Age at Natural Menopause and Risk of Ischemic Stroke: The Framingham Heart Study

Abstract

Background and Purpose— Women have increased lifetime stroke risk and more disabling strokes compared with men. Insights into the association between menopause and stroke could lead to new prevention strategies for women. The objective of this study was to examine the association of age at natural menopause with ischemic stroke risk in the Framingham Heart Study. Methods— Participants included women who survived stroke-free until age 60, experienced natural menopause, did not use estrogen before menopause, and who had complete data (n=1430). Participants were followed until first ischemic stroke, death, or end of follow-up (2006). Age at natural menopause was self-reported. Cox proportional hazards models were used to examine the association between age at natural menopause (<42, 42 to 54, ≥55) and ischemic stroke risk adjusted for age, systolic blood pressure, atrial fibrillation, diabetes, current smoking, cardiovascular disease and estrogen use. Results— There were 234 ischemic strokes identified. Average age at menopause was 49 years (SD=4). Women with menopause at ages 42 to 54 (hazard ratio=0.50; 95% CI: 0.29 to 0.89) and at ages ≥55 (hazard ratio=0.31; 95% CI: 0.13 to 0.76) had lower stroke risk compared with those with menopause <42 years adjusted for covariates. Women with menopause before age 42 had twice the stroke risk compared to all other women (hazard ratio=2.03; 95% CI: 1.16 to 3.56). Conclusion— In this prospective study, age at natural menopause before age 42 was associated with increased ischemic stroke risk. Future stroke studies with measures of endogenous hormones are needed to inform the underlying mechanisms so that novel prevention strategies for midlife women can be considered.