From the Journals

High testosterone in postmenopausal women may add CVD risk


Key clinical point: Levels of testosterone and estradiol after menopause correlated with increased cardiovascular risks later in life.

Major finding: A higher total testosterone to estradiol ratio was independently associated with increased risk of incident cardiovascular disease (hazard ratio, 1.19; 95% confidence interval, 1.02-1.40).

Study details: Analysis including 2,834 postmenopausal women in the MESA (Multi-Ethnic Study of Atherosclerosis) study.

Disclosures: Partial funding came from the American Heart Association’s Go Red for Women Research Network. Study authors reported disclosures related to Cordex Systems, Siemens Diagnostics, and other entities.

Source: Zhao D et al. J Am Coll Cardiol. 2018 Jun 5; 71:2555-66.

View on the News

New perspective on sex steroids and CV risk

This study offers new insights into the relationships between endogenous hormones and how they influence cardiovascular event risk, according to Virginia M. Miller, PhD, and Rekha Mankad, MD.

Previous observational studies have established that decreases in endogenous estrogen led to increases in cardiovascular event risk and incidence, Dr. Miller and Dr. Mankad said in an editorial referencing the study.

What’s less clear is the role of testosterone in cardiovascular risk and event incidence, both by itself and in relation to other endogenous hormones.

“Few studies have gone beyond singular associations of hormone levels with cardiovascular events,” the editorial authors wrote in the Journal of the American College of Cardiology.

The study by Zhao and her colleagues is unique in part because their analysis considers the ratio of testosterone to estradiol. In particular, they found that a higher testosterone to estradiol level was associated with a higher incidence of cardiovascular events overall and of coronary heart disease.

What was unexpected, according to Dr. Miller and Dr. Mankad, was a U-shaped association with incident heart failure. In subgroup analysis, investigators found a positive association between testosterone to estradiol ratio and heart failure with reduced ejection fraction but not with heart failure with preserved ejection fraction.

“By addressing a set of defined incident events, this study provides new information needed to develop mechanistic hypotheses of causal relationships of hormones with specific aspects of cardiac function,” the editorial authors wrote.

Dr. Miller and Dr. Mankad are both with the women’s health research center and department of cardiovascular disease at the Women’s Heart Clinic at the Mayo Clinic, Rochester, Minn. These comments are derived from their editorial in the Journal of the American College of Cardiology. Dr. Mankad had no disclosures, while Dr. Miller reported support from a National Institutes of Health grant.



In postmenopausal women, a higher level of testosterone in comparison to estrogen may increase the cardiovascular disease risk later in life, results of a recent analysis suggest.

A higher ratio of testosterone to estradiol was associated with the development of cardiovascular disease, coronary heart disease, and heart failure in postmenopausal women, according to results from an analysis based on 2,834 postmenopausal women in MESA (Multi-Ethnic Study of Atherosclerosis).

In addition, total testosterone levels were associated with increased cardiovascular disease and coronary heart disease, while estradiol is associated with a reduced risk of coronary heart disease and heart failure with reduced ejection fraction, investigators reported in the Journal of the American College of Cardiology.

Without any interventional studies as guidance, it’s not clear what the “best strategy” would be to modify sex hormone levels and reduce cardiovascular disease risk, wrote investigator Di Zhao, PhD, of the department of epidemiology at Johns Hopkins University Bloomberg School of Public Health, Baltimore, and her study coauthors.

“Nonetheless, a more androgenic sex hormone profile may identify a woman at higher risk for cardiovascular disease who may benefit from other risk-reducing strategies,” Dr. Zhao and her colleagues wrote in their report.

The postmenopausal women included in this analysis all had baseline measurements of testosterone, estradiol, dehydroepiandrosterone, and sex hormone–binding globulin levels between 2000 and 2002, according to the report.

After more than 12 years of follow-up, investigators found that a higher total testosterone to estradiol ratio was independently associated with an increased risk of incident cardiovascular disease (hazard ratio, 1.19; 95% confidence interval, 1.02-1.40), coronary heart disease (HR, 1.45; 95% CI, 1.19-1.78), and heart failure (HR, 1.31; 95% CI, 1.01-1.70).

Next Article: