Incidence of breakthrough bleeding in transgender and gender diverse individuals on long-term testosterone

BACKGROUND:Little is known about maintenance of amenorrhea in transgender and gender diverse individuals with uteri using long-term testosterone gender-affirming hormone therapy. Emerging data describes breakthrough bleeding in adolescents on long-term testosterone, as well as in adults seeking gender affirming hysterectomy. More studies are needed to better understand breakthrough bleeding patterns in transgender and gender diverse individuals on testosterone with uteri, including the frequency, timing, and etiology, and how these may differ in adults compared to younger populations. OBJECTIVES:The primary aim of this study was to characterize the incidence and patterns of breakthrough bleeding in a cohort of transgender and gender diverse individuals who had been on testosterone for greater than 12 months and had uteri in situ. Secondary aims included identifying the time to first bleed for those who experienced breakthrough bleeding as well as risk factors associated with breakthrough bleeding on testosterone. STUDY DESIGN:This was an IRB approved, single tertiary center, retrospective chart review of transgender and gender diverse individuals who had been on testosterone for at least one year. A primary survival analysis looking at the incidence of bleeding was combined with descriptive analyses and evaluation of factors associated with bleeding. RESULTS:Of the 279 patients included in the analysis, the median age of testosterone initiation was 22 years (IQR 19-41), with the median follow-up time 34 months (range 12-278). The absolute proportion of individuals who ever experienced breakthrough bleeding on testosterone was 34% (n=96, 95% CI [29, 40]). Patients who experienced breakthrough bleeding initiated testosterone at a younger age (20.5 vs 22.0 years, p=0.04), had lower mean serum testosterone levels (389.14 vs 512.7 ng/dL, p=0.001), were more likely to have a mean testosterone level <320ng/dL (52% vs 48% , p=.001), and had higher mean estradiol levels (62% vs 49%, p=0.003). Survival analyses estimated a breakthrough bleeding incidence rate of 0.09 per year (95% CI [.07-1.0]). While 58 people underwent a hysterectomy during the follow-up period, 64% of the cohort who maintained a uterus eventually experienced breakthrough bleeding. The median time to the initial bleeding episode was 22 (IQR 12-201) months after testosterone initiation. CONCLUSION(S):These results suggest a substantial fraction of transgender and gender diverse individuals using testosterone will experience at least one episode of breakthrough bleeding, even after their initial year using testosterone. We recommend that clinicians counsel all patients that breakthrough bleeding is a common occurrence, even after the first year on testosterone.