Testosterone-estrogen ratio signals CVD risk in post-menopausal women

A higher testosterone-to-estrogen ratio could be a harbinger of future cardiovascular disease (CVD) among post-menopausal women, according to a study published May 28 in the Journal of the American College of Cardiology.

Senior author Erin D. Michos, MD, MHS, with Johns Hopkins University School of Medicine, and colleagues followed 2,834 post-menopausal women from the Multi-Ethnic Study of Atherosclerosis, which enrolled participants who were free of CVD at baseline. They measured sex hormone concentrations with fasting serum samples and checked in with patients or family members every nine to 12 months to determine whether they had died, been admitted to the hospital or had any outpatient cardiovascular diagnoses or procedures.

Over an average follow-up of 12.1 years, the researchers found:

  • Each standard-deviation (SD) increase in total testosterone levels was associated with risk increases of 14 percent for CVD, 20 percent for coronary heart disease and 9 percent for heart failure.
  • Each SD increase in estradiol (an estrogen steroid hormone) was associated with risk reductions of 6 percent for CVD, 23 percent for coronary heart disease and 22 percent for heart failure.
  • Each SD increase in testosterone-estradiol ratio was linked to risk increases of 19 percent for CVD, 45 percent for coronary heart disease and 31 percent for heart failure.

"A woman's sex hormone levels and ratios of them isn't something that physicians regularly check," Michos said in a press release. "Because an imbalance in the proportion of testosterone to estrogen may affect heart disease risk, physicians may want to think about adding hormone tests to the toolbox of screenable risk factors, like blood pressure or cholesterol, to identify women who may be at higher risk of heart or vascular disease. But this needs further study."

Michos said it is still unclear what treatments could shift these hormone balances and result in meaningful risk reduction. For now, knowing a patient may be in danger of CVD could allow clinicians to propose other risk-reduction strategies, she said.

In a related editorial, Virginia M. Miller, PhD, and Rekha Mankad, MD—both with the Mayo Clinic Women’s Health Research Center in Rochester, Minnesota—proposed adding genetic testing to the equation to further personalize care.

“Individual variability in hormone profiles among women may reflect genetic variation in one more of the enzymes involved in steroid metabolism, and thus, the bioavailability of testosterone and estradiol,” they wrote. “Defining cardiovascular risk for women should account for individualized profiles of genetic variants in enzymes associated with steroid metabolism, uptake, and receptors in conjunction with risk for specific cardiovascular pathologies. This approach is precision medicine.”