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.

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.

Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: OASIS 1 and 2 Randomized Clinical Trials.

Importance: Safe and effective nonhormonal treatments for menopausal vasomotor symptoms (VMS) are needed. Objective: To evaluate the efficacy and safety of elinzanetant, a selective neurokinin-1,3 receptor antagonist, for the treatment of moderate to severe menopausal vasomotor symptoms. Design, Setting, and Participants: Two randomized double-blind phase 3 trials (OASIS 1 and 2) included postmenopausal participants aged 40 to 65 years experiencing moderate to severe vasomotor symptoms (OASIS 1: 77 sites in the US, Europe, and Israel from August 27, 2021, to November 27, 2023, and OASIS 2: 77 sites in the US, Canada, and Europe from October 29, 2021, to October 10, 2023). Intervention: Once daily oral elinzanetant, 120 mg, for 26 weeks or matching placebo for 12 weeks followed by elinzanetant, 120 mg, for 14 weeks. Main Outcomes and Measures: Primary end points included mean change in frequency and severity of moderate to severe vasomotor symptoms from baseline to weeks 4 and 12, measured by the electronic hot flash daily diary. Secondary end points included Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b total T score and Menopause-Specific Quality of Life questionnaire total score from baseline to week 12. Results: Eligible participants (mean [SD] age, OASIS 1: 54.6 [4.9] years; OASIS 2: 54.6 [4.8] years) were randomized to elinzanetant (OASIS 1: n = 199; OASIS 2: n = 200) or placebo (OASIS 1: n = 197; OASIS 2: n = 200). A total of 309 (78.0%) and 324 (81.0%) completed OASIS 1 and 2, respectively. For the elinzanetant and placebo groups, the baseline mean (SD) VMS per 24 hours were 13.4 (6.6) vs 14.3 (13.9) (OASIS 1) and 14.7 (11.1) v 16.2 (11.2) (OASIS 2). Baseline VMS severity was 2.6 (0.2) vs 2.5 (0.2) (OASIS 1) and 2.5 (0.2) vs 2.5 (0.2) (OASIS 2). Elinzanetant significantly reduced VMS frequency at week 4 (OASIS 1: -3.3 [95% CI, -4.5 to -2.1], P < .001; OASIS 2: -3.0 [95% CI, -4.4 to -1.7], P < .001) and at week 12 (OASIS 1: -3.2 [95% CI, -4.8 to -1.6], P < .001; OASIS 2: -3.2 [95% CI, -4.6 to -1.9], P < .001). Elinzanetant also improved VMS severity at week 4 (OASIS 1: -0.3 [95% CI, -0.4 to -0.2], P < .001; OASIS 2: -0.2 [95 CI, -0.3 to -0.1], P < .001) and week 12 (OASIS 1: -0.4 [95% CI, -0.5 to -0.3], P < .001; OASIS 2: -0.3 [95% CI, -0.4 to -0.1], P < .001). Elinzanetant improved sleep disturbances and menopause-related quality of life at week 12, and the safety profile was favorable. Conclusions and Relevance: Elinzanetant was well tolerated and efficacious for moderate to severe menopausal VMS. Trial Registration: ClinicalTrials.gov Identifier: OASIS 1: NCT05042362, OASIS 2: NCT05099159.

Vasomotor symptoms in midlife women with incident breast cancer: pink SWAN.

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

Predictors of increased risk for early treatment non-adherence to oral anti-estrogen therapies in early-stage breast cancer patients.

PURPOSE: Non-adherence to the oral anti-estrogen therapies (AET) tamoxifen and aromatase inhibitors in early-stage hormone receptor-positive breast cancer is associated with numerous negative clinical outcomes. Prior studies have identified that non-adherence is associated with psychological and menopause-related factors which are present during AET, but the presence of these characteristics prior to AET initiation has not been investigated. METHODS: Psychological and menopause symptoms (depression, generalized anxiety, insomnia, somatosensory amplification, hot flash frequency, and hot flash-related interference) were assessed pre-AET initiation as predictors of subsequent non-adherence in 73 participants (Mage = 55.0, SD = 10.1 years). Participants self-reported treatment adherence after three and 6 weeks on AET. Participants who did not initiate treatment were excluded from the analysis. RESULTS: Discriminant function analyses revealed that the hypothesized set of psychological and menopause symptoms at baseline (pre-AET) together statistically distinguished between those who were non-adherent (n = 19; 26.0%) from adherent (n = 54; 74.0%) at 6 weeks. Model classification accuracy was statistically significant (Wilks' ƛ = 0.782, χ2(6) = 15.50, p = 0.017) at the 6-week timepoint. Results were consistent at 3 weeks. Pre-AET psychological and menopause symptoms correctly classified 6-week treatment adherence 77.9% of the time. Depression contributed most to distinguishing between adherers and non-adherers. CONCLUSIONS: The presence of a composite profile of psychological and menopause symptoms prior to AET initiation may help to identify early treatment non-adherence. Results can be used to identify patients at risk for non-adherence and to guide psychological and symptom management interventions.

What happens after menopause? (WHAM): A prospective controlled study of depression and anxiety up to 12 months after premenopausal risk-reducing bilateral salpingo-oophorectomy.

OBJECTIVE: Risk-reducing bilateral salpingo-oophorectomy (RRBSO) substantially reduces ovarian cancer risk in women with pathogenic gene variants and is generally recommended by age 34-45 years. Natural menopause is a vulnerable period for mood disturbance, but the risk of depression and anxiety in the first 12 months after RRBSO and potential modifying effect of hormone therapy are uncertain. METHODS: Prospective controlled observational study of 95 premenopausal women planning RRBSO and a Comparison group of 99 premenopausal women who retained their ovaries,- 95% of whom were at population level risk of ovarian cancer. Clinically significant symptoms of depression and anxiety were measured using standardised instruments at baseline, 3, 6 and 12 months. Chi-square tests and adjusted logistic regression models compared differences between groups. RESULTS: Baseline symptoms and previous depression or anxiety did not differ between groups. At 3 months after RRBSO clinically significant depressive symptoms were doubled (14.5% vs 27.1%, p = 0.010), which persisted at 12 months. Depressive symptoms were stable in comparisons. At 3 months after RRBSO, clinically significant anxiety symptoms almost trebled (6.1% vs 17.7%, p = 0.014) before plateauing at 6 months and returning to baseline at 12 months. Compared to comparisons, RRBSO participants were at 3.0-fold increased risk of chronic depressive symptoms (Wald 95% CI 1.27-7.26), 2.3-fold increased risk of incident depression (95% Wald CI 1.08-5.13) and 2.0-fold increase of incident anxiety (Wald 95% CI 0.78-5.00). Depression and anxiety were slightly more common in Hormone Therapy users after RRBSO vs non-users. CONCLUSIONS: RRBSO leads to a rapid increase in clinically significant depressive and anxiety symptoms despite Hormone Therapy use.

Longitudinal Association Between Depressive Symptoms and Multidimensional Sleep Health: The SWAN Sleep Study.

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.

Psychosocial and health-related risk factors for depressive symptom trajectories among midlife women over 15 years: Study of Women's Health Across the Nation (SWAN).

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.

The role of sleep difficulties in the vasomotor menopausal symptoms and depressed mood relationships: an international pooled analysis of eight studies in the InterLACE consortium.

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

Treatment of Premenstrual Breakthrough of Depression With Adjunctive Oral Contraceptive Pills Compared With Placebo.

PURPOSE/BACKGROUND: Two-thirds of women with depressive disorders report reemergence of depression premenstrually, or premenstrual exacerbation (PME), despite effective treatment of the underlying mood disorder during the remainder of the cycle. There is a paucity of studies that rigorously assess treatments targeting PME. Open-label data suggest that augmentation of antidepressants with the oral contraceptive pill (OCP) drospirenone and ethinyl estradiol (DRSP/EE) improves depressive symptoms that break through treatment premenstrually. We now report results of a randomized placebo-controlled OCP augmentation trial. METHODS: Women with unipolar depressive disorders in remission on stable antidepressant doses with a 30% increase in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from the follicular to luteal phase were randomized to double-blind augmentation of antidepressant with either DRSP/EE or placebo for 2 months. The MADRS and Daily Record of Severity of Problems (DRSP) measures were anchored to the menstrual cycle phase. FINDINGS/RESULTS: Of 32 women randomized, 25 (n = 12 DRSP/EE, n = 13 placebo) completed the trial. Premenstrual MADRS scores declined by a median of 43.6% and 38.9% (P = 0.59), and premenstrual DRSP scores declined by a median of 23.5% and 20.9% (P = 0.62) in the DRSP/EE and placebo groups, respectively. There was a trend toward greater improvement in premenstrual DRSP scores for women with fewer lifetime depressive episodes (r = -0.40, P = 0.06). IMPLICATIONS/CONCLUSIONS: Findings from this small randomized trial suggest that OCP augmentation of antidepressants may not be effective for treating premenstrual breakthrough of depression. Future studies should target women established to have hormonal sensitivity prior to antidepressant therapy and those with fewer lifetime depressive episodes.

Trajectories of Vasomotor Symptoms and Carotid Intima Media Thickness in the Study of Women's Health Across the Nation.

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.

Placebo improvement in pharmacologic treatment of menopausal hot flashes: time course, duration, and predictors.

OBJECTIVES: To characterize the time course, duration of improvement, and clinical predictors of placebo response in treatment of menopausal hot flashes. METHODS: Data were pooled from two trials conducted in the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network, providing a combined placebo group (n = 247) and a combined active treatment group (n = 297). Participants recorded hot flash frequency in diaries twice daily during treatment (Weeks 0-8) and subsequent follow-up (Weeks 9-11). The primary outcome variable was clinically significant improvement, defined as a 50% or greater decrease in hot flash frequency from baseline and calculated for each week in the study. Subgroups were defined a priori using standard clinical definitions for significant improvement and partial improvement. Clinical and demographic characteristics of the participants were evaluated as predictors of improvement. RESULTS: Clinically significant improvement with placebo accrued each treatment week, with 33% significantly improved at Week 8. Of placebo responders who were improved at both Weeks 4 and 8, 77% remained clinically improved at Week 11 after treatment ended. Independent predictors of significant placebo improvement in the final multivariable model were African American race (odds ratio [OR] = 5.61, 95% confidence interval [CI] = 2.41-13.07, p < .001), current smokers (OR = 2.30, 95% CI = 1.05-5.06, p = .038), and hot flash severity in screening (OR = 1.45, 95% CI = 1.00-2.10, p = .047). CONCLUSIONS: Clinically significant improvement with placebo accrued throughout treatment with a time course similar to improvement with active drug. A meaningful number of participants in the placebo group sustained a clinically significant response after stopping placebo pills. The results suggest that nonspecific effects are important components of treatment and warrant further studies to optimize their contributions in clinical care.

Menopausal quality of life: RCT of yoga, exercise, and omega-3 supplements.

OBJECTIVE: The purpose of this study was to determine the efficacy of 3 nonhormonal therapies for the improvement of menopause-related quality of life in women with vasomotor symptoms. STUDY DESIGN: We conducted a 12-week 3 × 2 randomized, controlled, factorial design trial. Peri- and postmenopausal women, 40-62 years old, were assigned randomly to yoga (n = 107), exercise (n = 106), or usual activity (n = 142) and also assigned randomly to a double-blind comparison of omega-3 (n = 177) or placebo (n = 178) capsules. We performed the following interventions: (1) weekly 90-minute yoga classes with daily at-home practice, (2) individualized facility-based aerobic exercise training 3 times/week, and (3) 0.615 g omega-3 supplement, 3 times/day. The outcomes were assessed with the following scores: Menopausal Quality of Life Questionnaire (MENQOL) total and domain (vasomotor symptoms, psychosocial, physical and sexual). RESULTS: Among 355 randomly assigned women who average age was 54.7 years, 338 women (95%) completed 12-week assessments. Mean baseline vasomotor symptoms frequency was 7.6/day, and the mean baseline total MENQOL score was 3.8 (range, 1-8 from better to worse) with no between-group differences. For yoga compared to usual activity, baseline to 12-week improvements were seen for MENQOL total -0.3 (95% confidence interval, -0.6 to 0; P = .02), vasomotor symptom domain (P = .02), and sexuality domain (P = .03) scores. For women who underwent exercise and omega-3 therapy compared with control subjects, improvements in baseline to 12-week total MENQOL scores were not observed. Exercise showed benefit in the MENQOL physical domain score at 12 weeks (P = .02). CONCLUSION: All women become menopausal, and many of them seek medical advice on ways to improve quality of life; little evidence-based information exists. We found that, among healthy sedentary menopausal women, yoga appears to improve menopausal quality of life; the clinical significance of our finding is uncertain because of the modest effect.

Psychotropic-induced hyperprolactinemia: a clinical review.

BACKGROUND: Psychotropic medications, particularly select antipsychotics, are a common cause of drug-induced hyperprolactinemia. As high prolactin may be associated with hypogonadism, reproductive dysfunction, and bone loss, it is important to recognize this condition and understand its management. OBJECTIVE: The aim of this review is to evaluate the causes, signs, and symptoms associated with hyperprolactinemia, to describe mechanisms through which psychotropic medications elevate prolactin, and to suggest an evidence-based management approach for patients with psychotropic drug-induced hyperprolactinemia. METHODS: A PubMed/MEDLINE search was conducted on the topic of psychotropic agents as a cause of hyperprolactinemia. The material with most relevance to current psychiatric practice and of highest level of evidence was included in this review. CONCLUSION: Hyperprolactinemia should be evaluated in adult patients receiving psychotropic agents if signs and symptoms associated with hyperprolactinemia are present. It is also important to exclude pituitary and hypothalamic disease by magnetic resonance imaging if hyperprolactinemia is not definitely caused by psychotropic medications. As bone loss may occur because of hyperprolactinemia-mediated hypogonadism, bone mineral density (BMD) should be evaluated in patients with persistent high prolactin and reproductive dysfunction. Aripiprazole or other prolactin-sparing atypical antipsychotics may be alternatives or aripiprazole can be considered as adjunctive therapy in select cases of psychotropic-induced hyperprolactinemia.

Depressive symptoms over the final menstrual period: Study of Women's Health Across the Nation (SWAN).

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.

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.

The effect of experimentally induced sleep fragmentation and estradiol suppression on neurobehavioral performance and subjective sleepiness in premenopausal women.

STUDY OBJECTIVES: Menopause is associated with nighttime sleep fragmentation, declining estradiol, and impaired cognition. In a model of pharmacologically induced estradiol suppression mimicking menopause, we examined the impact of menopause-pattern sleep fragmentation on daytime neurobehavioral performance and sleepiness in premenopausal women. METHODS: Twenty premenopausal women completed two five-night inpatient studies in the mid-to-late follicular phase (estrogenized) and after pharmacological estradiol suppression (hypo-estrogenized). During each study, participants had an uninterrupted 8-hour sleep opportunity for two nights, followed by three nights where sleep was experimentally fragmented to mimic menopause-pattern sleep disturbance, and during which the sleep opportunity was extended to prevent shortening of the sleep duration. Neurobehavioral performance and subjective sleepiness were measured using the Psychomotor Vigilance Task and Karolinska Sleepiness Scale (KSS). RESULTS: Compared to unfragmented sleep, sleep fragmentation increased attentional lapses (+ 0.6 lapses, p < .05), slowed reaction time (+ 9.4 milliseconds, p < .01), and increased daytime sleepiness (+ 0.5 KSS score, p < .001). Estradiol suppression increased attentional lapses (+ 0.8; p < .001) and reaction time (+ 12.3, p < .01) but did not significantly affect daytime sleepiness. The effect of sleep fragmentation on neurobehavioral performance differed by estradiol state, such that the adverse effects of sleep fragmentation on attentional lapses (+ 0.9, trend p = .06) and reaction time (+ 15, p < .05) were observed only when estrogenized. CONCLUSIONS: Menopause-pattern sleep fragmentation and estradiol suppression worsened neurobehavioral performance and daytime sleepiness, even while sleep duration was not reduced. The adverse effects of sleep fragmentation in the context of an adequate sleep duration highlight the importance of sleep continuity as a vital aspect of good sleep health.