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

This study suggests that postmenopausal women with a higher ratio of testosterone to estradiol are at elevated risk for cardiovascular disease (CVD), coronary heart disease, and heart failure events, even though a higher level of estradiol was found to be associated with lower risk for coronary heart disease.

The final sample study size was produced from the MESA (Multi-Ethnic Study of Atherosclerosis) with testosterone, estradiol, dehydroepiandrosterone, and sex hormone binding globulin (SHBG) levels measured at baseline (2000 to 2002). This was hoped to overcome previous study size limitations.

While the study investigators conclude that:

sex hormone levels, especially higher total testosterone versus estrogen after menopause, may contribute to women's increased CVD risk later in life. However, in the absence of supportive interventional studies, the best strategy to modify sex hormone levels to affect CVD risk is still uncertain. Nonetheless, a more androgenic sex hormone profile may identify a woman at higher risk for CVD who may benefit from other risk-reducing strategies. 

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

The authors 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

The authors studied 2,834 post-menopausal women participating in the MESA (Multi-Ethnic Study of Atherosclerosis) with testosterone, estradiol, dehydroepiandrosterone, and sex hormone binding globulin (SHBG) levels measured at baseline (2000 to 2002). They 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 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 ratio (95% confidence interval [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 (95% CI: 1.01 to 1.29), 1.20 (95% CI: 1.03 to 1.40), 1.09 (95% CI: 0.90 to 1.34); estradiol: 0.94 (95% CI: 0.80 to 1.11), 0.77 (95% CI: 0.63 to 0.95), 0.78 (95% CI: 0.60 to 1.02); and testosterone/estradiol ratio: 1.19 (95% CI: 1.02 to 1.40), 1.45 (95% CI: 1.19 to 1.78), 1.31 (95% CI: 1.01 to 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, whereas higher estradiol levels were associated with a lower CHD risk. Sex hormone levels after menopause are associated with women’s increased CVD risk later in life.

Reference

Di Zhao, Eliseo Guallar, Pamela Ouyang, Vinita Subramanya, Dhananjay Vaidya, Chiadi E. Ndumele, Joao A. Lima, Matthew A. Allison, Sanjiv J. Shah, Alain G. Bertoni, Matthew J. Budoff, Wendy S. Post and Erin D. Michos. Endogenous Sex Hormones and Incident Cardiovascular Disease in Post-Menopausal Women. J Am Coll Cardiol. Volume 71, Issue 22, June 2018 DOI: 10.1016/j.jacc.2018.01.083

Content updated 20 June 2018