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Objective: We hypothesized that, among midlife women with vasomotor and/or genitourinary symptoms of menopause, (1) hormone therapy (HT) compared with complementary alternative medicine (CAM) will be associated with higher quality of life (QoL), and (2) race/ethnicity would modify associations of HT and CAM with QoL., Methods: Cross-sectional and longitudinal analyses of QoL in the Study of Women's Health Across the Nation participants using HT, CAM, or both. Women ( n = 2,514) completed a CAM use questionnaire and QoL assessments at baseline and every 1 to 2 years from 2002 to 2013. Associations between QoL and treatment, adjusted for covariates, and race/ethnicity-by-treatment interactions were analyzed using linear and mixed effects regression models., Results: During 7.8 (SD, 2.9) years of follow-up, 732 women (29%) reported HT of 2.4 (SD, 1.7) years, and 798 women (32%) reported CAM use of 2.1 (SD, 1.4) years. Overall, neither HT nor CAM was associated with QoL. However, the treatment-by-race/ethnicity interaction was significant for self-reported QoL ( P = 0.034 at baseline, P = 0.044 longitudinal). Among White women, self-reported QoL was higher in HT-only users than in those who used neither ( P = 0.030; d = 0.11; 95% confidence interval, 0.01-0.21). In contrast, Black women using HT only had lower self-reported QoL compared with Black women using neither ( P = 0.027; d = -0.21; 95% confidence interval, -0.40 to -0.02)., Conclusion: Comparisons between treatment type within each racial/ethnic group yielded significant differences in self-reported QoL. Clinicians should be aware of racial/ethnic differences in treatment preferences when counseling patients on treatment options for menopausal symptoms to provide optimal care., Video Summary: http://links.lww.com/MENO/B33 ., Competing Interests: Financial disclosure/conflicts of interest: Christmas reports Board of Trustees for The North American Menopause Society (NAMS), NAMS Scientific Program Committee, NAMS Editorial Board, Steering Committee for Core OutcoMes in MenopAuse (COMMA), Speaker Alliance Chicago and FDA Bone, Reproductive and Urologic Division (BRUDAC) Committee. Joffe receives grant support from the National Institutes of Health, Merck, and Pfizer. She serves/has served as a consultant to Bayer, Jazz, and Eisai. Her institution received funding from NeRRE/KaNDy and Que Oncology. Her spouse is an employee at Arsenal Biosciences and has equity in Merck. Santoro reports advisory board member for Astellas, Que Oncology, Amazon (Ember), and Menogenix Inc; consultant for Ansh Labs; NAMS Program Committee; past president Society for Reproductive Investigation; and nominating committee Endocrine Society. The other authors have nothing to disclose., (Copyright © 2022 by The North American Menopause Society.)

Objective: To examine depressive symptoms during postmenopause and the contribution of depressive symptom trajectories before the final menstrual period (FMP) and psychosocial/health factors to postmenopause depressive symptoms., Methods: Longitudinal analysis of depressive symptoms (Center for Epidemiologic Studies-Depression scale) collected every 1 to 2 years from 1996 to 2017 from 1,551 midlife women in the Study of Women's Health Across the Nation for a median follow-up of 19.0 years. Latent class growth analysis identified depression trajectories from baseline to FMP. Multivariable random effects (woman as random effect) linear or logistic regression models were conducted., Results: Women had higher odds of reporting high depressive symptom score (≥16) during postmenopause than when they were premenopausal (OR = 1.49, 95% CI, 1.09-2.04), but not when perimenopausal. Three pre-FMP trajectories were identified: Group 1 (47.7%), consistently low scores, Group 2 (39.9%), moderate scores below the high depressive symptom threshold, and Group 3 (12.4%), consistently high scores. Both the moderate (OR = 2.62, 95% CI, 1.89-3.66) and high score (OR = 6.88, 95% CI, 4.72-10.02) groups, compared with the consistently low group, had significantly higher postmenopausal depressive symptom scores. Other pre-FMP variables associated with high postmenopausal depressive symptoms were: higher odds of childhood trauma/maltreatment, poor role physical, high anxiety symptoms, sleep problems, high vasomotor symptoms, and lower odds for chronological aging and lower social support., Conclusions: Compared with premenopause, postmenopause remains a period of increased risk for higher depressive symptoms, especially for women with pre-FMP depressive symptoms. Pre-FMP depressive symptom trajectories are highly predictive of postmenopause depressive symptoms independent of health and psychosocial factors., Competing Interests: Financial disclosure/conflicts of interest: H.M.K. (NIA), H.J. (NIA, NCI), J.T.B. (NIA, NIMH), and N.E.A. (NIA, NCI) report grants from NIH during the period of the study. H.J. reports the following additional disclosures: Grants: Merck, Pfizer; Consulting: NeRRe/KaNDy, Eisai, Jazz, Bayer; Spouse: Arsenal Biosciences employee; Merck Research Labs equity; Tango equity. A.B.C. and Y.C. declared no conflicts of interest or financial involvement (including employment, fees, share ownership) or affiliation with any organization whose financial interests may be affected by material in the manuscript, or any other conflicts of interest which might potentially bias it., (Copyright © 2022 by The North American Menopause Society.)

Objective: To identify groups of women who share levels and patterns of change in follicle-stimulating hormone (FSH), self-reported sleep maintenance problems, and frequent vasomotor symptoms (VMS) up to 10 years before and after their final menstrual period and to evaluate their premenopausal characteristics., Method: Group-based multi-trajectory modeling grouped 1,407 women from the Study of Women's Health Across the Nation who had an observed natural menopause and did not use hormone therapy, based on repeated measures of FSH, sleep maintenance problems, and frequent VMS relative to final menstrual period. Multivariable analyses assessed race/ethnicity, body mass index, smoking, and depressive symptoms as predictors of group membership., Results: Women formed five distinct groups: (1) low symptoms (low VMS/sleep problems)/high FSH rise (N = 552; 39.2%); (2) moderate VMS and sleep problems/low FSH rise (N = 169; 12.0%); (3) dominant sleep problems (lower VMS/high sleep problems)/high FSH rise (N = 203; 14.4%); (4) dominant VMS (high VMS/lower sleep problems)/high FSH rise (N = 297; 21.1%)); and (5) high symptoms (high VMS/high sleep problems)/intermediate FSH rise (N = 186; 13.2%)). Multivariate analyses showed that race/ethnicity, premenopausal body mass index and depressive symptoms, and increasing depressive symptoms during the early phase of the transition predicted group membership., Conclusions: Women can be classified based on shared levels and patterns of FSH, sleep maintenance problems, and frequent VMS across the menopause transition. Either VMS or sleep maintenance problems can be dominant in the face of high FSH. Experiencing one menopause-related symptom or hormone profile does not automatically imply that another is also being experienced., Competing Interests: Financial disclosure/conflicts of interest: MMB: DSMB member: Cerus Corporation. HJ: Consultant/Advisory Board: NeRRe/KaNDy, Sojournix, Eisai, Jazz; Grant/Research Support: NIH, Merck, NeRRe/KaNDy, Pfizer, QUE Oncology; Spouse: Merck Research Lab—employee; Arsenal Biosciences—consulting and equity; Tango—equity. RCT: Consultant: Astellas, Virtue Health, Procter and Gamble, and Pfizer. All other authors have no conflicts., (Copyright © 2020 by The North American Menopause Society.)

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.

Objective: Depression risk increases during the menopausal transition (MT) and initial postmenopausal years-both times of significant fluctuations of estrogen. Research to date provides limited support for the hypothesis that estrogen fluctuations play a role in the greater susceptibility to midlife depression. Importantly, not all women report depressive symptoms during the MT, and recent reports suggest that duration of exposure to estradiol throughout the adult years may also play a role in vulnerability to depression. This study examines patterns of estrogen exposure during the reproductive years and risk of depression during the MT and early postmenopausal years., Methods: A longitudinal, US community-based, multiethnic study of menopause. Data were collected at baseline and annually for 10 years, and included 1,306 regularly menstruating premenopausal women, aged 42 to 52 years at study entry. The main outcome was incidence of high level of depressive symptoms, Center for Epidemiological Studies Depression Scale (CES-D) score at least 16, in the MT and initial postmenopausal years, independent of premenopausal depression symptoms. Risk factors examined were duration of estrogen exposure (menarche to MT), duration of hormonal birth control use, pregnancies, and lactation., Results: In a multivariate adjusted model, longer duration of estrogen exposure from menarche to MT onset was significantly associated with a reduced risk of depression (CES-D ≥16) during the MT and 10 years or less postmenopause (odds ratio 0.85, 95% confidence interval 0.78-0.92). Longer duration of birth control use was associated with a decreased risk of CES-D at least 16 (odds ratio 0.90, 95% confidence interval 0.83-0.98), but number of pregnancies or breastfeeding was not., Conclusions: Patterns of reproductive lifetime exposure to estrogen are associated with risk of high depressive symptoms during the MT and initial postmenopausal years; longer exposure to estrogen seemed protective.

Objective: This study aims to examine baseline and longitudinal associations between body mass index (BMI) and sexual functioning in midlife women., Methods: Midlife women (N = 2,528) from the Study of Women's Health Across the Nation reported on sexual functioning and underwent measurements of BMI annually beginning in 1995-1997, with follow-up spanning 13.8 years. Associations between baseline levels and longitudinal changes in BMI and sexual desire, arousal, intercourse frequency, and ability to climax were assessed with generalized linear mixed-effects models. Models were adjusted for demographic variables, depressive symptoms, hormone therapy use, alcohol intake, menopause status, smoking status, and health status., Results: Mean BMI increased from 27.7 to 29.1 kg/m2, whereas all sexual functioning variables declined across time (P values ≤ 0.001). Higher baseline BMI was associated with less frequent intercourse (P = 0.003; 95% CI, -0.059 to -0.012). Although overall change in BMI was not associated with changes in sexual functioning, years of greater-than-expected BMI increases relative to women's overall BMI change trajectory were characterized by less frequent intercourse (P < 0.001; 95% CI, -0.106 to -0.029) and reduced sexual desire (P = 0.020; 95% CI, -0.078 to -0.007)., Conclusions: Although women's overall BMI change across 13.8 years of follow-up was not associated with overall changes in sexual functioning, sexual desire and intercourse frequency diminished with years of greater-than-expected weight gain. Results suggest that adiposity and sexual functioning change concurrently from year to year. Further research should explore the impact of weight management interventions as a strategy for preserving sexual functioning in midlife women.

Objective: We examined whether women reporting nighttime pain would have more actigraphy-measured evidence for disturbed sleep and would report feeling less rested compared with women without nighttime pain., Methods: Up to 27 consecutive nights of actigraphy and sleep diary data from each participant were analyzed in this community-based study of 314 African-American (n = 118), white (n = 141), and Chinese (n = 55) women, aged 48 to 58 years, who were premenopausal, perimenopausal, or postmenopausal and were participating in the Study of Women's Health Across the Nation Sleep Study. Dependent variables were actigraphy-measured movement and fragmentation index, total sleep time, sleep efficiency, and diary self-report of "feeling rested" after waking up. All outcomes were fitted using linear mixed-effects models to examine covariate-adjusted associations between the independent variable (nighttime pain severity) and sleep outcomes., Results: Higher pain severity scores were associated with longer sleep duration but reduced sleep efficiency and less restful sleep. Women reporting nocturnal vasomotor symptoms had more sleep-related movement and sleep fragmentation, had reduced sleep efficiency, and were less likely to feel rested after wakening whether or not they reported pain., Conclusions: Midlife women who report higher nighttime pain levels have more objective evidence for less efficient sleep, consistent with self-reported less restful sleep. Nocturnal vasomotor symptoms also can contribute to restlessness and wakefulness in midlife women.

Objective: This study aims to evaluate patterns in actigraphy-defined sleep measures across the menstrual cycle by testing the hypothesis that sleep would be more disrupted in the premenstrual period (ie, within the 14 d before menses)., Methods: A community-based longitudinal study of wrist actigraphy-derived sleep measures was conducted in 163 (58 African American, 78 white, and 27 Chinese) late-reproductive-age (mean [SD], 51.5 [2.0] y) women from the Study of Women's Health Across the Nation Sleep Study. Daily measures of sleep (sleep efficiency [%] and total sleep time [minutes]) and movement during sleep (mean activity score [counts]) were characterized using wrist actigraphy across a menstrual cycle or 35 days, whichever was shorter. Data were standardized to 28 days to account for unequal cycle lengths and divided into four weekly segments for analyses., Results: Sleep efficiency declined gradually across the menstrual cycle, but the decline became pronounced on the fourth week (the premenstrual period). Compared with the third week, sleep efficiency declined by 5% (P < 0.0001) and mean total sleep time was 25 minutes less (P = 0.0002) on the fourth week. We found no significant differences between the mean for the second week and the mean for the third week. The association of weekly segments with sleep efficiency or total sleep time was modified by sociodemographic and lifestyle factors, including body mass index, race, study site, financial strain, marital status, and smoking., Conclusions: Among late-reproductive-age women, sleep varies systematically across the menstrual cycle, including a gradual decline in sleep efficiency across all weeks, with a more marked change premenstrually during the last week of the menstrual cycle. These sleep changes may be modified by altering lifestyle factors.

Objective: Little is known about the risk of anxiety in women during midlife and the menopausal transition. We examined anxiety as a cluster of four symptoms and determined the association between menopausal stage and high anxiety during 10 years of follow-up of 2,956 women of multiple race/ethnicities., Methods: This study was a longitudinal analysis of data from the multisite Study of Women's Health Across the Nation, a study of menopause and aging. Women were aged 42 to 52 at study entry. The outcome was high anxiety, with a score of 4 or greater on the sum of four anxiety symptoms rated according to frequency in the previous 2 weeks from 0 (none) to 4 (daily; upper 20%). Covariates included sociodemographics, health factors, stressors, and vasomotor symptoms., Results: Women with low anxiety at baseline were more likely to report high-anxiety symptoms at early or late perimenopause or postmenopause than at premenopause (odds ratio, 1.56-1.61), independent of multiple risk factors, including upsetting life events, financial strain, fair/poor perceived health, and vasomotor symptoms. Women with high anxiety at baseline continued to have high rates of high anxiety throughout follow-up, but odds ratios did not differ by menopausal stage., Conclusions: Women with high anxiety at premenopause may be more often anxious and are not at increased risk for high anxiety at specific stages of the menopausal transition. In contrast, women with low anxiety at premenopause may be more susceptible to high anxiety during and after the menopausal transition than before the menopausal transition.

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.

Objective: To compare age-adjusted and ethnic differences in prevalences of sleep difficulty at various stages of the menopausal transition and to determine the relative contribution of other factors, including vasomotor symptoms, sociodemographics, and psychological and physical health factors, to self-reported sleep difficulty in middle-aged women., Design: A community-based survey of women's health and menopausal symptoms was conducted between November 1995 and October 1997 at each of the seven US sites participating in the Study of Women's Health Across the Nation. A multiethnic sample of 12,603 Caucasian, African American, Chinese, Japanese, and Hispanic women aged 40 to 55 years was categorized into six groups: premenopausal, early perimenopausal, late perimenopausal, naturally postmenopausal, surgically postmenopausal, and postmenopausal receiving hormone replacement therapy. The women were asked whether they had experienced difficulty sleeping in the past 2 weeks., Results: Difficulty sleeping was reported by 38%. Age-adjusted rates were highest in the late perimenopausal (45.4%) and surgically postmenopausal (47.6%) groups. Among ethnic groups, rates ranged from 28% in Japanese women to 40% in Caucasian women. In the multivariate analysis, menopausal status was significantly associated with difficulty sleeping. Ethnicity, vasomotor and psychological symptoms, self-perceived health and health behaviors, arthritis, and education also were significantly associated with difficulty sleeping., Conclusions: These results suggest that stage of the menopausal transition, independent of other potential explanatory factors, is associated with self-reported sleep difficulty. Older age per se was not significantly associated with difficulty sleeping.