Global prevalence of early menopause and its association with cardiovascular outcomes: the PURE study

Abstract Background Female-specific risk factors for cardiovascular disease (CVD) are emerging as important indictors to flag high-risk women and one of those factors is early onset menopause. There is emerging evidence that women with premature menopause and early menopause have a substantially increased risk of CVD. Purpose The PURE study provides a unique opportunity to use the same cohort selection and same menopause identifying questions to assess the association of CVD outcomes and menopause age across socio-economic and geographical regions. Methods Women in the PURE study from 27 high, middle, and low-income countries were asked: "Do you still have periods?" and "How many years since you stopped menstruating?". Categories of menopause were "not yet reached menopause", premature menopause (<40years), early menopause (40≤age<45years) and common menopause (age≥45years). Multi-level Cox proportional hazards models of time to cardiovascular event were used, adjusting for age and INTERHEART Risk Score as fixed effects, and accounting for nested clustering at country and community levels with random effects. Results The cohort of 113,315 women from 26 countries had mean age of 51.0 years with 43.2% from rural areas and average follow-up time of 12.3 years. Women from the lower socio-economic regions reached menopause significantly earlier. By the ages of 47.5, 50.1, 50.2 and 50.5 years, 50% of women in the lower, lower-middle, upper-middle and upper-class socio-economic region, respectively, had reached menopause. Half of the African region participants reached menopause by age 48.3 years and in Europe this occurred at age 50.9 years. The hazard ratio (HR) for all-cause death for women with premature menopause, early menopause and common menopause was 1.3 (95% CI: 1.2,1.5), 1.3 (CI: 1.2,1.4) and 1.1 (CI: 1.0,1.2), respectively, compared to no menopause. Similarly, for fatal CVD the HRs were 1.5 (CI: 1.3,1.8), 1.4 (CI: 1.2,1.6), 1.2 (CI: 1.0,1.4), respectively, and for severe CVD the HRs were 1.4 (CI: 1.2, 1.6), 1.3 (CI: 1.2, 1.4), 1.1 (CI: 1.0, 1.2) for women with premature menopause, early menopause and common menopause, respectively, compared to no menopause. For all cause death the association with menopause age varied by socio-economic status (p<0.001) with the strongest association occurring within lower socio-economic countries with HR of 6.5 (CI:3.5, 12.1) for premature menopause, 6.6 (CI: 3.5,12.3) for early menopause, 5.7 (CI: 3.0, 10.5) for common menopause and for no menopause 4.8 (CI: 2.6, 8.9) compared to high income countries. Conclusion Early menopause was found to be more common in lower socio-economic countries and differed by region with African women having the earliest menopause age. This study provided further evidence of the association of death and CVD with premature and early menopause especially in lower socio-economic regions.

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