madman
Super Moderator
Abstract
Purpose: 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 the dose was escalated at the provider’s discretion. Over 96% of subjects were on 100–320 mg monthly (divided weekly or biweekly) at the 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 an 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. The occurrence of serious adverse effects is low and the inability to tolerate injections is very uncommon. SC-T is a safe and effective alternative to intramuscular testosterone in the initiation and maintenance of GAHT in TM/GD youth.
Background
Testosterone (T) replacement therapy is utilized in hypogonadal cis males and as gender-affirming hormone therapy (GAHT) for transmasculine and gender diverse (TM/GD) adults and youth.1,2 T replacement can be given as intramuscular (IM) injection, transdermally (patch or gel), orally, or as an implant. In addition to higher treatment costs often associated with transdermal formulations, patches may irritate skin and are unavailable in small/gradually incrementing doses, while T-gel carries the risk of inadvertent transfer to close contacts. Other T formulations considered less accessible or desirable include oral (not readily available for use in the United States) and implantable subcutaneous pellets (dose cannot be quickly adjusted as pellets are in place for several months and carry the risk of dermatitis, infection, or extrusion3 ). Therefore, it is often preferred to use an injectable form of T as GAHT. Subcutaneous testosterone (SC-T) injections are approved for T enanthate administration for adults only using a costly self-injector device. Studies in adult transgender patients have suggested that SC-T is well tolerated with stable and therapeutic serum T levels.4,5 Studies in hypogonadal adult cisgender males also indicate that SC-T is safe and well-tolerated with steady pharmacokinetic profile.6–8 Although one study using injectable depot T undecanoate (formulation not used in our Center) showed some preferred IM route over SC,9 another study using T cypionate and enanthate (the two formulations most commonly used in our center) showed all participants who had utilized both routes preferred SC administration.10
Thus, interest in SC-T for TM/GD youth has increased, but extensive pediatric data are lacking. Olson et al.11 showed good efficacy and tolerability of SC-T with favorable adverse effect profile in transgender youth and young adults (aged 13–24). The study limitations were a relatively small cohort (36 subjects) and short (6-month) follow-up. Since our clinic was established in 2012, we have almost exclusively had patients administer T-SC as opposed to IM. Patients at our center are started on biweekly (every 2 weeks) injections and at follow-up are offered to switch to weekly SC-T. Although some choose to stay on biweekly injections, the majority prefer weekly dosing especially if experiencing mood changes related to peak or nadir of biweekly SC-T dosing. Our large patient population has received SC-T over many years, which enables us to further characterize the efficacy, safety, and tolerability of SC-T in TM/GD youth. In our center, SC-T is typically initiated around age 14 or older, after multidisciplinary assessment of readiness, in youth with gender dysphoria who desire GAHT, and have no contraindications. We use a gradually increasing dose schedule in keeping with published guidelines.1,2
Conclusions/Discussion
This study, to date the largest pediatric study of SC-T, adds to the currently limited literature supporting the efficacy and safety of SC-T as an alternative to IM testosterone injections for GAHT in TM/GD youth. Dose of SC-T required to achieve mean total T levels in the goal range (400–700 ng/dL when measured midinjection1 ) and achieve the cessation of menses for the majority of our study subjects was 140–200 mg monthly, which is similar to or lower than those suggested by guidelines1 as adult doses for IM or SC-T (100– 200 mg every other week). Of note, a small subset of subjects did not achieve the ultimately intended dose due to limited follow-up and some subjects requested lower-than-typical doses.
As SC-T is not an FDA-approved route for T-cypionate, this publication is a valuable addition to the medical literature relevant not only to TM/GD individuals but also to cisgender hypogonadal adolescents and young adults. We conclude that SC-T is effective in TM/GD youth in achieving adult male serum T levels and cessation of menses. No subjects had to stop SC-T because of serious adverse effects on BP, acne, transaminases, lipid profile, or hematocrit. Overall, the tolerance of SC-T was very good. We recommend, based on our extensive experience, that providers consider SC-T as an excellent alternative to IM T for initiation and maintenance of GAHT in TM/GD youth.
Purpose: 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 the dose was escalated at the provider’s discretion. Over 96% of subjects were on 100–320 mg monthly (divided weekly or biweekly) at the 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 an 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. The occurrence of serious adverse effects is low and the inability to tolerate injections is very uncommon. SC-T is a safe and effective alternative to intramuscular testosterone in the initiation and maintenance of GAHT in TM/GD youth.
Background
Testosterone (T) replacement therapy is utilized in hypogonadal cis males and as gender-affirming hormone therapy (GAHT) for transmasculine and gender diverse (TM/GD) adults and youth.1,2 T replacement can be given as intramuscular (IM) injection, transdermally (patch or gel), orally, or as an implant. In addition to higher treatment costs often associated with transdermal formulations, patches may irritate skin and are unavailable in small/gradually incrementing doses, while T-gel carries the risk of inadvertent transfer to close contacts. Other T formulations considered less accessible or desirable include oral (not readily available for use in the United States) and implantable subcutaneous pellets (dose cannot be quickly adjusted as pellets are in place for several months and carry the risk of dermatitis, infection, or extrusion3 ). Therefore, it is often preferred to use an injectable form of T as GAHT. Subcutaneous testosterone (SC-T) injections are approved for T enanthate administration for adults only using a costly self-injector device. Studies in adult transgender patients have suggested that SC-T is well tolerated with stable and therapeutic serum T levels.4,5 Studies in hypogonadal adult cisgender males also indicate that SC-T is safe and well-tolerated with steady pharmacokinetic profile.6–8 Although one study using injectable depot T undecanoate (formulation not used in our Center) showed some preferred IM route over SC,9 another study using T cypionate and enanthate (the two formulations most commonly used in our center) showed all participants who had utilized both routes preferred SC administration.10
Thus, interest in SC-T for TM/GD youth has increased, but extensive pediatric data are lacking. Olson et al.11 showed good efficacy and tolerability of SC-T with favorable adverse effect profile in transgender youth and young adults (aged 13–24). The study limitations were a relatively small cohort (36 subjects) and short (6-month) follow-up. Since our clinic was established in 2012, we have almost exclusively had patients administer T-SC as opposed to IM. Patients at our center are started on biweekly (every 2 weeks) injections and at follow-up are offered to switch to weekly SC-T. Although some choose to stay on biweekly injections, the majority prefer weekly dosing especially if experiencing mood changes related to peak or nadir of biweekly SC-T dosing. Our large patient population has received SC-T over many years, which enables us to further characterize the efficacy, safety, and tolerability of SC-T in TM/GD youth. In our center, SC-T is typically initiated around age 14 or older, after multidisciplinary assessment of readiness, in youth with gender dysphoria who desire GAHT, and have no contraindications. We use a gradually increasing dose schedule in keeping with published guidelines.1,2
Conclusions/Discussion
This study, to date the largest pediatric study of SC-T, adds to the currently limited literature supporting the efficacy and safety of SC-T as an alternative to IM testosterone injections for GAHT in TM/GD youth. Dose of SC-T required to achieve mean total T levels in the goal range (400–700 ng/dL when measured midinjection1 ) and achieve the cessation of menses for the majority of our study subjects was 140–200 mg monthly, which is similar to or lower than those suggested by guidelines1 as adult doses for IM or SC-T (100– 200 mg every other week). Of note, a small subset of subjects did not achieve the ultimately intended dose due to limited follow-up and some subjects requested lower-than-typical doses.
As SC-T is not an FDA-approved route for T-cypionate, this publication is a valuable addition to the medical literature relevant not only to TM/GD individuals but also to cisgender hypogonadal adolescents and young adults. We conclude that SC-T is effective in TM/GD youth in achieving adult male serum T levels and cessation of menses. No subjects had to stop SC-T because of serious adverse effects on BP, acne, transaminases, lipid profile, or hematocrit. Overall, the tolerance of SC-T was very good. We recommend, based on our extensive experience, that providers consider SC-T as an excellent alternative to IM T for initiation and maintenance of GAHT in TM/GD youth.
