Single-Center Retrospective Analysis of Safety and Efficacy of Subcutaneous Estradiol Use in Transgender and Nonbinary Adolescents and Young Adults.

Purpose: The study aimed to characterize transgender and nonbinary (TGNB) adolescents and young adults on subcutaneous (SC) estradiol for feminizing gender-affirming hormone therapy and demonstrate efficacy and safety in these individuals.

Methods: A retrospective single-center chart review of TGNB adolescents and young adults up to 25 years old who received SC estradiol cypionate or SC estradiol valerate and completed laboratory testing between January 1, 2021, and January 1, 2024, was conducted. Mann-Whitney U tests were used for analysis.

Results: From transgender female (n = 37, 93%) and nonbinary (n = 3, 7%) individuals, 30 (75%) individuals demonstrated therapeutic serum estradiol concentrations (100-300 pg/mL) on SC estradiol cypionate, SC estradiol valerate, or both. Of the 23 patients using SC estradiol cypionate, 52% (n = 12) had therapeutic concentrations, but many were unable to titrate dosing due to nationwide shortage. Of the 32 patients on SC estradiol valerate, 75% (n = 24) achieved therapeutic concentrations. Serum testosterone concentrations were suppressed in all but one instance (97%, n = 35) of therapeutic serum estradiol concentrations; the majority of patients used simultaneous anti-androgens. To achieve therapeutic serum estradiol concentrations, the SC estradiol valerate dose (median 4 mg weekly, interquartile range [IQR]: 4-5.5) was significantly higher than the SC estradiol cypionate dose (median 2 mg weekly, IQR: 2-2.5), p < 0.001. No clinically significant adverse events occurred, including new transaminase elevation, severe dyslipidemia, or thromboembolism.

Conclusion: Many TGNB adolescents and young adults on SC estradiol administration achieved appropriate serum estradiol concentrations and no adverse events were reported, supporting continued use of SC estradiol in gender-affirming care.