PDF(Pubmed)
Abstract：
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.
摘要：
更年期标志着生命生殖阶段的结束。根据流行病学研究,自然绝经年龄异常（ANM）被认为是导致许多不良后果的原因，比如骨质疏松症，心血管疾病,和癌症。然而,这些关联的因果关系尚不清楚.一种称为孟德尔随机化（MR）的强大流行病学方法可用于阐明ANM与其他疾病或性状之间的因果关系。本综述描述了包括ANM作为暴露的MR研究，结果和调解人。对ANM的MR分析结果表明，较高的体重指数，教育水平差,初潮时年龄较早，第一次活产时的早期年龄，在第一次性交的早期，自身免疫性甲状腺疾病似乎与早期ANM病因有关。晚期ANM的病因似乎受到较高的游离甲状腺素4和亚甲基四氢叶酸还原酶基因突变的影响。此外，已发现早期ANM与骨质疏松症风险增加有因果关系。骨折,2型糖尿病,糖化血红蛋白,和胰岛素抵抗水平的稳态模型。此外,已发现晚期ANM与收缩压升高有因果关系，患乳腺癌的风险更高，子宫内膜癌,子宫内膜样卵巢癌，肺癌,长寿，气流阻塞,并降低患帕金森病的风险。ANM也是由出生体重和儿童体型引起的乳腺癌的介质。然而,由于使用的工具变量不同，一些研究结果不一致。对于MR之间或MR与其他类型的流行病学研究之间存在差异的性状，需要具有更有效的遗传变异的未来研究。
