A prospective comparison study of subcutaneous and intramuscular testosterone injections in transgender male adolescents

Objectives: This prospective study compares testosterone injection type and effects on biochemical changes, clinical effects, and quality of life amongst transgender and gender diverse (TGD) adolescents assigned female at birth (AFAB) over the first 6 months of subcutaneous (SQ) vs. intramuscular (IM) testosterone injections as part of their gender affirming care. Methods: Subjects were testosterone-naïve transgender adolescents, AFAB, ages 14-18 years old. Subjects were either randomized to injection type or selected a preferred injection type. At enrollment, subjects completed baseline labs and PedsQL™ quality of life questionnaire. At 3 month and 6 month follow up, subjects completed peak and trough testosterone levels, PedsQL™, masculinizing effects, and medication experience questionnaires. Results: Twenty-six subjects participated with a median age 15.5 years. By 6-month follow up, trough testosterone levels were comparable between the two groups. Peak testosterone levels were higher in the IM group at 3-month follow up. Mild adverse effects were rare (12%, all in SQ subjects) and limited to skin reaction only. Self-reported masculinization effects and quality of life were not statistically different between injection groups. A total of 92% of participants was self-injecting by 3-month follow up. Conclusions: In this prospective study, clinical and biochemical effects are similar between SQ and IM testosterone injections for transgender adolescents. Subjects expressed preference for both injection types. Both SQ and IM injection modalities are safe and effective for TGD youth initiating testosterone and both options should be offered to patients.