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

Objective: For women with pathogenic variants in BRCA1 and BRCA2, risk-reducing salpingo-oophorectomy (RRSO) at the recommended age causes surgical menopause. We previously reported elevated depressive symptoms at 6 and 12 months and elevated anxiety symptoms at 6 months after RRSO. We now report these outcomes at 24 months, their baseline and 12-month predictors and the effect of Menopausal Hormone Therapy (MHT)., Methods: Prospective controlled study of 59 premenopausal women planning RRSO and 91 comparisons who retained their ovaries. Depressive (CESD) and anxiety symptoms (GAD-7) were measured at baseline (before RRSO) and at 12 and 24 months. We used ordinary and logistic multivariable regression to estimate differences between and within groups at 24 months, before and after conditioning on baseline and 12 month measures., Results: Overall, depressive and anxiety symptoms were not elevated above baseline at 24 months and did not differ between RRSO and comparisons, before or after adjusting for previous measures (P > 0.05). Elevated depressive symptoms at 12 months (OR = 24, P < 0.001), and elevated anxiety symptoms at 12 months (OR = 13, P < 0.001), strongly predicted 24 month measures. Elevated depressive symptoms at baseline no longer predicted 24 month symptoms once 12 month symptoms were considered, but elevated baseline anxiety still predicted anxiety at 24 months, even when 12 month anxiety was considered. No association between MHT use and depressive or anxiety symptoms was observed., Conclusions: Depressive and anxiety symptoms are not elevated 24 months after RRSO. However, depressive symptoms at 12 months after RRSO are likely to persist at 24 months., Competing Interests: Declaration of competing interest MH is an editor for the Cochrane Gynaecology and Fertility Group and Clinical Expert for the UK National Institute of Clinical Care and Excellence (NICE) guidelines on menopause. She is funded by the National Health and Medical Research Council (NHMRC) through an Investigator Grant (L2) and also the Australian Medical Research Future Fund (MRFF). In the last 5 years she has received funding from Madorra P/L and Ovoca Bio (Australia) P/L for clinical research outside of the submitted work. SMD has received personal fees from AstraZeneca outside of the submitted work. TLN, EOK, AB and JLH have no declarations of competing interest. HJ is funded by the National Institutes of Health (NIH) and has received funding from Merck and Pfizer. She has consulted for Merck, Bayer and Hello Therapies., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The ways that mental health concepts are represented on social media could have significant implications for lay understandings and behavior. The current article reports an analysis of how trauma is represented on TikTok, one of the world's most popular social media platforms., Method: Following a search for content using the hashtag #trauma, 143 videos were subjected to qualitative content analysis to characterize the profiles of their producers, intended function, and trauma-related content., Results: Results show that most videos were produced by young White people, who drew on their personal experience of trauma to generate confessional narratives or raise awareness of trauma. Trauma was most often attributed to childhood adversity or relationship difficulties. A diverse range of behaviors and experiences were positioned as evidence of trauma., Conclusions: Findings are consistent with prior suggestions that trauma's boundaries are expanding in the form of "concept creep," but also draw attention to the role of humor and irony in social media invocations of the concept. Given the current near-ubiquity of social media consumption, particularly among young people, establishing the implications of exposure to this content should be a priority for future research. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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.

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: The aim of the study is to identify suitable definitions and patient-reported outcome measures (PROMs) to assess each of the six core outcomes previously identified through the COMMA (Core Outcomes in Menopause) global consensus process relating to vasomotor symptoms: frequency, severity, distress/bother/interference, impact on sleep, satisfaction with treatment, and side effects., Methods: A systematic review was conducted to identify relevant definitions for the outcome of side-effects and PROMs with acceptable measurement properties for the remaining five core outcomes. The consensus process, involving 36 participants from 16 countries, was conducted to review definitions and PROMs and make final recommendations for the measurement of each core outcome., Results: A total of 21,207 publications were screened from which 119 reporting on 40 PROMs were identified. Of these 40 PROMs, 36 either did not adequately map onto the core outcomes or lacked sufficient measurement properties. Therefore, only four PROMs corresponding to two of the six core outcomes were considered for recommendation. We recommend the Hot Flash Related Daily Interference Scale to measure the domain of distress, bother, or interference of vasomotor symptoms and to capture impact on sleep (one item in the Hot Flash Related Daily Interference Scale captures interference with sleep). Six definitions of "side effects" were identified and considered. We recommend that all trials report adverse events, which is a requirement of Good Clinical Practice., Conclusions: We identified suitable definitions and PROMs for only three of the six core outcomes. No suitable PROMs were found for the remaining three outcomes (frequency and severity of vasomotor symptoms and satisfaction with treatment). Future studies should develop and validate PROMs for these outcomes., Competing Interests: Financial disclosure/conflicts of interest: V.P. received past funding from Sigvaris AG. M.P. received institutional funding from University of Melbourne (Internal Grant Schemes), Royal Women's Hospital (Internal grant scheme), and Cancer Council NSW Project Grant RG 21-06, Centre for Research Excellence in Women's Health in Reproductive Life (CREWHiRL) Seed Funding and Project Support Grant, NHMRC (APP1163202), and Royal Children's Hospital Foundation. She received past funding from FertilityIQ webinar honorarium. She has received fee registration fees as an invited speaker by the Pacific Society of Reproductive Medicine 2023 Conference and had subsidized flights and accommodations as an invited speaker for the European Society of Human Reproduction and Embryology 2022 Conference. She was also given free registration as an invited speaker for the Annual Scientific Meeting of Breast Cancer Trials 2021. D.A. has consulted for Evestra, Exeltis, Lupin, Mithra, ObsEva, and TherapeuticsMD, received industry support for research from AbbVie, Mithra, Myovant, and ObsEva, and has stock holdings in Agile Therapeutics, InnovaGyn, Inc. N.A. receives ongoing institutional funding from the National Cancer Institute. J.C. is owner of JSCarpenter, LLC which received scale licensing fees from Mapi Research Trust (2022), consulting fees from the University of Wisconsin (spring 2022), and consulting fees from Simumetrix SMX Health (spring 2022). M.C. has been paid for developing and delivering educational presentations for Alliance Chicago, received fees for an educational video and speaking engagements with Fertility IQ, wrote a White Paper on GSM for Materna (no financial reimbursement), and is a member of The Menopause Society Board of Trustees. M.D. receives current institutional funding from National Institute of Health Research. She serves as a chief investigator on POISE study (research relevant to HRT) and a chief investigator for BLUSH study (research on treatment of menopause). She received past institutional funding from Best Practice & Research Clinical Obstetrics & Gynaecology as editor of volume on menopause management published 2022. She is an elected member of the Medical Advisory Council of the British Menopause Society, is a member of the ESHRE guideline update group on Premature Ovarian Insufficiency, is a member of the British Endocrine Society working group producing clinical guidelines on estrogen treatment, and is a member of the British Gynaecological Cancer Society working group producing clinical guidelines on HRT. T.H. received past funding from Besins and Astellas. M.H. receives ongoing funding from Rightsteps and current funding from Hello Therapeutics. L.K. has lectured and/or acted in an advisory capacity for Gedeon Richter, Dr. KADE Besins and Mithra. P.M. has received compensation as a member of the scientific advisory board of Astellas, Bayer, and Johnson & Johnson; compensation from AbbVie and Pfizer for consulting; and serves as a member of the scientific advisory board and has/had equity in Alloy, Estrigenix, and MidiHealth. She has received speaking fees and travel support from Mithra. R.E.N. has ongoing relationships with Abbott, Astellas, Bayer HealthCare AG, Besins Healthcare, Exeltis, Fidia, Gedeon Richter, HRA Pharma, Merck Healthcare, Novo Nordisk, Shionogi Limited, Theramex, and Viatris. N.P. has lectured and/or acted in an advisory capacity for Abbott, Lawley, Mithra, Novo, SeCur, and Viatris. S.R. has lectured and/or acted in an advisory capacity or conducted studies for Abbott, Bayer, Gedeon Richter, Mylan, Amgen, UCB, Theramex, and Viatris. J.S. receives grant/research support from AbbVie, Inc., Bayer Healthcare LLC., Dare´ Bioscience; Ipsen, Mylan/Viatris Inc., Myovant Sciences, Sebela Pharmaceuticals Inc. He acts as a consultant is on advisory boards for Bayer HealthCare Pharmaceuticals Inc., Besins Healthcare, California Institute of Integral Studies (CIIS), Dare´ Bioscience, Femasys Inc., Khyria, Madorra Pty Ltd., Mayne Pharma, Inc., and Vella Bioscience Inc. He serves on speaker's bureaus for Astellas Pharma, Inc., Mayne Pharma, Inc., Myovant Sciences, Inc., Pfizer Inc., Pharmavite LLC., Scynexis Inc. He is a stockholder (direct purchase) of Sermonix Pharmaceuticals. P.S. has received fees for giving educational presentations, participating in advisory boards and conducting research by Besins Healthcare, Astellas, Mylan, Labatec, Exeltis, Effik, Theramex, and Gedeon-Richter. A.J.V. has received fees for presentations and participation in an advisory board from Besins and Theramex. W.W. has received institutional support with an unrestricted grant from Pfizer and sits on the advisory boards of Pfizer, Lupin, and Biosyent. She has received fees for educational presentations for Lupin, Astellas, Bayer and Pfizer, and Biosyent. She is a board member of the International Menopause Society and the President of the Canadian Menopause Society. M.H. has received funding from Madorra for a study of a device to manage GU symptoms and is a clinical expert for the NICE Menopause Guidelines. J.T.G. is a speaker for NurtureMed Pharma, Bayer Phils, Corbridge Phils, and Zuellig Pharma. P.S. has a research consultancy relationship with Chugai Pharmaceuticals. H.J. receives grant funding from the National Institutes of Health, Merck, and Pfizer and is a consultant to Bayer, Merck, and Hello Therapeutics. She receives in kind support from Sage to her institution (drug provided to support NIH-funded trial), funds from Bayer support a pilot grant program she lead within an NIH-funded Center grant. Her spouse is employed by Arsenal Biosciences and receives equity from Merck Research Labs. N.J. is on the advisory board of Vira Health, UK. All other authors report no conflicts of interest., (Copyright © 2024 by The North American Menopause Society.)

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., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of interests MSH declares consultation for Rightsteps UK. HJ declares grant funding from the National Institutes of Health (grant numbers U54AG062322 and R01MH128617), Pfizer, and Merck; and consulting for Bayer, Merck, and Hello Therapeutics. MH declares salary funding from the Australian National Health and Medical Research Council, support for meeting attendance from the UK National Institute for Health and Care Excellence, and the following roles: principal investigator for a clinical trial of salpingectomy vs salpingo-oophorectomy for prevention of ovarian cancer (TUBA-WISP II); board member for Breastscreen Victoria; editor for the Cochrane Collaboration; recipient of a fellowship from the Lundbeck Foundation (2022-23); site investigator for a clinical trial of a non-hormonal agent (Q-122) for vasomotor symptoms in patients with breast cancer (QUE Oncology, 2020-22); and site investigator for a clinical trial of a medical device for treating vaginal dryness (Madorra). All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Author Disclosures Conflict of Interest Disclosures for this article can be found here., (Copyright © 2024. Published by Elsevier Inc.)

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/cm 2 ). 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., (Copyright © 2024 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: Readiness among laypeople to classify ordinary adversities as "trauma" may activate cognitive, social, and behavioral patterns that either promote proactive help-seeking or exacerbate mental health difficulties. Clinical understandings of trauma have expanded across recent decades to encompass a wide range of aversive experiences. While some have suggested lay understandings of trauma have expanded in parallel, minimal data directly reveal how the lay public conceptualize trauma. This study sought to establish the range of adversities that laypeople classify as traumatic., Method: In an online survey, U.K. participants ( N = 214) rated the traumatic nature of 80 adversities, half of which represented prototypical precursors of trauma (e.g., physical assault and sexual abuse), and half of which involved other adversities, not typically invoked in clinical definitions of trauma., Results: Prototypical precursors were judged significantly more traumatic than nonprototypical adversities, but many nonprototypical adversities were also deemed likely to cause trauma (e.g., facial disfigurement or being falsely accused of a crime). Individual variation in the propensity to interpret adversities as traumatic was significantly predicted by participants' age, ethnicity, and political orientation., Conclusions: This original evidence regarding the content and predictors of lay conceptions of trauma is relevant for sensitive delivery of clinical interventions, tailoring of other supports for populations experiencing adversity, and anticipating social responses to victims of specific adversities. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Parenting children with conduct problems (CP) is challenging, yet very little research has examined parenting using both quantitative and qualitative methods, from the perspective of the child and their parent/caregiver, and separately for those with high vs. low levels of callous-unemotional traits (HCU vs. LCU). One hundred and forty-six boys aged 11-16 [Typically developing (TD) n = 31; CP/HCU n = 35; CP/LCU n = 35] and their parents/caregivers completed the Alabama Parenting Questionnaire and provided a written qualitative statement describing their respective experiences of parenting/being parented. Parents/caregivers of CP/HCU boys reported more difficulty with child monitoring and supervision than parents of TD boys. This was echoed in qualitative reports of parents of CP/HCU boys reporting concerns regarding their child's safety. Parents/caregivers of both groups of CP boys reported more inconsistent discipline than parents of TD boys. Parental qualitative descriptions of challenging behavior in CP/HCU boys, and difficulties with setting boundaries and motivating CP/LCU boys, provided further insight to the potential triggers for inconsistent discipline. Qualitative reports from boys with CP indicated that they understood the parenting challenges their parents/caregivers faced. These findings replicate and extend previous work on the associations between parenting and CP. Children with CP/HCU and CP/LCU show some commonalities and differences in their parenting experiences and CP children and their parents/caregivers do not necessarily share all the same perceptions or concerns. CP interventions often involve parent/family engagement and this research highlights the continued importance of examining both parent and child perspectives., (© 2022. The Author(s).)

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 β = 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., Competing Interests: Declaration of conflicts of interest Dr. Klerman reports consulting income from the American Academy of Sleep Medicine Foundation, Circadian Therapeutics, National Sleep Foundation, and the Sleep Research Society Foundation; she has received travel support from the European Biological Rhythms Society and the Sleep Research Society; she is an unpaid member of the Scientific Advisory Board of Chronsulting; and her partner is founder, director, and chief scientific officer for Chronsulting. Dr. Joffe reports grants from NIH during the conduct of the study; grants from Pfizer, grants and personal fees from Merck, personal fees from Hello Therapeutics, personal fees from Bayer, outside the submitted work; and Spouse: Employee at Arsenal Biosciences; Equity at Merck Research Labs. Dr. Bertisch reports consulting fees from Idorsia Pharmaceuticals and ResMed. Other authors do not report any conflicts of interest., (Copyright © 2023 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.)

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., Competing Interests: Financial disclosure/conflicts of interest: C.C. and L.Z. are employees of Bayer CC AG. C.S. is an employee of Bayer AG. M.K., S.P., E.B., S.S., and M.T. are employees of NeRRe Therapeutics. J.B., as an employee of Cytel Inc, was a paid statistical consultant on this trial. R.A.A. has undertaken consultancy work for NeRRe Therapeutics and Sojournix Inc. J.A.S. has grant/research support from AbbVie, Inc, Bayer Healthcare LLC, Daré Bioscience, Ipsen, Mylan/Viatris Inc, Myovant Sciences, ObsEva SA, Sebela Pharmaceuticals Inc, and Viveve Medical; has been a consultant/advisory boards of Bayer HealthCare Pharmaceuticals Inc, Besins Healthcare, California Institute of Integral Studies, Camargo Pharmaceutical Services, LLC, Covance Inc, Daré Bioscience, DEKA M.E.L.A. S.r.l., Femasys Inc, KaNDy/NeRRe Therapeutics Ltd, Khyria, Madorra Pty Ltd, Mitsubishi Tanabe Pharma Development America, Inc, QUE Oncology Pty, Limited, Scynexis Inc, Sebela Pharmaceuticals, Inc, Sprout Pharmaceuticals, Inc, and Vella Bioscience Inc; has served on the Speaker's bureaus of Mayne Pharma, Inc, Myovant Sciences, Inc, Pfizer Inc, Pharmavite LLC, Scynexis Inc, and TherapeuticsMD; and is a stockholder (direct purchase) in Sermonix Pharmaceuticals. N.P. has undertaken consultancy and speaker's bureau work for a number of pharmaceutical companies including Bayer AG. H.J. has received grant funding from National Institutes of Health, Merck, Pfizer, and Hello Therapeutics; has undertaken consultancy work for Bayer, Jazz, and Eisai; and her spouse is an employee at Arsenal Biosciences and has equity at Merck., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The North American Menopause Society.)

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., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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: 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., Competing Interests: Financial disclosure/conflicts of interest: H.J. reports the following relationships (over the past 12 months): grant support from National Institutes of Health, Merck, Pfizer. Consultant and advisory fees from Eisai, Jazz, Bayer. Funding to institution from NeRRe/KANDy, Que-Oncology. Spouse is an employee of Arsenal Biosciences; Spouse has an equity stake in Merck Research Labs and Tango Therapeutics. E.O. receives funding from UpToDate. The other authors have nothing to disclose., (Copyright © 2022 by The North American Menopause Society.)

Loneliness is a rapidly growing problem globally and has attracted a great deal of attention in light of the COVID-19 pandemic. Young adults, and in particular, those residing in deprived areas are currently the loneliest group in the United Kingdom. Utilizing a novel-free association technique, young adults' experiences of loneliness were explored both prior to (n = 48) and during (n = 35) the COVID-19 pandemic. Drawing on social representations theory, a thematic analysis revealed that many young adults associated the experience of loneliness with their homes. Therefore, this comparative study aims to investigate how the home features in young adults' representations of loneliness, prior to and during the COVID-19 pandemic using a systematic qualitative methodology. Three salient themes emerged from the data in both periods: 'The Lonely Home,' 'The Socially Connected Home' and 'The Safe, Peaceful, Authentic Home'. 'The Lonely Home' and 'The Socially Connected Home' emerged as a dialogical antimony. Representations of home were similar across the two periods; however, there were some notable differences. In particular, the themes 'The Socially Connected Home' and 'The Safe, Peaceful, Authentic Home' were less frequently mentioned by the during-COVID-19 sample where the 'The Lonely Home' was more frequently mentioned by the during-COVID-19 sample. Overall, discussion of the home was more negatively valenced in the during-COVID-19 sample compared to the pre-COVID-19 sample. This comparative, exploratory study alerts us to the nature of the role that home plays in exacerbating or ameliorating loneliness both prior to and during the COVID-19 pandemic., (© 2022 The Authors. British Journal of Social Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

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 (β = 0.14; 95% CI, 0.04 to 0.24; P = 0.007), and higher FSH levels (β [1-unit increase] = 0.12; 95% CI, 0.02 to 0.22; P = 0.02), but not with progesterone (β [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 Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Disasters incurred by natural hazards affect young people most. Schools play a vital role in safeguarding the wellbeing of their pupils. Consideration of schools' psychosocial influence on children may be vital to resilience-building efforts in disaster-vulnerable settings. This paper presents an evidence-based conceptualization of how schools are psychosocially meaningful for children and youth in disaster settings. Drawing on Social Representations and Place Attachment Theories, we explore the nature of group-based meaning-making practices and the meanings that emerge concerning school environments in disaster settings. We contribute a novel understanding of how schools may mitigate psychosocial risk for young people by considering how schools are conceptualised at four levels: (1) as physical environment, (2) as social arena, (3) as a place with individual and (4) group-based significance. In each of these domains schools can foster disaster resilience in young people. This paper highlights the evidence concerning the functions of schools beyond their capacity as educational institutions, critically considering their social and physical functions in their communities. This evidence can inform stakeholders involved in disaster resilience building., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pacheco, Parrott, Oktari and Joffe.)

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 17β 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., Competing Interests: Financial disclosure/conflicts of Interest: S.D.R. reports research funding from Bayer and royalties from UpToDate. S.B. reports his institution has received research grants from MIB, AbbVie, and Transition Therapeutics, on which he is the PI. These grants are unrelated to the work. C.M.M. reports grant support from Merck Inc and consultant and advisory fees from Scynexis and UpToDate. H.J. reports grant support from Merck, Pfizer, NeRRe/KaNDy, and Que Oncology, and consultant and advisory fees from Bayer, Eisai, and Jazz. H.J.'s spouse is an employee of Arsenal Biosciences and has an equity stake in Merck Research Labs and Tango Therapeutics. The other authors declare no conflict of interest., (Copyright © 2022 by The North American Menopause Society.)

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., Competing Interests: Financial disclosure/conflicts of interest: N.E.A. reports internal pilot funding from the Wake Forest School of Medicine. H.J. reports money paid to the institution (current) from Merck and Pfizer and from (past) NErre/KaNDy and Que Oncology, money paid to her from Bayer, consulting contracts no longer active from Jazz and Esai, and that her spouse is an employee of Arsenal Biosciences and has an equity stake in Merck Research Labs and Tango Therapeutics. J.M.P. reports money paid to her from (past) Abbvie, Biohaven, Lundbeck advisory board and American Headache Society (travel costs). R.C.T. reports money paid to her from (current) Astellis Pharma, Bayer, Happy Health, and Viva Health, and from (past) Pfizer Inc., Proctor & Gamble, and Virtue Health. The other authors have nothing to report., (Copyright © 2022 by The North American Menopause Society.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (Copyright © 2022 President and Fellows of Harvard College.)

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.)

COVID-19 has required researchers to adapt methodologies for remote data collection. While virtual interviewing has traditionally received limited attention in the qualitative literature, recent adaptations to the pandemic have prompted increased discussion and adoption. Yet, current discussion has focussed on practical and ethical concerns and retained a tone of compromise, of coping in a crisis. This paper extends the nascent conversations begun prior to the pandemic to consider the wider methodological implications of video-call interviews. Beyond the short-term, practical challenges of the pandemic, these adaptations demonstrate scope for longer-term, beneficial digitalisation of both traditional and emergent interview methods. Updating traditional interview methods digitally has demonstrated how conversion to video interviewing proves beneficial in its own right. Virtual focus-group-based research during COVID-19, for example, accessed marginalised populations and elicited notable rapport and rich data, uniting people in synchronous conversation across many environments. Moreover, emergent interview methods such as the Grid Elaboration Method (a specialised free-associative method) demonstrated further digitalised enhancements, including effective online recruitment with flexible scheduling, virtual interactions with significant rapport, and valuable recording and transcription functions. This paper looks beyond the pandemic to future research contexts where such forms of virtual interviewing may confer unique advantages: supporting researcher and participant populations with mobility challenges; enhancing international research where researcher presence or travel may be problematic. When opportunities for traditional face-to-face methods return, the opportunity for virtual innovation should not be overlooked., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Disasters can have long-lasting impacts on mental health. Intrusive memories have been found to be common and persistent in the aftermath of earthquakes., Objective: To explore, using diaries, intrusive memories' presence, content, characteristics, and relationship with probable post-traumatic stress disorder (PTSD) in a small rural community exposed to mass destruction and loss of life., Methods: Survivors of the 2016-2017 Central Italy earthquakes ( N  = 104) were first interviewed to investigate the presence of intrusive memories of the disaster. Those that reported intrusive memories were subsequently asked to complete a 7-day paper-and-pen diary tracking their spontaneous memories of the earthquake events., Results: Twenty months after the earthquakes, 49% ( n  = 51) of the sample reported having experienced intrusive memories post-earthquake and 38% ( n  = 39) reported at least one intrusive memory in their diaries. Memories were rated as being distressing, vivid, and experienced as a mixture of images and thoughts. The content of intrusive memories generally focused on sensations and experiences during the earthquake. Other common categories of content were the material environment and physical objects as well as human loss & death. Several memories had a social focus. A minority of memories contained more positive content as well as content from before and after the earthquake. Some participants (28%) experienced repeated intrusive memories of the same content. Memories of participants with and without probable PTSD did not significantly differ on characteristics or content., Conclusions: Intrusive memories can be common, distressing, and persistent occurrences following disasters, even in survivors not suffering from probable PTSD., Highlights: Intrusive memories were common, distressing, and vivid more than 1-year post-disaster.They captured peri-earthquake sensations, material destruction, death, and social interactions.No difference in content or characteristics was found between participants with and without probable PTSD., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

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., Competing Interests: Financial disclosures/conflicts of interest: N.F.S. reports receiving advisory fees from Astellas and Que-Oncology, research support from Menogenix, Inc (paid to the University of Colorado), and consultant fees from Ansh Labs. H.J. reports receiving grant support Merck, Pfizer, Que-Oncology, and NeRRe/KaNDy and consultant and advisory fees from Eisai, Jazz, and Bayer. H.J. also reports her spouse is an employee of Arsenal Biosciences and has an equity stake in Merck Research Labs and Tango Therapeutics., (Copyright © 2022 by The North American Menopause Society.)

Introduction: Most women develop MS before menopause. Menopausal hot flashes can worsen MS symptoms, and could be relieved with hormone therapy. Our objective was to evaluate feasibility, tolerability and symptom response of Duavee® (bazedoxifene + conjugated estrogen) in a Phase Ib/IIa double-blind randomized controlled clinical trial., Methods: We randomized 24 peri/postmenopausal women with MS and symptomatic hot flashes 1:1 to Duavee® versus placebo. Evaluations occurred at baseline and 2 months., Results: Groups were balanced for age (mean 51.2 ± 3.6 years), EDSS [median 3 (IQR:2.5, 4.5)], and MS duration. 21/24 participants completed the study., Feasibility: Enrollment was protracted (34 months), partially due to concerns about hormone therapy safety., Tolerability: treatment group participants reported greater satisfaction and fewer missed doses; one participant (placebo) developed new MRI lesions; liver function testing remained normal for all patients., Symptoms: Hot Flash Related Daily Interference scale at 2 months was lower in treatment vs. placebo group [median (IQR) of 4 (0.5, 14) vs. 9 (0, 33)]. Between-group differences were not statistically significant., Conclusion: Despite perceived benefits in MS, estrogens have perceived risks that represent a hurdle to enrollment. With appropriate education and screening of participants, the favorable study retention (87%) and treatment satisfaction observed in the current study support the feasibility of a longer, powered trial to evaluate whether a proven treatment for menopausal symptoms, Duavee®, could also improve MS-related function in menopausal women with MS., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Young adults are currently the loneliest demographic in the UK and other Western countries, yet little is known about how they see the causes of their loneliness. Thus, the objective of this study is to explore the subjective causes of loneliness among young adults (18-24 years old), particularly those of lower socio-economic status (SES) who are in employment, renting and living in the most deprived areas, since they are the loneliest in the UK. Utilising a free association technique and thematic analysis, and embedded in a phenomenological framework, the subjective causes of loneliness in a matched sample of 48 young adults in the four most deprived boroughs of London are found to cluster around five themes: The Feeling of Being Disconnected, Contemporary Culture, Pressure, Social Comparison and Transitions Between Life Stages. Disconnection arises from feeling one does not matter, is not understood or is unable to express oneself. Challenges pertaining to social media and materialism in contemporary culture contribute to loneliness as does pressure associated with work, fitting in and social comparison. Social media play a major role in exacerbating these experiences. Finally, transitions between life stages such as breakups, loss of significant others and transitory stages to do with education and employment are felt to cause loneliness. The findings suggest potential avenues for loneliness reduction., Competing Interests: The authors have declared that no competing interests exist.

Background: Historically, females have been underrepresented in clinical trials evaluating the safety and efficacy of investigational drugs and devices. We assessed participation by sex in recent clinical trials., Methods: We extracted data over a 4-year period (2016-2019) from ClinicalTrials.gov on US-based, pharmaceutical industry or government-funded Phase 1-3 clinical trials of drugs and devices. We included trials with adult cardiovascular, psychiatric, and cancer endpoints whose protocol planned to enroll both sexes. Average proportions of females enrolled per trial were described overall and by disease area., Results: Across 1433 trials including 302,664 participants in our analysis, on average, 41.2% were female. Females were underrepresented compared with their proportion of the disease population in cardiovascular disease trials (41.9% female participants vs. 49% female population with cardiovascular disease). In psychiatry, where females comprise 60% of patients, the mean participation of females in clinical trials was 42.0%. Similarly, for cancer trials, where 51% of patients are female, only 41.0% of cancer clinical trial participants were female. For each therapeutic area analyzed, the participation of females in clinical trials fell short of the benchmark derived from national prevalence data., Conclusions: While the participation of females in clinical trials has improved compared to previous reports, sex-based gaps still persist between trial populations and those expected to use these drugs/devices based on distributions of diseases in the population. Given potential sex-based differences in treatment responses and toxicities, adequate inclusion of females in clinical trials remains critical., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Study Objectives: The neuropeptide orexin promotes wakefulness, modulates thermoregulation, increases after menopause, and is normalized in women receiving estrogen therapy, suggesting a role for orexin antagonism as a treatment for the vasomotor symptom (VMS)-associated insomnia disorder. We tested the efficacy of the dual orexin receptor antagonist suvorexant for chronic insomnia related to nighttime VMS., Methods: In a double-blind, placebo-controlled trial, 56 women with chronic insomnia associated with nighttime VMS, Insomnia Severity Index (ISI) scores ≥15, and >30 min of diary-rated wake after sleep-onset (WASO) were randomized to receive oral suvorexant 10-20 mg (n = 27) or placebo (n = 29) nightly for 4 weeks. Analysis of within-person change in ISI was adjusted for baseline ISI and race., Results: Mean baseline ISI scores were 18.1 (95% CI, 16.8 to 19.4) and 18.3 (95% CI, 17.2 to 19.5) in the suvorexant and placebo groups, respectively (p = .81). The average 4-week ISI within-person decrease from baseline was greater on suvorexant (-8.1 [95% CI, -10.2 to -6.0]) compared to placebo (-5.6 [95% CI, -7.4 to -3.9], p = .04). Compared to placebo, nighttime diary-rated VMS frequency was significantly reduced with suvorexant (p < .01). While diary-rated WASO and total sleep time trended toward improvement on suvorexant, findings were not significant after adjustment for multiple comparisons. Daytime VMS and other sleep-related outcomes did not differ between groups. Suvorexant was well tolerated., Conclusion: These results suggest that suvorexant is likely a well-tolerated and efficacious treatment for VMS-associated insomnia disorder and reduces nighttime VMS. Antagonism of orexin receptors could provide a novel therapeutic option for midlife women with VMS-associated chronic insomnia., Clinical Trial Information: Efficacy of Suvorexant in the Treatment of Hot Flash-associated Insomnia, https://clinicaltrials.gov/ct2/show/NCT03034018, ClinicalTrials.gov Identifier: NCT03034018., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Previous work implicates high pro-inflammatory biomarkers in mood disturbance and low brain-derived neurotrophic factor (BDNF) levels in major depression. However, in hormonally-sensitive premenstrual dysphoric disorder (PMDD), BDNF levels are higher when mood is worse. Perimenopausal depression has not been studied to date. We evaluated whether BDNF and inflammatory cytokines predict mood symptoms across the menstrual cycle in hormonally-sensitive perimenopausal depression symptoms., Methods: Data from 49 time points derived from mid-to-late follicular phase [M/L-FP] and peri‑menstrual assessments of 14 perimenopausal women ages 38-52 with ovulatory menstrual cycles 24-35 days long across 1-2 cycles for mood symptoms, BDNF levels, cytokines, gonadal steroids. Depression was assessed with Montgomery-Åsberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI); irritability with Kellner Symptom Questionnaire Anger-Hostility subscale (SQ); overall psychological distress with Profile of Mood States (POMS). Mixed models were run on dependent measures of MADRS (primary endpoint) and other mood outcomes (BDI, POMS, SQ) with independent variables of interest (each biomarker, cycle phase), controlling for cycle number and participant., Results: After FDR adjustment, BDNF levels showed consistent significant positive relationships to MADRS (β=0.00053; p = 0.0028), POMS (β=0.00153; p = 0.0394), SQ (β=0.00053; p = 0.0067), and BDI (β=0.00039; p = 0.0231). Cycle phase did not affect this relationship. No other biomarker consistently predicted affective symptom severity., Limitations: Small sample size and large number of comparisons., Conclusion: In women with perimenopausal depression symptoms, BDNF is elevated in association with more severe mood symptomatology, resembling the pattern in hormonally-sensitive PMDD and suggesting a hormonally-sensitive mood disorder biomarker profile distinct from that of major depression., (Copyright © 2021. Published by Elsevier B.V.)

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., (© 2021. The Author(s).)

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.)

Purpose: Younger women are at risk for depression and related symptoms following breast cancer. The Pathways to Wellness study, a randomized, multi-institution, three-arm trial, tested the efficacy of two behavioral interventions for younger breast cancer survivors with elevated depressive symptoms: mindful awareness practices (MAPs) and survivorship education (SE) (Clincaltrials.gov identifier: NCT03025139)., Methods: Women diagnosed with breast cancer at or before 50 years of age who had completed treatment and had elevated depressive symptoms were randomly assigned to 6 weeks of MAPs, SE, or wait-list control (WLC). Assessments were conducted preintervention and postintervention and at 3-month and 6-month postintervention follow-ups. Analyses compared each intervention to WLC using linear mixed models. The primary outcome was change in depressive symptoms from preintervention to postintervention on the Center for Epidemiologic Studies-Depression Scale; secondary outcomes included change in fatigue, insomnia, and vasomotor symptoms., Results: Two hundred forty-seven women (median age = 46 years) were randomly assigned to MAPs (n = 85), SE (n = 81), or WLC (n = 81). MAPs and SE led to significant decreases in depressive symptoms from preintervention to postintervention relative to WLC (mean change relative to WLC [95% CI]: MAPs, -4.7 [-7.5 to -1.9]; SE, -4.0 [-6.9 to -1.1]), which persisted at 6-month follow-up for MAPs (mean change relative to WLC [95% CI]: MAPs, -3.7 [-6.6 to -0.8]; SE, -2.8 [-5.9 to 0.2]). MAPs, but not SE, also had beneficial effects on fatigue, insomnia, and vasomotor symptoms that persisted at 6-month follow-up ( P < .05)., Conclusion: Mindfulness meditation and SE reduced depressive symptoms in younger breast cancer survivors. These interventions can be widely disseminated over virtual platforms and have significant potential benefit for quality of life and overall survivorship in this vulnerable group., Competing Interests: Ann H. PartridgePatents, Royalties, Other Intellectual Property: I receive small royalty payments for co-authoring the breast cancer survivorship section of UpToDateTravel, Accommodations, Expenses: Novartis Antonio C. WolffConsulting or Advisory Role: Ionis PharmaceuticalsPatents, Royalties, Other Intellectual Property: Antonio Wolff has been named as inventor on one or more issued patents or pending patent applications relating to methylation in breast cancer, and has assigned his rights to JHU, and participates in a royalty sharing agreement with JHUOpen Payments Link: https://openpaymentsdata.cms.gov/physician/357301/summary Hadine JoffeEmployment: MerckLeadership: MerckStock and Other Ownership Interests: Merck, ArsenalBio, Tango TherapeuticsConsulting or Advisory Role: Kandy Therapeutics, Sojournix, Eisai, Jazz PharmaceuticalsResearch Funding: Pfizer, Merck, QUE Oncology, Kandy Therapeutics Patricia A. GanzLeadership: Intrinsic LifeSciencesStock and Other Ownership Interests: Xenon Pharma, Intrinsic LifeSciences, Silarus Therapeutics, Teva, Novartis, Merck, Johnson & Johnson, Pfizer, GlaxoSmithKline, Abbott LaboratoriesConsulting or Advisory Role: InformedDNA, Vifor Pharma, Ambys Medicines, Global Blood Therapeutics, GlaxoSmithKline, Ionis Pharmaceuticals, Akebia Therapeutics, Protagonist Therapeutics, Regeneron, Sierra Oncology, Rockwell Medical Technologies Inc, Astellas Pharma, Gossamer Bio, American Regent, Disc Medicine, Blue Note TherapeuticsResearch Funding: Sierra OncologyPatents, Royalties, Other Intellectual Property: Related to iron metabolism and the anemia of chronic disease, UpToDate royalties for section editor on survivorshipTravel, Accommodations, Expenses: Intrinsic LifeSciencesNo other potential conflicts of interest were reported.

Cognitive theories of posttraumatic stress disorder (PTSD) suggest that intrusive memories result from disrupted information processing during traumatic memory encoding and are characterized by fear, helplessness, and horror at recall. Existing naturalistic studies are limited by the absence of direct comparisons between specific moments that do and do not correspond to intrusive memories. We tested predictions from cognitive theories of PTSD by comparing peritraumatic responses during moments experienced as intrusive memories versus distressing moments of the same traumatic event from the same individual not experienced as intrusive memories. A further comparison was with highly distressing moments experienced during the same event by individuals without intrusive memories. We utilized a psychometrically generated model to distinguish different peritraumatic reactions. Moments experienced as intrusive memories were characterized by higher peritraumatic distress, immobility, cognitive overload, and somatic dissociation when compared both to distressing moments from the same individual that did not intrude and to the most distressing memories of individuals without intrusions. Exploratory analyses indicated that at recall, intrusive memories were characterized by higher levels of primary traumatic emotions such as anxiety, fear, and helplessness in comparison with nonintrusive memories. Findings from this novel naturalistic design support predictions made by cognitive theories of PTSD and have implications for research and preventative interventions targeting intrusive memories. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Purpose: We previously demonstrated that sex influences response to immune checkpoint inhibitors. In this article, we investigate sex-based differences in the molecular mechanisms of anticancer immune response and immune evasion in patients with NSCLC., Experimental Design: We analyzed (i) transcriptome data of 2,575 early-stage NSCLCs from seven different datasets; (ii) 327 tumor samples extensively characterized at the molecular level from the TRACERx lung study; (iii) two independent cohorts of 329 and 391 patients, respectively, with advanced NSCLC treated with anti-PD-1/anti-PD-L1 drugs., Results: As compared with men, the tumor microenvironment (TME) of women was significantly enriched for a number of innate and adaptive immune cell types, including specific T-cell subpopulations. NSCLCs of men and women exploited different mechanisms of immune evasion. The TME of females was characterized by significantly greater T-cell dysfunction status, higher expression of inhibitory immune checkpoint molecules, and higher abundance of immune-suppressive cells, including cancer-associated fibroblasts, MDSCs, and regulatory T cells. In contrast, the TME of males was significantly enriched for a T-cell-excluded phenotype. We reported data supporting impaired neoantigens presentation to immune system in tumors of men, as molecular mechanism explaining the findings observed. Finally, in line with our results, we showed significant sex-based differences in the association between TMB and outcome of patients with advanced NSCLC treated with anti-PD-1/PD-L1 drugs., Conclusions: We demonstrated meaningful sex-based differences of anticancer immune response and immune evasion mechanisms, that may be exploited to improve immunotherapy efficacy for both women and men., (©2021 American Association for Cancer Research.)

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.)

Sleep disturbances and insomnia are common among breast cancer survivors, and can have a significant effect on quality of life and numerous other significant outcomes. Among risks for sleep disturbance is the introduction of anti-estrogen endocrine therapies. The possible contributing factors to sleep disturbance in endocrine therapy are complex, and include pre-existing sleep disorders, the effects of chemotherapy and other treatments, and concurrent symptoms such as hot flashes. In addition, sleep disturbance in menopause, the natural downregulation of reproductive hormones in older age, is a common occurrence, and can offer a model for understanding the high prevalence of sleep problems in breast cancer survivors on endocrine therapy, as well as suggesting possible treatments such as behavioral interventions and pharmaceuticals. Altogether, significantly more research is needed to better understand and address sleep disturbance in breast cancer survivors on endocrine therapy in order to support quality of life and treatment adherence., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Women remain underrepresented within academic medicine despite past and present efforts to promote gender equity. The authors discuss how the COVID-19 pandemic could stymie progress toward gender parity within the biomedical workforce and limit the retention and advancement of women in science and medicine. Women faculty face distinct challenges as they navigate the impact of shelter-in-place and social distancing on work and home life. An unequal division of household labor and family care between men and women means women faculty are vulnerable to inequities that may develop in the workplace as they strive to maintain academic productivity and professional development without adequate assistance with domestic tasks and family care. Emerging data suggest that gender differences in academic productivity may be forthcoming as a direct result of the pandemic. Existing gender inequities in professional visibility, networking, and collaboration may be exacerbated as activities transition from in-person to virtual environments and create new barriers to advancement. Meanwhile, initiatives designed to promote gender equity within academic medicine may lose key funding due to the economic impact of COVID-19 on higher education. To ensure that the gender gap within academic medicine does not widen, the authors call upon academic leaders and the broader biomedical community to support women faculty through deliberate actions that promote gender equity, diversity, and inclusion. The authors provide several recommendations, including faculty needs assessments; review of gender bias within tenure-clock-extension offers; more opportunities for mentorship, sponsorship, and professional recognition; and financial commitments to support equity initiatives. Leadership for these efforts should be at the institutional and departmental levels, and leaders should ensure a gender balance on task forces and committees to avoid overburdening women faculty with additional service work. Together, these strategies will contribute to the development of a more equitable workforce capable of transformative medical discovery and care., (Copyright © 2021 by the Association of American Medical Colleges.)

Young adults (16-24 years old) are currently the loneliest group in Western countries. In particular, young adults of lower socio-economic status (SES) living in the most deprived areas are loneliest in the United Kingdom. This mixed-methods study explored the experience of loneliness among this under-explored demographic in London. Using a novel free association technique, the experience of loneliness was found to be characterized by: a sense of isolation, negative emotions and thoughts, coping and a positive orientation to aloneness. An exploration of these themes revealed that: one can feel isolated or excluded even when surrounded by people; the experience of loneliness is accompanied by a set of interrelated feelings and thoughts like rumination; and technological and/or non-technological outlets can be used to cope. Social media play both a positive and negative role in loneliness, and loneliness is not always experienced negatively. The quantitative data indicated that this sample was lonely. By providing insight into young adults' loneliness, the findings indicate what types of interventions are likely to diminish it., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fardghassemi and Joffe.)

Objective: To examine the effects of prescription sleep medications on patient-reported sleep disturbances., Design: Retrospective cohort., Setting: Longitudinal cohort of community-dwelling women in the USA., Participants: Racially and ethnically diverse middle-aged women who reported a sleep disturbance., Interventions: New users of prescription sleep medications propensity score matched to women not starting sleep medications., Main Outcomes and Measures: Self-reported sleep disturbance during the previous 2 weeks-difficulty initiating sleep, waking frequently and early morning awakening-using a 5-point Likert scale, ranging from no difficulty on any night (rating 1) to difficulty on 5 or more nights a week (rating 5). Sleep disturbances were compared at 1 year (primary outcome) and 2 years of follow-up., Results: 238 women who started sleep medications were matched with 447 non-users. Participants had a mean age of 49.5 years and approximately half were white. At baseline, sleep disturbance ratings were similar: medication users had a mean score for difficulty initiating sleep of 2.7 (95% CI 2.5 to 2.9), waking frequently 3.8 (95% CI 3.6 to 3.9) and early morning awakening 2.8 (95% CI 2.6 to 3.0); non-users ratings were 2.6 (95% CI 2.5 to 2.7), 3.7 (95% CI 3.6 to 3.9) and 2.7 (95% CI 2.6 to 2.8), respectively. After 1 year, ratings for medication users were 2.6 (95% CI 2.4 to 2.8) for initiating sleep, 3.6 (95% CI 3.4 to 3.8) for waking frequently and 2.8 (95% CI 2.6 to 3.0) for early morning awakening; for non-users, the mean ratings were 2.3 (95% CI 2.2 to 2.5), 3.5 (95% CI 3.3 to 3.6) and 2.5 (95% CI 2.3 to 2.6), respectively. None of the 1 year changes were statistically significant nor were they different between medication users and non-users. Two-year follow-up results were consistent, without statistically significant reductions in sleep disturbance in medication users compared with non-users., Conclusions: These analyses suggest that women who initiated sleep medications rated their sleep disturbances similar after 1 and 2 years. The effectiveness of long-term sleep medication use should be re-examined., Competing Interests: Competing interests: DHS also receives support from NIH-P30-AR072577. He has received salary support from research grants to Brigham and Women’s Hospital for unrelated work from AbbVie, Amgen, Corrona, Genentech and Pfizer., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)