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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

S R Mishra 1H-F Chung 1M Waller 1G D Mishra 1

BJOG. 2021 Apr;128(5):809-821. doi: 10.1111/1471-0528.16524. .

Abstract

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.