Breakthrough Bleeding in Transgender and Gender Diverse Adolescents and Young Adults on Long-Term Testosterone

STUDY OBJECTIVE: Amenorrhea is a goal of many transgender and gender diverse adolescent and young adult (TGD AYA) patients on testosterone gender-affirming hormone therapy (T-GAHT). Breakthrough bleeding can contribute to worsening gender dysphoria. Our objective was to evaluate breakthrough bleeding in TGD AYA on T-GAHT. DESIGN: Institutional review board-approved retrospective cohort. SETTING: Tertiary-care children's hospital. PARTICIPANTS: TGD AYA on T-GAHT >1 year. INTERVENTIONS: None; observational. MAIN OUTCOME MEASURES: Presence of, and risk factors for, breakthrough bleeding. RESULTS: Of the 232 patients who met inclusion criteria, one-fourth (n = 58) had 1 or more episodes of breakthrough bleeding, defined as bleeding after more than 1 year on T-GAHT. In comparing patients with breakthrough bleeding to those without, there were no significant differences between age of initiation, body mass index (BMI), race/ethnicity, testosterone type used, use of additional menstrual suppression, serum testosterone, or estradiol levels. Patients with breakthrough bleeding patients were on T-GAHT longer (37.3 ± 17.0 vs 28.5 ± 14.6 months, P < .001) and were more likely to have endometriosis (P = .049). Breakthrough bleeding began at a mean of 24.3 ± 17.2 months after T-GAHT initiation. Of those with breakthrough bleeding, 46 (79.3%) had no known cause, 10 (17.2%) bled only with missed T-GAHT doses, and 2 (3.4%) bled only when withdrawing from concomitant menstrual suppression. No breakthrough bleeding management method was found to be superior. CONCLUSION: Breakthrough bleeding is relatively common (25%) on T-GAHT despite early amenorrhea. Most cases do not have an identifiable cause. Our data did not show superiority of any 1 method for managing breakthrough bleeding on T-GAHT.