Background and Aim: Little is known about whether early menopause in Chinese ethnicity is associated with acute myocardial infarction (AMI). We aimed to determine whether self-reported early menopause (either surgical or natural menopause at an age <50 year) was associated with first AMI in Chinese women. Methods: The study population was from the INTERHEART China Study, part of the INTERHEART global study. INTERHEART global study was a standardized case-control study that was designed to evaluate the risk factors for first AMI among 52 countries. Data for demographic factors, education, income, and cardiovascular risk factors were obtained by structured questionnaires. A standard set of questions that inquired about menstrual history was included in the interview. Results: Of the 1,771 Chinese women, 1,563 (88.3%) reported either natural or surgical menopause. In univariate logistic regression model, women with early menopause had higher risk of AMI (odds ratio [OR]: 1.51; 95% confidence interval [CI]: 1.23-1.87). After controlling for age, birth control measures, type of menopause, and other traditional risk factors (including waist/hip ratio, lifestyle factors, history of hypertension and diabetes, psychosocial factors, and apolipoprotein B [ApoB]/A1 [ApoA1]), the risk for AMI remained (OR: 1.36; 95% CI: 1.03-1.79). The population attributable risk for AMI in women with early menopause at <50 years was 10.1% (95% CI: 4.0-20.0) compared with women who had menopause at ≥50 years. Conclusion: Early menopause is associated with increased risk of AMI in Chinese women, independent of other traditional coronary heart disease risk factors.

Menopause marks the end of the reproductive phase of life. Based on epidemiological studies, abnormal age at natural menopause (ANM) is thought to contribute to a number of adverse outcomes, such as osteoporosis, cardiovascular disease, and cancer. However, the causality of these associations remains unclear. A powerful epidemiological method known as Mendelian randomization (MR) can be used to clarify the causality between ANM and other diseases or traits. The present review describes MR studies that included ANM as an exposure, outcome and mediator. The findings of MR analyses on ANM have revealed that higher body mass index, poor educational level, early age at menarche, early age at first live birth, early age at first sexual intercourse, and autoimmune thyroid disease appear to be involved in early ANM etiology. The etiology of late ANM appears to be influenced by higher free thyroxine 4 and methylene tetrahydrofolate reductase gene mutations. Furthermore, early ANM has been found to be causally associated with an increased risk of osteoporosis, fracture, type 2 diabetes mellitus, glycosylated hemoglobin, and the homeostasis model of insulin resistance level. In addition, late ANM has been found to be causally associated with an increased systolic blood pressure, higher risk of breast cancer, endometrial cancer, endometrioid ovarian carcinoma, lung cancer, longevity, airflow obstruction, and lower risk of Parkinson\'s disease. ANM is also a mediator for breast cancer caused by birth weight and childhood body size. However, due to the different instrumental variables used, some results of studies are inconsistent. Future studies with more valid genetic variants are needed for traits with discrepancies between MRs or between MR and other types of epidemiological studies.

OBJECTIVE: Menopause is linked to a higher risk of cardiovascular disease. However, it is unclear whether premature menopause (defined as menopause before the age of 40 years) or early menopause (defined as menopause before the age of 45 years) is associated with an increased risk of heart failure or atrial fibrillation. This study aimed to examine the most reliable evidence on the relationship between early menopause and the risk of heart failure and atrial fibrillation.
METHODS: A comprehensive literature search was performed in three online databases, Embase, Web of Science, and PubMed, from database establishment to April 1, 2023. The results were presented as hazard ratios with 95 % confidence intervals. The I2 statistic was employed to assess heterogeneity, and the Egger\'s test was used to determine publication bias.
RESULTS: Nine cohort studies were included in the analysis, with a total of 6,255,783 postmenopausal women. Women with premature and early menopause had an increased risk of heart failure (HR: 1.39, 95 % CI: 1.31-1.47; HR: 1.23, 95 % CI: 1.10-1.37, respectively) and atrial fibrillation (HR: 1.15, 95 % CI: 1.01-1.31; HR: 1.08, 95 % CI: 1.04-1.13, respectively) when compared with women who had undergone menopause after the age of 45 years. Subgroup analysis showed that, compared with early menopause, premature menopause has a stronger association with an increased risk of heart failure and atrial fibrillation.
CONCLUSIONS: Women who undergo premature menopause or early menopause have a higher risk of heart failure and atrial fibrillation compared with women who undergo menopause in the normal age range. These reproductive factors need to be considered for measures that might reduce the risk of heart failure and atrial fibrillation.

UNASSIGNED: Transition into menopause is associated with an increased risk of cardiovascular disease (CVD). However, it is unclear whether the association exists between premature menopause (defined as age at menopause 40 years) or early menopause (defined as age at menopause 40-45 years) and CVD or cardiovascular risk factors. The aim of this review was to comprehensively evaluate and meta-analyze the most reliable evidence about the relationship between menopausal age and the risk of long-term cardiometabolic disease.
UNASSIGNED: A comprehensive literature search of the PubMed, Web of Science, and Embase databases from inception to October 1, 2022, for titles and abstracts with a restriction to English language papers led to the discovery of the studies. Data are expressed as the Hazard Ratio (HR) with 95% confidence intervals (CI). The degree of heterogeneity was measured using the I-square (I 2) index.
UNASSIGNED: 921,517 participants from 20 cohort studies published between 1998 and 2022 were considered. Compared to women with menopause at age >45 years, women with premature menopause (PM) or early menopause (EM) had a higher risks of type 2 diabetes (RR: 1.32, 95% CI: 1.08-1.62; RR: 1.11, 95% CI: 0.91-1.36, respectively), hyperlipidemia (RR: 1.21, 95% CI: 1.05-1.39; RR: 1.17, 95% CI: 1.02-1.33, respectively), coronary heart disease (RR: 1.52, 95% CI: 1.22-1.91; RR: 1.19, 95% CI: 1.07-1.32, respectively), stroke (RR: 1.27, 95% CI: 1.02-1.58; RR: 1.13, 95% CI: 0.97-1.32, respectively) and total cardiovascular event (RR: 1.36, 95% CI: 1.16-1.60; RR: 1.14, 95% CI: 0.97-1.35, respectively). No difference was found for hypertension in PM or EM women (RR: 0.98, 95% CI: 0.89-1.07; RR: 0.97, 95% CI: 0.91-1.04, respectively). Additionally, we also found that PM women, but not EM women, were linked with an increased risk of ischemic and hemorrhagic stroke. However, this is not in line with the conclusion that both PM and EM had a higher risk of total stroke.
UNASSIGNED: Women with PM or EM have a higher risk of developing long-term CVD, compared to women with menopause at age >45 years. Therefore, we recommend early lifestyle interventions (e.g., maintaining a healthy lifestyle) and medical treatments (e.g., timely initiation of menopausal hormone therapy) to decrease the risk of cardiometabolic disease in early or premature menopausal women.
UNASSIGNED: PROSPERO, identifier CRD42022378750.

OBJECTIVE: The TMEM150B gene, which promotes cell survival under stress conditions by modulating autophagy, is closely associated with age at natural menopause, early menopause and premature ovarian insufficiency (POI) in European women. However, whether gene variants of TMEM150B contribute to the pathogenesis of POI needs to be determined.
METHODS: A case-control genetic study in 408 Han Chinese women with non-syndromic POI, in which all exons and exon-intron boundaries of the TMEM150B gene were screened by Sanger sequencing; the results were analysed by statistics and bioinformatics.
RESULTS: Two novel variants located in the 3\' untranslated region of the TMEM150B gene were identified, but bioinformation analyses showed that neither was potentially disease-causing. Six known single-nucleotide polymorphisms (SNP) were found, and they were not potentially causative for POI. The intronic SNP rs11668344 was also detected in the POI patients; no significant differences were found in either genotype or allele frequencies compared with the control population.
CONCLUSIONS: The results suggest that the perturbations in the TMEM150B gene are not a common explanation for POI in Chinese women. The role of autophagy in the pathogenic mechanism of POI needs further exploration.

OBJECTIVE: To observe the effectiveness and safety of menopause-related hormone therapy (MHT) to prevent bone loss in Chinese women during the menopausal transition and early menopause, as well as to evaluate the effects of 5-year MHT on overall health to add Level I evidence for the prevention of osteoporosis using MHT.
METHODS: This clinical study was a prospective, double-blind, randomized, parallel placebo-controlled study. Chinese women in the menopausal transition and early menopause were randomly allocated to the MHT group or the placebo group. All subjects received a 5-year intervention. The effectiveness of MHT for bone mineral density (BMD) and bone metabolism and the safety of MHT in relation to glycolipid metabolism, breast cancer, and cardiovascular disease were studied.
RESULTS: In the MHT group, women in both transition and early menopause showed a significant increase in lumbar and femoral neck BMD after the 1st year of therapy; BMD tended to decrease in the 3rd year but ultimately was sustained at stable levels that were near the baseline levels. In the placebo group, BMD decreased at both sites. Metabolism indexes and breast ultrasound examination findings did not differ significantly between the MHT and placebo groups. Three cases of breast cancer and three cases of cardiovascular disease were diagnosed during follow-up. One breast cancer case and two cardiovascular disease cases occurred in the MHT group.
CONCLUSIONS: Five-year sequential therapy with estrogen and progesterone can increase or maintain the BMD of women in their menopausal transition and early menopause. This regimen had no negative effect on glycolipid metabolism and did not increase the risk of breast cancer or cardiovascular events.

Insights into common genetic susceptibility between primary ovarian insufficiency (POI) and natural or early menopause have delivered an innovative way of assessing the genetic mechanisms involved in POI. PRIM1 plays a crucial role in DNA replication by synthesizing RNA primers for Okazaki fragments. It is closely associated with age at natural menopause, early menopause and POI in European women. In this study, we aimed to investigate whether mutations in PRIM1 contribute to POI in Chinese women. All exons and exon-intron boundaries of PRIM1 gene were sequenced in 192 Han Chinese women with non-syndromic POI. No plausible mutations were identified. The results suggest that the perturbations in PRIM1 gene are not a common explanation for POI in Chinese women.

Early menopause has been found to be associated with higher risk of cardiovascular disease. Our objective was to investigate the impact of early menopause on clinical outcomes for women undergoing percutaneous coronary intervention (PCI). We observed female patients with coronary artery disease (CAD) undergoing PCI and found that women with early menopause (≤46 years old) were more likely to have CAD risk factors and more severe coronary lesions. During the 18-month follow-up, early menopause was associated with similar risk of death and myocardial infarction but higher risk of target lesion revascularization (TLR; 7.8% vs 5.3%, P = .003) and major adverse cardiovascular events (MACEs; 11.3% vs 9.0%, P = .007). After adjustment, early menopause was an independent risk factor for 18-month MACEs (hazard ratio [HR], 1.54; 95% confidence interval [CI] 1.18-2.00) and TLR (HR 1.61; 95% CI 1.21-2.13). In conclusion, for women undergoing PCI, early menopause is associated with higher risk of MACE, which is mainly driven by risk of TLR.