Promoting good mental health over the menopause transition.

The potential risk for mental health conditions over the menopause transition shapes women's expectations and informs putative physiological mechanisms regulating women's mental health. We review evidence from prospective studies reporting on associations between mental health conditions and the menopause transition. Major depressive disorder and the more prevalent subthreshold depressive symptoms are the most common conditions studied. We reviewed 12 prospective studies reporting depressive symptoms, major depressive disorder, or both over the menopause transition and found no compelling evidence for a universal increased risk for either condition. However, specific subgroups of participants, primarily defined by menopause-related risk factors (ie, vasomotor symptoms that are severe or disturb sleep, a long duration of the transition, or reproductive hormone dynamics) and psychosocial risk factors (eg, stressful life events), were vulnerable to depressive symptoms. The increased risk of major depressive disorder over the menopause transition appears predominantly in individuals with previous major depressive disorder. Greater focus on recognising risk factors in primary care is warranted. On the basis of scarce data, we found no compelling evidence that risk of anxiety, bipolar disorder, or psychosis is universally elevated over the menopause transition. Potential misattribution of psychological distress and psychiatric disorders to menopause could harm women by delaying accurate diagnosis and the initiation of effective psychotropic treatments, and by creating negative expectations for people approaching menopause. A paradigm shift is needed. We conclude with recommendations for the detection and treatment of depressive symptoms or major depressive disorder and strategies to promote good mental health over the menopause transition, while responsibly preparing and supporting those at risk.

A Positive Psychology Intervention for Caregivers of Hematopoietic Stem Cell Transplantation Survivors (PATH-C): Initial Testing and Single-Arm Pilot Trial.

Caregivers of patients with hematologic malignancies undergoing allogeneic hematopoietic stem cell transplantation (HSCT) play a crucial role in supporting their loved ones through physical, emotional, and practical challenges. This role has been associated with high levels of psychological distress and low levels of positive psychological well-being (PPWB). Positive psychology interventions for caregivers in other disease groups (eg, breast cancer) have been associated with improved outcomes. However, positive psychology interventions that specifically address HSCT caregivers' psychological needs are currently lacking. The goal of this single-arm open-pilot trial was to determine the feasibility and acceptability of the Positive Affect in the Transplantation of Hematopoietic Stem Cells (PATH) intervention for HSCT Caregivers to identify caregiver preferences to tailor PATH for HSCT caregivers. Adult caregivers of HSCT recipients were eligible for PATH during the HSCT recipient's first 100 d post-transplant. We defined, a priori, feasibility as >60% of participants who start the intervention completing ≥6/9 intervention sessions and acceptability as weekly ratings of ease and utility of the PP exercises ≥7/10 on a 10-point Likert Scale (0 = very difficult/not helpful; 10 = very easy/very helpful). We conducted semistructured qualitative exit interviews (n = 15) to explore HSCT caregivers' perception of PATH's content, benefits of PATH, as well as facilitators and barriers to engaging with the intervention. Transcribed interviews were analyzed using framework-guided rapid analysis by 2 coders. The intervention was feasible with 83% (15/18) of caregivers who started the intervention completing ≥6/9 intervention sessions. Among caregivers who completed ≥6/9 intervention sessions, ratings of ease (mean = 8.1; 95% CI: 7.4, 8.7) and utility (mean = 8.3; 95% CI: 7.8, 8.9) also exceeded our a priori threshold of ≥7/10. Caregivers identified benefits of PATH, including identifying and responding to emotions, dedicating time to self-care, and cultivating important relationships. Sociodemographic factors (eg, being retired) and the manualized structure of PATH were cited as facilitators to intervention engagement. Barriers to PATH engagement included lack of time and competing caregiving responsibilities. Caregivers preferred remote intervention delivery within the first 100 d post HSCT. This is the first study to show a 9-wk, phone-delivered positive psychology intervention is feasible in caregivers of allogeneic HSCT recipients. Our findings also underscore the specific preferences of this population for positive psychology interventions. Larger studies are warranted to establish the efficacy of these interventions in addressing persistent unmet psychological needs for HSCT caregivers.

Work Productivity Among Younger Breast Cancer Survivors: The Impact of Behavioral Interventions for Depression.

OBJECTIVES: The Pathways to Wellness randomized controlled trial found that 2 behavioral interventions, mindfulness awareness practices and survivorship education, reduced depressive symptoms in younger breast cancer survivors (BCSs) compared with wait-list control. This secondary analysis examines whether the interventions led to reduced loss of work productivity among younger BCSs and whether such reductions were mediated by reductions in depressive symptoms. METHODS: The Work Productivity and Activity Impairment scale was used to measure work productivity loss at 4 assessment time points. Correlates of productivity loss at enrollment were examined using multivariable linear regression. Differences in change over time in productivity loss between each intervention group and control were assessed using linear mixed models. Reduced depressive symptoms were tested as a mediator of reduced productivity loss. RESULTS: Of 247 trial participants, 199 were employed and included in the analyses. At enrollment, higher productivity loss was associated with chemotherapy receipt (P = .003), younger age (P = .021), more severe cognitive problems (P = .002), higher musculoskeletal pain severity (P = .002), more depressive symptoms (P = .016), and higher fatigue severity (P = .033). The mindfulness intervention led to significantly less productivity loss compared with control at all 3 postintervention assessment points (all P < .05), with about 54% of the effect mediated by reduction in depressive symptoms. Survivorship education was not associated with reduced loss of productivity. CONCLUSIONS: These findings suggest that addressing depressive symptoms through behavioral interventions, such as mindfulness, may mitigate impacts on work productivity in younger BCSs.

Associations of adverse childhood and lifetime experiences with sleep quality and duration among women in midlife.

OBJECTIVES: Many women experience sleep problems during midlife. Associations of adverse lifetime experiences-more common among women-with sleep outcomes are understudied. METHODS: We studied 476 women enrolled in Project Viva 1999-2002. At enrollment, participants reported any lifetime history of abuse and/or financial hardship. At midlife follow-up ∼20 years later, they reported a history of up to 10 adverse childhood experiences (ACEs); 7-day sleep quality (patient-reported outcomes measurement information system sleep disturbance and sleep-related impairment T-scores); and past month average sleep duration. We examined associations of adverse experiences with sleep outcomes, adjusted for childhood sociodemographic variables. We also explored mediation by current depression and anxiety symptoms, hot flash severity, general health, and body mass index. RESULTS: ACEs were common: 301 women (63%) reported one or more. Each additional ACE was associated with higher midlife sleep disturbance (adjusted ß = 0.65 points, 95% confidence interval [CI]: 0.27, 1.02) and sleep-related impairment (0.98, 95% CI: 0.54, 1.41) T-scores, and with sleep duration <6 hour/night (odds ratio 1.19, 95% CI: 1.00, 1.42), but not with continuous sleep duration (-2 minutes, 95% CI: -5, 1). Adverse experiences in adulthood were less consistently associated with sleep quality but were associated with sleep duration, for example, financial hardship during the index pregnancy was associated with 75 minutes (95% CI: -120, -29) shorter sleep duration 2 decades later. Associations of ACEs with sleep disturbance and sleep-related impairment were mediated by midlife depression anxiety and physical health but not by hot flash severity or body mass index. CONCLUSIONS: Adverse lifetime experiences have deleterious associations with sleep duration and quality in midlife women.

A pilot study of light exposure as a countermeasure for menstrual phase-dependent neurobehavioral performance impairment in women.

OBJECTIVE: To examine effects of menstrual phase and nighttime light exposure on subjective sleepiness and auditory Psychomotor Vigilance Task performance. METHODS: Twenty-nine premenopausal women (12 =Follicular; 17 =Luteal) completed a 6.5-hour nighttime monochromatic light exposure with varying wavelengths (420-620 nm) and irradiances (1.03-14.12 µW/cm2). Subjective sleepiness, reaction time, and attentional lapses were compared between menstrual phases in women with minimal (<33%) or substantial (≥33%) light-induced melatonin suppression. RESULTS: When melatonin was not suppressed, women in the follicular phase had significantly worse reaction time (mean difference=145.1 ms, 95% CI 51.8-238.3, p < .001, Cohen's D=1.9) and lapses (mean difference=12.9 lapses, 95% CI 4.37-21.41, p < .001, Cohen's D=1.7) compared to women in the luteal phase. When melatonin was suppressed, women in the follicular phase had significantly better reaction time (mean difference=152.1 ms, 95% CI 43.88-260.3, p < .001, Cohen's D=1.7) and lapses (mean difference=12.3 lapses, 95% CI 1.14-25.6, p < .01, Cohen's D=1.6) compared to when melatonin was not suppressed, such that their performance was not different (p > .9) from women in the luteal phase. Subjective sleepiness did not differ by menstrual phase (mean difference=0.6, p > .08) or melatonin suppression (mean difference=0.2, p > .4). CONCLUSIONS: Nighttime light exposure sufficient to suppress melatonin can also mitigate neurobehavioral performance deficits associated with the follicular phase. Despite the relatively small sample size, these data suggest that nighttime light may be a valuable strategy to help reduce errors and accidents in female shift workers.

Effects of Sleep Fragmentation and Estradiol Decline on Cortisol in a Human Experimental Model of Menopause.

CONTEXT: Perturbations to the hypothalamic-pituitary-adrenal (HPA) axis have been hypothesized to increase postmenopausal cardiometabolic risk. Although sleep disturbance, a known risk factor for cardiometabolic disease, is prevalent during the menopause transition, it is unknown whether menopause-related sleep disturbance and estradiol decline disturb the HPA axis. OBJECTIVE: We examined the effect of experimental fragmentation of sleep and suppression of estradiol as a model of menopause on cortisol levels in healthy young women. METHODS: Twenty-two women completed a 5-night inpatient study during the mid-to-late follicular phase (estrogenized). A subset (n = 14) repeated the protocol after gonadotropin-releasing hormone agonist-induced estradiol suppression. Each inpatient study included 2 unfragmented sleep nights followed by 3 experimental sleep fragmentation nights. This study took place with premenopausal women at an academic medical center. Interventions included sleep fragmentation and pharmacological hypoestrogenism, and main outcome measures were serum bedtime cortisol levels and cortisol awakening response (CAR). RESULTS: Bedtime cortisol increased 27% (P = .03) and CAR decreased 57% (P = .01) following sleep fragmentation compared to unfragmented sleep. Polysomnographic-derived wake after sleep-onset (WASO) was positively associated with bedtime cortisol levels (P = .047) and negatively associated with CAR (P < .01). Bedtime cortisol levels were 22% lower in the hypoestrogenized state compared to the estrogenized state (P = .02), while CAR was similar in both estradiol conditions (P = .38). CONCLUSION: Estradiol suppression and modifiable menopause-related sleep fragmentation both independently perturb HPA axis activity. Sleep fragmentation, commonly seen in menopausal women, may disrupt the HPA axis, which in turn may lead to adverse health effects as women age.

Efficacy and safety of elinzanetant, a selective neurokinin-1,3 receptor antagonist for vasomotor symptoms: a dose-finding clinical trial (SWITCH-1).

OBJECTIVE: Neurokinin (NK)-3 and NK-1 receptors have been implicated in the etiology of vasomotor symptoms (VMS) and sleep disturbances associated with menopause. This phase 2b, adaptive, dose-range finding study aimed to assess the efficacy and safety of multiple doses of elinzanetant (NT-814), a selective NK-1,3 receptor antagonist, in women experiencing VMS associated with menopause, and investigate the impact of elinzanetant on sleep and quality of life. METHODS: Postmenopausal women aged 40 to 65 years who experienced seven or more moderate-to-severe VMS per day were randomized to receive elinzanetant 40, 80, 120, or 160 mg or placebo once daily using an adaptive design algorithm. Coprimary endpoints were reduction in mean frequency and severity of moderate-to-severe VMS at weeks 4 and 12. Secondary endpoints included patient-reported assessments of sleep and quality of life. RESULTS: Elinzanetant 120 mg and 160 mg achieved reductions in VMS frequency versus placebo from week 1 throughout 12 weeks of treatment. Least square mean reductions were statistically significant versus placebo at both primary endpoint time points for elinzanetant 120 mg (week 4: -3.93 [SE, 1.02], P < 0.001; week 12: -2.95 [1.15], P = 0.01) and at week 4 for elinzanetant 160 mg (-2.63 [1.03]; P = 0.01). Both doses also led to clinically meaningful improvements in measures of sleep and quality of life. All doses of elinzanetant were well tolerated. CONCLUSIONS: Elinzanetant is an effective and well-tolerated nonhormone treatment option for postmenopausal women with VMS and associated sleep disturbance. Elinzanetant also improves quality of life in women with VMS.

Improving biobehavioral health in younger breast cancer survivors: Pathways to Wellness trial secondary outcomes.

BACKGROUND: The Pathways to Wellness trial tested the efficacy of 2 interventions for younger breast cancer survivors: mindful awareness practices (MAPs) and survivorship education (SE). This planned secondary analysis examines intervention effects on stress, positive psychological outcomes, and inflammation (Clincaltrials.gov NCT03025139). METHODS: Women diagnosed with breast cancer at or before age 50 years who had completed treatment and had elevated depressive symptoms were randomly assigned to 6 weeks of MAPs, SE, or wait-list control (WLC). Assessments conducted at pre- and postintervention and at 3- and 6-month follow-up measured general stress perceptions, cancer-related intrusive thoughts and worry, positive affect, meaning and peace in life, altruism and empathy, and markers of inflammation. Analyses compared change in outcomes over time in each intervention group relative to WLC using linear mixed models. RESULTS: A total 247 women were randomly assigned to MAPs (n = 85), SE (n = 81), or WLC (n = 81). MAPs statistically significantly decreased intrusive thoughts and worry at postintervention and 3-month follow-up relative to WLC (P < .027) and statistically significantly increased positive affect and meaning and peace at postintervention, with positive affect persisting at 3-month follow-up (P < .027). SE statistically significantly decreased intrusive thoughts at 3-month follow-up and statistically significantly increased positive affect at 6-month follow-up relative to WLC (P < .01). Proinflammatory gene expression increased in WLC relative to MAPs (P = .016) but did not differ from SE. There were no intervention effects on other outcomes. CONCLUSION: MAPs had beneficial effects on psychological and immune outcomes in younger breast cancer survivors and is a promising approach for enhancing biobehavioral health.

Sleep timing, sleep regularity, and psychological health in early late life women: Findings from the Study of Women's Health Across the Nation (SWAN).

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 (ß = 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 (ß = -0.18, 95% CI = -0.33, -0.03), depressive (ß = 1.36, 95% CI = 0.29, 2.44) and anxiety (ß = 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.

Menopause hormone therapy and complementary alternative medicine, quality of life, and racial/ethnic differences: the Study of Women's Health Across the Nation (SWAN).

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 .

Longitudinal associations of psychosocial stressors with menopausal symptoms and well-being among women in midlife.

OBJECTIVE: We examined longitudinal associations of psychosocial stressors with menopausal symptoms and well-being of women in midlife in a longitudinal cohort. METHODS: This study is based on 682 women from Project Viva, a prospective cohort enrolled in 1999 to 2002 during pregnancy (median age = 33.3 y) and followed for almost two decades. In pregnancy, women self-reported psychosocial stressors (history of physical and sexual abuse and financial instability, from childhood to the current pregnancy). In 2017 to 2021 (median age, 51.6 y), they reported their menopausal symptoms (0-44 point scale) and well-being (general health [good/fair/poor vs excellent/very good], generalized anxiety symptoms, and depressive symptoms [both-more than minimal levels vs none/minimal]). We performed multivariable and logistic regression models to examine associations of psychosocial stressors with outcomes, adjusting for covariates. RESULTS: History of physical abuse (reported by 37.3%) was associated with worse menopausal symptoms in the somatovegetative (odds ratio [OR], 0.46 points; 95% confidence interval [CI], 0.04-0.87 points) and psychological (OR, 0.52 points; 95% CI, 0.07-0.97 points) domains and with worse general health (OR, 1.73; 95% CI, 1.17-2.55) and greater depressive symptoms (OR, 1.74; 95% CI, 1.05-2.87). History of sexual abuse (7.7%) was associated with worse menopausal symptoms (OR, 2.81 points; 95% CI, 1.05-4.56) and worse general health (OR, 2.04; 95% CI, 1.04-4.03) but not with depressive symptoms. History of financial instability (10.8%) was associated with worse menopausal symptoms (1.92 points; 0.49 to 3.34), worse general health (OR, 2.16; 95% CI, 1.24-3.75), and greater depressive symptoms (OR, 2.68; 95% CI, 1.44-4.98). We observed no association between psychosocial stressors and generalized anxiety symptoms assessed at midlife. CONCLUSIONS: Psychosocial stressors were associated with worse menopausal symptoms and well-being decades after initial report.

Changes in serum endogenous estrogen concentrations are mediators of the effect of low-dose oral estradiol on vasomotor symptoms.

OBJECTIVES: The aim of this study was to quantify changes in serum total estradiol (E2) and estrone (E1) concentrations with initiation of low-dose oral estradiol treatment and evaluate whether changes in concentrations mediate the effect of treatment in reducing vasomotor symptom (VMS) frequency. METHODS: We analyzed baseline and week 8 (W8) data from 171 perimenopausal and postmenopausal women with VMS enrolled in low-dose 17ß estradiol ( n = 72) and placebo ( n = 99) groups of a randomized clinical trial. RESULTS: From baseline to W8, women in the low-dose estradiol group had a fourfold increase in E2, resulting in a W8 E2 of 23 pg/mL, and a fivefold increase in E1, resulting in a W8 E1 of 110.7 pg/mL. In contrast, E2 and E1 among women in the placebo group were unchanged from baseline to W8. Changes in E2 and E1 from baseline to W8 met criteria for mediating the effect of low-dose estradiol treatment on VMS frequency. With change in estrogen concentration added to treatment assignment in a regression model predicting W8 VMS frequency, the effect of treatment with low-dose estradiol versus placebo was attenuated, with change in E2 representing a 44.1% reduction ( P = 0.03) and change in E1 representing a 69.5% reduction ( P = 0.02) in total intervention effect. CONCLUSION: Among perimenopausal and postmenopausal women with VMS, treatment with low-dose oral estradiol versus placebo results in four- to fivefold increases in serum E2 and E1. The increases in serum E2 and E1 with low-dose oral estradiol treatment seem to mediate in part the effect of treatment in reducing VMS frequency.

Disruption of Sleep Continuity During the Perimenopause: Associations with Female Reproductive Hormone Profiles.

CONTEXT: Nocturnal vasomotor symptoms (nVMS), depressive symptoms (DepSx), and female reproductive hormone changes contribute to perimenopause-associated disruption in sleep continuity. Hormonal changes underlie both nVMS and DepSx. However, their association with sleep continuity parameters resulting in perimenopause-associated sleep disruption remains unclear. OBJECTIVE: We aimed to determine the association between female reproductive hormones and perimenopausal sleep discontinuity independent of nVMS and DepSx. METHODS: Daily sleep and VMS diaries, and weekly serum assays of female reproductive hormones were obtained for 8 consecutive weeks in 45 perimenopausal women with mild DepSx but no primary sleep disorder. Generalized estimating equations were used to examine associations of estradiol, progesterone, and follicle stimulating hormone (FSH) with mean number of nightly awakenings, wakefulness after sleep onset (WASO) and sleep-onset latency (SOL) adjusting for nVMS and DepSx. RESULTS: Sleep disruption was common (median 1.5 awakenings/night, WASO 24.3 and SOL 20.0 minutes). More awakenings were associated with estradiol levels in the postmenopausal range (ß = 0.14; 95% CI, 0.04 to 0.24; P = 0.007), and higher FSH levels (ß [1-unit increase] = 0.12; 95% CI, 0.02 to 0.22; P = 0.02), but not with progesterone (ß [1-unit increase] = -0.02; 95% CI, -0.06 to 0.01; P = 0.20) in adjusted models. Female reproductive hormones were not associated with WASO or SOL. CONCLUSION: Associations of more awakenings with lower estradiol and higher FSH levels provide support for a perimenopause-associated sleep discontinuity condition that is linked with female reproductive hormone changes, independent of nVMS and DepSx.

The longitudinal relation of inflammation to incidence of vasomotor symptoms.

OBJECTIVE: Vasomotor symptoms (VMS), the most frequently reported symptoms during the menopausal transition, have been associated with inflammation. Whether inflammation is a risk factor for or a consequence of VMS remains unclear. The objectives of these analyses were to determine if elevated proinflammatory marker levels were associated with increased incident VMS in women without VMS at baseline and whether these associations varied by menopause transition stage or race/ethnicity. METHODS: We used longitudinal data on incident VMS, high-sensitivity C-reactive protein (hs-CRP; n = 1,922) and interleukin-6 (IL-6; n = 203) from 13 follow-up visits in the Study of Women's Health Across the Nation, which included five racial/ethnic groups of midlife women. We performed multivariable discrete-time survival analyses to determine adjusted hazard ratios (aHRs) for the association of these proinflammatory markers with incident VMS in women without VMS at baseline. RESULTS: We found no significant associations of incident VMS with dichotomized hs-CRP (>3 vs ≤3 mg/L) at baseline, concurrent or prior visit (aHRs, 1.04-2.03) or IL-6 (>1.44 vs ≤1.44 pg/mL) at visit 1, concurrent or prior visit (aHRs, 0.67-1.62), or continuous hs-CRP or IL-6 values over 13 follow-up visits (with nonsignificant adjusted increased hazards ranging from 0% to 2%). CONCLUSIONS: Our results showed no significant association of the proinflammatory biomarkers, hs-CRP or IL-6, either concurrently or with subsequent incident VMS, indicating that inflammation was unlikely to be a risk factor for VMS. Thus, clinical treatments directed at reducing inflammation would be unlikely to reduce the occurrence of VMS.

Risk of high depressive symptoms after the final menstrual period: the Study of Women's Health Across the Nation (SWAN).

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.

Sleep Fragmentation and Estradiol Suppression Decrease Fat Oxidation in Premenopausal Women.

CONTEXT: Body fat gain associated with menopause has been attributed to estradiol (E2) withdrawal. Hypoestrogenism is unlikely to be the only contributing factor, however. OBJECTIVE: Given the links between sleep and metabolic health, we examined the effects of an experimental menopausal model of sleep fragmentation on energy metabolism. METHODS: Twenty premenopausal women (age 21-45 years) underwent a 5-night inpatient study during the mid-to-late follicular phase (estrogenized; n = 20) and the same protocol was repeated in a subset of the participants (n = 9) following leuprolide-induced E2 suppression (hypo-estrogenized). During each 5-night study, there were 2 nights of unfragmented sleep followed by 3 nights of fragmented sleep. Indirect calorimetry was used to assess fasted resting energy expenditure (REE) and substrate oxidation. RESULTS: Sleep fragmentation in the estrogenized state increased the respiratory exchange ratio (RER) and carbohydrate oxidation while decreasing fat oxidation (all P < 0.01). Similarly, in the hypo-estrogenized state without sleep fragmentation, RER and carbohydrate oxidation increased and fat oxidation decreased (all P < 0.01); addition of sleep fragmentation to the hypo-estrogenized state did not produce further effects beyond that observed for either intervention alone (P < 0.05). There were no effects of either sleep fragmentation or E2 state on REE. CONCLUSION: Sleep fragmentation and hypoestrogenism each independently alter fasting substrate oxidation in a manner that may contribute to body fat gain. These findings are important for understanding mechanisms underlying propensity to body fat gain in women across the menopause transition.

Menopausal Hormone Therapy and the Mind: The Role of Hormone Replacement in the Prevention and Treatment of Cognitive Decline, Dementia, and Cognitive Dysfunction of Depression.

LEARNING OBJECTIVES: After participating in this activity, learners should be better able to:• Outline the clinical recommendations for menopausal hormone treatment related to cognitive concerns• Debate and discuss the various research pieces on the use of menopausal hormone therapy cognitive decline, dysfunction, and dementia. ABSTRACT: Menopause has been associated with subjective cognitive dysfunction and elevated rates of depression. While menopausal hormone therapy (MHT) is Food and Drug Administration-approved for the treatment of vasomotor symptoms related to menopause, a potential role for MHT in treating and preventing cognitive decline, dysfunction, and dementia has remained unclear and a topic of continued interest and debate across decades of research. Increasing numbers of patients are seeking help for subjective cognitive decline, and those with poorer mental health are substantially more likely to perceive themselves to be at high risk of developing dementia; thus, mental health professionals are likely to encounter such patients and may be asked to provide advice concerning MHT, cognition, and indications for MHT use. Here, we synthesize the neurobiological effects of MHT, make recommendations for its use in current clinical practice in the contexts of cognitive dysfunction associated with major depressive disorder, cognitive decline, and Alzheimer's disease, and discuss the frontiers being explored by ongoing research on this topic. We conclude that MHT to improve cognitive functioning has only a few scenarios where it would be recommended and that particular caution may be warranted for carriers of the APOE ε4 allele.

NAMS 2021 Utian Translational Science SymposiumSeptember 2021, Washington, DCCharting the path to health in midlife and beyond: the biology and practice of wellness.

ABSTRACT: Charting the Path to Health in Midlife and Beyond: The Biology and Practice of Wellness was a Translational Science Symposium held on Tuesday, September 21, 2021. Foundational psychosocial and behavioral approaches to promote healthy aging and strategies to disseminate this information were discussed. The following synopsis documents the conversation, describes the state of the science, and outlines a path forward for clinical practice. Wellness, in its broadest sense, prioritizes an orientation toward health, and an embrace of behaviors that will promote it. It involves a journey to improve and maintain physical and mental health and overall well-being to fully engage and live one's best life. It is more about recognizing and optimizing what one can do than what one cannot do and emphasizes the individual's agency over changing what they are able to change. Wellness is therefore not a passive state but rather an active goal to be sought continually. When viewed in this fashion, wellness is accessible to all. The conference addressed multiple aspects of wellness and embraced this philosophy throughout.