Exploring the causal association between epigenetic clocks and menopause age: insights from a bidirectional Mendelian randomization study.

Background: Evidence suggests a connection between DNA methylation (DNAm) aging and reproductive aging. However, the causal relationship between DNAm and age at menopause remains uncertain. Methods: Employing established DNAm epigenetic clocks, such as DNAm Hannum age acceleration (Hannum), Intrinsic epigenetic age acceleration (IEAA), DNAm-estimated granulocyte proportions (Gran), DNAm GrimAge acceleration (GrimAgeAccel), DNAm PhenoAge acceleration (PhenoAgeAccel), and DNAm-estimated plasminogen activator inhibitor-1 levels (DNAmPAIadjAge), a bidirectional Mendelian randomization (MR) study was carried out to explore the potential causality between DNAm and menopausal age. The primary analytical method used was the inverse variance weighted (IVW) estimation model, supplemented by various other estimation techniques. Results: DNAm aging acceleration or deceleration, as indicated by Hannum, IEAA, Gran, GrimAgeAccel, PhenoAgeAccel, and DNAmPAIadjAge, did not exhibit a statistically significant causal effect on menopausal age according to forward MR analysis. However, there was a suggestive positive causal association between age at menopause and Gran (Beta = 0.0010; 95% confidence interval (CI): 0.0004, 0.0020) in reverse MR analysis. Conclusion: The observed increase in granulocyte DNAm levels in relation to menopausal age could potentially serve as a valuable indicator for evaluating the physiological status at the onset of menopause.

Psoriasis in women with psoriatic arthritis: hormonal effects, fertility, and considerations for management at different stages of life.

OBJECTIVE: This review examines skin manifestations in women with spondyloarthritis, with a particular focus on psoriatic arthritis (PsA) and associated psoriasis. METHODS: A narrative review of the bibliography was conducted using the main databases (PubMed, Scopus, EMBASE). RESULTS: The review showed that the clinical course of PsA and psoriasis in women is influenced by hormonal fluctuations that occur at different stages of life, such as menstruation, pregnancy, postpartum, and menopause. Gender differences in the epidemiology of PsA and psoriasis are discussed and attributed to biological, hormonal, and environmental differences. The role of estrogen in modulating immune responses and its impact on the severity of PsA and psoriasis are reviewed. Special emphasis is placed on the psychosocial impact of visible skin lesions on women's quality of life and fertility problems associated with psoriasis. Treatment strategies are also taken into account, favoring personalized approaches that consider the safety of treatments during pregnancy and breastfeeding. CONCLUSIONS: The review highlights the importance of a holistic and gender-sensitive approach to the management of PsA and psoriasis in women, promoting the integration of physical treatment with support for emotional well-being.

Women living with HIV: identifying and managing their menopause, age-related, and psychosocial health needs in a metropolitan sexual health service in Sydney, Australia.

Background Aging women living with HIV are significantly affected by menopause and comorbidities, yet international and Australian HIV guidance on the management of women is scarce. This study aimed to identify gaps in clinical management of menopause, age-related comorbidities, and psychosocial health of women living with HIV attending our metropolitan sexual health service. Methods A clinical audit of all cisgender women who attended Sydney Local Health District Department of Sexual Health Medicine for ongoing routine HIV care between 1 January 2021 and 1 January 2023 was undertaken. Results Twenty-seven patient files were examined. Half (13/27, 48.1%) of women were age 45years and older, of whom 6/13 (46.2%) were postmenopausal and 4/13 (30.8%) did not have menopause status recorded. In the prior 12months, most women had their blood pressure (19/27, 70.4%), total cholesterol (21/27, 77.8%), glycated haemoglobin (21/27, 77.8%), estimated glomerular filtration rate (27/27, 96.3%), and liver function tests (26/27, 96.3%) measured. Smoking and alcohol intake was documented for less than half of women (13/27, 48.1%; and 12/27, 44.4%; respectively). In women aged 45years and older, absolute cardiovascular disease risk was calculated in 2/13 (15.4%), and none had a Fracture Risk Assessment Tool score or cognitive screen performed in the prior 12months. One-fifth (5/27, 18.5%) had a documented history of depression or anxiety. Of those screened, half (4/8, 50.0%) disclosed past intimate partner violence. Conclusions Our service has now implemented a reference tool to guide routine monitoring of women living with HIV, with sections dedicated to reproductive health and psychological wellbeing. Australian HIV management guidelines would benefit from specific guidance for women.

General self-efficacy as a moderator between severity of menopausal symptoms and satisfaction with life in menopausal women.

The study aimed to determine whether self-efficacy acts as a moderator between the severity of menopausal symptoms and life satisfaction. The research tools were: The Generalized Self-Efficacy Scale (GSES), The Satisfaction with Life Scale (SWLS) The Menopause - Specific Quality of Life (MENQOL), and a standardized questionnaire comprising questions on the participants' characteristics. 516 women using health care services who had menopausal symptoms took part in the study. Self-efficacy (GSES) (r = -0.176; p < 0.001) and life satisfaction (SWLS) (r = -0.106; p = 0.016) were negatively correlated with the severity of menopausal symptoms (MENQOL). The self-efficacy correlated positively with satisfaction with life (r = 0.278; p < 0.001). A low level of self-efficacy was associated with a significant and negative relationship between the severity of menopausal symptoms and satisfaction with life (p = 0.005), while at a high and moderate level of self-efficacy, the severity of menopausal symptoms was not associated with life satisfaction (p > 0.05). Self-efficacy moderates the relationship between the severity of menopausal symptoms and life satisfaction in menopausal women. The moderating function of self-efficacy is that, at its low level, an increase in the severity of menopausal symptoms reduces life satisfaction, while at medium and high levels, an increase in the severity of menopausal symptoms does not reduce life satisfaction.

The vaginal microbiome of transgender men receiving gender-affirming hormonal therapy in comparison to that of cisgender women.

The vaginal microbiome of trans men and menopausal women is suspected to be similar due to a lack of estrogen leading to the absence of lactobacilli. However, data are scarce. We performed an analysis of the vaginal microbiome of trans men (n = 25) in comparison to that of menopausal (n = 25) and premenopausal women (n = 25). The vaginal microbiome of trans men and menopausal women showed a higher alpha diversity than that of premenopausal women. Various beta diversity indices (e.g., Bray‒Curtis (Un-)Weigthed Unifrac), showed significant differences in community composition between trans men and premenopausal (p < 0.001) and menopausal women (p < 0.001). The vaginal microbiome of trans men is characterized by a loss of Lactobacillus and an increase in bacteria associated with the intestinal flora (e.g., Campylobacter, Anaerococcus, Dialister, Prevotella). The abundance of Dialister and Prevotella decreased with the length of hormonal therapy in trans men. The Nugent score, Pap smear and HPV status did not differ between the study groups. The vaginal microbiome of trans men differs from that of premenopausal women but shows similarities to that of menopausal women. The duration of hormonal therapy in trans men may have important impacts on the vaginal microbiome and thus possibly on the risk for STIs.

Role of serum estradiol and C-telopeptide on musculoskeletal pain in menopausal women.

Musculoskeletal pain is one of the common symptoms of menopause syndrome throughout the world. Estradiol is the most potent and abundant derivative of estrogen and is associated with musculoskeletal pain, stiffness, and depressed mood during the menopausal transition. C-telopeptide is a molecule released during osteoclastic bone resorption and degradation of type I collagen, which is reported to have higher levels in individuals with musculoskeletal pain. An observational analytical study with a cross-sectional design was used in this research. Estradiol and C-telopeptide levels were measured in this study using enzyme-linked immunosorbent assay (ELISA). Musculoskeletal pain was assessed using the Nordic Musculoskeletal Questionnaire (NMQ) and the Menopause Quality of Life Questionnaire (MENQOL). Musculoskeletal pain was determined if the participant answered "yes" on questions number 12, 14 and 25 on the MENQOL. Data analysis was performed using the independent Student t-test for normally distributed data and the Mann-Whitney test for non-normally distributed data. A correlation test was performed using the Pearson correlation test for normally distributed data and the Spearman correlation test for non-normally distributed data. The results showed a non-significant relationship between estradiol and C-telopeptide levels with musculoskeletal pain assessed using the NMQ or MENQOL questionnaires. The correlation test also showed no correlation between estradiol and C-telopeptide levels in women with and without musculoskeletal pain.

Role of estradiol and C-reactive protein levels on genitourinary syndrome in menopausal women.

Menopause leads to decreased estradiol levels affecting tissue health and causing local inflammation in the genital organs and urinary tract. The rise of blood C-reactive protein (CRP) levels in menopausal women may indicate systemic inflammation associated with estradiol decline. The aim of this study was to determine the relationship between serum estradiol and CRP levels on genitourinary syndrome in menopausal women. A cross-sectional study was conducted among menopausal women who had not experienced menstruation for at least 12 consecutive months at Prof. dr. Chairuddin P. Lubis Hospital, Medan, Indonesia, in 2023. Estradiol and CRP levels were measured using enzyme-linked immunosorbent assay (ELISA) and the presence of genitourinary syndrome was assessed using the Menopause-Specific Quality of Life (MENQOL) questionnaire. The mean levels of estradiol and CRP were compared to menopausal women with and without genitourinary syndrome with the Mann-Whitney test. To assess the correlation between estradiol and CRP levels, and between their levels with the presence of genitourinary symptoms, the Spearman correlation test was used. The genitourinary syndrome was reported in 25% of the total included menopausal women. Our data indicated that the mean estradiol levels were not significantly different between menopausal women with and without genitourinary syndrome (9.13±2.47 pg/mL vs 18.96±31.23 pg/mL, p=0.881). The mean serum CRP level of menopausal women with genitourinary syndrome (9.72±6.30 mg/L) was higher than that of women without the syndrome (2.09±1.26 mg/L) with p<0.001. In addition, serum CRP level, not estradiol, was correlated with the symptom score of genitourinary syndrome. This study highlights that to identify and manage genitourinary syndrome, monitoring of CRP levels is essential in menopausal women.

Comparison of leptin and estrone levels between normal body mass index and obese menopausal women.

Postmenopausal women often experience hormonal changes and shifts in fat composition, affecting weight gain and obesity. Understanding the link between hormones, especially estrogen and leptin, is key to managing weight and lowering disease risk in menopausal women. The aim of this study was to compare the levels of leptin and estrone in menopausal women with normal weight and obesity. A cross-sectional study was conducted on menopausal women, either normal body mass index (BMI) or obese, at H. Adam Malik General Hospital, Medan, Indonesia. Blood samples were collected to measure leptin and estrone levels using the enzyme-linked immunosorbent assay (ELISA) method. The differences in leptin levels between groups were analyzed using the Wilcoxon test, while the correlation between BMI and leptin was examined using the Pearson correlation test. The disparity in estrone levels in both groups was analyzed using the Mann-Whitney test and the correlations between variables were assessed using the Spearman or Pearson correlation tests as appropriate. The mean leptin levels in normal BMI and obesity groups were 17.73±4.96 and 25.46±12.95 ng/mL, respectively, and were statistically different (p=0.006). The mean estrone levels in menopausal women with normal BMI and obesity were 943.23±391.79 and 851.38±282.23 ng/mol, respectively and were not statistically different (p=0.564). A significant positive correlation was found between BMI and leptin level (r=0.59; p<0.001), while BMI and estrone were not significantly correlated (r=0.083; p=0.559). In conclusion, leptin level was significantly different between BMI groups and had a strong positive correlation with BMI. This finding could be an important insight in body weight management and disease risk prevention in menopausal women.

Menopausal symptoms and utilization of menopausal hormone therapy among women aged 40-60 years in Addis Ababa, Ethiopia: a cross-sectional study.

BACKGROUND: The onset of menopause leads to diminished estrogen exposure, resulting in a high morbidity burden related to menopausal symptoms. Menopausal hormonal therapy is an effective therapy that offers more advantages than disadvantages for women aged less than 60 years or who have had menopause for less than 10 years. OBJECTIVE: This study aimed to assess the prevalence of menopausal symptoms, identify factors associated with menopausal symptoms, and assess the use of menopausal hormone therapy among women aged 40-60 who visited the gynecological clinics of three hospitals in Addis Ababa, Ethiopia. METHODS: A facility-based cross-sectional study was conducted from January 2022 to June 2022 at Gandhi Memorial Hospital, Tikur Anbessa Hospital, and Zewditu Memorial Hospital on 296 middle-aged women. Data were collected using an interviewer-administered structured questionnaire and analyzed for sociodemographic factors, utilization of menopausal hormone therapy, and prevalence of menopausal symptoms using the menopause rating scale. Data were analyzed using SPSS version 25. Bivariate and multivariate logistic regression analyses were performed to identify independent predictors of each subscale of menopausal symptoms. The strength of the association was measured using odds ratios with 95% confidence intervals, and statistical significance was set at a value of P < 0.05. RESULT: The prevalence of menopausal symptoms was 89.9%. According to the menopausal rating scale, the frequency of reported symptoms was hot flushes (54.7%), muscle and joint pain (32.1%) on the somatic subscale; physical and mental exhaustion (55.1%), irritability (48.6%) on psychological subscale; and sexual problems (41.3%), bladder problems (39.2%) on urogenital subscale. This study also showed that the age of women [aOR: 0.317, 95%CI (0.102, 0.990)], and monthly family income [aOR = 0.182, 95% CI (0.041, 0.912)] were significantly associated with somatic menopausal symptoms. There was no utilization of menopausal hormonal therapy to treat menopausal symptoms and to prevent complications. CONCLUSION: The prevalence of menopausal symptoms is high; however, the utilization of individualized administration of menopausal hormone therapy according to symptoms is negligible. It appears essential for these institutions to work on service availability and delivery of menopausal hormone therapy for those in need of wider benefits for their clients.

Leukocyte telomere length and memory circuitry and cognition in early aging: Impact of sex and menopausal status.

Telomere length (TL) is an important cellular marker of biological aging impacting the brain and heart. However, how it is related to the brain (e.g., cognitive function and neuroanatomic architecture), and how these relationships may vary by sex and reproductive status, is not well established. Here we assessed the association between leukocyte TL and memory circuitry regional brain volumes and memory performance in early midlife, in relation to sex and reproductive status. Participants (N = 198; 95 females, 103 males; ages 45-55) underwent structural MRI and neuropsychological assessments of verbal, associative, and working memory. Overall, shorter TL was associated with smaller white matter volume in the parahippocampal gyrus and dorsolateral prefrontal cortex. In males, shorter TL was associated with worse working memory performance and corresponding smaller white matter volumes in the parahippocampal gyrus, anterior cingulate cortex, and dorsolateral prefrontal cortex. In females, the impact of cellular aging was revealed over the menopausal transition. In postmenopausal females, shorter TL was associated with poor associative memory performance and smaller grey matter volume in the right hippocampus. In contrast, TL was not related to memory performance or grey and white matter volumes in any memory circuitry region in pre/perimenopausal females. Results demonstrated that shorter TL is associated with worse memory function and smaller volume in memory circuitry regions in early midlife, an association that differs by sex and reproductive status. Taken together, TL may serve as an early indicator of sex-dependent brain abnormalities in early midlife.

Trajectories of peripheral white blood cells count around the menopause: a prospective cohort study.

BACKGROUND: Menopause significantly impacts the immune system. Postmenopausal women are more susceptible to infection. Nonetheless, the pattern of change in peripheral white blood cell counts around the menopause remains poorly understood. METHODS: We conducted a prospective longitudinal cohort study with repeated measurements using Kailuan cohort study of 3632 Chinese women who participated in the first checkup (2006-2007) and reached their final menstrual period (FMP) by the end of the seventh checkup (2018-2020). Peripheral WBC count indicators included total white blood cells (TWBC), neutrophils (NEUT), lymphocytes (LYM), and monocytes (MON). Multivariable mixed effects regressions fitted piece-wise linear models to repeated measures of WBC count indicators as a function of time before or after the final menstrual period (FMP). Interaction and subgroup analysis were used to explore the effects of age and body mass index (BMI) on changes in WBC indicators around FMP. RESULTS: WBC count indicators decreased before the FMP, and the reduction in TWBC, NEUT, and MON continued for 2 years following the FMP. LYM and NEUT declined during < -1 years and - 4 ∼ + 2 years relative to FMP, respectively. A reduction in MON was observed pre-FMP, extending continuously through the two-year period post-FMP. TWBC declined from - 3 to + 2 years relative to FMP, but both MON and TWBC increased during > + 2 years. The baseline age had an interaction effect on changes in WBC indicators during specific menopausal stages, except for TWBC. Individuals in different age subgroups showed distinct trajectories for NEUT, LYM and MON around the FMP. High baseline BMI had a synergistic effect on changes in specific menopause segments for TWBC, LYM, and MON. The impact of menopause on TWBC and LYM was postponed or counterbalanced in high BMI individuals. Individuals in three BMI subgroups experienced similar MON changes around FMP, and there were slight variations during < -4 years. CONCLUSIONS: Menopause was associated with count changes of peripheral WBC. The trajectories of various WBC types differ around menopause. Age and BMI affected WBC trajectory around menopause. The menopause period may represent a window of opportunity to promote immune health in middle-aged women.

[Hypertension and menopause: physiopathology and impact of the hormonal therapy]. / Hypertension artérielle et ménopause : physiopathologie et impact des traitements hormonaux.

Menopause, as a consequence of ovarian follicular decline, induces estrogen deficiency and metabolic changes that increase the cardiovascular risk in women. In particular, there is an increase in blood pressure during menopause. Menopausal hormonal therapy can be prescribed to women with symptoms of menopause to improve their quality of life. This article reviews the current literature on the pathophysiological mechanisms that explain blood pressure changes at menopause and describes the impact of menopausal hormone therapy on blood pressure.

La ménopause, conséquence d'une déplétion folliculaire ovarienne, induit une carence hormonale et des modifications métaboliques augmentant le risque cardiovasculaire chez la femme. Une hausse de la tension artérielle peut notamment être observée. Le traitement hormonal de la ménopause peut être prescrit aux femmes présentant des symptômes climactériques afin d'améliorer leur qualité de vie. Cet article revoit la littérature actuelle sur les mécanismes physiopathologiques expliquant les changements tensionnels à la ménopause et décrit l'impact des traitements hormonaux de la ménopause sur la tension artérielle.

Knowledge and Awareness Toward Menopausal Hormone Therapy in a Fourth-Tier City of China.

BACKGROUND Menopausal hormone therapy (MHT) has been receiving increasing attention in developed countries. The purpose of this study was to investigate understanding of menopause and acceptance of MHT in Qinhuangdao, China. MATERIAL AND METHODS We analyzed data from 186 perimenopausal patients on topics including menopausal symptoms and acceptance of and adherence to MHT treatment. We also surveyed 100 medical staff on menopausal-related knowledge. RESULTS Group A consisted of 41 patients treated with MHT for more than 1 cycle, group B consisted of 49 patients who had received MHT but had stopped it for more than 3 months, and group C consisted of 96 patients who never received MHT. There was a significant difference among them in modified Kupermann scores before treatment (P<0.05), but the difference disappeared after MHT (P>0.05). In group C, 32 patients (33%) were unaware of MHT, 60 (62.5%) were worried about the risk of breast/endometrial cancer, 24 (25%) were worried about high costs, and 67 (70%) had no obvious symptoms and did not want MHT. Similarly, in group B, most people stopped MHT for fear of breast or endometrial cancer. A survey targeting 100 medical staff in our hospital found 14 people (14%) knew about and were willing to accept MHT, 44 people (44%) knew about MHT but were afraid to use it, and 42 people (42%) did not know about MHT at all. CONCLUSIONS MHT has not yet been accepted by the majority of people, even medical staff, in Qinhuangdao, China, and much further progress is needed.

Interactions of depression, anxiety, and sleep quality with menopausal symptoms on job satisfaction among middle-aged health workers in England: a STROBE-based analysis.

BACKGROUND: This study examined the association between menopausal symptoms and job satisfaction, and ascertained whether three psychosomatic factors (e.g., anxiety, depression, and sleep quality) interact with menopausal symptoms on job satisfaction. METHODS: A cross-sectional design with sensitivity analysis was adopted. The participants of the study were clinical health workers in England. Data from 154 health workers were analyzed with the hierarchical linear regression (HLR) analysis. RESULTS: There was a negative association between menopausal symptoms and job satisfaction (ß = -0.38; t = -4.81, p < 0.001), but this relationship became non-significant after adjusting for work stress, self-reported health, job tenure, and resilience at work. An interaction between menopausal symptoms and the psychosomatic factors was found. The strength of the negative association between menopausal symptoms and job satisfaction was weakened by sleep quality (ß = 0.05; t = 0.48; p > 0.05) but was strengthened by anxiety (ß = -0.22; t = -2.28; p < 0.05) and depression (ß = -0.24; t = -2.16; p < 0.05). CONCLUSION: Menopausal symptoms can be directly associated with lower job satisfaction and indirectly associated with lower job satisfaction through its interaction with depression and anxiety. Menopausal symptoms can weaken the positive association between sleep quality and job satisfaction.

Experiences of menopausal transition among populations exposed to chronic psychosocial stress in the United States: a scoping review.

BACKGROUND: The transition to menopause is a significant event affecting health, well-being, and quality of life. Menopause typically occurs between the ages of 44-57, accompanied by symptoms such as hot flashes, mood changes, and sleep disturbances. Being postmenopausal also increases the risk of cardiovascular disease, stroke, and osteoporosis. Despite its importance, menopause is under-researched and under-discussed, particularly concerning the impact of chronic psychosocial stress. METHODS: A scoping review of qualitative, quantitative, and mixed methods research was conducted to map existing literature on the transition to menopause among populations experiencing chronic psychosocial stress in the United States. The review followed the PRISMA-ScR methodology, systematically searching literature in PubMed and SCOPUS databases using MeSH terms. Studies were included which focused on menopausal symptoms and psychosocial stressors. Data extraction and charting were performed using Covidence software. RESULTS: Fifteen studies were included, highlighting relationships between socioeconomic status, intimate partner violence, childhood abuse, and racial disparities which influenced menopausal experiences. Lower- income, higher perceived stress, and negative attitudes towards menopause were associated with increased psychological and somatic symptoms and early onset of menopause (prior to age 45). African American women were found to experience earlier onset and more severe vasomotor symptoms compared to their White counterparts. Women veterans used hormone therapy more frequently than the general population, particularly those with mood or anxiety disorders. The review also identified a geographic bias, with most studies conducted in the Northeast, Midwest, and Western regions of the United States. CONCLUSIONS: This review underscores the necessity of considering social, cultural, and environmental factors in understanding menopausal experiences and addressing health disparities. Future research should aim to include diverse populations and adopt longitudinal and qualitative study designs to capture the dynamic nature of menopausal experiences. Policies and interventions directed at improving the well-being of women experiencing menopause in the context of chronic psychosocial stress are warranted. TRIAL REGISTRATION: N/A.

Associations of urinary heavy metals with age at menarche, age at menopause, and reproductive lifespan: A cross-sectional study in U.S. women.

Female reproductive timing and lifespan, with a close relation to long-term health outcomes, have been altered in U.S. women over the past decades. However, epidemiologic evidence of the potential causes was lacking. On the basis of 1981 naturally postmenopausal women from the National Health and Nutrition Examination Survey 1999-2020, this study aimed to investigate the associations of urinary heavy metals with age at menarche, age at menopause, and reproductive lifespan. Multivariate generalized linear regression and addictive models were used for single metal exposure analysis, and weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were employed for mixed exposures. In the fully adjusted model, higher urinary antimony concentration was associated with earlier age at menarche of 0.137 years, while higher concentrations of cadmium, cesium, lead, antimony, and thallium were associated with delayed age at menopause of 0.396-0.687 years. Additionally, urinary barium, cesium, lead, antimony, and thallium levels were associated with longer reproductive lifespan ranging between 0.277 and 0.713 years. Both WQS and BKMR models showed significantly positive associations of metal mixtures with age at menopause (ß: 0.667, 95 % CI: 0.120-1.213) and reproductive lifespan (ß: 0.686, 95 % CI: 0.092-1.280), with cadmium and lead identified as principal contributors. In conclusion, heavy metal exposures were associated with reproductive timing and lifespan of U.S. women, highlighting the need for further prevention and intervention strategies.

Causal association of menstrual reproductive factors on the risk of osteoarthritis: A univariate and multivariate Mendelian randomization study.

OBJECTIVE: Several observational studies have revealed a potential relationship between menstrual reproductive factors (MRF) and osteoarthritis (OA). However, the precise causal relationship remains elusive. This study performed Mendelian randomization (MR) to provide deeper insights into this relationship. METHODS: Utilizing summary statistics of genome-wide association studies (GWAS), we conducted univariate MR to estimate 2 menstrual factors (Age at menarche, AAM; Age at menopause, AMP) and 5 reproductive factors (Age at first live birth, AFB; Age at last live birth, ALB; Number of live births, NLB; Age first had sexual intercourse, AFSI; Age started oral contraceptive pill, ASOC) on OA (overall OA, OOA; knee OA, KOA and hip OA, HOA). The sample size of MRF ranged from 123846 to 406457, and the OA sample size range from 393873 to 484598. Inverse variance weighted (IVW) method was used as the primary MR analysis methods, and MR Egger, weighted median was performed as supplements. Sensitivity analysis was employed to test for heterogeneity and horizontal pleiotropy. Finally, multivariable MR was utilized to adjust for the influence of BMI on OA. RESULTS: After conducting multiple tests (P<0.0023) and adjusting for BMI, MR analysis indicated that a lower AFB will increase the risk of OOA (odds ratio [OR] = 0.97, 95% confidence interval [CI]: 0.95-0.99, P = 3.39×10-4) and KOA (OR = 0.60, 95% CI: 0.47-0.78, P = 1.07×10-4). ALB (OR = 0.61, 95% CI: 0.45-0.84, P = 2.06×10-3) and Age AFSI (OR = 0.66, 95% CI: 0.53-0.82, P = 2.42×10-4) were negatively associated with KOA. In addition, our results showed that earlier AMP adversely affected HOA (OR = 1.12, 95% CI: 1.01-1.23, P = 0.033), and earlier ASOC promote the development of OOA (OR = 0.97, 95% CI: 0.95-1.00, P = 0.032) and KOA (OR = 0.58, 95% CI: 0.40-0.84, P = 4.49×10-3). ALB (OR = 0.98, 95% CI: 0.96-1.00, P = 0.030) and AFSI (OR = 0.98, 95% CI: 0.97-0.99, P = 2.66×10-3) also showed a negative association with OOA but they all did not pass multiple tests. The effects of AAM and NLB on OA were insignificant after BMI correction. CONCLUSION: This research Certificates that Early AFB promotes the development of OOA, meanwhile early AFB, ALB, and AFSI are also risk factors of KOA. Reproductive factors, especially those related to birth, may have the greatest impact on KOA. It provides guidance for promoting women's appropriate age fertility and strengthening perinatal care.

The prognostic role of remnant cholesterol in Asian menopausal women received percutaneous coronary intervention with acute coronary syndrome.

BACKGROUND: Remnant cholesterol (RC) exert a significant influence on atherosclerotic cardiovascular disease development. However, the prognostic implications of RC in menopausal women received percutaneous coronary intervention (PCI) who experiencing acute coronary syndrome (ACS) remain uncertain. METHODS: RC was derived by subtracting the sum of high-density lipoprotein cholesterol and low-density lipoprotein cholesterol from the total cholesterol. Kaplan-Meier survival and Cox regression analysis were employed for assessing the correlation between continuous RC levels and composite and individual adverse events in Q1-Q4 quartiles. Receiver operator characteristic (ROC) curves, derived from Cox regression, were employed for analyzing the relationship between RC and both composite and individual adverse events. RESULTS: 1505 consecutive menopausal women who underwent PCI and diagnosed with ACS were included. Kaplan-Meier survival analysis demonstrated a progressive reduction in composite adverse event survival rates across the four groups, observed in both the general population and among diabetic individuals, as RC values increased (Log-rank P < 0.001). The analysis of multivariate Cox regression indicated RC remained independently associated with both composite and individual adverse events. ROC analysis showed that RC enhanced the area under the curve both in total and diabetic populations for composite adverse events. CONCLUSION: Among menopausal women diagnosed with ACS who underwent PCI, heightened levels of RC were found to be independently correlated with an increased occurrence of adverse events.