Testosterone Therapy May Raise Heart Disease Risk in Women

The U.S. Food and Drug Administration (FDA) hasn’t approved testosterone therapy for women in any form, but doctors often prescribe it off-label to treat low libido in women.

“Testosterone therapy has gained increasing attention as a potential treatment for women experiencing symptoms associated with menopause,” says the lead study author, Xuezhi Jiang, MD, PhD, a professor of obstetrics and gynecology at the Drexel University College of Medicine in Philadelphia. “However, unlike estrogen-based menopausal hormone therapy, the long-term cardiovascular safety of testosterone therapy in women remains poorly understood.”

While the study raises concern, doctors who treat women in menopause say more work is needed before they'll advise women to avoid testosterone therapy altogether. Here’s why.

Heart Disease Rates Were Higher Among Testosterone Users

For the study, researchers analyzed data from the TriNetX US Collaborative Network, a collection of anonymized health data. They divided more than 6,300 women ages 45 and older into two groups: those who’d used testosterone and those who hadn’t. The researchers excluded women with existing heart disease and followed the participants for about three years.

The researchers discovered that women who used testosterone therapy had a significantly increased risk of cardiovascular disease compared with non-users: 3.8 percent versus 0.5 percent. However, the absolute rates — meaning the number of women who used testosterone therapy and developed cardiovascular disease — were low.

“Our findings demonstrate an association between testosterone therapy and cardiovascular events, but they do not establish that testosterone directly causes these events,” Dr. Jiang says.

Research Didn’t Find a Cause for the Link, but There Are a Few Theories

This particular study wasn’t designed to explore the underlying cause of this association — it merely found a link. The authors have some ideas, though.

“Testosterone may influence cardiovascular health through its effects on cholesterol metabolism, blood pressure, vascular function, and other metabolic pathways,” Jiang says. These effects may depend on the dose of testosterone therapy, how it’s taken, and the blood testosterone concentrations that someone achieves during treatment, he says.

“Another important consideration is that testosterone therapy in women is sometimes prescribed using formulations or doses that may produce testosterone levels above the normal physiological range for women,” Jiang says. Because testosterone therapy is not approved for use in women, doctors who prescribe it often use very low doses of male formulations, which may still be too much. “The cardiovascular consequences of prolonged exposure to these higher levels remain uncertain,” Jiang says.

But Jiang also says it’s possible that women who receive testosterone therapy have additional differences that influence their heart disease risk that haven’t been identified.

Outside Experts Say the Findings Are an Early ‘Safety Signal’

“The results certainly seem significant,” says Mary Jane Minkin, MD, a clinical professor of obstetrics, gynecology, and reproductive sciences at the Yale School of Medicine in New Haven, Connecticut. “For many years, folks have wondered whether higher testosterone exposures are partly responsible for the higher risks of cardiac disease in men compared with women, who have relatively low testosterone levels.” But Dr. Minkin says this is an early finding and not yet conclusive.

Lauren Streicher, MD, a clinical professor of obstetrics and gynecology at the Northwestern University Feinberg School of Medicine in Chicago, agrees. “Even the study authors say this is something we should look at but that it shouldn’t inform practice,” she says. “We cannot make the conclusion that it will cause heart disease — it’s just an observation at this point.”

Stephanie Faubion, MD, a women’s health researcher at Mayo Clinic in Jacksonville, Florida, and the medical director of the Menopause Society, calls the findings a “safety signal” for now. “The risk is up to eight times bigger based on these findings — that’s significant,” she says. “But you’re talking about a small number of cases to begin with.”

“Ultimately, our findings underscore the need for well-designed prospective studies to better establish the long-term cardiovascular safety of testosterone therapy in women,” Jiang says.

Women Need More Safety Data Around Testosterone Therapy, According to Doctors

The study suggests that more work is needed on cardiovascular disease risk and testosterone therapy, along with overall safety data on the potential impact of the treatment for women. “We don’t have an FDA-approved testosterone product for women anyway,” Dr. Faubion points out.

Still, doctors say many women are asking for the treatment, despite a lack of data to support its use beyond treating low libido. “These days, everyone is asking for testosterone,” Minkin says. “Women should not be looking to testosterone to cure brain fog, because there is no data on that whatsoever.”

Dr. Streicher concurs. “There is a legitimate reason to take testosterone therapy — to boost low libido — and other reasons people might take it,” she says. “A lot of women who take testosterone therapy are looking for other benefits.”

If you’re interested in using testosterone therapy, Faubion stresses the importance of speaking with a healthcare provider who treats low libido. “What testosterone therapy is being used for is often inappropriate,” she says.