Risks Arising from Hormone Therapy in Transgender Individuals Are Secondary

As more individuals seek transgender hormone therapy, clinicians will want to be prepared to monitor for increased risks of cardiovascular events.

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

There are 1.4 million adults in the United States who identify as transgender, which is about double previous estimates,1 according to data derived from the Behavioral Risk Factor Surveillance System gathered by the Centers for Disease Control and Prevention.

Coupled with an increasing number of young adults, those ages 18-24 years old are most likely of any age to identify as transgender, making it very likely that at least a few of your patients will present to your office for care. How prepared and comfortable are you?

Taking transgender hormone therapy increases the risk of cardiovascular events.

Exploring the Risk of Cardiovascular Events with Transgender Hormone Therapy

Investigators at the Williams Institute at the University of California in Los Angeles confirmed the need to improve the medical and social services, as well as public policies, to meet the needs of this growing subset of the population.1

One current clinical concern drawing attention is the potential for increased risk of cardiovascular events in transgender individuals who are receive transgender hormone therapy (THT). Appreciating the risks and need for ongoing monitoring and interveiton will be necessary since THT is a lifelong therapeutic reality for these individuals.

Prior studies have focused on other population cohorts who have received long-term hormone therapy, such as adults with hypogonadsim and postmenopausal women, have reported associations with HT and increased risk of cardiovascular disease.2,3

However, it is unclear whether the perceived increased risk of cardiovascular events in transgender adults translates to a greater occurrence in this population. To this end, a group of investigators from the Netherlands reviewed the medical records of all 6,793 patientsreceiving transgender hormone therapy who were seen in their clinic between 1982-2015.4

Assessing Patients Who Are Transitioning for Increased CVD Outcomes

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=3,927); any individuals who had experienced a cardiovascular event before starting transgender hormone therapy were excluded.4

In this cohort, 2,517 individuals were transgender women (individuals assigned male sex at birth; median age 30 years) and 1,358 were transgender men (individuals assigned female sex at birth; median age 23 years).4 Only three of the nearly 4,000 participants had had more than one CVE; in those cases, 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 ethinyl estradiol could be responsible for some of the observed cardiovascular risk in transgender women.

Consequently, they replaced ethinyl estradiol in 2001 with “more natural hormones” such as 17-β estradiol. “In addition, we performed subanalyses in which we excluded transwomen who started THT before 2001,” said study lead author Nienke M. Nota, MD, in the Division of Endocrinology at the Amsterdam University Medical Center in the Netherlands. “However, only for VTEs, the SIRs of this subpopulation were more favorable than the SIRs for the total population (3.92 versus 5.52 when using women as reference, and 3.39 versus 4.55 when using men as reference).” 

The mean duration of follow-up after THT 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 identify 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 Risks Is Warranted Particularly in Transgender Women

“Our study population was relatively young, and a large proportion of the population were smokers,” said Dr. Nota. “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 typically switch the type of hormone therapy taken several times over the course of the study.”

“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,” Dr. Nota told EndocrineWeb.

These study findings were similar to those of another recent cohort study based on data from electronic medical records by Getahun, et al,5 in which transfeminine (n=2,842) and transmasculine (n=2,118) adults were compared to cisgender men (n=48,686) and cisgender women (n=48,775), with a higher incidence of venous thromboembolism and ischemic stroke rates reported among transfeminine individuals as compared to 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, as well as experiencing higher rates of MI when compared with cis-women.4,5 While Gutahun study group did not draw conclusions regarding an elevated risk for cardiovascular events in transmen, there was a trend suggesting that transmen receiving testosterone may be at higher risk for MI.5

Cardiovascular Risk Must Be Managed Irrespective of Hormone Therapy

“As reported by others, transgender women have more thrombotic events than either cis-women and cis-men–as evidenced by more deep venous thromboses (DVTs) and a greater number of strokes. Although there is no evidence of specific causation (as 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 but agreed to review the data.

“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 slight increase in the occurrence of clotting events, the findings need to be considered with 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 care. 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.

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,” Dr. Safer told EndocrineWeb—reducing blood pressure, encouraging smoking cessation, addressing need for weight control, and closer, ongoing monitoring, particularly of CVD risks, to catch any increase in risks early will assure the best level of care for patients who identify as transgender.

Continue Reading:
Putting Transgender Medical Care Into Context for Practitioners
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