The prevalent trajectory of early menopause associated with PM2.5 exposure across 1956-2018 extrapolated from LightGBM algorithm.

BACKGROUND: Fine particulate matter (PM2.5) is noxious to female reproductive development and facilitates the occurrence of subsequent diseases. Early menopause is initiative factor of female aging. But due to the lack of historical exposure of PM2.5, we could not gain insight into the linkage between ambient PM2.5 exposure and early menopause. METHODS: We conducted a community-based retrospective cross-sectional study and pooled 1173 postmenopausal women. The machine learning algorithm of LightGBM was processed to derive the historical concentrations of PM2.5 based on aerography of 1956-2022. The quantile g-computation and binary logistic regression were employed to estimate the mixed and single associations between PM2.5 and early menopause. RESULTS: The visibility topped the most important feature for derivations of historical PM2.5 concentrations. The R2 of 10-fold cross-validation and predictive capability during processing were all above 0.8. The prevalence of early menopause was 7.3 %. Each 10 µg/m3 PM2.5 increased the prevalence of early menopause during prior 2 years exposure (OR: 1.49, 95 %CI: 1.03-2.16) and spring and autumn (OR: 1.28, 95 %CI: 1.07-1.54). After adjusting the reverse effects of temperature, the prior 2 years exposure of PM2.5 remained positively associated with early menopause in the fourth quantile vs the first quantile (OR: 3.36, 95 %CI: 1.53-7.36) in the spring and autumn. The higher BMI (OR: 1.40, 95 %CI: 1.14-1.72), waistline (OR: 1.42, 95 %CI: 1.09-1.85) and unfavourable dietary habits of less meat (OR: 1.72, 95 %CI: 1.11-2.68), more fried food (OR: 2.39, 95 %CI: 1.15-4.99) elevated the prevalence of early menopause. CONCLUSIONS: The accurate environmental exposure assessment of historical PM2.5 vigorously promoted the researches on the relationship between PM2.5 and early menopause. It sounds the alarm on female infertility menace associated with particulate matter especially during the turbulent 2 years before menopause.

Sex differences in all-cause mortality and life span between women with premature menopause and men: propensity score matching analysis.

OBJECTIVE: This study investigated sex differences in all-cause mortality and life span between women undergoing premature menopause and men using propensity score matching analysis. METHODS: Data were from the National Health and Nutrition Examination Survey (1999-2018) and the National Health and Nutrition Examination Survey III (1988-1994). We included 3,214 women experiencing premature menopause and 23,067 men. The participants were all older than 40 years. Propensity score matching analysis created matched cohorts of women and men using a 1:1 ratio. We employed Cox proportional hazard models to estimate unadjusted and adjusted hazard ratios (HR) (95% confidence interval [CI]) for the association between sex and both all-cause mortality and survival up to the 75th percentile of life span. A subgroup analysis examined the effects of hormone therapy on mortality and life span. RESULTS: Compared with men in the matched cohorts, the adjusted HR values (95% CI) for all-cause mortality in women with age at menopause at <35, 35 to 39, and <40 years were 0.65 (0.54-0.78), 0.72 (0.59-0.87), and 0.67 (0.60-0.76), respectively. However, the adjusted HR values (95% CI) for women and men to survive to the 75th percentile of life span were not statistically significant. Besides, there was no significant difference in the mean life span between deceased women and men in the matched cohorts. In the subgroup analysis, the mean life span did not differ significantly between deceased women taking hormone therapy and men. However, the average life span of women never using hormone therapy was significantly longer than that of men (78.3 ± 11.6 vs 76.6 ± 11.9 years, P = 0.0154). CONCLUSIONS: Women experiencing premature menopause had lower risks of all-cause mortality than men, but the advantage that women had in terms of life span was insignificant.

Exposure to organophosphate esters and early menopause: A population-based cross-sectional study.

Organophosphate esters (OPEs), increasingly used as new flame retardants and plasticizers in various products, have been found to have reproductive toxicity with overt endocrine disruption potential, yet the relationship between OPEs and early menopause remains unexplored. In the present study, we included 2429 women who participated in the U.S. National Health and Nutrition Examination Survey data (2011-2020) and had data of five urinary OPE metabolite levels and information of menopause characteristics, to investigate the associations of OPEs exposure with premature ovarian insufficiency (POI) and age of menopause. Multivariable adjusted linear and logistic regression were used to assess the associations of urinary OPE metabolites with age of menopause and POI, respectively. Quantile g computation (QGC) models were used to assess the relative contribution of individual metabolites to associations of OPE metabolites mixture. After adjusting for covariates, urinary bis(2-chloroethyl) phosphate (BCEP) concentration was inversely associated with menopause age (ß = - 0.21; 95% confidence interval (CI): 0.41, - 0.002). Higher urinary BCEP level (>median) was associated with earlier age at menopause (ß = -1.14, 95% CI: 1.83, - 0.46), and elevated odds of having POI (OR = 1.93; 95% CI: 1.02, 3.66). These associations were robust to the further adjustment of cardiometabolic diseases and related traits (e.g., body mass index). Further QGC analyses confirmed that BCEP was the dominant metabolite contributing most to the associations of OPEs mixture with age of menopause (weight = 49.5%) and POI (weight = 75.1%). No significant associations were found for the other four OPE metabolites. In this cross-sectional study, urinary BCEP level was associated with earlier menopause and increased odds of POI, highlighting the potential negative impacts of this chemical and its parent compound tris(2-chloroethyl) phosphate on ovarian function. Further studies are required to validate our findings and reveal potential underlying mechanisms.

Rising premature menopause and variations by education level in India.

The proportion of women experiencing premature menopause is on the rise in India, particularly in the age groups of 30-39 years. Consequently, there is a need to understand the factors influencing the prevalence of premature menopausal status among women. Our study uses the data from 180,743 women gathered during the latest Indian version of the Demography Health Survey (National Family Health Survey-5). Our results suggest that close to 5% of women in rural areas and 3% of women in urban areas experience premature menopause, and this figure varies across Indian States. The regression results show that surgical menopause, lower levels of education, poorer wealth index, rural residence, female sterilization, and insurance coverage are key drivers of premature menopause. One of the striking factors is that the prevalence of premature menopause among those with the lowest levels of education (6.85%) is around seven times higher than those with the highest level of education (0.94%). We conducted a decomposition analysis to delve into the factors contributing to this inequality. The results show that undergoing a hysterectomy (surgical menopause) account for 73% of the gap in premature menopausal rates between women with the lowest and highest levels of education. This indicates that women with poor education are more likely to undergo hysterectomy at a younger age. This finding warrants further exploration as we would expect that women from lower socio-economic background would have limited access to surgical care, however, our results suggest otherwise. This perhaps indicates a lack of awareness, lack of alternative treatment options, and over-reliance on surgical care while neglecting conservative management. Our results have implications for addressing the diverse needs of the increasing number of women in their post-menopause phase and for focusing on conservative treatment options for these women.

Factors affecting age at menopause and their relationship with ovarian reserve: a comprehensive review.

OBJECTIVE: The aim of this article was to discuss all the factors affecting the age at menopause and their correlation with ovarian reserve. MATERIALS AND METHODS: A narrative review of original articles was performed using PubMed until December 2023. The following keywords were used to generate the list of citations: 'menopause', 'ovarian reserve' 'oocytes quality and quantity', 'ovarian ageing'. RESULTS: Menopause is the final step in the process of ovarian ageing and is influenced by the oocyte pool at birth. Conditions that accelerate follicle depletion during the reproductive lifespan lead to premature ovarian insufficiency (POI) and premature ovarian failure (POF), while a higher ovarian reserve is associated with a delayed time to menopause. Reproductive history, sociodemographic, lifestyle and iatrogenic factors may impact ovarian reserve and the age at menopause. CONCLUSIONS: Some factors affecting the age at menopause are modifiable and the risks of early menopause may be preventable. We hypothesise that by addressing these modifiable factors we may also preserve ovarian reserve. However, further interventional studies are needed to evaluate the effects of the described strategies on ovarian reserve.

The age of menopause is determined by the process of follicle depletion, which leads to a decrease in the quantity and quality of oocytes. Various factors such as demographics, menstrual patterns, reproductive history, family history, genetics, and lifestyle choices appear to influence the age at which natural menopause occurs. Some of these factors can be modified. Considering the relationship between ovarian reserve and the age of natural menopause, is it possible to intervene on these modifiable factors to preserve ovarian reserve?

Is There an Association Between Endometriosis, Early Menopause, and Cardiovascular Disease?

Large-scale studies show endometriosis linked to earlier menopause onset. Recent research targeting women with laparoscopically diagnosed endometriosis found an increase in cases of early natural menopause. Furthermore, recent large-scale cohort studies have found a correlation between endometriosis and an increased risk of cardiovascular disease (CVD). Understanding the causality of early menopause, particularly natural menopause, and cardiovascular risks in women with endometriosis could help medical professionals develop effective strategies for early prevention and new therapies. Endometriosis, early menopause, and cardiovascular risks may be linked by primary or secondary mechanisms. Primary mechanisms involve shared pathways that can lead to all morbidities, while secondary occur due to delayed consequences of management strategies. In these large-scale cohort studies, relevant risk and confounding factors, such as oophorectomy, were considered to refine estimates of associations. However, none of the studies considered endometriotic cystectomy, a globally accepted treatment for endometriosis-associated pelvic pain and infertility, as a mediating factor. There is substantial evidence to indicate that endometriotic cystectomy harms ovarian reserve and may lead to early menopause in cases of multiple surgeries or bilateral cases. Early menopause is a well-established risk factor for CVD. To thoroughly examine the link between endometriosis and early menopause, particularly natural menopause, and their connection with cardiovascular risks, it is imperative to consider all the possible factors that may affect the results, such as endometriotic cystectomy. This will enable us to obtain the most accurate and adjusted hazard ratio.

Effect of early menopause on cognition and brain morphology in an Urban Indian Cohort.

BACKGROUND: Evidence for the effect of early menopause on cognition among older women is not consistent and is scant among the Indian population. METHODS: We aimed to examine the effect of early menopause (≤45 years) on cognitive performance and brain morphology among older dementia-free females of the TLSA cohort using a multiple linear regression analysis. RESULTS: In a sample of 528 women, 144 (27%) had early menopause. The linear regression analysis showed that women with early menopause performed poorly in cognition and had lesser total gray matter volume [ß = -11973.94, p = 0.033], left middle frontal [ß = -353.14, p = 0.033], and left superior frontal [ß = -460.97, p < 0.026] volume. CONCLUSION: Dementia-free women with early menopause had poorer cognition, lower total gray matter, and frontal lobe. More research is needed to explore the link between earlier menopause and cognitive decline and develop ways to address it. HIGHLIGHTS: Evidence on the effect of early menopause on brain morphology is inconsistent and scant in low and middle-income countries, such as India. In a cohort of dementia-free individuals in urban Bangalore, we observed that participants with early menopause had significantly lower cognitive performance and lower total gray matter and frontal lobe volume. We recommend increasing awareness of this fact among the medical community and the general public. There is an urgent need to explore the underlying biological mechanism and to discover effective interventions to mitigate the effect.

Age at natural menopause and associated factors with early and late menopause among Chinese women in Zhejiang province: A cross-sectional study.

OBJECTIVES: Menopause is a significant life transition for women, impacting their physical and psychological health. The age at natural menopause (ANM) and its associated factors have differed by race and region. This study aimed to investigate ANM and associated factors of early and late menopause among Chinese women in Zhejiang province. METHODS: A cross-sectional study was conducted using a multi-stage stratified cluster sampling method to recruit 8,006 women aged 40-69 years who had resided in Zhejiang province for over 6 months between July 2019 and December 2021. Self-reported ANM and sociodemographics, lifestyle behaviors, reproductive history, and health-related factors were collected using questionnaires in face-to-face surveys. ANM were categorized into three groups: early menopause (<45 years), normal menopause (45-54 years), and late menopause (≥55 years). Kaplan-Meier survival analysis was utilized to calculate the median ANM. Multivariable multinomial logistic regression was employed to explore the associated factors of early menopause and late menopause. RESULTS: A total of 6,047 women aged 40-69 years were included for survival analysis, with 3,176 of them for the regression analysis. The overall median ANM was 51 years (Inter-quartile range [IQR]: 51-52). Women who were smokers (odds ratio [OR]:4.54, 95% confidence interval [CI]:1.6-12.84), had irregular menstrual cycles (OR:1.78, 95% CI:1.12-2.83) and hypertension (OR:1.55, 95% CI:1.09-2.21) had a higher odds ratio of early menopause, while central obesity (OR:1.33, 95% CI:1.03-1.73) and hyperlipidemia (OR:1.51, 95% CI:1.04-2.18) were factors associated with late menopause. CONCLUSIONS: This study revealed the associations between ANM and various factors among Chinese women. These factors included socio-demographic factors such as age; life behavior factors like current or prior smoking status; reproductive history factors such as irregular menstrual cycles, miscarriages, and breastfeeding; and health-related factors like central adiposity, hypertension, and hyperlipidemia. These findings provided a basis for understanding factors associated with ANM.

The role of sex hormone binding globulin levels in the association of surgical and natural premature menopause with incident type 2 diabetes.

OBJECTIVE: To examine associations of surgical and natural menopause before the age of 40 years with the risk of type 2 diabetes (T2D) in women. METHODS: A total of 273,331 women from the United Kingdom were recruited between 2006 and 2010 in the UK Biobank (UKB) study, and 146,343 women aged 40 to 69 years who were postmenopausal at baseline were included in the analysis. Surgical menopause and natural premature menopause were defined as bilateral oophorectomy before the age of 40 and menopause before the age of 40 without oophorectomy, respectively. Multivariable Cox regression models were used to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association between premature menopause and the incidence of T2D. RESULTS: During a median follow-up of 10.4 years, 47 women with surgical premature menopause, 244 women with natural premature menopause, and 4724 women without premature menopause developed T2D. Compared with women without premature menopause, both surgical premature menopause (adjusted HR = 1.46, 95 % CI: 1.09-1.95; P = 0.01) and natural premature menopause (adjusted HR = 1.20, 95 % CI: 1.06-1.37; P < 0.01) were associated with higher risks of incident T2D in the multivariable-adjusted models. Additionally, we observed a significant interaction between levels of sex hormone binding globulin (SHBG) (Pinteraction < 0.01) and the effects of premature menopause on incident T2D. The association between premature menopause and T2D risk appeared to be stronger in women with higher SHBG levels. Furthermore, a joint association was detected between premature menopause and the genetic risk score (GRS) of T2D, with a higher score indicating a higher risk of developingT2D. The highest risk of T2D was observed with higher T2D GRS and surgical premature menopause (adjusted HR = 2.61, 95 % CI: 1.65-4.12; P < 0.01). CONCLUSIONS: Surgical menopause and natural menopause before the age of 40 years were associated with an increased risk of T2D among postmenopausal women. The findings also suggest potential interactions of premature menopause with SHBG levels, with the association appearing to be stronger in higher SHBG levels, as well as a joint association between menopause status and genetic risk factors on T2D incidence.

Early menopause and hormone therapy as determinants for lung health outcomes: a secondary analysis using the PLCO trial.

RATIONALE: Early natural menopause (early-M; <45 years of age) increases the risk of lung morbidities and mortalities in smokers. However, it is largely unknown whether early-M due to surgery demonstrates similar effects and whether menopausal hormone therapy (MHT) is protective against lung diseases. OBJECTIVES: To assess the associations of early-M and MHT with lung morbidities and mortalities using the prospective Prostate, Lung, Colorectal and Ovarian (PLCO) trial. METHODS: We estimated the risk among 69 706 postmenopausal women in the PLCO trial, stratified by menopausal types and smoking status. RESULTS: Early-M was associated with an increased risk of most lung disease and mortality outcomes in ever smokers with the highest risk seen for respiratory mortality (HR 1.98, 95% CI 1.34 to 2.92) in those with bilateral oophorectomy (BO). Early-M was positively associated with chronic bronchitis, and all-cause, non-cancer and respiratory mortality in never smokers with natural menopause or BO, with the highest risk seen for BO- respiratory mortality (HR 1.91, 95% CI 1.16 to 3.12). Ever MHT was associated with reduced all-cause, non-cancer and cardiovascular mortality across menopause types regardless of smoking status and was additionally associated with reduced risk of non-ovarian cancer, lung cancer (LC) and respiratory mortality in ever smokers. Among smokers, ever MHT use was associated with a reduction in HR for all-cause, non-cancer and cardiovascular mortality in a duration-dependent manner. CONCLUSIONS: Smokers with early-M should be targeted for smoking cessation and LC screening regardless of menopause types. MHT users had a lower likelihood of dying from LC and respiratory diseases in ever smokers.

Risk-reducing salpingectomy with delayed oophorectomy to prevent ovarian cancer in women with an increased inherited risk: insights into an alternative strategy.

Epithelial ovarian cancer (EOC) is the most lethal type of gynaecological cancer, due to lack of effective screening possibilities and because the disease tends to metastasize before onset of symptoms. Women with an increased inherited risk for EOC are advised to undergo a risk-reducing salpingo-oophorectomy (RRSO), which decreases their EOC risk by 96% when performed within guideline ages. However, it also induces premature menopause, which has harmful consequences. There is compelling evidence that the majority of EOCs originate in the fallopian tube. Therefore, a risk-reducing salpingectomy with delayed oophorectomy (RRS with DO) has gained interest as an alternative strategy. Previous studies have shown that this alternative strategy has a positive effect on menopause-related quality of life and sexual health when compared to the standard RRSO. It is hypothesized that the alternative strategy is non-inferior to the standard RRSO with respect to oncological safety (EOC incidence). Three prospective studies are currently including patients to compare the safety and/or quality of life of the two distinct strategies. In this article we discuss the background, opportunities, and challenges of the current and alternative strategy.

Endocrine consequences of breast cancer therapy and survivorship.

Breast cancer survivorship is increasing, due to earlier diagnosis of the disease and more effective therapies. Long-term endocrine sequelae, including early menopause, bone health, fertility implications and menopausal symptoms, are important survivorship issues. Ovarian failure is common with chemotherapy and options for preserving fertility in young women include ovarian suppression during chemotherapy and oocyte or embryo cryopreservation before chemotherapy. Tamoxifen as adjunct therapy in premenopausal women leads to ovarian stimulation, sometimes ovulation and occasionally pregnancy with important teratogenic implications. Aromatase inhibitor therapy with or without gonadotrophin releasing hormone (GnRH) agonist leads to profound bone loss and anti-resorptive therapy is advised to prevent fracture. Tamoxifen acts to preserve bone in postmenopausal women but not premenopausal women. Pregnancy is not discouraged in young women with early breast cancer, even to the point of pausing adjunct therapy in order to conceive. However, menopausal hormone therapy is discouraged even years later. Non-hormonal therapy for menopausal symptoms in breast cancer survivors is available but, in some cases, estrogen-containing therapy may be worthy of consideration for quality of life in the informed patient.

To whom and by whom: Discussions of sexual health, fertility, and premature menopause with women with locally advanced cervical cancer.

PURPOSE: To investigate whether gynecologic and radiation oncologists document discussions of chemoradiation treatment's gonadotoxicity for patients with cervical cancer and what patient and physician factors make discussions more likely. METHODS AND MATERIALS: Women with LACC treated with definitive CRT between 2009 and 2022 were included. Visit notes with gynecologic and radiation oncologists were reviewed for sexual health discussions. Fertility and premature menopause discussions were only evaluated among premenopausal patients. Variables of interest including demographics and staging were collected. Univariate and multivariate analyses were conducted using Rv4.2.1. RESULTS: A total of 93 women were included (22-91 years old). Most were Stage IIB (32%) or IIIB (34%). Sexual health discussions occurred among 74.2% of patients and did not have a significant relationship with any patient factors. Fertility discussions occurred with 17.5% of the 57 premenopausal patients and were more likely among younger patients (≤31.9, p < 0.001) with fewer children (≤1, p < 0.001). Premature menopause discussions occurred among 73.7% of premenopausal patients and were more likely among younger patients (≤39.0, p = 0.015). CONCLUSIONS: It is promising to see that oncologists are discussing sexual health and premature menopause with most patients. The limited fertility discussions suggest that oncologists are less likely to discuss fertility as women approach the age of menopause or already have children. Involvement of reproductive endocrinologists and psychologists may provide patients with a more comprehensive understanding of long-term quality of life.

Left ventricular global longitudinal strain is worse in BRCA mutation positive breast cancer patients prior to cancer treatment and premature menopause.

PURPOSE: Breast cancer patients with mutations in human tumor suppressor genes BRCA1 and BRCA2 are at higher risk of cardiovascular disease (CVD) than the general population, as they are frequently exposed to cardiotoxic chemotherapy, anti-estrogen therapy, radiation, and/or oophorectomy for cancer-related treatment and prophylaxis. Animal and cell culture models suggest that BRCA mutations may play an independent role in heart failure. We sought to evaluate cardiac structure and function in female BRCA1 and BRCA2 mutation carriers with breast cancer compared to BRCA wildtype women with breast cancer. METHODS: We performed a 1:2 age- and hypertension-matched retrospective cohort study comparing BRCA1 and BRCA2 mutation carriers (n = 38) versus BRCA wildtype controls (n = 76) with a new diagnosis of breast cancer. Echocardiographic data were obtained within 6 months of breast cancer diagnosis and prior to chemotherapy, anti-estrogen therapy, radiation, or oophorectomy. Left ventricular global longitudinal strain (LV-GLS), a highly sensitive marker of LV function, was measured using QLab 15 (Philips Healthcare). RESULTS: In the total cohort of 114 patients with a new diagnosis of breast cancer, the median age was 45 ± 11 years and the prevalence of hypertension was 8%. There were no differences in traditional cardiovascular disease risk factors between cases and controls. BRCA carriers had lower LV-GLS (- 18.1% ± 4.7% vs. - 20.1% ± 3.8%, p = 0.02) and greater right atrial area (12.9 cm2 ± 2.7 cm2 vs. 11.8 cm2 ± 2.0 cm2, p = 0.04) compared to controls; however, both LV-GLS and right atrial area were within the normal range. Compared to controls, BRCA carriers had a trend toward worse LV posterior wall thickness (0.89 cm ± 0.15 cm vs. 0.83 cm ± 0.16 cm, p = 0.06) although not statistically significant. CONCLUSION: In women with newly diagnosed breast cancer and prior to treatment, LV-GLS was worse in BRCA1 and BRCA2 mutation carriers compared to those with BRCA wildtype. These findings suggest that BRCA mutations may be associated with subtle changes in cardiac function. Whether differences in GLS translate to increased cardiovascular risk in women with BRCA mutations needs to be further characterized.

Comparison of Metabolic Syndrome (MetS) Risk and Nutritional Status According to Menopause Age and the Impact of Socioeconomic Status on MetS Prevalence in Postmenopausal Women: A Cross-Sectional Study Based on the 8th Korea National Health and Nutrition Examination Survey (KNHANES).

The increased life expectancy and the occurrence of premature menopause prolong the mean postmenopausal phase in women's lifespans. Although the roles of poor socioeconomic status (SES), anthropometric characteristics, and nutritional status in premature menopause and the health of postmenopausal women are well understood, the differences in nutritional status and metabolic syndrome (MetS) prevalence in postmenopausal women depending on their menopause age are less explored. Furthermore, the association between SES and MetS risk in postmenopausal women is not studied. Thus, this study aimed to compare distinct nutritional status and MetS risk between women with premature menopause and natural menopause. Additionally, the association among SES, health-related lifestyle behaviors (HLBs), and MetS risk in postmenopausal women was studied. This study included 31,799 postmenopausal women from the 8th National Health and Nutrition Examination Survey (KNHANES). The relationship between disease prevalence and nutrient intake of the subjects was analyzed using analysis of variance (GLM), and Scheffé test was performed. Multiple logistic regression analysis was used to evaluate the association among SES, HLBs, and MetS as well as premature menopause. Women with premature menopause showed poor SES, anthropometric characteristics, and HLBs compared with women with natural menopause. Additionally, premature menopausal women had markedly lower intakes of protein, polyunsaturated fatty acid, n-3 fatty acid, and ß-carotene, but higher intakes of energy, carbohydrate, saturated fatty acid, and sugar than women with natural menopause (p < 0.0001). Premature menopausal women showed significantly higher MetS prevalence by having hypertriglyceridemia (p < 0.0001), hypertension (p = 0.0145), and reduced HDL cholesterol levels (p < 0.0001) relative to natural menopausal women. Furthermore, our findings indicate a substantial link among SES, HLBs, and the risk of premature menopause. In postmenopausal women, deteriorating SES and HLBs appear to influence the prevalence of MetS. Notably, our study reveals that higher intakes of protein, calcium, phosphate, and iron are correlated with a lower risk of developing MetS. These observations suggest that proactive nutritional education for premature menopausal women is necessary to improve MetS risk and their nutritional status. Also, SES-dependent interventions regarding nutrition and HLBs in postmenopausal women will be significant to lower MetS risk, MetS-derived chronic disease, and mortality in postmenopausal women.

Human mesenchymal stem cells derived exosomes improve ovarian function in chemotherapy-induced premature ovarian insufficiency mice by inhibiting ferroptosis through Nrf2/GPX4 pathway.

BACKGROUND: Chemotherapy exposure has become a main cause of premature ovarian insufficiency (POI). This study aimed to evaluate the role and molecular mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hUMSC-Exos) in ovarian function protection after chemotherapy. METHODS: hUMSC-Exos were applied to cyclophosphamide-induced premature ovarian insufficiency mice and human ovarian granulosa tumor cells (KGN) to determine their effects on follicular development and granulosa cell apoptosis. Evaluation was done for iron ion and reactive oxygen species (ROS) production, lipid peroxidation levels, and changes in iron death-related molecules (nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Glutathione Peroxidase enzyme 4 (GPX4), and Solute carrier family 7 member 11 cystine glutamate transporter (SLC7A11; xCT)). Furthermore, rescue experiments using an Nrf2 inhibitor were performed to assess the therapeutic effects of hUMSC-Exos on granulosa cells. RESULTS: hUMSC-Exos promoted ovarian hormone levels and primary follicle development in POI mice and reduced granulosa cell apoptosis. After hUMSC-Exos treatment, the ROS production, free iron ions and lipid peroxidation levels of granulosa cells decreased, and the iron death marker proteins Nrf2, xCT and GPX4 also decreased. Furthermore, the Nrf2 inhibitor ML385 significantly attenuated the effects of hUMSC-Exos on granulosa cells. CONCLUSION: hUMSC-Exos inhibit ferroptosis and protect against CTX-induced ovarian damage and granulosa cell apoptosis through the Nrf2/GPX4 signaling pathway, revealing a novel mechanism of hUMSC-Exos in POI therapy.

The mechanisms of MicroRNA 21 in premature ovarian insufficiency mice with mesenchymal stem cells transplantation : The involved molecular and immunological mechanisms.

Umbilical cord-derived mesenchymal stem cell (UCMSC) transplantation has been deeply explored for premature ovarian insufficiency (POI) disease. However, the associated mechanism remains to be researched. To explore whether and how the microRNA 21 (miR-21) functions in POI mice with UCMSCs transplantation, the autoimmune-induced POI mice model was built up, transplanted with or without UCMSCs transfect with the LV-hsa-miR-21-5p/LV-hsa-miR-21-5p-inhibition, with the transfection efficiency analyzed by QRT-PCR. Mice hormone secretion and the anti-Zona pellucida antibody (AZPAb) levels were analyzed, the ovarian morphological changes and folliculogenesis were observed, and the ovarian apoptosis cells were detected to evaluate ovarian function. The expression and localization of the PTEN/Akt/FOXO3a signal pathway-related cytokines were analyzed in mice ovaries.Additionally, the spleen levels of CD8 + CD28-T cells were tested and qualified with its significant secretory factor, interleukin 10 (IL-10). We found that with the LV-hsa-miR-21-5p-inhibition-UCMSCs transplantation, the mice ovarian function can be hardly recovered than mice with LV-NC-UCMSCs transplantation, and the PTEN/Akt/FOXO3a signal pathway was activated. The expression levels of the CD8 + CD28-T cells were decreased, with the decreased levels of the IL-10 expression. In contrast, in mice with the LV-hsa-miR-21-5p-UCMSCs transplantation, the injured ovarian function can be reversed, and the PTEN/AKT/FOXO3a signal pathway was detected activated, with the increased levels of the CD8 + CD28-T cells, and the increased serum levels of IL-10. In conclusion, miR-21 improves the ovarian function recovery of POI mice with UCMSCs transplantation, and the mechanisms may be through suppressing the PTEN/AKT/FOXO3a signal pathway and up-regulating the circulating of the CD8 + CD28-T cells.

Association of muscle disorders in late postmenopausal women according to the type of experienced menopause.

OBJECTIVE: Musculoskeletal disorders frequently affect postmenopausal women. This study aims to compare muscle disorders between women according to the type of experienced menopause: premature (PM) or normal age of menopause (NAM). METHODS: This was a cross-sectional study conducted in nine Latin American countries in which late postmenopausal women (55 to 70 years) were surveyed with a general questionnaire, the Menopause Rating Scale (MRS: item #4 exploring musculoskeletal discomfort), and strength, assistance with walking, rising from a chair, climbing stairs, and falling questionnaire (risk of sarcopenia). RESULTS: A total of 644 women were included: 468 who had NAM, and 176 who had PM (116 spontaneous and 60 surgical). The overall mean age of the participants was 60.9 ± 4.2 years. Women who had PM experienced more musculoskeletal discomfort (33.5% vs 20.9%, P < 0.001) and a higher likelihood of sarcopenia (35.2% vs 19.9%, P < 0.001) than women who had a NAM. Women who had surgical PM exhibited a higher prevalence of severe musculoskeletal discomfort (46.7% vs 29.3%, P < 0.02) and a higher likelihood of sarcopenia (45.0% vs 27.6%, P < 0.02) than women who had a NAM. After adjusting for covariates (age, body mass index, menopausal hormone therapy use, physical activity, education, cigarette consumption, use of antidepressants, sexual activity, comorbidities, and having a partner), our logistic regression model determined that spontaneous PM was not associated with higher odds of musculoskeletal discomfort and higher odds of sarcopenia. On the other hand, women who had surgical PM were more likely to experience musculoskeletal discomforts (odds ratio: 2.26; 95% confidence interval: 1.22-4.17) and higher odds for sarcopenia (odds ratio: 2.05; 95% confidence interval: 1.16-3.65) as compared to women who experienced a NAM. CONCLUSIONS: Women experiencing surgical PM have a higher likelihood of developing muscle disorders. This underscores the potential significance of hormonal levels in influencing musculoskeletal health during postmenopause.

Possible association between subclinical hypothyroidism and age at menopause in Colombian women.

OBJECTIVE: To evaluate the association between subclinical hypothyroidism with early menopause, premature menopause, and last menstrual bleeding before the natural age of menopause. METHODS: This was a cross-sectional study conducted in 643 postmenopausal women aged 40-69 years. Groups were formed according to last menstrual episode: ≥45 [Natural age at menopause], 40-44 and [Early menopause], <40 [Premature menopause], and <45 [last menstrual episode before the natural age of menopause]. The Zulewski scale was applied to identify manifestations related to hypothyroidism and subclinical hypothyroidism, diagnosed with a serum TSH > 4.5 µIU/mL plus T4-free between 0.7 and 1.9 ng/dL. RESULTS: It was found that 24.4% had the last menstrual episode before the natural age of menopause, 18.6% had early menopause, and 5.7% had premature menopause. Subclinical hypothyroidism was diagnosed in 4.5% of patients. Among women with subclinical hypothyroidism, there was a higher frequency of early menopause, premature menopause, and last menstrual episode before the natural age of menopause, than in women without subclinical hypothyroidism (p < 0.05). Paresthesia (50%) and dry skin (40.7%) were the most reported hypothyroidism-related manifestations. Early menopause, premature menopause, and last menstrual episode before the natural age of menopause were associated with subclinical hypothyroidism, OR: 3.37 [95% CI: 1.40-8.10], OR: 4.31 [95% CI: 1.24-14.97], and OR: 3.57 [95% CI: 1.57-8.10], respectively. CONCLUSIONS: The last menstrual episode before the natural age of menopause, early menopause, and premature menopause were significantly associated with a higher chance of subclinical hypothyroidism.