Hormones for Gender Dysphoria Associated With Cardiovascular Risk

People with gender dysphoria who are taking hormones to transition may face increased risks for certain cardiovascular events, according to a new report, which is the largest study to date examining such outcomes. 

Overall, hormone therapy was associated with increased odds of ischemic stroke, myocardial infarction, and pulmonary embolism but not with arrhythmias, heart failure, or all-cause mortality.

An estimated one to 1.6 million people identify as transgender in the United States, and use of hormones is increasing in this group, particularly among younger ages, say the researchers. Transgender men, those assigned as female at birth who wish to transition to being a man — will be prescribed testosterone if they decide on hormone therapy, whereas transgender women will take estrogen. 

Dr Ibrahim Ahmed

“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,” lead author Ibrahim Ahmed, MD, a third-year resident at Mercy Medical Center in Pennsylvania, said in a statement from the American College of Cardiology (ACC).

Ahmed presented the findings at the ACC Annual Scientific Sessions. 

“Looking at a person’s medical and family history should definitely be part of the screening protocol before they even start hormone replacement therapy,” he added. 

“It is also important that people considering this therapy are made aware of all the risks.”

The researchers were not able to separate out the risks for trans men vs trans women in their study.

Dr Thomas Delougherty

Thomas Deloughery, MD, a professor of medicine in hematology and medical oncology at Oregon Health and Science University, who was not involved in the study, noted that the risks appeared to be different for male-to-female vs female-to-male transition. “It would have been helpful to have that separated out,” he said.

“Thrombosis — both arterial and venous — are major side effects of patients undergoing gender-affirming [hormone] therapy, so knowing the risk is important for counseling patients when they are considering treatment,” Deloughery told Medscape Medical News.

Quantifying the Cardiovascular Risks of Hormone Therapy

Ahmed and colleagues retrospectively analyzed the 2019 Nationwide Inpatient Sample database to identify hospital admissions in adults with diagnoses of gender dysphoria. They focused primarily on cardiovascular outcomes, with length of stay and costs in US dollars examined as secondary endpoints.

Among 21,335 adults with gender dysphoria, 1675 patients used hormone therapy at some point, with the average age of those included in the study being in their early 30s. 

Compared with those who had not taken hormones, those who had ever used hormone therapy had a significant — seven times — increased risk for ischemic stroke (odds ratio [OR], 7.15; P < .001), an almost six times increased risk for ST-elevation myocardial infarction (OR, 5.9; P < .05) , and nearly five times the risk for pulmonary embolism (OR, 4.92; P < .001).

In contrast, hormone therapy wasn’t associated with any significant increase in the risk for atrial fibrillation, diabetes, hypertension, hemorrhagic stroke, or systolic heart failure. 

The groups had similar rates of all-cause mortality, at 0.6% for the hormone-therapy cohort vs 0.48% for the nonhormone cohort. The groups also had similar mean lengths of stay in the hospital (about 6 days) and average total hospitalization charges ($61,012 vs $49,930).

Ways to Mitigate the Risk

The researchers could only determine whether the study participants had ever used any hormone therapy and not additional factors such as the duration of treatment, age of hormone therapy initiation, and method of administration.

Dr Vin Tangpricha

Vin Tangpricha, MD, PhD, a professor of medicine in endocrinology at the Emory University School of Medicine, told Medscape Medical News that it would have been helpful to have more information “regarding whether the hormone dose, duration, preparation, concentration in blood, receipt of the hormones alone, or the continued gender minority stress that comes with transitioning…is the cause of these associated events.” 

Ahmed agreed: “I’m curious to see if the method of administration alters the outcomes. 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.”

Deloughery, the hematologist, said: “While there are risks of therapy, these can be mitigated with avoidance of ethinyl estradiol, use of transdermal hormone therapy in high thrombotic risk patients, and thrombosis risk factor control.” 

Ahmed reported no disclosures. Tangpricha and Deloughery reported no relevant disclosures.

ACC 2023. Presented March 5, 2023. Abstract

Carolyn Crist is a health and medical journalist who reports on the latest studies for Medscape, MDedge, and WebMD.

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