Limited data show limited evidence of harm with gender-affirming hormone therapy for transgender individuals

EBM Focus - Volume 15, Issue 24

Reference: Transgend Health. 2020 Mar 16;5(1):1-9

Transgender individuals face enormous barriers in accessing healthcare, and two of the most important might be a lack of experience among many clinicians and limited available evidence. Most transgender individuals seek gender-affirming hormone therapy (HT), yet most non-specialists hesitate to prescribe hormonal therapy without more information about safety. Studies show that HT improves quality of life for transgender people. On the other hand, a retrospective cohort study published last year found a small but significant increase in the risk of venous thromboembolism (VTE) among trans women and myocardial infarction (MI) among transgender individuals receiving HT (Nota et al., 2019).

A more recent cohort study of transgender individuals at an Illinois health center examined the association between HT and cardiovascular events such as VTE, hypertension, and MI. The health center provided care to over 6,500 transgender individuals from 2006 to 2018. Over 98% of the cohort had received HT, which was confirmed by chart review of prescriptions or laboratory records. A total of 2,509 trans women (mean age 30 years, 54.9% White) and 1,893 trans men (mean age 26 years, 66% White) participated. Nearly 40% of individuals smoked and over half had overweight or obesity (58.7% of trans women, 66.6% of trans men). The primary outcome was cardiovascular events captured by ICD codes within the electronic record. The event rate among trans women exposed to estrogen was low; 0.8% experienced a VTE and 2.1% were diagnosed with hypertension. There was no significant association between serum estradiol levels and rates of VTE (odds ratio [OR] 0.99, 95% CI 0.84-1.18) or hypertension (OR 1.02, 95% 0.92-1.13) after adjustment for race, insurance, HIV, and age, and mediation for body mass index. Recent prescription for a progestin was associated with an increased risk of VTE (adjusted OR 17.7, 95% CI 1.97-158.6; mediated OR 20, 95% CI 2.14-187.2) but not HTN in both adjusted and mediated analyses. Similarly, hypertension was not associated with either testosterone levels or prescriptions for HT in trans men. MI occurred infrequently in both groups (11 in trans women, 2 in trans men) and VTE occurred in only 3 trans men, numbers the authors determined to be too small for statistical analysis.

This study has threats to validity, including a relatively young population and low event rate. Additionally, the small percentage of individuals not receiving HT were far more likely to have a history of known CVD, making it difficult to apply these data to a higher-risk group. The authors included most typical confounders in the analysis but did not include tobacco use. A broader critique of transgender health research must include a discussion about the limited funding for this research and a resulting scarcity of evidence for clinicians. Improving patient outcomes for transgender indiviudals requires more robust research. This study reduces but does not eliminate uncertainty when caring for transgender patients.

For more information, see the topics Hormone therapy for the adult female transgender patient and Hormone therapy for the adult male transgender patient in DynaMed.

DynaMed EBM Focus Editorial Team

This EBM Focus was written by Carina Brown, MD, Assistant Professor at Cone Health Family Medicine Residency. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School, Dan Randall, MD, Deputy Editor for Internal Medicine at DynaMed, and Katharine DeGeorge, MD, MS, Associate Professor of Family Medicine at the University of Virginia and Clinical Editor at DynaMed.