Thrombosis Risk in Transgender Adolescents Receiving Gender-Affirming Hormone Therapy

An estimated 2-3% of US youth identify as transgender or gender non-conforming (hereafter transgender). Transgender youth may suffer from gender dysphoria, a condition associated with many health risks, including high risk of suicide. Transgender individuals have a 40% greater risk of attempting suicide than cis-gender individuals. Gender-affirming hormone therapy (GAHT) is associated with improvement of gender dysphoria and amelioration of the risk of suicide. GAHT consists of either estrogen [for transgender women (TGW)] or testosterone [for transgender men (TGM)]. However, GAHT may be associated with other risks, most notably thrombosis. Numerous studies documented increased thrombosis risk in cis-gender women using exogenous estrogen for contraception or hormone replacement therapy. Studies of GAHT suggest a risk of thrombosis with estrogen use; however, this data is not uniform. Studies of testosterone replacement in cis-gender show conflicting results with respect to thrombosis risk. All previous studies examining the risk of thrombosis with GAHT have included adults exclusively. Therefore we sought to determine the risk of thrombosis in a cohort of transgender youth receiving standardized GAHT regimens. Transgender youth have potential for a much longer exposure to GAHT, thus having different life-time risk of thrombosis than patients that start GAHT at an older age. Of all 1406 patients seen at the Cincinnati Children's Medical Center Transgender Health Clinic since its inception, 611 subjects started GAHT and were eligible for inclusion in the cohort. Of these, 176 (28.8%) identified as female, 416 (68.1%) as male, and 19 (3.1%) as non-binary. Thrombosis risks were common among the cohort: 34.5% had obesity, 15.4% used tobacco, 4.6% had migraine with aura, and 8.0% had a family history of thrombosis. Three subjects had a prior history of thrombosis: 2 with venous thromboembolism (VTE) and one with a stroke. 53.7% of the cohort had previously used hormones, most commonly for menstrual suppression. Of those with prior hormone use, the vast majority had used progesterone-only methods (5.7% previously used estrogen-containing contraceptives). All patients initiating GAHT were treated according to current guidelines with monitoring of estrogen and testosterone levels and titration of GAHT doses accordingly. Overall, 29.8% initiated estrogen therapy and 70.2% started testosterone therapy. Among the cohort, 17 individuals were referred to Hematology for evaluation for thrombosis risk prior to starting GAHT. The most common laboratory abnormality for these individuals was elevated factor VIII, elevated plasminogen-activator inhibitor 1 (PAI-1), and the PAI-1 polymorphism. Two TGW and one TGM started thromboprophylaxis prior to initiating GAHT due to thrombotic risk factors. Despite the presence of preexisting risk factors, no individual in the cohort developed a thrombosis (VTE or stroke) during GAHT. This is the first study to examine thrombosis risk of GAHT in an exclusively adolescent and young adult population. While there were no incidents of thrombosis in our cohort, we found individuals at risk for thrombosis. Careful history and counseling regarding risks are needed when discussing initiation of GAHT for transgender individuals. Additionally, further studies looking at long-term risk are needed.