Study Links Heart Disease Risk to High Testosterone

Researchers may finally have evidence to explain why men have a higher prevalence of heart disease than premenopausal women, based on new research recently presented at the Endocrine Society’s 97th annual meeting in San Diego.

“Men have higher androgens and lower estrogens than premenopausal women, and this profile may explain why men have lower HDL and worse glycemic indices than women,” says study presenter and lead investigator Elaine Yu, MD, MSc, an assistant professor at Harvard Medical School in Boston. “Both of these risk factors may predispose men to developing cardiovascular disease earlier than premenopausal women.”
_________________________________________________________________________________________________________________________________________________________________

RELATED CONTENT
Testosterone Therapy May Protect Against Heart Attacks
Testosterone Doubles Heart Attack Risk in Certain Men
_________________________________________________________________________________________________________________________________________________________________

Yu and her colleagues recruited 2 cohorts of healthy men, ages 20 to 50, to determine whether estrogen or testosterone regulated various cardiovascular risk factors. They compared the two groups of men after temporarily altering their hormone levels with a combination of medications.

All 400 participants received goserelin (Zoladex, AstraZeneca) to suppress their own production of testosterone and estrogen. For 4 months, 198 of the men were randomized to receive daily treatment with either a placebo gel or 1.25 g, 2.5 g, 5 g, or 10 g of testosterone gel (AndroGel, AbbVie). This regimen resulted in very low, prepubescent-like levels of testosterone up to high-normal levels.

The 202 men in the other group received the same treatment as the first group, but also received anastrozole (Arimidex, AstraZeneca) to block their testosterone from converting to estrogen, which resulted in very low levels of estrogen. Researchers then looked at the participants’ weight, markers of heart disease and diabetes, and measures of muscle fat.

“We found that testosterone negatively regulates HDL while estrogen deficiency causes worsening of fasting glucose and insulin resistance in men,” Yu says. “Importantly, neither androgens nor estrogens regulate LDL or blood pressure.”

Given that this research suggests both androgens and estrogens are important for cardiovascular outcomes in men, it’s possible that measurements of testosterone and/or estradiol could be used to help predict cardiovascular risk in men, but Yu emphasizes that further research would be needed to verify these hypotheses.

She and her colleagues plan to study the effects of testosterone and estrogen on inflammatory markers as well as hormones related to fat metabolism and cardiovascular function. 

“It is important to evaluate whether other cardiovascular risk factors are similarly regulated by gonadal steroids in men,” Yu says. “An improved understanding of these effects may help to explain sex differences in cardiovascular disease.”

The drugmakers provided the medications used in this study at no cost, and grants from the National Institutes of Health and AbbVie supported the research.

—Colleen Mullarkey

Reference

Yu E. Effects of androgens and estrogens on cardiometabolic parameters in young adult men. Presented at The Endocrine Society’s 97th Annual Meeting, San Diego, Calif. March 7, 2015. Abstract OR34-1.