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Menopausal transition is a period of psychological vulnerability, yet suicidality remains underassessed. Hormone replacement therapy (HRT) may influence mood symptoms, but its mental health effects – particularly regarding suicidality – are poorly understood.
Aims
To evaluate changes in depressive symptoms, menopause-related distress and suicidality among menopausal women attending a specialist clinic, and explore whether outcomes differed across HRT regimens and baseline risk factors.
Method
We analysed routinely collected data from 957 women attending a UK menopause clinic. All participants received some form of treatment following their initial consultation. Participants completed the Patient Health Questionnaire-9 (PHQ-9) and Menopause Depression Rating Scale (MENO-D) at baseline and follow-up (2–6 months later). Mixed-design analyses of variance assessed changes over time, including interaction effects for HRT type and baseline risk factors (body mass index (BMI), smoking, suicidality, antidepressant use).
Results
Depressive symptoms and menopause-related psychological distress significantly declined over time (around 46% reduction on average). The largest improvements were observed among women receiving oestrogen–progesterone–testosterone combinations, although similar gains were also seen in oestrogen–progesterone and oestrogen–testosterone groups. Suicidality (PHQ-9 item 9) decreased by 92% among those with baseline ideation, but this was not moderated by HRT type. Self-worth (MENO-D item 4) also improved, but similarly showed no significant moderation by HRT regimen. Higher BMI was associated with worse baseline mental health, but did not moderate treatment outcomes.
Conclusions
Combined HRT, including formulations with testosterone, was associated with substantial improvements in mental health outcomes. Suicidality was a distinct symptom profile, often underdetected by general depression scores. However, findings are exploratory and should be interpreted cautiously because of the lack of a control group, observational design and small sample sizes in some subgroups. These results highlight the need for menopause-sensitive mental health assessments and integration of psychological screening into routine menopausal care.
Menopause is a natural physiological process, but its effects on the brain remain poorly understood. In England, approximately 15% of women use hormone-replacement therapy (HRT) to manage menopausal symptoms. However, the psychological benefits of HRT are not well established. This study aims to investigate the impact of menopause and HRT on mental health, cognitive function, and brain structure.
Methods
We analyzed data from nearly 125,000 participants in the UK Biobank to assess associations between menopause, HRT use, and outcomes related to mental health, cognition, and brain morphology. Specifically, we focused on gray matter volumes in the medial temporal lobe (MTL) and anterior cingulate cortex (ACC).
Results
Menopause was associated with increased levels of anxiety, depression, and sleep difficulties. Women using HRT reported greater mental health challenges than post-menopausal women not using HRT. Post-hoc analyses revealed that women prescribed HRT had higher levels of pre-existing mental health symptoms. In terms of brain structure, MTL and ACC volumes were smaller in post-menopausal women compared to pre-menopausal women, with the lowest volumes observed in the HRT group.
Conclusions
Our findings suggest that menopause is linked to adverse mental health outcomes and reductions in gray matter volume in key brain regions. The use of HRT does not appear to mitigate these effects and may be associated with more pronounced mental health challenges, potentially due to underlying baseline differences. These results have important implications for understanding the neurobiological effects of HRT and highlighting the unmet need for addressing mental health problems during menopause.
This review synthesizes current evidence linking alterations in the gut microbiome to menopausal transition. The gut microbiota plays a crucial role in numerous physiological processes, particularly due to its bidirectional communication with the brain via multiple neural, endocrine and immune pathways. Menopause-associated oestrogen decline disrupts this axis, influencing not only gastrointestinal function and microbial diversity but also mood, cognition and inflammation. The oestrobolome is a community of gut bacteria capable of modulating circulating oestrogen levels. Taken together, research suggests a complex dynamic interplay between the intestinal microbiota and sex hormones, potentially contributing to menopausal symptoms and related comorbidities. Understanding these interactions offers promising avenues for intervention, as dietary strategies (such as isoflavones), lifestyle modifications and targeted probiotic therapies may help restore balance within the gut-brain axis and support brain health during and after the menopausal transition. Here, we highlight the importance of an integrative, microbiome-informed approach to midlife women’s health, emphasizing innovative, non-pharmacological strategies to promote long-term well-being in women.
While depressive symptoms are common during menopausal transition, the relationship between the two remains unclear. Therefore, this study aimed to examine the longitudinal changes in depressive symptoms among middle-aged Korean women and identify those with elevated and worsening symptoms during this period.
Methods
A total of 1,178 participants who underwent comprehensive health examinations at Kangbuk Samsung Hospital in Korea were followed for a median of 10.8 years (IQR, 9.2–11.6; maximum, 12.7), including all women who reached natural menopause during follow-up, with only data prior to HRT initiation included. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D), and menopausal stages were classified according to the STRAW + 10 criteria and final menstrual period (FMP). Linear mixed-effects models and group-based trajectory modelling (GBTM) were applied to evaluate longitudinal changes in depressive symptoms and to identify distinct trajectories in the severity and stability of depressive symptoms.
Results
The age-adjusted prevalence of CES-D ≥ 16 was 11.0%, 11.5%, 11.2% and 12.4%, with corresponding mean scores of 6.7, 6.6, 6.9 and 7.1 across stages. After adjusting for time-varying age and covariates, menopausal stage transitions were not significantly associated with higher levels of depressive symptoms, whether analysed as continuous or binary variables. For binary CES-D (≥16), the estimated coefficients (95% CI) were 0.10 (–0.20 to 0.41) for early transition, 0.09 (–0.21 to 0.39) for late transition and 0.26 (–0.09 to 0.61) for post-menopause. Similarly, time relative to the FMP (–11 to +9 years) showed no significant association with depressive symptoms. GBTM identified three distinct trajectories: most participants (75.5%) maintained consistently low depressive symptoms throughout the transition, whereas 5.8% showed worsening symptoms. Poor sleep quality (OR 5.83, 95% CI 3.25 to 10.45) and moderate-to-severe vasomotor symptoms (OR 2.95, 95% CI 1.30 to 6.70) were significantly associated with the worsening trajectory. Suicidal ideation was higher in this group (45.4% at baseline, increasing to 70.5% at follow-up).
Conclusions
Most women maintained low depressive symptoms during the menopausal transition; however, a subset experienced worsening symptoms linked to menopause-related physical symptoms. Medical visits for menopause-related symptoms may provide opportunities for screening depressive symptoms in higher-risk women, though the screening effectiveness requires further evaluation.
According to existing evidence, during menopause transition, women with psychosis may present with exacerbated psychiatric symptoms, due to age-related hormonal changes.
Aims
We aimed to (a) replicate this evidence, using age as a proxy for peri/menopausal status; (b) investigate how clinical presentation is affected by concomitant factors, including hyperprolactinaemia, dose and metabolism of prescribed antipsychotics using cross-sectional and longitudinal analyses.
Method
Secondary analysis on 174 women aged 18–65, from the IMPaCT (Improving physical health and reducing substance use in psychosis) randomised controlled trial. We compared women aged below (N = 65) and above 40 (N = 109) for (a) mental health status with the Positive and Negative Syndrome Scale (PANSS) and Montgomery Asberg Depression Rating Scale; (b) current medications and (c) prolactin levels, at baseline and at follow-up (12/15 months later).
Results
Women aged above 40 showed higher baseline PANSS total score (mean ± s.d. = 53.4 ± 14.1 v. 48.0 ± 13.0, p = 0.01) and general symptoms scores (28.0 ± 7.4 v. 25.7 ± 7.8, p = 0.03) than their younger counterparts. Progressive sub-analysis revealed that this age-related difference was observed only in women with non-affective psychosis (n = 93) (PANSS total score: 57.1 ± 13.6 v. 47.0 ± 14.4, p < 0.005) and in those prescribed antipsychotic monotherapy with olanzapine or clozapine (n = 25) (PANSS total score: 63 ± 16.4 v. 42.8 ± 10.9, p < 0.05).
Among all women with hyperprolactinaemia, those aged above 40 also had higher PANSS positive scores than their younger counterparts. No longitudinal differences were found between age groups.
Conclusions
Women aged above 40 showed worse psychotic symptoms than younger women. This difference seems diagnosis-specific and may be influenced by antipsychotics metabolism. Further longitudinal data are needed considering the menopause transition.
The menopausal period in women is characterized by neuroendocrine alterations, which is in part mediated by the reduction in circulating estrogen. During this transition, many perimenopausal and menopausal women experience sleep disturbances and increased susceptibility to sleep-related disorders. Sleep disruptions are partially attributed to nighttime vasomotor symptoms (VMS), which exacerbates the insomnia risk in the menopausal woman. Converging data implicate the orexin system in the pathophysiology of insomnia and VMS, particularly through regulation of arousal, thermoregulation, and sympathetic outputs. Estrogen decline due to menopause is postulated to modulate orexin signaling, thereby heightening sympathetic drive and thermoregulatory instability. Given this potential mechanistic framework, orexin receptor antagonists, notably dual orexin receptor antagonists (DORAs), have been proposed as alternative menopausal therapeutics. Herein, we aim to examine preclinical, translation, and clinical literature assessing the therapeutic potentials of DORAs as a nonhormonal intervention for the mitigation of insomnia and VMS in midlife women.
This article describes a trainee-led women’s health project aimed at connecting psychiatry and gynaecology to better meet the needs of perimenopausal and menopausal women. Cognitive–behavioural therapy (CBT) is a NICE-recommended treatment for menopause-related vasovagal symptoms. A menopause-focused CBT (mCBT) group intervention for women unable to take hormone replacement therapy was developed and piloted in collaboration with local menopause specialists. This article documents some of the challenges experienced and insights gained along the way by the trainees who developed it.
This systematic review and meta-analysis aimed to review existing measures of subjective cognition during menopause and to estimate the correlation between subjective and objective cognition in perimenopausal and postmenopausal women.
Method:
Eligible studies reported scores for at least one subjective and objective measure of cognition for perimenopausal or postmenopausal women. EMBASE, Medline, and PsycINFO were searched for eligible studies on November 22nd 2024. The risk of bias in individual studies was evaluated using a modified QUADAS-2 form. The results of the review were summarized in narrative form. Studies that reported correlations between subjective and objective cognition were synthesized using a multilevel meta-analysis.
Results:
The sample included 5629 participants over 24 studies, including 295 perimenopausal women, 5086 postmenopausal women, and 248 women across mixed peri- and post-menopausal samples. Twelve measures of subjective cognition were used across studies. Six studies were included in the meta-analysis. A small significant correlation was observed between subjective cognition and objective measures of learning efficiency (r = .12; CI = .02 to .23). Correlations across other cognitive domains were non-significant.
Conclusions:
Our findings suggest subjective cognition may be associated with performance on measures of learning efficiency, offering a starting point for further research on menopausal brain fog. The present findings highlight the need for a reliable measure of subjective cognitive symptoms associated with menopause. Additionally, a better characterization of the neuropsychological profile of menopausal brain fog is needed to progress research in this field and ultimately improve clinical support for women experiencing these symptoms.
Psychological symptoms in perimenopause and early menopause are common. The impact of menopausal hormone therapy (MHT) on menopausal mood symptoms is unclear.
Aims
To assess the impact of 17β-oestradiol ± micronised progesterone or the levonorgestrel-releasing intrauterine device, and/or transdermal testosterone, on depressive and anxiety symptoms in peri- and postmenopausal women.
Method
A real-world retrospective cohort study set in the largest specialist menopause clinic in the UK. The Meno-D questionnaire measured mood-related symptoms.
Results
The study included 920 women: 448 (48.7%) perimenopausal, and 435 (47.3%) postmenopausal. Following initiation/optimisation of MHT, mean Meno-D scores decreased by 44.59% (95% CI −46.83% to −42.34%, P < 0.001) after average 107 days follow-up. Mood symptoms significantly improved (P < 0.01 per symptom). Improvement occurred in peri- and postmenopausal women. All MHT regimens improved mental health including both progestogen types (body-identical progesterone and levonorgestrel-releasing intrauterine device), MHT initiation strategy (oestradiol ± a progestogen versus oestradiol ± a progestogen and testosterone, 45.38 v. 48.53%, respectively, P = 0.47) and MHT optimisation strategy (MHT users treated with a higher oestradiol dose versus testosterone added versus both a higher oestradiol dose and testosterone, 34.70, 43.93 and 43.25%, respectively, P = 0.38).
Conclusions
Use of menopausal hormone therapy was associated with significant improvement in mood in peri- and postmenopausal women. Prospective studies and randomised clinical trials are needed to assess the effects of different regimens in different patient populations over longer time periods.
Preclinical and clinical research have devoted limited attention to women’s health. Animal models centred on female-specific factors will improve our understanding of mental health disorders. Exploring the heterogeneity of mental health disorders, in concert with attention to female-specific factors, will accelerate the discovery of efficacious treatments for mental health disorders.
This study aimed to understand primary healthcare providers’ beliefs about barriers and facilitators providing culturally competent midlife care to migrant women.
Background:
Primary healthcare is the entry level to the health system. It is usually the first point of contact in accessing the healthcare system and provides a range of services including health promotion and prevention. Migrant women are less likely to access and engage in health screening and health promotion activities and consequently may miss out on optimal health in older age.
Methods:
A cross-sectional study including two free-text questions, part of an online survey, was thematically analysed. 76 primary healthcare providers answered the free-text questions.
Findings:
Competing priorities as a result of migration and settlement experiences, the healthcare systems’ limited resources to respond to the needs of migrant population and culturally informed beliefs and behaviour about menopause were viewed as barriers to midlife care for migrant women. Flexible models of primary healthcare and coordinated engagement with community groups were proposed to address these barriers. Primary healthcare providers perceived the current primary healthcare model to be inadequate to address the additional needs of migrant women. A review of the model of care may include ‘task shifting’ where nurses provide advanced care to migrant women in midlife. Perceptions of midlife and menopause are informed by culture. Hence, a culturally informed health promotion programme led by migrant women may be one strategy to address the limited participation in preventative healthcare including health screening at the time around menopause.
This paper advocates for a holistic approach to the menopause transition and challenges the current dominant narrative that frames this transition primarily in biological terms. It examines the psychological, social and cultural dimensions, addresses the stigma faced by older women and advocates for the vital role psychiatrists have to play in supporting postmenopausal women.
The transition into menopause marks a significant stage in a woman’s life, indicating the end of reproductive capability. This period, encompassing perimenopause and menopause, is characterized by declining levels of estrogen and progesterone, leading to various symptoms such as hot flashes, sleep disturbances, sexual dysfunction, and mood irregularities. Moreover, cognitive functions, notably memory, may decline during this phase.
Objective
This exploratory study aimed to evaluate psychological factors in a sample of 98 women recruited from a diagnostic-assistance hospital pathway (AOUP).
Methods
Psychological variables, including depression, anxiety, stress, sleep quality, memory, personality traits, and mindfulness, were assessed using psychometric questionnaires. Machine learning techniques were employed to identify independent variables strongly correlated with higher levels of depression measured by BDI-II.
Results
The findings revealed positive associations between depression and anxiety, stress, low mood, poor sleep quality, and memory complaints, while mindfulness showed a negative correlation. Remarkably, the machine learning analysis achieved a high classification accuracy in distinguishing between individuals with different levels of depression (low vs high).
Conclusions
These results underscore the importance of addressing psychological factors during menopause and offer valuable insights for future research and the development of targeted clinical interventions aimed at enhancing mental health and quality of life for women during this transitional phase.
Sleep and epilepsy have bidirectional relationships, and various endocrine interactions. Besides the commonly observed increase in seizure frequency in association with sleep loss or with sleep disorders, such as sleep apnea, seizures themselves may lead to sleep fragmentation. Furthermore, nocturnal seizures may be associated with more severe and longer lasting respiratory consequences, as well as higher risk of sudden death. It is common for sleep to change during pregnancy in relation to endocrine changes and these changes may in turn affect seizure frequency. Overall, estrogens may have excitatory effects and may increase the consolidation of wakefulness and decrease REM sleep duration. Progesterone tends to have a sedative effect and the decrease in level may lead to more complaints of insomnia pre-menstrual and after menopause. Common sleep disorders are discussed. Obstructive sleep apnea becomes much more common after menopause, and sometimes may be seen in the third trimester of pregnancy as a result of weight gain. Restless legs syndrome is more common in pregnancy. Overall, insomnia is more common in women. Consideration should be given to comorbid primary sleep disorders whenever symptoms of insomnia or hypersomnolence are reported by patients with epilepsy.
Edited by
Laurie J. Mckenzie, University of Texas MD Anderson Cancer Center, Houston,Denise R. Nebgen, University of Texas MD Anderson Cancer Center, Houston
Cancer treatments can induce temporary or permanent menopause and lead to persistent menopausal symptoms. In reproductive age women, cancer treatment may impair fertility but evaluating fertility and managing contraception can be complex. Managing menopausal symptoms and contraceptive decisions after cancer treatment can be challenging for women and their care providers. In this chapter, we present concepts for managing these consultations and some specific advice for women in particular situations.
Why is it so difficult for older women in our society to feel that they are seen and heard? What matters in our society is not the quality of a woman’s mind, but her appearance of aging. Yet older women are still trying to find meaning in life, despite the impact on their mental and physical health of the menopause, children leaving home, retirement from work, problems in relationships, caring for others and coping with chronic ill health. Women carry a heavy burden of intergenerational caring – for partners, parents, children and grandchildren. As they age, women experience sequential losses in life, of roles that have been important to us. Suicide rates are rising in older women for reasons unknown, and depression can be more severe. Electroconvulsive therapy (ECT) can be life-saving. Alzheimer’s disease is twice as common in women, but we do not know why. Given the massive impact of dementia on women, research is still inadequately funded. Together with younger women we must consider what a feminist old age might look like and, as we age, work at staying engaged with the world. There are things older women can both share with, and learn from, younger women.
During the menopausal transition, women often encounter a range of physical and psychological symptoms which negatively impact on health-related quality of life (HRQoL)(1). Diet quality has previously been identified as a modifiable factor associated with mitigating the severity of these symptoms in peri-menopausal and menopausal women(2). We therefore explored the independent associations between adherence to a Mediterranean diet (MedDiet) and the severity of menopausal symptoms in peri-menopausal and menopausal women living in Australia. We also explored the association between MedDiet adherence and HRQoL in this same cohort of women. We conducted a cross-sectional study of Australian peri-menopausal or menopausal women aged between 40 to 60 years. An 86-item self-administered questionnaire was used to assess the relationship between adherence to a MedDiet and severity of symptoms. MedDiet adherence was assessed using the Mediterranean Diet Adherence Screener (MEDAS), the Menopause Rating Scale (MRS) was used to assess the severity of menopausal symptoms related to somatic, psychological and urinary-genital symptoms and the 36-item short form survey instrument (SF-36) was used to assess HRQoL. Multivariable linear regression analysis (and 95% CI) was used to investigate the independent association between adherence to a MedDiet, severity of menopausal symptoms and HRQoL subscales using one unadjusted and five adjusted predictor models. A total of n = 207 participants (50.7 ± 4.3 years; BMI: 28.0 ± 7.4 kg/m2) were included in the final analyses. Participants reported low-moderate adherence to a MedDiet (5.2 ± 1.8; range: 1-11). We showed that MedDiet adherence was not associated with severity of menopausal symptoms. However, when assessing individual dietary constituents of the MEDAS, we showed that low consumption of sugar-sweetened beverages (<250ml per day) was inversely associated with joint and muscle complaints, independent of all covariates (β = −0.149; CI: −0.118, −0.022; P = 0.042). Furthermore, adherence to a MedDiet was positively associated with the physical function subscale of HRQoL (β = 0.173, CI: 0.001, 0.029; P = 0.031) and a low intake of red and processed meats (≤ 1 serve per day) was positively associated with the general health subscale (β = 0.296, CI: 0.005, 0.014; P = <0.001), independent of all covariates used in the fully adjusted model. Our results suggest that diet quality may be related to severity of menopausal symptoms and HRQoL in peri-menopausal and menopausal women. However, exploration of these findings using longitudinal analyses and robust clinical trials are needed to better elucidate these findings.
Edited by
Nevena V. Radonjić, State University of New York Upstate Medical University,Thomas L. Schwartz, State University of New York Upstate Medical University,Stephen M. Stahl, University of California, San Diego
Differences in blood concentration of sex hormones in the follicular (FP) and luteal (LP) phases may influence energy metabolism in women. We compared fasting energy metabolism and sweet taste preference on a representative day of the FP and LP in twenty healthy women (25·3 (sd 5·1) years, BMI: 22·2 (sd 2·2) kg/m2) with regular self-reported menses and without the use of hormonal contraceptives. From the self-reported duration of the three prior menstrual cycles, the predicted FP and LP visits were scheduled for days 5–12 and 20–25 after menses, respectively. The order of the FP and LP visits was randomly assigned. On each visit, RMR and RQ by indirect calorimetry, sweet taste preference by the Monell two-series forced-choice tracking procedure, serum fibroblast growth factor 21 by a commercial ELISA (FGF21, a liver-derived protein with action in energy balance, fuel oxidation and sugar preference) and dietary food intake by a 24-h dietary recall were determined. Serum progesterone and oestradiol concentrations displayed the expected differences between phases. RMR was lower in the FP v. LP (5042 (sd 460) v. 5197 (sd 490) kJ/d, respectively; P = 0·04; Cohen effect size, drm = 0·33), while RQ showed borderline significant higher values (0·84 (sd 0·05) v. 0·81 (sd 0·05), respectively; P = 0·07; drm = 0·62). Also, in the FP v. LP, sweet taste preference was lower (12 (sd 8) v. 16 (sd 9) %; P = 0·04; drm = 0·47) concomitant with higher serum FGF21 concentration (294 (sd 164) v. 197 (sd 104) pg/ml; P < 0·01; drm = 0·66). The menstrual cycle is associated with changes in energy expenditure, sweet taste preference and oxidative fuel partitioning.
We investigated whether women who participated in a household survey in England were more likely to screen positive for possible generalised anxiety disorder and depression during and after menopause. We used logistic regression in secondary cross-sectional analyses of 1413 participants from the 2014 Adult Psychiatric Morbidity Survey data, adjusting for potential confounders (including age, deprivation score and chronic disease).
We found that participants who were post-menopausal were more likely to screen positive for possible depression compared with participants who were pre-menopausal (3.9% v. 1.7%; adjusted odds ratio 3.91, 95% CI 1.23–12.46), but there was no association with perimenopause. We found no evidence of an association between menopausal stage and possible generalised anxiety disorder or symptom score. Clinicians should be aware of the association between menopause and depression, to best support women. Future research could focus on to what extent associations are driven by somatic features, and how this might be modified.