Next Gen Innovators
Next Gen Innovators
May 29, 2018
2 min read

Elevated testosterone to estradiol ratios increase CVD risk in postmenopausal women

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Erin D. Michos
Erin D. Michos

Postmenopausal women who had higher testosterone to estradiol ratios had an increased risk for incident CVD, CHD and HF events, according to a study published in the Journal of the American College of Cardiology.

Elevated levels of testosterone increased the incidence of CHD and CVD, and elevated estradiol levels decreased the risk for CHD, according to the study.

“Although sex hormone levels may be linked to future cardiovascular events, it is unclear what the best intervention is to modify sex hormone levels for risk reduction,” Erin D. Michos, MD, MHS, associate professor of medicine at Johns Hopkins University School of Medicine and a Cardiology Today Next Gen Innovator, said in a press release. “However, a sex hormone profile higher in male hormones may identify a woman at higher risk for cardiovascular disease who may benefit from other risk reduction strategies.”

MESA data

Di Zhao, PhD, research associate in the department of epidemiology at Johns Hopkins Bloomberg School of Public Health, and colleagues analyzed data from 2,834 women (mean age, 65 years) from the MESA study who were postmenopausal and free from CVD at baseline.

Baseline evaluations included sex hormone concentrations, lifestyle factors, demographic characteristics, menopausal status and medication use.

Follow-up was conducted over the phone every 9 to 12 months for CV outpatient diagnoses and procedures, hospital admissions and deaths. Endpoints of interest were the development of CHD, CVD or HF. Researchers identified outcome events through 2013.

During a median follow-up of 12.1 years, 171 women developed CHD, 283 were diagnosed with CVD and 103 women had HF.

A 1-standard-deviation increase in log-transformed total testosterone was associated with increased risk for CVD (HR = 1.14; 95% CI, 1.01-1.29) and CHD (HR = 1.2; 95% CI, 1.03-1.4). The association was not statistically significant for HF (HR = 1.09; 95% CI, 0.9-1.34).

An estradiol level increase of 1 standard deviation was associated with lower risk for CHD (HR = 0.77; 95% CI, 0.63-0.97) and HF (HR = 0.78; 95% CI, 0.6-1.02), but not overall CVD events (HR = 0.94; 95% CI, 0.8-1.11).

Increased risk for CVD

A 1-standard-deviation increase in the log-transformed testosterone to estradiol ratio was linked to an increased risk for CVD (HR = 1.19; 95% CI, 1.02-1.4), CHD (HR = 1.45; 95% CI, 1.19-1.78) and HF (HR = 1.31; 95% CI, 1.01-1.7).


Sex hormone-binding globulin and dehydroepiandrosterone levels were not associated with CHD, CVD, hard CVD, all HF, hard CHD or ischemic stroke.

“Several biological mechanisms may underlie the association between endogenous sex hormones and CVD and its risk factors in women,” Zhao and colleagues wrote. “Estrogens can promote vasodilation through increasing plasma concentrations of endothelium-derived relaxing factor nitric oxide and can inhibit the renin angiotensin system by reducing transcription of angiotensin-converting enzyme. In addition to its favorable effects on lipids, estrogens can also reduce blood pressure through increasing endothelial vasodilator function and modulating autonomic function. Additionally, estrogen is thought to regulate specific inflammatory markers and cytokines. By contrast, testosterone can induce vasoconstriction and increased platelet aggregation through upregulation of thromboxane.”

In a related editorial, Virginia M. Miller, PhD, professor of physiology and surgery and director of the Women’s Health Research Center at Mayo Clinic, and Rekha Mankad, MD, echocardiographer and cardiologist at Mayo Clinic, wrote: “Defining cardiovascular risk for women should account for individualized profiles of genetic variants in enzymes associated with steroids metabolism, uptake, and receptors in conjunction with risk for specific cardiovascular pathologies. This approach is precision medicine.” – by Darlene Dobkowski

Disclosures: This study was partly supported by the American Heart Association Go Red for Women Strategic Focused Research Network. Michos reports she received an honorarium from Siemens Diagnostics. Zhao, Miller and Mankad report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

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