Hormone Therapy Linked to CV Risk During Gender Transition

Megan Brooks

February 20, 2019

Individuals receiving hormone therapy during gender transition have an increased incidence of acute cardiovascular events, including myocardial infarction (MI), stroke, and venous thromboembolic events (VTE), compared with the general population, a Dutch cohort study shows.

"Although we found an increased cardiovascular risk in transgender individuals on hormone therapy, we believe that the benefits of hormone therapy outweigh the potential hormone-induced increased cardiovascular risk," Nienke Nota, MD, Amsterdam University Medical Center, the Netherlands, told the theheart.org | Medscape Cardiology.

"We believe that physicians can reduce the risk for cardiovascular events in the transgender population by giving lifestyle advice and by regularly monitoring and managing cardiovascular risk factors, such as lipid spectrum, glucose levels, and blood pressure," said Nota.

The study was published online February 18 in Circulation.

Previous literature suggests that exogenous sex hormones play a role in the risk for cardiovascular events in cisgender men and women, Nota explained. "To date, studies in transgender individuals on hormone therapy have mainly focused on cardiovascular risk factors, and large studies examining cardiovascular disease as an outcome factor are scarce."

To gauge the risk for cardiovascular events in transgender individuals receiving hormone therapy, the researchers studied 2517 transgender women (median age, 30 years) who received estrogen with or without androgen suppressors, and 1358 transgender men (median age, 23 years) who received testosterone as part of their transition. Transwomen were followed for an average of about 9 years after the start of hormone therapy, and transmen were followed for an average of 8 years after treatment initiation.

Transwomen had a higher adjusted incidence of stroke and VTE than reference women and men, and both transwomen and transmen had a higher risk for MI than reference women.

CVD Risk
End Point SIR (95% CI) WIth Women as Reference SIR (95% CI) With Men As Reference
Transwomen vs Women and vs Men
Stroke 2.42 (1.65–3.42) 1.80 (1.23–2.56)
MI 2.64 (1.81–3.72) 0.79 (0.54–1.11)
VTE 5.52 (4.36–6.90) 4.55 (3.59–5.69)
Transmen vs Women and vs Men
Stroke 1.72 (0.70 to 3.58) 1.46 (0.59 to 3.04)
MI 3.69 (1.94 to 6.42) 1.00 (0.53 to 1.74)
VTE 0.41 (0.07 to 1.37) 0.36 (0.06 to 1.19)
SIR = standardized incidence ratio; CI = confidence interval

Because ethinylestradiol could be responsible for the increased cardiovascular risk in transwomen, the researchers conducted subanalyses that excluded transwomen who started transgender hormone therapy before 2001; after that, ethinylestradiol was replaced with more natural estrogens.

Except for VTE, the SIRs of this subpopulation were not lower than the SIRs of the total population, they report.

Important Part of Care

The researchers note that the study was not designed to tease out the mechanism behind the increased cardiovascular risk during gender transition hormone therapy. They also caution that the study was based on a review of medical records and could not account for risk factors, such as smoking, psychosocial stressors, and dietary and exercise habits. Although these risk factors likely contribute to the increased cardiovascular risk, the researchers suggest that transgender hormone therapy might also contribute to increased risk.

Reached for comment on the study, Nieca Goldberg, MD, director, Joan H. Tisch Center for Women's Health at NYU Langone, New York CIty, and spokesperson for the American Heart Association, said that "hormone therapy is an important part of care for people undergoing a gender transition and we should make sure that we can use this therapy as healthfully as possible for these people."

"We should always remember the risks that are associated with hormone therapy, including the potential for blood clotting and increased risk for heart attack and stroke. When thinking about hormone therapy, there should be an assessment of the patient's overall cardiovascular health and the patient needs to understand the benefits and the potential risks," said Goldberg.

Finally, she said, "we need to learn more about the mechanisms behind the increased risk of hormone therapy in this patient population."

The study received no specific funding. Nota and Goldberg have declared no relevant conflicts of interest.

Circulation. Published online February 18, 2019. Abstract