People with gender dysphoria on hormone replacement therapy (HRT) as part of gender affirmation therapy have substantially increased odds of serious cardiac events and other problems, including ischaemic stroke, pulmonary embolism, ST-elevation myocardial infarction (STEMI), non-STEMI, drug abuse, and hypothyroidism.

Between 1 million to 1.6 million Americans identify as transgender, according to the study’s first author Ibrahim Ahmed, MD, who presented the results at the American College of Cardiology 2023 Annual Scientific Sessions.¹ Among this population, HRT use is rising rapidly, especially among teens and young adults. The aim of this retrospective study was twofold: to characterize the demographics of patients with gender dysphoria using HRT, and to study the impact of this therapy on cardiovascular outcomes in the setting of gender dysphoria, of which little is known. The researchers accessed the 2019 Nationwide Inpatient Sample database to identify admissions of adults diagnosed with gender dysphoria and use of HRT. The primary outcome was cardiovascular events in HRT users versus non-users.

Of 21,335 identified patients with gender dysphoria, 1,675 had used HRT. Compared with non-users, patients in the HRT cohort were slightly older (31 vs 34 years) and were less often women (47% vs 55%); race distribution was similar in the two groups.

HRT was significantly associated with:

• ischemic stroke: OR, 7.15 (95% CI, 2.74–18.67; P<0.001);
• pulmonary embolism: OR, 4.92 (95% CI, 2.08–11.62; P<0.001);
• STEMI: OR, 5.90 (95% CI, 1.07–32.42; P<0.05);
• non-STEMI: OR, 3.30 (95% CI, 1.20–9.04; P<0.05).

HRT was not significantly associated with atrial fibrillation, diabetes mellitus, hypertension, hemorrhagic stroke, and systolic heart failure, Dr. Ahmed added. The all-cause mortality rate in HRT users was similar: 0.60% versus 0.48% (P=0.774). The mean length of hospital stay was also similar (5.71 vs 6.09 days; P=0.321), as was the mean total hospitalization charge ($61,012 vs $49,930; P=0.598).

“It’s all about risks and benefits,” said Dr. Ahmed. “Starting transitioning is a big part of a person’s life and helping them feel more themselves, but HRT also has numerous side effects. It’s not free of risk.” He added that “a careful risk-benefit discussion” should precede HRT in patients with gender dysphoria.

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