Slight Cardiovascular Risk Seen in Hormone-treated Transgender Women

For individuals receiving transgender hormone therapy, the focus of clinical care should be on reducing known cardiovascular risk factors to support optimal patient outcomes.

With Nienke M. Nota, MD, and Joshua D. Safer, MD

There are 1.4 million adults in the United States —or 0.6% of the adult population—who identify as transgender, which is about double previous estimates in addition to an increasing number of young adults, 18-24 years old,  identify as transgender And while this survey did not include children (< 18 years), there was an acknowledged.1 This study also highlighted the need for medical and social services, as well as public policies, for this growing population.

One current clinical concern drawing attention is the potential for increased risk of cardiovascular events in transgender individuals who receive transgender hormone therapy (HT). Studies on other populations who have received use long-term hormone therapy, such as hypogonadal adults and postmenopausal women, have previously demonstrated some associations with HT and CVD in specific subsets of these patient populations.2,3

Focus on usual lifestyle factors is key for transgender patients receiving hormone therapy.

Does Hormone Therapy Raise Concerns for the Transgender Community?

Since it is unclear whether the perceived increased risk of cardiovascular events in transgender adults translates to a greater occurrence in this population, a group of investigators from the Netherlands reviewed the medical records of all 6793 patients who were seen in their clinic between 1982-2015, in an effort to elucidate the significance of this risk.4

Patients who had received transgender hormone therapy prescribed by their clinic or an affiliate and had had at least one follow-up visit were enrolled (n=3927); any individuals who had experienced a cardiovascular event before starting transgender hormone therapy were excluded.4

In this cohort, 2517 were transgender women (individuals assigned male sex at birth) and 1358 were transgender men (individuals assigned female sex at birth).4 Only three of the nearly 4000 patients experienced more than one cardiovascular event but only data from the first event was considered.4

The transgender hormone therapy was as follows: estrogens (with or without anti-androgens) for transgender women and testosterone for transgender men. The investigators noted that hormone therapy has experienced some changes during this time including lower doses of ethinylestradiol prescribed and a switch to “more natural hormones” such as 17-β estradiol.

In addition, the researchers performed a subanalysis that excluded transgender women who started hormone therapy prior to 2001 to rule out the type of hormone used in event occurrences. However, only for venous thromboembolisms was the SIRs of this more limited population more favorable than the SIRs found for the total population (3.92 versus 5.52 when using transwomen as the reference value, and 3.39 versus 4.55 when using transmen as the reference).

The mean duration of follow-up after initiation of hormone therapy was 9.1 years for transwomen and 8.1 years for transmen. The standardized incidence ratios (SIRs) demonstrated a higher adjusted incidence of stroke and venous thromboembolism for transwomen compared with cis-women or cis-men (women and men whose gender identity matches the sex that they were assigned at birth, respectively). Both transgender men and women experienced a higher risk of myocardial infarction (MI) compared with cis-women, but transgender men had the same rate of MI as cis-men.4

Mitigating CVD Risk is Warranted Particularly in Transgender Women

EndocrineWeb spoke with the study’s lead author Nienke M. Nota, MD, in the Division of Endocrinology at the Amsterdam University Medical Center in the Netherlands, who said that “our study population was relatively young, and a large part of the population was smokers.”

“We were not able to control for factors such as smoking owing to the retrospective study design. We were also not able to look at the different types of hormones, as most transgender individuals switch several times from the type of hormone therapy,” said Dr. Nota. “However, we believe that the CV risks persist over time when the increased risk is caused by HT, as transgender individuals usually receive lifelong HT.”

These findings were similar to those of another recent cohort study looking at data from electronic medical records by Getahun, et al,5 in which 2842 transfeminine and 2118 transmasculine adults were compared to 48,686 cisgender men and 48,775 cisgender women, with a higher incidence of venous thromboembolism and ischemic stroke rates were reported among transfeminine persons compared with cis-women.

Both of these transgender hormone studies identified higher rates of stroke and venous thromboembolism in transwomen relative to cis-men and cis-women, and higher rates of MI compared with cis-women.4,5 While the authors of the Getahun study did not draw conclusions regarding an increased risk for cardiovascular events in transmen, there was a trend suggesting that transmen receiving testosterone were at higher risk for MI.5

Monitor and Manage CVD Risk Irrespective of Hormone Therapy

“As reported by others, the transgender women have more thrombotic events than cis-women and cis-men – as evidenced by more deep venous thromboses (DVTs) and in more strokes. Although there is no evidence of specific causation (as is noted by the study authors), this is consistent with findings from the Getahun study,” said Joshua D. Safer, MD, FACP, executive director of the Mount Sinai Center for Transgender Medicine and Surgery at the Icahn School of Medicine at Mount Sinai, and President of the US Professional Association for Transgender Health who wasn’t involved in either of the cited studies.

“These results are, for the most part, reassuring and consistent with what we’ve been seeing and how we’ve been thinking – the results are confirmatory of findings from both smaller and the more recent larger Getahun studies,” said Dr. Safer. The findings are reassuring for transmen but suggest some concern regarding cardiovascular risks in transgender women who appear to have an elevated estrogen-related risk for thromboembolism.4,5

While the findings point to a somewhat increased occurrence in clotting events, the findings need to be considered with the proper perspective, said both experts.  

“Physicians should be aware of the increased cardiovascular risk in transgender individuals who are taking hormones to assist in their transition. We believe that physicians have the ability to reduce these known cardiovascular-related events in transgender patients by counseling them on lifestyle strategies to reduce their risk and by regularly monitoring and managing risk factors such as the lipid spectrum, glucose levels, and blood pressure,” Dr. Nota told EndocrineWeb.

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Similarly, these findings “may indicate the need for long-term vigilance in identifying vascular side effects of cross-sex estrogen,” according to Getahun et al. Dr. Safer agreed: “the absolute risk is not large, but it does seem possible based on the outcomes reported by this study. More importantly, it is not likely that any transwomen will change their plans to forgo estrogen based on concerns for cardiovascular events; however, we do need to emphasize the importance of general preventive measures for cardiovascular disease,”—blood pressure, smoking cessation, weight control, and closer, ongoing monitoring to catch any increase in risks early.

There were no financial conflicts with regard to the cited papers.

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