Cross-sex Hormones and Acute Cardiovascular Events in Transgender Persons

Anjoli Punjabi, Pharm.D, MPH, FQHC Urban Network

Background: Some transgender persons undergo cross-sex hormone therapy to align their physical appearance with their gender identity. There is concern that this therapy may lead to increased risk of acute cardiovascular events (ACVEs), including venous thromboembolism (VTE), ischemic stroke, and myocardial infarction. However, population-based evidence for the association between cross-sex hormone therapy and risk of ACVEs is inconsistent and limited. Please note the following definitions as they will be referenced throughout:

  • Transgender: Denoting a person whose gender identity differs from their birth sex.

    • Transfeminine: Denoting a person who was assigned male at birth, but identifies with femininity to a greater extent than masculinity

    • Transmasculine: Denoting a person who was assigned female at birth, but identifies with masculinity to a greater extent than femininity.

  • Cisgender: Denoting a person whose sense of personal identity and gender corresponds with their birth sex.

Objective: To compare ACVE incidence rates in a cohort of transgender persons with rates in a matched cisgender men and women reference cohort.  

Study Design: The Kaiser Permanente Health systems in Georgia and California conducted an electronic medical record–based cohort study of transgender members who had an index date (first evidence of transgender status) from 2006 through 2014. Each transgender participant was matched to ten male or female cisgender enrollees by year of birth, race/ethnicity, study site, and index date enrollment. The total number of participants in the study was 2842 transfeminine (matched to 48,686 cisgender men) and 2118 transmasculine members (matched to 48,774 cisgender women) with a mean follow-up of 4.0 and 3.6 years, respectively. ACVEs were identified from diagnostic codes (ICD-9 and ICD-10) codes through the end of 2016 in transgender and reference cohorts. Multivariable Cox proportional hazards models were utilized to compare ACVE rates between the transfeminine and transmasculine cohorts, the hormone initiation cohorts (transgender participants who started estrogen or testosterone after the index date), and among members in the matched cisgender reference groups, after controlling for confounding factors.

Results: It was found that transfeminine participants had a higher incidence of VTE, with 2- and 8-year risk differences of 4.1 (95% CI, 1.6 to 6.7) and 16.7 (CI, 6.4 to 27.5) per 1000 persons relative to cisgender men; and 3.4 (CI, 1.1 to 5.6) and 13.7 (CI, 4.1 to 22.7) relative to cisgender women.

Conclusions: The evidence was insufficient to draw conclusions regarding risk among transmasculine participants due to limited number of occurring ACVEs in this group.  More pronounced differences for VTE and ischemic stroke were observed among transfeminine participants who initiated hormone therapy (estrogen) during the follow-up period. One trend that was observed in this group was that VTE rates increased after 2 years of follow-up and continued to rise for another 5 to 6 years.

Key Point: Results may indicate that clinicians need to increase vigilance in identifying long-term vascular side effects of estrogen therapy in transgender patients. The risk for ACVEs in this population must be weighed against the benefits of treatment.

Reference:

  1. Getahum H, Nash R, Flanders DW, et al. Cross-sex Hormones and Acute Cardiovascular Events in Transgender Persons. Annals of Internal Medicine. [published online July 10, 2018]. doi: 10.7326/M17-2785.