American Diabetes Association
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Early Menopause and Cardiovascular Disease Risk in Women With or Without Type 2 Diabetes: A Pooled Analysis of 9,374 Postmenopausal Women

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posted on 2021-09-02, 19:12 authored by Yilin Yoshida, Zhipeng Chen, Robin L. Baudier, Marie Krousel-Wood, Amanda H. Anderson, Vivian A. Fonseca, Franck Mauvais-Jarvis

Early menopause may be associated with higher cardiovascular disease (CVD) risk. Type 2 diabetes (T2DM), coupled with early menopause, may result in even greater CVD risk in women. We examined CVD risk in women with early compared to normal-age menopause, with and without T2DM overall and by race/ethnicity.


We pooled data from the Atherosclerosis Risk in Communities Study, the Multi-Ethnic Study of Atherosclerosis, and the Jackson Heart Study. We included women with data on menopausal status, menopausal age, and T2DM, excluding pre- or peri-menopausal women, and those with prevalent CVD. Outcomes included incident coronary heart disease (CHD), stroke, heart failure (HF), and atherosclerotic cardiovascular disease (ASCVD; CHD or stroke). We estimated the risk associated with early (<45 years) compared to normal-age menopause using Cox proportional hazards models. Covariates included age, race/ethnicity, education, body mass index, blood pressure, cholesterol, smoking, alcohol consumption, antihypertensive medication, lipid-lowering medication, hormone therapy use, and pregnancy history.


We included 9,374 postmenopausal women for a median follow-up of 15 years. We observed 1,068 CHD, 659 stroke, 1,412 HF and 1,567 ASCVD events. T2DM significantly modified the effect of early menopause on CVD risk. Adjusted HRs for early menopause and the outcomes were greater in women with T2DM versus without (CHD 1.15, 1.00-1.33 vs 1.09, 1.03-1.15; stroke 1.21, 1.04-1.40 vs 1.10, 1.04-1.16; ASCVD 1.29, 1.09-1.51 vs 1.10, 1.04-1.17; HF 1.18, 1.00-1.39 vs 1.09, 1.03-1.16)). The modifying effect of T2DM on the association between early menopause and ASCVD was only statistically significant in black compared to white women.


Early menopause was associated with increased risk for CVD in postmenopausal women. T2DM may further augment the risk, particularly in black women.


This project was supported by a grant (NIH K12HD043451) from the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the Building Interdisciplinary Research Careers in Women's Health (BIRCWH) Scholar. FMJ was supported by NIH grants (DK107444 and DK074970), a U.S. Department of Veterans Affairs Merit Award (BX003725) and the Tulane Center of Excellence in Sex-Based Biology & Medicine. AHA was supported by NIH grants (R01DK104730, R01DK107566 and P20GM109036) and the Tulane University Translational Science Institute.