Sex Hormones, CVD, and Heart Failure in Women

Study Questions:

Are sex hormone levels associated with incident cardiovascular disease (CVD), coronary heart disease (CHD), and heart failure (HF) in women?

Methods:

Post-menopausal women participating in the MESA (Multi-Ethnic Study of Atherosclerosis) were studied. Testosterone, estradiol, dehydroepiandrosterone, and sex hormone binding globulin (SHBG) levels were measured at baseline and associated with outcomes using multivariable adjusted Cox hazard models.

Results:

The mean age of the 2,834 women was 65 years ± 9 years. The hazard ratio (95% confidence interval [CI]) associated with 1 standard deviation greater log-transformed sex hormone level for the respective outcomes of CVD, CHD, and HF were as follows: total testosterone: 1.14 (95% CI, 1.01-1.29), 1.20 (95% CI, 1.03-1.40), 1.09 (95% CI, 0.90-1.34); estradiol: 0.94 (95% CI, 0.80-1.11), 0.77 (95% CI, 0.63-0.95), 0.78 (95% CI, 0.60-1.02); and testosterone/estradiol ratio: 1.19 (95% CI, 1.02-1.40), 1.45 (95% CI, 1.19-1.78), 1.31 (95% CI, 1.01-.70). Levels of SHBG and dehydroepiandrosterone were not associated with CVD, CHD, and HF.

Conclusions:

Sex hormone levels in post-menopausal women were associated with increased CVD risk. Higher testosterone/estradiol ratio was associated with CVD, CHD, and HF; testosterone was associated with increased CVD and CHD; and estradiol was associated with lower CHD risk.

Perspective:

Prior studies of sex hormone levels and CVD have yielded contradictory results. In this study, with 12 years of follow-up and adjustment for various risk factors, a more androgenic hormone profile among post-menopausal women was associated with increased risk of CVD, CHD, and HF. This finding seems plausible given our understanding of the CV effects of sex hormones. Estrogen can induce vasodilation, inhibit the renin-angiotensin system, and regulate inflammatory markers and cytokines. Estrogen is associated with lower blood pressure and more favorable lipid profile. Testosterone can induce vasoconstriction, increase platelet aggregation, and increase visceral fat accumulation. Testosterone is associated with cardiometabolic risk factors including blood pressure, dyslipidemia, higher weight, C-reactive protein levels, and insulin resistance. Unfortunately, how to use this information is unclear. Prior studies of exogenous hormone therapy in post-menopausal women were not beneficial for primary prevention of CVD. Measurement of endogenous hormone levels could be useful as a tool for risk stratification, but further studies are needed.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Lipid Metabolism, Acute Heart Failure

Keywords: Cardiovascular Diseases, Coronary Disease, Dehydroepiandrosterone, Estradiol, Estrogens, Gonadal Steroid Hormones, Heart Failure, Metabolic Syndrome X, Postmenopause, Primary Prevention, Risk Factors, Sex Hormone-Binding Globulin, Testosterone


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