Duration of estrogen exposure during reproductive years, age at menarche and age at menopause, and risk of cardiovascular disease events, all-cause and cardiovascular mortality: a systematic review and meta-analysis

Background Little is known about the estrogen exposure measurement and mutual effect of age at menarche and age at menopause in the risk of cardiovascular disease (CVD) events. Objectives To evaluate estrogen exposure measurement and describe mutual effect of age at menarche and age at menopause in the risk of CVD events. Search strategy Systematic review of literature in PubMed, Embase and Web of Science for studies published up to 28 June 2020. Selection criteria Observational studies related to estrogen exposure measurement, including mutual effect of age at menarche and age at menopause and risk of CVD events. Data collection and analysis Synthesis of evidence was conducted by reviewing individual estimates, followed by meta-analysis. The study received no external funding. Main results A total of 75 studies were included in synthesis of evidence, of which 17 studies were included in meta-analysis. Reproductive lifespan (age at menopause - age at menarche), endogenous estrogen exposure and total estrogen exposure were used for estrogen exposure measurement. Reproductive lifespan was by far the most commonly used method for estrogen exposure measurement. A shorter reproductive lifespan was associated with a higher risk of CVD events; the pooled relative risk (95% CI) was 1.31 (1.25-1.36) for stroke events. Robust epidemiological studies with measurement of estrogen exposure and associated health risk would strengthen the evidence. Conclusions Reproductive lifespan was the most commonly used method for estrogen exposure measurement in epidemiological studies. A shorter reproductive lifespan was associated with a higher risk of CVD events, particularly stroke. Tweetable abstract A systematic review and meta-analysis found that women with a shorter reproductive lifespan have a higher risk of stroke events.