Biopsychosocial factors intersecting with weekly sleep difficulties in the menopause transition.

OBJECTIVES: Sleep difficulties are common in the menopause transition and increase risk for a variety of physical and psychological problems. The current study investigated potential interactions between psychosocial variables and within-person changes in ovarian hormones in predicting perimenopausal sleep problems as well as the potential interactions between poor sleep and psychosocial factors in predicting worsened mood, affect, and attention. STUDY DESIGN: The sample included 101 perimenopausal individuals. Participants completed 12 weekly assessments of self-reported sleep outcomes, depressive mood and affect, and attention function, and of estrone glucuronide (E1G) and pregnanediol glucuronide (PdG) levels (urinary metabolites of estradiol and progesterone, respectively); they also had 24-h tracking of vasomotor symptoms. Other psychosocial variables such as trauma history and stressful life events were assessed at baseline. RESULTS: A history of depression, baseline depressive symptoms, trait anxiety, and more severe and bothersome vasomotor symptoms predicted worsened sleep outcomes. Recent stressful life events, trauma history, and person-centred E1G and PdG changes did not predict sleep outcomes. However, there was an interaction whereby person-centred E1G decreases predicted lower sleep efficiency in those with higher baseline depressive symptoms. Higher baseline depression and trauma history also amplified the effect of vasomotor symptoms on sleep outcomes. In evaluating the effect of poor sleep on psychological and cognitive outcomes, stressful life events emerged as a moderating factor. Finally, trauma history and poor sleep interacted to predict worsened attention function. CONCLUSIONS: The current study suggests that certain individuals may be at greater risk of perimenopausal sleep problems and the resulting negative effects on mood and cognition.

Quercetin alleviates depressive-like behavior by modulating acetyl-H3K9 mediated ferroptosis pathway in hypothalamus of perimenopausal depression rat model.

Perimenopausal depression is a subtype of depression and is prevalent among perimenopausal women, which has brought a heavy burden to family and society. The pathogenesis of perimenopausal depression is still unclear, which affects the prevention and treatment of perimenopausal depression to a certain extent. Quercetin is a flavonoid compound, and has estrogenic activity and pharmacological effects such as antioxidant, anti-inflammatory, and neuroprotective effects. This study investigated whether quercetin improved perimenopausal depression-like behaviors and potential mechanism. The results demonstrated that quercetin could alleviate the depression-like behaviors in perimenopausal depression rat model, inhibit astrocyte activation, improve ferroptosis-associated mitochondrial damage (such as mitochondrial pyknosis and mitochondrial cristae reduction) in hypothalamus, increase the expressions of histone 3 lysine 9 acetylation (acetyl-H3K9), ferroptosis-associated protein including glutathione peroxidase 4 (GPX4) and Xc- antiporter (SLC7A11), and reduce the expressions of endoplasmic reticulum stress-related proteins including inositol-requiring enzyme 1 (IRE1α), phosphorylated IRE1α (p-IRE1α), X-box binding protein 1 (XBP1) and glucose-regulated protein 78 (GRP78) in hypothalamus of perimenopausal depression rat model. Furtherly, in vitro study indicated that quercetin could restore histone acetylase (HAT)/histone deacetylase (HDAC) homeostasis through binding to estrogen receptors and increase the expression of acetyl-H3K9, inhibiting ferroptosis through IRE1α/XBP1 pathway in astrocytes of hypothalamus. Our findings demonstrated that acetyl-H3K9 is a crucial target in development of perimenopausal depression, and quercetin exhibited antidepressant effects through modulating acetyl-H3K9 mediated ferroptosis in perimenopausal depression. Quercetin might be the prevention and adjuvant treatment strategy of perimenopausal depression.

A novel method for quantifying affective sensitivity to endogenous ovarian hormones.

Increased sensitivity to ovarian hormone changes is implicated in the etiology of reproductive mood disorders across the female lifespan, including menstrually-related mood disorders, perinatal mood disorders, and perimenopausal depression. Developing a method to accurately quantify sensitivity to endogenous hormone fluctuations may therefore facilitate the prediction and prevention of these mental health conditions. Here, we propose one such method applying a synchrony analysis to compute time-lagged cross-correlations between repeated assessments of endogenous hormone levels and self-reported affect. We apply this method to a dataset containing frequent repeated assessments of affective symptoms and the urinary metabolites of estradiol (E2) and progesterone (P4) in 94 perimenopausal females. These preliminary findings suggest that, with further refinement and validation, the proposed method holds promise as a diagnostic tool to be used in clinical practice and to advance research investigating the etiology of reproductive mood disorders.

Effects of mind-body exercise on perimenopausal and postmenopausal women: a systematic review and meta-analysis.

IMPORTANCE: The increasing attention to the management of perimenopausal and postmenopausal women parallels the growth of the aging population. Although hormone therapy is commonly used to alleviate menopausal symptoms, it carries a potential risk of cancer. Recently, mind-body exercises have emerged as innovative approaches for improving menopausal symptoms and bone health. However, research findings have needed to be more consistent, highlighting the significance of this study's systematic review of mind-body exercise effects on perimenopausal and postmenopausal women. OBJECTIVE: This study aims to evaluate the impact of mind-body exercises, including tai chi, yoga, Pilates, qigong, baduanjin, and mindfulness-based stress reduction, on bone mineral density, sleep quality, anxiety, depression, and fatigue among perimenopausal and postmenopausal women. EVIDENCE REVIEW: Four electronic databases-PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science-were systematically searched from inception until July 2023. The search focused exclusively on randomized controlled trials to examine the impact of mind-body exercise interventions on perimenopausal and postmenopausal women. The methodological quality of the included studies was evaluated using the Cochrane Bias Risk Assessment tool. FINDINGS: A total of 11 randomized controlled trials, comprising 1,005 participants, were included in the analysis. Traditional meta-analysis indicated that mind-body exercise significantly enhanced bone mineral density in perimenopausal and postmenopausal women compared with control groups, with a standardized mean difference (SMD) of 0.41 (95% CI, 0.17 to 0.66; P = 0.001, I2 = 7%). In addition, significant improvements were observed in sleep quality (SMD, -0.48; 95% CI, -0.78 to -0.17; P = 0.002, I2 = 76%), anxiety reduction (SMD, -0.80; 95% CI, -1.23 to -0.38; P = 0.0002, I2 = 84%), depressive mood (SMD, -0.80; 95% CI, -1.17 to -0.44; P < 0.0001, I2 = 79%), and fatigue (SMD, -0.67; 95% CI, -0.97 to -0.37; P < 0.0001, I2 = 0%). CONCLUSIONS AND RELEVANCE: The findings of this meta-analysis demonstrate that mind-body exercise positively influences bone mineral density, sleep quality, anxiety, depression, and fatigue among perimenopausal and postmenopausal women.

Obstetric and psychiatric history as predictors for psychosomatic symptoms among Korean perimenopausal women.

OBJECTIVES: Menopause presents various physical and psychological disturbances for women and comes at a high financial cost. Therefore, this study aimed to identify factors influencing menopause symptoms. STUDY DESIGN: Data of Korean perimenopausal women aged 40-60 (n = 1060; mean age, 46.03 ± 4.08) were collected by a research company. Participants were classified into a "functional" group (n = 716) or a "dysfunctional" group (n = 344) according to the severity of their perimenopausal psychosomatic symptoms. To investigate the association of obstetric and psychiatric history with membership of the "dysfunctional" group, a hierarchical logistic regression analysis was conducted. RESULTS: The outcomes of all three hierarchical logistic regression models presented significant overall model fit. Among the independent variables, family history of menopausal symptoms, menarcheal age, number of pregnancies, history of postpartum depression, postpartum psychosis, and other psychiatric disorders were positively associated with being in the "dysfunctional" group, whereas age and number of deliveries were negatively associated with being in the "dysfunctional" group. CONCLUSION: A short reproductive period and short exposure to estrogen due to late menarche and early menopausal transition may be related to severe perimenopausal symptoms. The relationship between the history of postpartum mental illness and severe perimenopausal symptoms may be associated with heightened sensitivity to hormonal triggers when a woman is exposed to fluctuating ovarian sex steroid levels. The relationship between parity or gravidity and the severity of menopausal symptoms in Korean women differed from that in studies conducted in other countries, possibly due to the low birth rate in Korea.

Cognitive Problems in Perimenopause: A Review of Recent Evidence.

PURPOSE OF REVIEW: To review recent research regarding cognitive problems during perimenopause, including which menopause-related symptoms, demographic variables, stress exposures, and neural biomarkers are associated with cognitive problems and which interventions demonstrate efficacy at improving cognitive performance. RECENT FINDINGS: Cognitive problems are common during perimenopause and have a significant impact on a substantial proportion of women. Evidence continues to indicate that verbal learning and verbal memory are the cognitive functions that are most negatively affected during perimenopause, and new research suggests that perimenopause may also be associated with deficits in processing speed, attention, and working memory. Recent research suggests that the cognitive profiles of women transitioning through perimenopause are heterogenous - with some showing strengths and others demonstrating weaknesses in particular cognitive domains. Depression, sleep problems, and vasomotor symptoms in perimenopause may be associated with cognitive difficulties. Recent neuroimaging studies are identifying changes in activity patterns within brain regions that correlate with cognitive performance in perimenopause, but future causal studies are needed to understand the neural mechanisms of cognitive problems during this time. Although clinical treatment studies for cognitive concerns have historically focused on postmenopause, some small trials in perimenopausal samples have been conducted recently but are frequently underpowered. Current guidelines from the North American Menopause Society do not support the use of hormone therapy at any age for cognitive problems. Animal research demonstrates that estradiol and levonorgestrel combined may alleviate working memory problems. Much progress has been made in understanding how perimenopause impacts cognition, and more research is needed to better identify who is at highest risk and how to meaningfully prevent and alleviate cognitive problems during this reproductive stage. Larger-scale randomized intervention trials specifically during perimenopause are urgently needed to address cognitive concerns in this population of women. More consistent reproductive staging, inclusion of covariates, and analyses examining perimenopause specifically would improve study quality and the ability to draw clear conclusions from this research.

A survey of medical cannabis use during perimenopause and postmenopause.

OBJECTIVE: Expanding access to legal cannabis has dovetailed with increased interest in medical cannabis (MC) use; however, there is a paucity of research examining MC use to alleviate menopause-related symptoms. This survey study assessed patterns of MC use in perimenopausal and postmenopausal individuals. METHODS: Participants (perimenopausal, n = 131; postmenopausal, n = 127) completed assessments of menopause-related symptomatology and cannabis use, including modes of use, type of use, and menopause-related symptoms addressed by MC use. RESULTS: Most participants reported current cannabis use (86.1%) and endorsed using MC for menopause-related symptoms (78.7%). The most common modes of use were smoking (84.3%) and edibles (78.3%), and the top menopause-related symptoms for MC use were sleep disturbance (67.4%) and mood/anxiety (46.1%). Relative to postmenopausal participants, perimenopausal participants reported significantly worse menopause-related symptomatology on the vasomotor and psychosocial subscales of the Menopause-Specific Quality of Life Questionnaire ( P s ≤ 0.04), including greater burden of anxiety ( P = 0.01) and hot flash ( P = 0.04) symptoms. In addition, perimenopausal participants reported higher incidence of depression ( P = 0.03) and anxiety diagnoses ( P < 0.01), as well as increased use of MC to treat menopause-related mood/anxiety symptoms relative to postmenopausal participants ( P = 0.01). CONCLUSIONS: Results suggest that many individuals are currently using MC as an adjunctive treatment for menopause-related symptoms, particularly sleep disturbance and mood/anxiety. Future research should examine the impact of different MC use characteristics (e.g., cannabinoid profiles) on the efficacy of MC use for menopause-related symptoms. Increased severity and prevalence of mood and anxiety symptoms in perimenopausal participants suggest promising targets for clinical trials of cannabinoid-based therapies.

Hormonal Agents for the Treatment of Depression Associated with the Menopause.

Perimenopause marks the transition from a woman's reproductive stage to menopause. Usually occurring between 42 and 52 years of age, it is determined clinically by the onset of irregular menstrual cycles or variable cycle lengths. Women are at an increased risk of depression and anxiety during perimenopause and the menopausal transition. Depressive symptoms experienced in perimenopause are often more severe compared to pre- and post-menopause. During menopausal transition, the impact of fluctuating estrogen in the central nervous system (CNS) can have negative psychological effects for some women. Traditional first-line management of menopausal depression involves antidepressants, with modest outcomes. The positive effects of estrogen treatment in the CNS are becoming increasingly recognised, and hormonal therapy (HT) with estrogen may have a role in the treatment of menopausal depression. In this review we will outline the prevalence, impact and neurochemical basis of menopausal-associated depression, as well as hormone-based approaches that have increasing promise as effective treatments.

The Cortisol and ACTH Response to Dex/CRH Testing in Women With and Without Perimenopausal Depression.

CONTEXT: Abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are frequent accompaniments of depression, and studies have documented the role of stress and stressful life events in the ontogeny of perimenopausal depressions (PMD). Because HPA axis function in women is further modulated both by aging and ovarian steroids, it is possible that a dysregulated HPA axis contributes to the increased risk of PMD. OBJECTIVE: We examined HPA axis function in perimenopausal women with and without depression using the combined dexamethasone-corticotropin-releasing hormone (Dex/CRH) test. METHODS: Dex/CRH tests were performed on 20 women with PMD and 20 women who were also perimenopausal but without current or past depression (control women). Main outcome measures were plasma levels of cortisol and adrenocorticotropin (ACTH) and 24-hour urinary free cortisol (UFC). Five women took chronic stable medications, otherwise all women were medically healthy, and both groups were comparable with respect to reproductive stage and age. Standardized symptom rating scales were administered to each woman prior to Dex/CRH testing. RESULTS: No group differences were present in either baseline or stimulated ACTH and cortisol secretion. Baseline plasma measures of estradiol, progesterone, and 24-hour UFC levels similarly did not differ in PMD and control women. CONCLUSION: Despite reports of increased stress responsiveness in PMD, we observed no abnormalities of HPA axis activity associated with PMD compared with women without depression. These findings suggest that PMD is not uniformly associated with HPA dysregulation and could reflect underlying pathophysiologic processes that are distinct from women with nonreproductive-related depressions.

Biopsychosocial predictors of depressive symptoms in the perimenopause-findings from the Swiss Perimenopause Study.

OBJECTIVE: The perimenopause is associated with increased hormone fluctuations and an elevated risk of depression. A number of predictors of depressive symptoms in the menopausal transition have previously been suggested. The purpose of this study was to investigate a set of biopsychosocial predictors of depressive symptoms in perimenopausal women. METHODS: This cross-sectional study, investigating 114 perimenopausal women (according to the STRAW criteria) aged 40-56 years, was conducted within the scope of the Swiss Perimenopause Study. Multiple regression analyses were performed to identify the most accurate model predicting perimenopausal depressive symptoms. Depressive symptoms were assessed with the German version of the Center of Epidemiologic Studies Depression Scale (CES-D). Validated questionnaires were used to examine psychophysiological complaints, stress, self-esteem, self-compassion, body image, and social support. Estradiol (E2) and progesterone (P4) were assessed through saliva samples, and follicle-stimulating hormone and luteinizing hormone were determined through dried blood spot samples. Seven saliva samples per participant were used to investigate absolute levels and fluctuations of sex steroids. All other variables were measured once. RESULTS: Multiple regression analyses revealed that E2 fluctuations (ß=0.15, P = 0.015), history of depression (ß=0.14, P = 0.033), menopausal symptoms (ß=0.47, P < 0.0001), perceived stress (ß=0.17, P = 0.014), body image (ß= -0.25, P = 0.014) and self-esteem (ß=-0.35, P < 0.0001) were predictive of perimenopausal depressive symptoms (R2 = 0.60). P4 fluctuations and absolute levels of hypothalamic-pituitary-gonadal hormone were not statistically significant. CONCLUSIONS: E2 fluctuations were shown to be predictive of depressive symptoms in the perimenopause. Moreover, the presence of burdensome complaints and chronic stress as well as a poor self-evaluation seem to promote depressive symptoms in perimenopausal women.

IL-6 Response to Psychosocial Stress Predicts 12-month Changes in Cardiometabolic Biomarkers in Perimenopausal Women.

OBJECTIVE: Cardiometabolic diseases are the number one cause of mortality, accounting for over one third of all deaths in the United States. Cardiometabolic risk further increases with psychosocial stress exposure and during menopausal transition in women. Because disease risk and stress burden are associated with aberrant immune signaling, we hypothesized that responses of interleukin-6 (IL-6) to psychosocial stress may predict longitudinal cardiometabolic outcomes in perimenopausal women. METHODS: We conducted post hoc analyses in 151 perimenopausal or early postmenopausal women participants in a previously completed study. At study onset, participants underwent the Trier Social Stress Test (TSST), and plasma IL-6 was measured repeatedly before and during the 1 hour post-TSST. Subsequently, participants were randomly assigned to either hormonal treatment (HT) or placebo and followed for 12 months to determine longitudinal changes in cardiometabolic biomarkers. RESULTS: Greater IL-6 reactivity to stress, measured with baseline-adjusted area under the curve, predicted 12-month decrease in flow-mediated dilatation of the brachial artery (P = 0.0005), a measure of endothelial-dependent vascular function, but not in endothelial-independent function measured with nitroglycerin-mediated dilatation (P = 0.17). Greater baseline IL-6 levels predicted 12-month increase in insulin resistance based on the homeostatic model assessment of insulin resistance score (P = 0.0045) and in the number of criteria met for metabolic syndrome (P = 0.0008). These predictions were not moderated by HT. CONCLUSIONS: Greater baseline IL-6 levels as well as its reactivity to stress may predict worsening in distinct cardiometabolic biomarkers as women transition to menopause. Interleukin-6 reactivity predicts decline in endothelial-dependent vascular function, whereas baseline IL-6 presages accumulation of metabolic risk.

[Hormone replacement therapy in peri- and postmenopause]. / Hormontherapie in der Peri- und Postmenopause.

Peri- and postmenopausal disorders can have a significant impact on quality of life. Hormone replacement therapy (HRT) might be necessary in order to decrease women's symptoms. The German S3 guideline "Peri- and Postmenopause-Diagnostics and Therapy" (2020) provides recommendations that include the most recent evidence as well as the Women's Health Initiative (WHI) study results from 2002 and 2004. These results led to reduced prescription patterns due to a high risk of cardiovascular diseases as well as an increased risk for breast cancer if HRT had been administered. Both ongoing analyses of subgroups and other studies extenuated the WHI data, since the increased risks were neither generalizable to the typical postmenopausal patient (regarding age and risk profile) nor to the medication being used today. This article summarizes all aspects of HRT in peri- and postmenopausal women (indications, contraindications, practical approaches, risks, prevention) and provides recommendations with respect to the most recent S3 guideline.

Calidad de vida y su relación con la percepción de estrés y el perfil antropométrico en mujeres adultas / Quality of life and its relationship to stress perception and anthropometric profile in adult women

La perimenopausia produce cambios hormonales y emocionales, que podrían influir en la calidad de vida como en la percepción de estrés de las mujeres. El objetivo de este estudio fue evaluar la calidad de vida y su relación con la percepción de estrés y el perfil antropométrico en mujeres adultas. Se efectuó un estudio transversal en mujeres adultas (40-65 años) que concurrieron a la Fundación Hemocentro Buenos Aires (FHBA). El estado nutricional se evaluó con el índice de masa corporal (IMC) y circunferencia de cintura (CC). La calidad de vida se valoró mediante el cuestionario de calidad de vida (CV) de la Organización Mundial de la Salud (WHOQoL-Bref). La percepción de estrés (PS) se valoró por escala de estrés percibido (PSS-10). Se incluyeron 128 mujeres (52,3% premenopáusicas y 47,7 % posmenopáusicas). El 56,3% refirió tener una CV entre bastante buena y muy buena. La prevalencia de sobrepeso y obesidad fue de 60,2% (IC 95%; 51,5 - 68,2%). La percepción de CV se asoció inversamente al IMC (p= 0,0031) al igual que los dominios físico (p= 0,016) y psicológico de CV (p= 0,001). Asimismo, la PS se asoció de manera inversa a la precepción de CV (p= 0,008) y los cuatro dominios de CV.

Perimenopause produces hormonal and emotional changes, which could influence quality of life as well as stress perception in women. The objective of this study was to evaluate quality of life and its relationship with stress perception and anthropometric profile in adult women. A cross-sectional study was carried out in adult women (40-65 years old) who attended the Fundación Hemocentro Buenos Aires. Nutritional status was evaluated with body mass index (BMI) and waist circumference (WC). Quality of life was assessed using the World Health Organization quality of life questionnaire. Perception of stress was assessed by the perceived stress scale (PSS-10). We included 128 women (52.3% premenopausal and 47.7% postmenopausal). Over half (56.3%) reported having a quality of life between fairly good and very good. The prevalence of overweight and obesity was 60.2% (95% CI, 51.5 - 68.2%). The perception of quality of life was inversely associated to the BMI (p= 0.0031) as well as the physical (p= 0.016) and psychological domains of quality of life (p= 0.001). Similarly, perceived stress was associated inversely with the quality of life perception (p= 0.008) and the four quality of life domains.

Impact of Estradiol Variability and Progesterone on Mood in Perimenopausal Women With Depressive Symptoms.

CONTEXT: Women are at increased risk for depressive symptoms during the menopause transition. Changes in estradiol secretion and presence of vasomotor symptoms (VMS) contribute to perimenopausal depressive symptoms, but links with progesterone have not been investigated. OBJECTIVE: To determine whether estradiol variability, ovulatory levels of progesterone, and VMS burden are independently associated with perimenopausal depressive symptomatology. DESIGN AND INTERVENTION: Depressive symptoms, serum levels of estradiol and progesterone, and VMS frequency were assessed weekly in an 8-week observational study. Association of mood with estradiol variability, ovulatory levels of progesterone, and VMS frequency were estimated using generalized estimating equation models. SETTING: Academic medical center. PATIENTS: Fifty unmedicated perimenopausal women with mild-to-moderate depressive symptoms (mean Montgomery-Åsberg Depression Rating Scale [MADRS] score 15.5 ± 5.3). MAIN OUTCOME MEASURE: Depressive symptoms (MADRS score). RESULTS: During the study, 90.0% of participants had varying estradiol levels, 51.1% had ovulatory progesterone levels, and 90% had VMS. Greater estradiol variability and absence of progesterone levels consistent with ovulation, but not VMS frequency, are associated with higher levels of depressive symptoms (ß = 0.11 [95% confidence interval (95% CI), 0.04 to 0.18; P = 0.001]; ß = -2.62 [95% CI, -4.52 to -0.71; P = 0.007], respectively), after accounting for higher body mass index, lifetime history of depression, and stressful life events. CONCLUSIONS: Increasing dysregulation of ovarian hormones, but not VMS, associates with more depressive symptom burden during perimenopause. These results suggest that perimenopausal mood instability is driven by the underlying hormonal dysregulation of the menopause transition involving changes in both estradiol and progesterone.

Antidepressant-like effects of Xiaochaihutang in perimenopausal mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaochaihutang (XCHT) is a traditional Chinese medicine prescription for thousand years in China. Our previous researches show that XCHT has antidepressant-like effects in several depression models, but effect and mechanism of XCHT in perimenopausal depression are still vague. AIM OF THE STUDY: To reveal the antidepressant-like effect and mechanism of XCHT in perimenopausal mice. MATERIALS AND METHODS: Perimenopausal depression model is executed by ovariectomy combined with chronic unpredictable mild stress (OVX-CUMS). Tail suspension test (TST), forced swim test (FST), elevated plus-maze (EPM), novelty suppressed feeding (NSF) and locomotor activity are used to assess antidepressant-like effects of XCHT. The Level of estradiol (E2), follicle-stimulating hormone (FSH), gonadotrophin releasing hormone (GnRH), corticosterone (CORT), adrenocorticotrophic hormone (ACTH) and corticotropin releasing hormone (CRH) are evaluated by ELISA. Antidepressant mechanisms of XCHT in OVX-CUMS mice are analyzed by 5-hydroxytryptamine (5-HT), tryptophan hydroxylase 2 (TPH2) and estrogen receptor α and ß (ERα/ß). RESULTS: The results show that OVX-CUMS significantly increases the immobility time in TST and FST, increases latency to feed, decreases food consumption in NSF and both the time spend and number of entries in open arms in EPM. While, oral administration of XCHT can significantly normalize above depression-like behaviors in OVX-CUMS mice. Moreover, XCHT also remarkably normalized levels of 5-HT, 5-HIAA, E2, GnRH, CORT, ACTH and CRH in OVX-CUMS mice. Finally, the expression of ERß and TPH2 are decreased by OVX-CUMS in prefrontal cortex and hypothalamus, and XCHT can restore these decrease. CONCLUSION: Current findings suggest XCHT can alleviate perimenopausal depression-like behaviors, restore 5-HT and hormones in OVX-CUMS mice, which may be related to normalizing the functions of HPA/HPO axis and enhancing expression of ERß and TPH2 in prefrontal cortex and hypothalamus.

PI3K-AKT Signaling Activation and Icariin: The Potential Effects on the Perimenopausal Depression-Like Rat Model.

Icariin is a prenylated flavonol glycoside isolated from Epimedium herb, and has been shown to be its main bioactive component. Recently, the antidepressant-like mechanism of icariin has been increasingly evaluated and demonstrated. However, there are few studies that have focused on the involvement of the phosphatidylinositol 3-kinase (PI3K)/serine-threonine protein kinase (AKT) signaling in mediating the perimenopausal depression effects of icariin. Perimenopausal depression is a chronic recurrent disease that leads to an increased risk of suicide, and poses a significant risk to public health. The aim of the present study was to explore the effect of icariin on the expression of the PI3K-AKT pathway related to proteins in a rat model of perimenopausal depression. Eighty percent of the left ovary and the entire right ovary were removed from the model rats. A perimenopausal depression model was created through 18 days of chronic unpredictable stimulation, followed by the gavage administration of target drugs for 30 consecutive days. We found that icariin administered at various doses significantly improved the apparent symptoms in the model rats, increased the organ indices of the uterus, spleen, and thymus, and improved the pathological changes in the ovaries. Moreover, icariin administration elevated the serum levels of female hormone estradiol (E2), testosterone (T), and interleukin (IL)-2, decreased those of follicle stimulating hormone (FSH) and luteotropic hormone (LH), promoted the expression levels of estrogen receptor (ER) and ERα in the hypothalamus, and increased those of serotonin (5-HT), dopamine (DA), and noradrenaline (NA) in the brain homogenate. Furthermore, icariin elevated the expression levels of AKT, phosphorylation-akt (p-AKT), PI3K (110 kDa), PI3K (85 kDa), and B-cell lymphoma 2 (Bcl-2) in the ovaries, and inhibited those of Bax. These results show that icariin administration rebalanced the disordered sex hormones in perimenopausal depression rats, regulated the secretion of neurotransmitters in the brain, boosted immune function, and improved the perimenopausal syndrome. The mechanism of action may be related to the regulation of the expression of PI3K-AKT pathway-related proteins.

Assessment of perimenopausal depression: A review.

BACKGROUND: Within the female life cycle, the perimenopause is considered as a critical period for the development of depression. Prevalence rates are particularly high during this phase. Perimenopausal depression is characterized by affective symptoms as well as menopause-specific somatic complaints. Currently, a variety of questionnaires are used to assess mood during the perimenopause. The aim of this review is to determine the instruments employed to assess perimenopausal depression. METHODS: We searched the databases PubMed, Cochrane Library and PsycINFO for human studies investigating perimenopausal depression, and subsequently screened for the assessment instruments used to measure mood and menopause. A total of 37 articles were included. RESULTS: Altogether, 14 different instruments were applied to assess mood during menopause. The CES-D was by far the most frequently used depression scale, appearing in 16 out of the 37 studies. The methods used to identify perimenopausal status and symptoms were inconsistent. LIMITATIONS: Due to lacking information about data and methodology, a selection bias is conceivable. Additionally, a publication bias is possible. Finally, there is inevitable subjectivity in the screening process of a systematic search. CONCLUSIONS: The assessment of depression in the menopausal transition is highly heterogeneous, reducing the overall comparability of study results. Furthermore, menopausal complaints are not sufficiently taken into account. Accordingly, the use of a menopause-specific depression scale is highly recommended in order to account for physical and mood-related symptoms in the menopausal transition.

Epidemiology and Risk Factors of Menopause Syndrome Among Uyghur, Han, and Kazak Women in Xinjiang, China.

BACKGROUND This study analyzed the epidemiology and the risk factors of menopause syndrome (MPS) among Uyghur, Han, and Kazak women in Xinjiang. MATERIAL AND METHODS This was a cross-sectional study. The stratified-cluster random-sampling method was used. A total of 3382 women aged 40 to 60 years of age were included from Urumqi City, Kashgar City, Altay City, Ili Kazakh Autonomous Prefecture, Künes County, Mongolkure County, Tekes County,Talede town, Alemale Township, and Ulugchat County (Kashgar Prefecture) in Xinjiang Province. A questionnaire was used to survey the clinical characteristics of MPS. Logistic regression analysis was used to analyze the MPS risk factors among Uyghur, Han, and Kazak women. RESULTS Oral contraceptives, negative life events, and menopause stages can influence MPS in Han women. In addition, occupation, body weight, mental illness, drug or alcohol abuse, and income level also affect the MPS of Uyghur women. In contrast to Han and Uyghur participants, education, menopausal pattern (natural or artificial), reproductive factors, and smoking are risk factors of MPS in Kazakh women. CONCLUSIONS The menopausal stages and the risk factors for MPS are different among Uyghur, Han, and Kazak women.