Safety and Efficacy of Subcutaneous Testosterone Among Transmasculine and Gender-Diverse Youth

Subcutaneous testosterone (SC-T) injections were found to be a safe and effective alternative to intramuscular testosterone among transmasculine and gender-diverse (TM/GD) youth, according to results of a retrospective, single-center study published in Transgender Health.

TM/GD youth (N=119) receiving gender-affirming hormone therapy for more than 6 months at Rady Children’s Hospital in San Diego, California, between 2012 and 2020 were included in this study. SC-T was typically given at a starting dosage of 25 to 50 mg biweekly, escalating to 100 to 320 mg monthly administered weekly or biweekly. Average total and free testosterone levels, menstrual suppression, and safety were evaluated.

TM/GD youth presented at an average age of 16 (range, 10.1-19.8) years, they started SC-T at 16.5 (range, 13-19.9) years, 92.5% identified as transmale or male, 66.4% were White, 20.2% were obese, 16% were overweight, and 83.2% were not using menstrual suppression therapy prior to SC-T.

Over a median follow-up of 1.9 years (range, 6 months to 5.5 years), the SC-T dose increased every 3 to 6 months, as guided by serum testosterone level and patient preference. At the final follow-up visit, 79% of study participants were receiving a 100 mg to 200 mg monthly dosage, and 18% of study participants were receiving a 240 mg to 320 mg monthly dosage.

Mean total and free testosterone levels ranged from 274 to 534 ng/dL and 43 to 129 pg/mL for those receiving 100 mg SC-T, and mean levels were 460 ng/dL and 92 pg/mL for those receiving 200 mg SC-T, respectively.

Most individuals with sufficient data (n=78) stopped menses (97.4%) with a 200 mg SC-T dose, and approximately one-half (53.9%) stopped menses with a 140 mg SC-T dose. Cessation of menses occurred at an average of 4.7 months after initiation of SC-T. Time to menses arrest was significantly longer among study participants who began treatment with a 50 mg SC-T dose (5.4 months; P =.025).

Significant increases in BMI were reported during SC-T treatment (P <.001); however, no differences were observed for BMI Z-scores prior to the start of treatment and at the last follow-up visit (P =.334).

Significant effects were observed between SC-T monthly dose and final testosterone level (P =.003), change in total testosterone level (P =.003), change in aspartate aminotransferase level (P =.010), final hematocrit (P =.024), and final alanine aminotransferase level (P =.050).

Mild injection site reactions were reported by 11.8% of study participants, and acne management was started by 19.3% of study participants. No study participant developed hypertension. One individual developed obesity and worsening dyslipidemia, for which they were prescribed a low-dose statin.

Treatment with SC-T was discontinued in 4 individuals, all of whom switched to treatment with a testosterone gel formulation. 

A limitation of this study is that the data were collected at a single center in a large metropolitan area; therefore, the findings may not be generalizable.

Treatment with SC-T was found in this study to be a safe and effective alternative to intramuscular testosterone among TM/GD youth undergoing gender-affirming hormone therapy. The study authors recommend SC-T in this population despite the fact that it is not a delivery method that has been approved by the US Food and Drug Administration.

Reference

Laurenzano SE, Newfield RS, Lee E, Marinkovic M. Subcutaneous testosterone is effective and safe as gender-affirming hormone therapy in transmasculine and gender-diverse adolescents and young adults: a single center’s 8-year experience. Transgend Health. 2021;6(6):343-352. doi:10.1089/trgh.2020.0103