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Updated: Nov 7, 2025

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Published on: January 10, 2025
Breakthrough Bleeding in Transgender and Gender Diverse Adolescents and Young Adults on Long-Term Testosterone
Frances Grimstad1, Jessica Kremen2, Jessica Shim1
1Division of Gynecology, Department of Surgery, Boston Children's Hospital, Boston, Massachusetts; Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, Massachusetts.
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.
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