Endogenous Sex Hormones and Incident Cardiovascular Disease in Postmenopausal Women: MESA

This MESA (Multi-Ethnic Study of Atherosclerosis) prospective cohort study followed 2,834 postmenopausal women with baseline sex hormone measurements — total testosterone, free testosterone, estradiol, DHEA, and SHBG — to assess their associations with incident cardiovascular disease, coronary heart disease, and heart failure over follow-up.

Higher total testosterone and a higher testosterone-to-estradiol ratio were independently associated with increased risk of CVD and CHD in postmenopausal women, after adjusting for traditional cardiovascular risk factors, medications, and menopausal characteristics. Higher estradiol was inversely associated with CHD, suggesting a protective estrogen effect in postmenopausal women. The testosterone/estradiol ratio specifically predicted heart failure, particularly heart failure with reduced ejection fraction (HFrEF).

The MESA cohort’s multi-ethnic composition (White, Black, Hispanic, Chinese-American) and careful covariate adjustment make this one of the most methodologically rigorous sex hormone–cardiovascular disease association studies available. The finding that the androgenic hormonal milieu (relative testosterone excess over estradiol) predicts cardiovascular risk adds a hormonal dimension to postmenopausal cardiovascular risk assessment not captured by standard risk factors.

The clinical implications are observational: we cannot conclude that testosterone is causal or that reducing it would lower cardiovascular risk. However, the data suggest that postmenopausal women’s cardiovascular risk profile is partially shaped by their endogenous hormonal environment, independent of conventional risk factors.

We rate the evidence strong for observational data. A well-powered MESA prospective study in 2,834 postmenopausal women demonstrating that higher testosterone and testosterone/estradiol ratio predict CVD and CHD — providing evidence for hormonal influences on cardiovascular risk in postmenopausal women beyond conventional risk factors.