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Objectives: To examine the associations of actigraphy-assessed sleep timing and regularity with psychological health in early late life women, whose circadian rhythms may be impacted by aging., Design: Cross-sectional., Participants: A racially/ethnically diverse sample of 1197 community-dwelling women (mean age 65 years) enrolled in the Study of Women's Health Across the Nation., Measures: Actigraphy-assessed sleep measures included timing (mean midpoint from sleep onset to wake-up) and regularity (standard deviation of midpoint in hours). Psychological health measures included a composite well-being score, the Center for Epidemiological Studies Depression Scale, and the Generalized Anxiety Disorder-7 Scale. Linear and logistic regression models, adjusted for covariates (including sleep duration), tested associations between sleep and psychological health measures., Results: After covariate adjustment, a sleep midpoint outside of 2:00-4: 00 AM was significantly associated with depressive symptoms (β = 0.88, 95% CI = 0.06, 1.70) and scoring above the cut-point for clinically significant depressive symptoms (OR = 1.72, 95% CI = 1.15, 2.57). Sleep irregularity was significantly associated with lower psychological well-being (β = -0.18, 95% CI = -0.33, -0.03), depressive (β = 1.36, 95% CI = 0.29, 2.44) and anxiety (β = 0.93, 95% CI = 0.40, 1.46) symptoms, and scoring above the cut-point for clinically significant depressive (OR = 1.68, 95% CI = 1.01, 2.79) and anxiety (OR = 1.62, 95% CI = 1.07, 2.43) symptoms., Conclusion: Above and beyond sleep duration, a sleep midpoint outside of 2:00-4:00 AM was associated with depressive symptoms while sleep irregularity was associated with multiple psychological health domains in late life women., Competing Interests: Declaration of conflicts of interest The authors have declared no conflicts of interest., (Copyright © 2022 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Study Objectives: To evaluate how change in menopausal status related to spectral analysis and polysomnographic measures of sleep characteristics., Methods: The Study of Women's Health Across the Nation (SWAN) Ancillary Sleep Study evaluated sleep characteristics of 159 women who were initially pre- or early perimenopausal and repeated the assessment about 3½ years later when 38 were pre- or early perimenopausal, 31 late perimenopausal, and 90 postmenopausal. Participants underwent in-home ambulatory polysomnography for two to three nights. Average EEG power in the delta and beta frequency bands was calculated during NREM and REM sleep, and sleep duration, wake after sleep onset (WASO), and apnea hypopnea index (AHI) were based on visually-scored sleep., Results: The women who transitioned to postmenopause had increased beta NREM EEG power at the second assessment, compared to women who remained pre-or early premenopausal; no other sleep measures varied by change in menopausal status. In multivariate models the associations remained; statistical controls for self-reported hot flashes did not explain findings. In secondary analysis, NREM beta power at the second assessment was greater among women who transitioned into the postmenopause after adjustments for initial NREM beta power., Conclusions: Sleep duration and WASO did not vary by menopause transition group across assessments. Consistent with prior cross-sectional analysis, elevated beta EEG power in NREM sleep was apparent among women who transitioned to postmenopause, suggesting that independent of self-reported hot flashes, the menopausal transition is associated with physiological hyperarousal during sleep., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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.)

Study Objectives: To determine whether actigraphy-assessed indices of sleep are associated with cognitive performance in women, and explore whether these associations vary by race/ethnicity., Methods: Participants were 1,126 postmenopausal community-dwelling females (mean age 65 years) from the observational Study of Women's Health Across the Nation (SWAN); 25% were black, 46% white, 13% Chinese, 11% Japanese, and 5% Hispanic. Actigraphy-assessed sleep measures included total sleep time, wake after sleep onset (WASO), and fragmentation. Cognitive measures included immediate and delayed verbal memory, working memory, and information processing speed. All measures were assessed in conjunction with SWAN annual visit 15., Results: Across the sample, after covariate adjustment, greater WASO and fragmentation were concurrently associated with slower information processing speed. Black participants had significantly worse sleep relative to other race/ethnic groups. Significant race/sleep interactions were observed; in black, but not white, participants, greater fragmentation was concurrently associated with worse verbal memory and slower information processing speed, and greater WASO was concurrently associated with slower information processing speed. Sleep-cognitive performance associations were not different in Chinese and Japanese participants relative to white participants., Conclusions: Greater wakefulness and fragmentation during sleep are concurrently associated with slower information processing. Sleep continuity impacted concurrent cognitive performance in black, but not white, women. This effect may not have been detected in white women because their sleep was largely within the normal range. Future longitudinal studies in diverse samples are critical to further understand whether race/ethnicity moderates the influence of sleep on cognitive performance., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

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.)

Our study objectives were to evaluate the age-related changes in actigraphy measures of sleep duration, continuity, and timing across 12 years in midlife women as they traversed the menopause, and to take into account factors affecting women's sleep that also change with age. Black, white, and Chinese women were recruited from the Study of Women's Health Across the Nation (SWAN) to participate in an ancillary sleep study on two occasions over 3 years apart and a third assessment 12 years after the first (N = 300, mean ages, 52, 55, and 64 at the three assessments). Women had at least four consecutive nights of actigraphy (95% with 7 nights) and sleep diaries, and self-reported sleep complaints measured at each time point. Partial correlations adjusted for time between assessments across the 12 years were significant and moderate in size (r's = .33-.58). PROC MIXED/GLIMMIX multivariate models showed that sleep duration increased over time; wake after sleep onset (WASO) declined, midpoint of sleep interval increased, and sleep latency and number of sleep complaints did not change between the first and third assessments. Blacks and whites had a greater increase in sleep duration than Chinese. Taken together, the results of this longitudinal study suggest that sleep may not worsen, in general, in midlife women. Perhaps, the expected negative effect of aging in midlife into early old age on sleep is overstated., (© 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.)

Objective: Investigate temporal patterns of sleep maintenance problems in women who became surgically menopausal (hysterectomy with bilateral oophorectomy) before their final menstrual period and examine whether presurgery trajectories of sleep maintenance problems are related to problems staying asleep postsurgery., Methods: Longitudinal analysis of sleep self-reports collected every 1 to 2 years from 1996 to 2013 from 176 surgically menopausal women in the Study of Women's Health Across the Nation, a seven-site community-based, multiethnic/multiracial, cohort study. Median follow-up was 15.3 years (4.2 years presurgery, 10.2 years postsurgery). Group-based trajectory modeling was used to identify patterns of problems staying asleep, and the presurgery trajectories were used to predict similar postsurgery sleep problems., Results: Four trajectory patterns of sleep maintenance problems were identified: low (33.5% of women), moderate (33.0%), increasing during presurgery (19.9%), and high (13.6%). One-fifth of women reported a presurgery increase in these problems. Postsurgically, problems staying asleep remained associated with similar levels of presurgical problems, even after adjusting for postsurgical early morning awakening, frequent vasomotor symptoms, and bodily pain score (βlow = -1.716, βmoderate = -1.144, βincreasing = -0.957, βhigh = -1.021; all P values <0.01)., Conclusions: Sleep maintenance problems were relatively stable across time postsurgery. These data are remarkably consistent with our trajectory results across the natural menopause, suggesting that presurgical assessment of sleep concerns could help guide women's expectations postsurgically. Although reassuring that sleep complaints do not worsen postsurgically for most surgically menopausal women, referral to a sleep specialist should be considered if sleep symptoms persist or worsen after surgery.

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.)

Study Objectives: The Menopause Strategies: Finding Lasting Answers for Symptoms and Health network conducted three randomized clinical trials (RCTs) testing six interventions treating vasomotor symptoms (VMS), and also collected self-reported sleep outcomes. A fourth RCT assessed an intervention for insomnia symptoms among women with VMS. We describe these seven interventions' effects relative to control in women with comparably severe insomnia symptoms and VMS., Methods: We analyzed pooled individual-level data from 546 peri- and postmenopausal women with Insomnia Severity Index (ISI) ≥ 12, and ≥14 bothersome VMS/week across the four RCTs. Interventions included the following: escitalopram 10-20 mg/day; yoga; aerobic exercise; 1.8 g/day omega-3 fatty acids; oral 17-beta-estradiol 0.5-mg/day; venlafaxine XR 75-mg/day; and cognitive behavioral therapy for insomnia (CBT-I). Outcome measures were ISI and Pittsburgh Sleep Quality Index (PSQI) over 8-12 weeks of treatment., Results: CBT-I produced the greatest reduction in ISI from baseline relative to control at -5.2 points (95% CI -7.0 to -3.4). Effects on ISI were similar for exercise at -2.1 and venlafaxine at -2.3 points. Comparably small decreases in ISI were observed with escitalopram, yoga, and estradiol. The largest reduction in PSQI from baseline was with CBT-I at -2.7 points (-3.9 to -1.5), although PSQI decreases of 1.2 to 1.6 points were significantly better than control with escitalopram, exercise, yoga, estradiol, and venlafaxine. Omega-3 supplements did not improve insomnia symptoms., Conclusions: This study's findings support current recommendations for CBT-I as a first line treatment in healthy midlife women with insomnia symptoms and moderately bothersome VMS., (© Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Objective: Sleep disturbances are common among women in midlife; prevalence increases among perimenopausal/postmenopausal women with vasomotor symptoms. Paroxetine 7.5 mg is the only nonhormonal treatment that has been approved in the United States for moderate to severe vasomotor symptoms associated with menopause. In two pivotal phase 3 studies evaluating its efficacy and safety, improvements in sleep disturbances were also prospectively evaluated., Methods: Postmenopausal women with moderate to severe vasomotor symptoms were randomly assigned to paroxetine 7.5 mg (n = 591) or placebo (n = 593) once daily for 12 weeks (both studies) or 24 weeks (24-wk study). Predefined assessments on weeks 4, 12, and 24 included number of nighttime awakenings attributed to vasomotor symptoms, sleep-onset latency, sleep duration, and sleep-related adverse events. The two studies' data for weeks 1 to 12 were pooled., Results: At baseline, participants reported a mean of 3.6 awakenings/night attributed to vasomotor symptoms. Nighttime awakenings attributed to vasomotor symptoms were significantly reduced within 4 weeks of initiating paroxetine 7.5 mg treatment (39% reduction vs 28% for placebo; P = 0.0049), and reductions were sustained through 12 or 24 weeks of treatment. Paroxetine 7.5 mg treatment also significantly increased nighttime sleep duration (week 4, +31 vs +16 min for placebo; P = 0.0075), but no significant between-group differences in sleep-onset latency or sleep-related adverse events such as sedation were observed., Conclusions: In postmenopausal women treated for menopausal vasomotor symptoms, paroxetine 7.5 mg significantly reduces the number of nighttime awakenings attributed to vasomotor symptoms and increases sleep duration without differentially affecting sleep-onset latency or sedation.

Study Objectives: Determine effects of low-dose estradiol and low-dose venlafaxine on self-reported sleep measures in menopausal women with hot flashes., Design: 3-arm double-blind randomized trial. Participants assigned in a 2:2:3 ratio to 17β estradiol 0.5 mg/day (n = 97), venlafaxine XR 75 mg/day (n = 96), or placebo (n = 146) for 8 weeks., Setting: Academic research centers., Participants: 339 community-dwelling perimenopausal and postmenopausal women with ≥2 bothersome hot flashes per day., Measurements and Results: Insomnia symptoms (Insomnia Severity Index [ISI]) and sleep quality (Pittsburgh Sleep Quality Index [PSQI]) at baseline, week 4 and 8; 325 women (96%) provided ISI data and 312 women (92%) provided PSQI data at baseline and follow-up. At baseline, mean (SD) hot flash frequency was 8.1/day (5.3), mean ISI was 11.1 (6.0), and mean PSQI was 7.5 (3.4). Mean (95% CI) change from baseline in ISI at week 8 was -4.1 points (-5.3 to -3.0) with estradiol, -5.0 points (-6.1 to -3.9) with venlafaxine, and -3.0 points (-3.8 to -2.3) with placebo (P overall treatment effect vs. placebo 0.09 for estradiol and 0.007 for venlafaxine). Mean (95% CI) change from baseline in PSQI at week 8 was -2.2 points (-2.8 to -1.6) with estradiol, -2.3 points (-2.9 to -1.6) with venlafaxine, and -1.2 points (-1.7 to -0.8) with placebo (P overall treatment effect vs. placebo 0.04 for estradiol and 0.06 for venlafaxine)., Conclusions: Among perimenopausal and postmenopausal women with hot flashes, both low dose oral estradiol and low-dose venlafaxine compared with placebo modestly reduced insomnia symptoms and improved subjective sleep quality., Clinical Trial Registration: NCT01418209 at www.clinicaltrials.gov., (© 2014 Associated Professional Sleep Societies, LLC.)

Objective: The aim of this study was to determine the effect of escitalopram on insomnia symptoms and subjective sleep quality in healthy perimenopausal and postmenopausal women with hot flashes., Methods: A randomized, blinded, multicenter, placebo-controlled parallel-group 8-week trial with 205 women (95 African American, 102 white, 8 other) was conducted between July 2009 and June 2010. The participants received escitalopram (10-20 mg/d) or placebo. Insomnia symptoms (Insomnia Severity Index [ISI]) and subjective sleep quality (Pittsburgh Sleep Quality Index [PSQI]) at weeks 4 and 8 were the prespecified secondary outcomes. A total of 199 women (97%) provided ISI data, and 194 (95%) women provided PSQI data at follow-up., Results: At baseline, mean hot flash frequency was 9.78 per day (SD, 5.60), mean ISI was 11.4 (SD, 6.3), and mean PSQI was 8.0 (SD, 3.7). Treatment with escitalopram reduced ISI at week 8 (mean difference, -2.00; 95% CI, -3.43 to -0.57; P < 0.001 overall treatment effect), with mean differences of -4.73 (95% CI, -5.72 to -3.75) in the escitalopram group and -2.73 (95% CI, -3.78 to -1.69) in the placebo group. The reduction in PSQI was greater in the escitalopram than in the placebo group at week 8 (mean difference, -1.31; 95% CI, -2.14 to -0.49; P < 0.001 overall treatment effect). Clinical improvement in insomnia symptoms and subjective sleep quality (≥50% decreases in ISI and PSQI from baseline) was observed more frequently in the escitalopram group than in the placebo group (ISI, 50.0% vs 35.4%, P = 0.04; PSQI, 29.6% vs 19.2%, P = 0.09)., Conclusions: Among healthy perimenopausal and postmenopausal women with hot flashes, escitalopram at 10 to 20 mg/day compared with placebo reduced insomnia symptoms and improved subjective sleep quality at 8 weeks of follow-up.

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.

Background: The antidepressant effect of estrogen in women undergoing the menopause transition is hypothesized to be mediated by central nervous system effects of increasing estradiol on mood or through a pathway involving suppression of hot flashes and associated sleep disturbance. Estrogen therapy (ET) and the hypnotic agent zolpidem were selected as interventions in a three-arm, double-blind, placebo-controlled trial to distinguish the effects of estradiol, sleep, and hot flashes on depression., Methods: Women with depressive disorders, hot flashes, and sleep disturbance were randomly assigned to transdermal 17β-estradiol 0.05 mg/d, zolpidem 10 mg/d, or placebo for 8 wk. Changes in serum estradiol, perceived sleep quality, objectively measured sleep, and hot flashes were examined as predictors of depression improvement [Montgomery-Åsberg Depression Rating Scale (MADRS)] using multivariate linear regression., Results: Seventy-two peri/postmenopausal women with depression disorders were randomized to 17β-estradiol (n = 27), zolpidem (n = 31), or placebo (n = 14). There was no significant difference between groups in depression improvement (overall MADRS decrease 11.8 ± 8.6). Increasing estradiol (P = 0.009) and improved sleep quality (P < 0.001) predicted improved mood in adjusted models but reduced hot flashes (P = 0.99) did not. Post hoc subgroup analyses revealed that the therapeutic effect of increasing estradiol levels on mood was seen in perimenopausal (P = 0.009), but not postmenopausal, women., Conclusions: For women with menopause-associated depression, improvement in depression is predicted by improved sleep, and among perimenopausal women, by increasing estradiol levels. These results suggest that changes in estradiol and sleep quality, rather than hot flashes, mediate depression during the menopause transition. Therapies targeting insomnia may be valuable in treating menopause-associated depression.

Objective: To examine the efficacy and tolerability of escitalopram (ESCIT) compared to estrogen and progestogen therapy (EPT) for the treatment of symptomatic peri- and postmenopausal women., Design: Forty women (aged 40-60 years) with depressive disorders and menopause-related symptoms were randomly assigned to an 8-week open trial with ESCIT (flexible dose, 10-20 mg/day; fixed dose, 10 mg/day for the first 4 weeks) or estrogen plus progestogen therapy (ethinyl estradiol 5 microg/day plus norethindrone acetate 1 mg/day). Primary outcome measures included Montgomery-Asberg Depression Rating Scale and the Greene Climacteric Scale at week 8. Secondary outcome measures included the Clinical Global Impressions as well as sleep and quality of life assessments., Results: Thirty-two women (16 on EPT, 16 on ESCIT) were included in the analyses. Full remission of depression (score of <10 on the Montgomery-Asberg Depression Rating Scale) was observed in 75% (12/16) of subjects treated with ESCIT, compared to 25% (4/16) treated with EPT (P = 0.01, Fisher's exact tests). Remission of menopause-related symptoms (>50% decrease in Greene Climacteric Scale scores) was noted in 56% (9/16) of women treated with ESCIT compared to 31.2% (5/16) on EPT (P = 0.03, Pearson's chi2 tests). Improvement in sleep, hot flashes, and quality of life was observed with both treatments., Conclusions: ESCIT is more efficacious than EPT for the treatment of depression and has a positive impact on other menopause-related symptoms. ESCIT may constitute a treatment option for symptomatic menopausal women who are unable or unwilling to use hormone therapy.