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

Abstract

To describe our Center's 8-year experience with subcutaneous testosterone (SC-T) as gender-affirming hormone therapy (GAHT) in transmasculine and gender-diverse (TM/GD) youth. Methods: An Institutional Review Board (IRB)-approved retrospective study for 119 TM/GD subjects who started SC-T at age 13-19 and received SC-T for > 6 months between 2012 and 2020. Results: SC-T was typically started at 25-50 mg biweekly and dose was escalated at provider's discretion. Over 96% of subjects were on 100-320 mg monthly (divided weekly or biweekly) at last follow-up. There was an overall increase in mean total and free testosterone (T) over the dose range ( p = 0.003), with mean total and free T levels of 460 ng/dL and 92 pg/mL, respectively, at a monthly SC-T dose of 200 mg. For subjects on SC-T without additional menstrual suppression, 54% had cessation of menses at 140 mg monthly and 97% at 200 mg monthly. On average, menses stopped 4.7 (standard deviation 3.0) months after starting SC-T. There was a decrease in high-density lipoprotein and increase in hematocrit from baseline to follow-up. Body mass index Z-scores did not change significantly with treatment. Mild acne was common; severe acne and significant injection site reactions were uncommon. Sustained hypertension, transaminitis, and dyslipidemia were infrequent. Conclusions: SC-T is well tolerated and effective in reaching recommended T levels and stopping menses in TM/GD youth. Occurrence of serious adverse effects is low and inability to tolerate injections is very uncommon. SC-T is a safe and effective alternative to intramuscular testosterone in initiation and maintenance of GAHT in TM/GD youth.

Masculinising and feminising hormone interventions for adolescents experiencing gender dysphoria or incongruence: a systematic review

“…Studies were published from 2006 to 2022 (with 60% from 2020 to 2022 (n=32)), and conducted in the Netherlands (n=17),25–41 US (n=24),42–65 Israel (n=3),66–68 Belgium (n=2),69 70 Canada (n=2)71 72 and one in Brazil,73 Finland,74 Germany,75 Spain76 and the UK77 (online supplemental table S2).…”

“…Of the 53 studies, 12 were cohorts comparing adolescents experiencing gender dysphoria/incongruence receiving hormones with a comparator,34 37–39 42 43 46 49 54 64 75 76 9 cross-sectional with comparator25 45 50 51 57 60 65 73 77 and 32 pre–post designs 26–33 35 36 40 41 44 47 48 52 53 55 56 58 59 61–63 66–72 74. Over half of the studies (n=30) used retrospective chart review.…”

“…One cohort study measuring side effects only was rated as high-quality,54 33 were moderate25 30–41 45 47 48 50–53 55 56 59–63 66 67 69 70 74 76 and 19 low 26–29 42–44 46 49 57 58 64 65 68 71–73 75 77. Of the 12 cohort studies, (the only studies to include a comparator group and assess outcomes over time), 6 were rated as high or moderate quality (figure 2, online supplemental table S4).…”

Extended Use of Histrelin Implant in Pediatric Patients

“…In transmales, suppression with HI allowed for a gradual increase in GAHT dose without concerns of menstruation starting/recurring. Although not U.S. Food and Drug Administration (FDA) approved, SC-T administration was shown to be safe and efficacious in TG/NB youth 17 and was the primary method of T treatment in both centers.…”

Reversible interventions for menstrual management in adolescents and young adults with gender incongruence

“…Testosterone therapy alone can offer therapeutic amenorrhea, usually within 3-6 months 3,26,[28][29][30] Many patients will prefer to use testosterone therapy alone to achieve this end, although there are several important caveats to consider, including the possibility that amenorrhea with testosterone therapy alone is not always possible. 26 Testosterone, while it does result in amenorrhea, does not provide complete ovulatory suppression and is not a contraceptive; [31][32][33] in addition, it may cause fetal harm. 34 In patients who engage in sexual activity that may result in pregnancy, the use of testosterone alone should not be considered adequate for pregnancy prevention.…”