal and postpartum depressive symptoms., Setting: 1662 participants in Project Viva, a US cohort study., Design: Mothers indicated mid-pregnancy and six month postpartum depressive symptoms on the Edinburgh postpartum depression scale (EPDS). Associations of sociodemographic factors with odds of scoring >12 on the EPDS were estimated., Main Results: The prevalence of depressive symptoms was 9% at mid-pregnancy and 8% postpartum. Black and Hispanic mothers had a higher prevalence of depressive symptoms compared with non-Hispanic white mothers. These associations were explained by lower income, financial hardship, and higher incidence of poor pregnancy outcome among minority women. Young maternal age was associated with greater risk of antenatal and postpartum depressive symptoms, largely attributable to the prevalence of financial hardship, unwanted pregnancy, and lack of a partner. The strongest risk factor for antenatal depressive symptoms was a history of depression (OR = 4.07; 95% CI 3.76, 4.40), and the strongest risk for postpartum depressive symptoms was depressive symptoms during pregnancy (6.78; 4.07, 11.31) or a history of depression before pregnancy (3.82; 2.31, 6.31)., Conclusions: Financial hardship and unwanted pregnancy are associated with antenatal and postpartum depressive symptoms. Women with a history of depression and those with poor pregnancy outcomes are especially vulnerable to depressive symptoms during the childbearing year. Once these factors are taken in account, minority mothers have the same risk of antenatal and postpartum depressive symptoms as white mothers.