Hormone Therapy Ups CV Risk in Transgender Individuals

Hormone therapy taken as part of the transitioning process appears to increase the risk of cardiovascular events for both trans women, who were assigned male sex at birth but have a female gender identity, and trans men, who were initially assigned female sex but have a male gender identity. The findings stem from a large observational analysis from the Netherlands.

Specifically, transgender women had higher risks of stroke and venous thromboembolism (VTE) than did cisgender men and women whose identity matched their birth sex. Both trans women and trans men had a higher risk of MI than did cis women, Nienke M. Nota, MD (Amsterdam University Medical Center, the Netherlands), and colleagues report in a research letter published online February 18, 2019, ahead of print in Circulation.

Hormone therapy is a known risk factor for cardiovascular events in hypogonadal men whose bodies do not make enough testosterone and in postmenopausal women. But little is known about how hormones taken as part of gender transition affect trans men and trans women, who tend to be younger but may be experiencing psychosocial stressors, the researchers say.

“To date, studies in transgender individuals on hormone therapy have mainly focused on cardiovascular risk factors, and large studies examining [outcomes] are very scarce,” Nota told TCTMD via email. The present study provides greater insight into the link between hormone therapy and cardiovascular events, and uniquely shows the added risk extends not only to trans women but to trans men, she added.

“Physicians should be aware of the increased cardiovascular risk in transgender people” and tailor care accordingly, she said, “by giving lifestyle advice and by regularly monitoring and managing cardiovascular risk factors” such as lipid, glucose, and blood pressure levels.

“Transgender people often ask about the long-term risk of hormone therapy and some are worrying about it, especially about venous thrombosis. However, for almost all transgender individuals the benefits of hormone therapy outweigh the potential risks of hormone therapy,” Nota observed.

For almost all transgender individuals the benefits of hormone therapy outweigh the potential risks of hormone therapy. Nienke M. Nota

For their study, the researchers analyzed data on 2,517 transgender women (median age 30) who took estrogen with or without androgen suppressors and 1,358 transgender men (median age 23) who received testosterone at their center’s gender clinic between 1972 and 2015. Mean follow-up duration was 9 years for trans women and 5 years for trans men.

Compared with cisgender women and men in the general Dutch or Norwegian population, trans women had substantially more cardiovascular events. The one exception was MI, for which cisgender men had the highest risk.

Events per 100,000 Person-Years

Additionally, trans men had a significantly higher risk of MI compared with cisgender women (11 vs three events per 100,000 person-years).

Nota emphasized that the analysis cannot prove a causal relationship. As mentioned in the paper, the investigators were not able to adjust for smoking status or stressors, for example.

There are several potential mechanisms that might explain the findings, though. Hormone therapy may be affecting lipid levels, coagulability, and insulin sensitivity, Nota suggested. “However, other factors possibly also play a role: transgender individuals are probably more vulnerable to minority stress (psychological distress experienced by people who are members of a group that is stigmatized by mainstream society). In addition, because of the increased distress it is possible that transgender individuals have a [less healthy] lifestyle such as more alcohol usage and a higher smoking prevalence.”