Meta‐analysis: Early Age at Natural Menopause and Risk for All‐Cause and Cardiovascular Mortality
Luyao Huan, Xiangling Deng, Mengyang He, Shunhong Chen, Wenquan Niu
Abstract
Aims . The aim of this meta‐analysis was to comprehensively evaluate the association of early age at natural menopause with the risk for all‐cause and cardiovascular mortality. Methods . Literature retrieval was done on August 4, 2020. Article selection and data extraction were completed independently and in duplicate. Early age at natural menopause was grouped into premature menopause (<40 years), early menopause (40‐44 years), and relatively early menopause (45‐49 years). Effect‐size estimates are summarized as hazard ratio (HR) or relative risk (RR) with 95% confidence interval (CI). Results . Sixteen articles involving 321,233 women were meta‐analyzed. Overall analyses revealed a statistically significant association of early age at natural menopause with all‐cause mortality risk (HR adjusted = 1.08, 95% CI: 1.03 to 1.14, P = 0.002; RR adjusted = 1.05, 95% CI 1.01 to 1.08, P = 0.005), but not with cardiovascular mortality risk. In dose‐response analyses, the association with all‐cause mortality was significant for premature menopause with (HR adjusted = 1.10; 95% CI: 1.01 to 1.21; P = 0.034) and without (RR adjusted = 1.34; 95% CI: 1.08 to 1.66; P = 0.007) considering follow‐up intervals. As for cardiovascular mortality, marginal significance was noted for premature menopause after considering follow‐up intervals (HR = 1.09; 95% CI: 1.00‐1.19; P = 0.045). Subgroup analyses indicated that gender, country, and follow‐up periods were possible causes of heterogeneity. There was an overall low probability of publication bias. Conclusions . Our findings indicate that premature menopause is a promising independent risk factor for both all‐cause and cardiovascular mortality.