Experience with subcutaneous testosterone for gender-affirming hormone therapy in transgender men at a tertiary care center

Subcutaneous (SC) administration of testosterone has been proposed as a safe, effective, and well-tolerated alternative in gender-affirming hormone therapy for transgender men. However, its use in Spain is limited, with no indication in the product information.

To evaluate the efficacy, safety, dosing requirements, and acceptability of subcutaneous testosterone cypionate in trasgender men followed at a tertiary Gender Identity Reference Unit.

We conducted a retrospective longitudinal observational study at Hospital Universitario Doctor Peset (Valencia, Spain) from January 2024 through September 2025. Twenty-eight transgender men receiving weekly subcutaneous testosterone cypionate (initial dose, 50 mg/week) were included, both treatment-naïve individuals and those previously treated with other testosterone formulations. Serum total testosterone and estradiol concentrations, liver function tests, lipid profile, hematocrit, menstrual status, acne development, and treatment tolerability were analyzed.

At 2 months, mean (SD) serum testosterone concentration was 6.2 (2.9) ng/mL, and at 6 months, 5.1 (1.5) ng/mL, remaining within the physiologic male reference range. Dose adjustment was required in 7 patients (25%). Amenorrhea was achieved in 92.9% of participants. No clinically significant changes in liver enzymes or lipid profile were observed. The incidence of polycythemia was low. No local injection-site reactions were reported, and all participants expressed satisfaction with the SC route of administration.

Subcutaneous testosterone cypionate was safe, effective, well tolerated, and highly accepted in transgender men, achieving stable serum testosterone and estradiol levels within the target range. This route may represent a viable alternative for gender-affirming hormone therapy in clinical practice.