Endogenous Sex Hormones and Incident Cardiovascular Disease in Post-Menopausal Women

Abstract

Background Higher androgen and lower estrogen levels are associated with cardiovascular disease (CVD) risk factors in women. However, studies on sex hormones and incident CVD events in women have yielded conflicting results. Objectives We assessed the associations of sex hormone levels with incident CVD, coronary heart disease (CHD), and heart failure (HF) events among women without CVD at baseline. Methods We studied 2,834 post-menopausal women participating in MESA with testosterone, estradiol, dehydroepiandrosterone, and sex hormone binding globulin (SHBG) levels measured at baseline (2000–2002). We used Cox hazard models to evaluate associations of sex hormones with each outcome, adjusting for demographics, CVD risk factors, and hormone therapy use. Results The mean (SD) age was 64.9 (8.9) years. During 12.1 years of follow-up, 283 CVD, 171 CHD, and 103 HF incident events occurred. In multivariable-adjusted models, the Hazard Ratios (95% CI) associated with 1 SD greater log-transformed sex hormone level for the respective outcomes of CVD, CHD, and HF were as follows: Total testosterone: 1.14 (1.01–1.29), 1.20 (1.03–1.40), 1.09 (0.90–1.34); Estradiol: 0.94 (0.80–1.11), 0.77 (0.63–0.95), 0.78 (0.60–1.02); Testosterone/Estradiol ratio: 1.19 (1.02–1.40), 1.45 (1.19–1.78), 1.31 (1.01–1.70). Dehydroepiandrosterone and SHBG levels were not associated with these outcomes. Conclusions Among post-menopausal women, a higher testosterone/estradiol ratio was associated with an elevated risk for incident CVD, CHD, and HF events, higher levels of testosterone associated with increased CVD and CHD, while higher estradiol levels were associated with a lower CHD risk. Sex hormones levels after menopause are associated with women’s increased CVD risk later in life. Condensed abstract We studied 2,834 post-menopausal women in the Multi-Ethnic Study of Atherosclerosis. Higher total testosterone/estradiol ratio was independently associated with an elevated risk for incident CVD, CHD, and HF events. After >12 years of follow-up, the multivariable-adjusted Hazard Ratios (95% CI) associated with 1 SD greater log-transformed total testosterone/estradiol ratio for incident CVD, CHD and HF events were 1.19 (1.02–1.40), 1.45 (1.19–1.78), 1.31 (1.01–1.70), respectively. Sex hormones levels after menopause are associated with women’s increased CVD risk later in life.