Research Article| Volume 34, ISSUE 5, P706-716, October 2021

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

  • Frances Grimstad
    Address correspondence to: Frances Grimstad, MD, MS, Division of Gynecology, Department of Surgery, Boston Children's Hospital, Boston, 333 Longwood Avenue, 02115, MA. Phone: 617 355-7648.
    Division of Gynecology, Department of Surgery, Boston Children's Hospital, Boston, Massachusetts

    Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, Massachusetts
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  • Jessica Kremen
    Division of Endocrinology, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts

    Department of Pediatrics, Harvard Medical School, Boston, Massachusetts
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  • Jessica Shim
    Division of Gynecology, Department of Surgery, Boston Children's Hospital, Boston, Massachusetts

    Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, Massachusetts
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  • Brittany M. Charlton
    Department of Pediatrics, Harvard Medical School, Boston, Massachusetts

    Division of Adolescent/Young Adult Medicine, Boston Children's Hospital, Boston, Massachusetts

    Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts

    Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
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  • Elizabeth R. Boskey
    Department of Plastic and Oral Surgery, Boston Children's Hospital, Boston, Massachusetts

    Center for Gender Surgery, Boston Children's Hospital, Boston, Massachusetts
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Published:April 25, 2021DOI:


      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.


      Institutional review board−approved retrospective cohort.


      Tertiary-care children's hospital.


      TGD AYA on T-GAHT >1 year.


      None; observational.

      Main Outcome Measures

      Presence of, and risk factors for, breakthrough bleeding.


      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.


      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.

      Key Words

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