Gender Affirmation Hormones Come With Cardiovascular Tradeoffs

Use of hormone replacement therapy (HRT) was associated with excess cardiovascular risks for people with gender dysphoria, according to a U.S. population-based study.

Compared with hospitalized patients with gender dysphoria who had never used hormone replacements, those taking this gender affirmation therapy had higher rates for a range of in-hospital cardiovascular events:

• Ischemic cerebrovascular accident (OR 7.15, 95% CI 2.74-18.67)
• ST-elevation myocardial infarction (OR 5.90, 95% CI 1.07-32.42)
• Non-ST-elevation myocardial infarction (OR 3.30, 95% CI 1.20-9.04)
• Pulmonary embolism (OR 4.92, 95% CI 2.08-11.62)

On the other hand, HRT was not associated with any increase in deaths, incident atrial fibrillation, diabetes, hypertension, hemorrhagic stroke, or heart failure, found researchers led by Ibrahim Ahmed, MD, a internal medicine resident at Mercy Catholic Medical Center in Darby, Pennsylvania. Their poster was released ahead of presentation at the upcoming American College of Cardiology annual meeting in New Orleans.

Ahmed stressed careful discussion with patients regarding the risks and benefits of gender-affirming hormone therapies.

“Starting transitioning is a big part of a person’s life and helping them feel more themselves, but hormone replacement therapy also has a lot of side effects — it’s not a risk-free endeavor,” he said in a press release. “Looking at a person’s medical and family history should definitely be part of the screening protocol before they even start hormone replacement therapy.”

The researcher cited prior reports showing that hormone therapies in pre- and postmenopausal women are linked to increased cardiovascular risks such as stroke and blood clotting events.

“It was therefore expected that a similar risk would be conferred in gender dysphoric patients,” Ahmed told MedPage Today in an email. “However, we must be equally mindful of the alternative (i.e., untreated gender dysphoria) as it may lead to severe depression, substance abuse and/or suicide. Therefore the best decision is an informed decision by a patient and their physician.”

Recent data suggest that approximately 1.6 million people identify as transgender in the United States. HRT for people assigned male at birth is typically estrogen and for people assigned female at birth is usually testosterone.

Gender-affirming hormones have been associated with better mental health for young transgender and nonbinary people. However, small studies have shown increased cardiovascular risks and mortality in transgender women using hormone therapy. Drops in HDL cholesterol also have been reported in transgender men using testosterone.

With more research, “the expectation is that cardiologists and other internists will be able to deliver improved care in this population as well as reduce disparities in care,” Ahmed said.

His study used data from the 2019 Nationwide Inpatient Sample database, the largest publicly available all-payer inpatient care database in the United States, which contains nationally-representative data on more than seven million hospital stays. It included 21,335 people with gender dysphoria, of whom 1,675 had used HRT.

This HRT-using group was slightly older (mean 34 vs 31 years old, P<0.05) and with fewer females (47.0% vs 54.5%, P<0.05) than those not using HRT.

No between-group differences were observed in terms of race, income, alcohol abuse, or depression. However, those taking hormone replacement therapy had higher rates of substance use disorder (OR 1.41, 95% CI 1.03-1.92) and hypothyroidism (OR 2.16, 95% CI 1.43-3.27).

HRT did not correlate with a person’s mean length of stay in the hospital (5.7 vs 6.1 days, P=0.321) nor total hospitalization charges ($61,011.71 vs $49,930.34, P=0.598).

Ahmed acknowledged that his analysis did not account for duration or type of hormone therapy.

“I’m curious to see if the method of administration alters the outcomes,” Ahmed said in the press release. “Is one way of giving hormone replacement therapy better or associated with a lower risk of cardiovascular outcomes? If so, then that should be the focus for how we give these patients their hormone replacement therapy going forward.”