METHODS AND FINDINGS: Genetic instruments to proxy 12 risk factors were constructed by identifying single nucleotide polymorphisms (SNPs) that were robustly (P < 5 × 10-8) and independently associated with each respective risk factor in previously reported genome-wide association studies. These risk factors included genetic liability to 3 factors (endometriosis, polycystic ovary syndrome, type 2 diabetes) scaled to reflect a 50% higher odds liability to disease. We obtained summary statistics for the association of these SNPs with risk of overall and histotype-specific invasive epithelial ovarian cancer (22,406 cases; 40,941 controls) and low malignant potential tumours (3,103 cases; 40,941 controls) from the Ovarian Cancer Association Consortium (OCAC). The OCAC dataset comprises 63 genotyping project/case-control sets with participants of European ancestry recruited from 14 countries (US, Australia, Belarus, Germany, Belgium, Denmark, Finland, Norway, Canada, Poland, UK, Spain, Netherlands, and Sweden). SNPs were combined into multi-allelic inverse-variance-weighted fixed or random effects models to generate effect estimates and 95% confidence intervals (CIs). Three complementary sensitivity analyses were performed to examine violations of MR assumptions: MR-Egger regression and weighted median and mode estimators. A Bonferroni-corrected P value threshold was used to establish strong evidence (P < 0.0042) and suggestive evidence (0.0042 < P < 0.05) for associations. In MR analyses, there was strong or suggestive evidence that 2 of the 12 risk factors were associated with invasive epithelial ovarian cancer and 8 of the 12 were associated with 1 or more invasive epithelial ovarian cancer histotypes. There was strong evidence that genetic liability to endometriosis was associated with an increased risk of invasive epithelial ovarian cancer (odds ratio [OR] per 50% higher odds liability: 1.10, 95% CI 1.06-1.15; P = 6.94 × 10-7) and suggestive evidence that lifetime smoking exposure was associated with an increased risk of invasive epithelial ovarian cancer (OR per unit increase in smoking score: 1.36, 95% CI 1.04-1.78; P = 0.02). In analyses examining histotypes and low malignant potential tumours, the strongest associations found were between height and clear cell carcinoma (OR per SD increase: 1.36, 95% CI 1.15-1.61; P = 0.0003); age at natural menopause and endometrioid carcinoma (OR per year later onset: 1.09, 95% CI 1.02-1.16; P = 0.007); and genetic liability to polycystic ovary syndrome and endometrioid carcinoma (OR per 50% higher odds liability: 0.89, 95% CI 0.82-0.96; P = 0.002). There was little evidence for an association of genetic liability to type 2 diabetes, parity, or circulating levels of 25-hydroxyvitamin D and sex hormone binding globulin with ovarian cancer or its subtypes. The primary limitations of this analysis include the modest statistical power for analyses of risk factors in relation to some less common ovarian cancer histotypes (low grade serous, mucinous, and clear cell carcinomas), the inability to directly examine the association of some ovarian cancer risk factors that did not have robust genetic variants available to serve as proxies (e.g., oral contraceptive use, hormone replacement therapy), and the assumption of linear relationships between risk factors and ovarian cancer risk.
CONCLUSIONS: Our comprehensive examination of possible aetiological drivers of ovarian carcinogenesis using germline genetic variants to proxy risk factors supports a role for few of these factors in invasive epithelial ovarian cancer overall and suggests distinct aetiologies across histotypes. The identification of novel risk factors remains an important priority for the prevention of epithelial ovarian cancer.
METHODS: A total of 1875 community-dwelling climacteric women were included in this study. The Pittsburgh Sleep Quality Index (PSQI) and the Menopause Rating Scale (MRS) were adopted to assess sleep quality and menopausal symptoms, respectively. Data were collected 4 times from March 2019 to December 2019, at a 3-month interval.
RESULTS: The Cross-lagged analysis showed that worse sleep quality and more severe menopausal symptoms over time after controlling for specified covariates, and more severe menopausal symptoms were predicted by declined sleep quality. The Generalized estimation equation model showed that education level, marital status, chronic diseases, life events, income, and age were the influential factors of sleep quality, while menopausal symptoms were impacted by marital status and income.
CONCLUSIONS: Increasing negative sleep quality and more severe menopausal symptoms over time contribute to the health burden of climacteric women. Menopausal symptoms could be alleviated by sleep quality improvement, which is influenced by education level, marital status, chronic diseases, life events, age, and economic factors.
METHODS: We analysed the relationship between pre-diagnostic prolactin levels and the risk of in situ breast cancer overall, and by menopausal status and use of postmenopausal hormone therapy (HT) at blood donation. Conditional logistic regression was used to assess this association in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, including 307 in situ breast cancer cases and their matched control subjects.
RESULTS: We found a significant positive association between higher circulating prolactin levels and risk of in situ breast cancer among all women [pre-and postmenopausal combined, ORlog2=1.35 (95% CI 1.04-1.76), Ptrend=0.03]. No statistically significant heterogeneity was found between prolactin levels and in situ cancer risk by menopausal status (Phet=0.98) or baseline HT use (Phet=0.20), although the observed association was more pronounced among postmenopausal women using HT compared to non-users (Ptrend=0.06 vs Ptrend=0.35). In subgroup analyses, the observed positive association was strongest in women diagnosed with in situ breast tumors<4 years compared to ≥4 years after blood donation (Ptrend=0.01 vs Ptrend=0.63; Phet=0.04) and among nulliparous women compared to parous women (Ptrend=0.03 vs Ptrend=0.15; Phet=0.07).
CONCLUSIONS: Our data extends prior research linking prolactin and invasive breast cancer to the outcome of in situ breast tumours and shows that higher circulating prolactin is associated with increased risk of in situ breast cancer.
METHODS: PubMed, EMBASE, Medline, Cochrane Library, CINAHL, PEDro, and Airiti Library were searched from inception until May 5, 2023. Randomized controlled trials that examined exercise, vitamin D and protein supplementation effects on muscle mass, strength, and physical function. Quality assessment used the Cochrane risk of bias tool, and analysis employed Comprehensive Meta-Analysis version 2.0.
RESULTS: A total of 27 randomized controlled trials, involving 1,989 participants were identified. Meta-analysis results showed exercise improved lean body mass (SMD = 0.232, 95% CI: 0.097, 0.366), handgrip strength (SMD = 0.901, 95% CI: 0.362, 1.441), knee extension strength (SMD = 0.698, 95% CI: 0.384, 1.013). Resistance training had a small effect on lean body mass, longer exercise duration (> 12 weeks) and higher frequency (60-90 min, 3 sessions/week) showed small to moderate effects on lean body mass. Vitamin D supplementation improved handgrip strength (SMD = 0.303, 95% CI: 0.130, 0.476), but not knee extension strength. There was insufficient data to assess the impact of protein supplementation on muscle strength.
CONCLUSIONS: Exercise effectively improves muscle mass, and strength in menopausal women. Resistance training with 3 sessions per week, lasting 20-90 min for at least 6 weeks, is most effective. Vitamin D supplementation enhances small muscle group strength. Further trials are needed to assess the effects of vitamin D and protein supplementation on sarcopenia prevention.
REGISTRATION NUMBER: This review was registered on PROSPERO CRD42022329273.
METHODS: A face-to-face interview using a validated questionnaire was conducted with 324 Sarawakian women aged 40-65 to determine the mean age of menopause and perceptions and experiences of menopause among these women.
RESULTS: The mean age ± standard deviation of the women was 51.37 ± 5.91 years. Ninety (27.8%) participants were premenopausal, 124 (38.5%) perimenopausal and 110 (33.7%) postmenopausal. The majority of these women (228; 70.4%) were local indigenous inhabitants of Sarawak. The findings show that 22.5% of the participants agreed that problems during menopause are a natural process. While 21.9% of the participants suggested that menopause should be treated medically, 32.3% argued that natural approaches for menopause symptoms are better than hormonal treatments. Seventy-five per cent of the women agreed that the absence of menses after menopause is a relief; meanwhile, 61.2% stated that menopause causes unpleasant symptoms. Notably, 51.7% were not sure whether women become less sexually attractive after menopause, and 51.1% were uncertain as to whether they feel less of a woman following menopause. Finally, 81.7% of participants were unsure if sexual activity is more enjoyable after menopause, and 71.9% were uncertain whether changes in life during menopause are more stressful. Among the different menopausal stages, the premenopausal group of women were noted to have more positive perceptions of menopause compared to the peri- and postmenopausal women. The study also observed that women with a better educational background generally had more positive perceptions of menopause.
CONCLUSIONS: The women's perceptions of menopause in this study were found to correspond to those in other studies on Asian women. Women with higher levels of education and premenopausal women comparatively expressed more positive opinions regarding menopause. Lastly, most of the women noted that menopausal symptoms are unpleasant, but that the absence of menses after menopause is a relief.