Testosterone Use in Adolescent Males: Current Practice and Unmet Needs

Abstract

Testosterone replacement therapy (TRT) is routinely prescribed in adolescent males with constitutional delay of growth and puberty (CDGP) or hypogonadism. With many new testosterone (T) formulations entering the market targeted for adults, we review current evidence and TRT options for adolescents and identify areas of unmet needs. We searched PubMed for articles (in English) on testosterone therapy, androgens, adolescence, and puberty in humans. The results indicate that short-term use of T enanthate (TE) or oral T undecanoate is safe and effective in inducing puberty and increasing growth in males with CDGP. Reassuring evidence is emerging on the use of transdermal T to induce and maintain puberty. Long-term safety and efficacy of TRT for puberty completion and maintenance have not been established. Current TRT regimens are based on consensus and expert opinion, while evidence-based guidelines are lacking. Limited guidance exists on when and how T should be administered and optimal strategies for monitoring therapy once it is initiated. Only TE and T pellets are FDA approved for use in adolescent males in the US. Despite the introduction of a wide variety of new T formulations, they are designed for adults, and their metered doses are difficult to titrate in adolescents. In conclusion, TRT in adolescent males is hindered by lack of long-term safety and efficacy data and limited options approved for use in this population. Additional research is needed to identify the route, dose, duration, and optimal timing for TRT in adolescents requiring androgen therapy.

Expert Opinion on the Diagnosis and Management of Male Hypogonadism in India

“…Oral testosterone capsules (40 mg, 3 times daily) are recommended in patients with LOH or functional hypogonadism based on findings from certain clinical studies [ 24 ]. However, there are no data to support the effectiveness of testosterone treatment in the management of functional central hypogonadism (or nongonadal illness), for which lifestyle measures are proven to be effective.…”

Growth, growth potential, and influences on adult height in the transgender and gender‐diverse population

“…Current dosing protocols for pubertal induction for gender‐affirming estradiol and testosterone administration are predominantly derived from experience with cis‐gender hypogonadal patients and initial studies in adolescents support its safety 3,90‐94 . Pediatric endocrinologists previously manipulated height in cis‐gender girls through administration of high‐dose estrogen to attenuate adult height by accelerating epiphyseal fusion 95‐97 .…”

“…Current dosing protocols for pubertal induction for gender-affirming estradiol and testosterone administration are predominantly derived from experience with cis-gender hypogonadal patients and initial studies in adolescents support its safety. 3,[90][91][92][93][94] Pediatric endocrinologists previously manipulated height in cis-gender girls through administration of high-dose estrogen to attenuate adult height by accelerating epiphyseal fusion. [95][96][97] While this practice has fallen out of favor, this approach may still be practiced by some pediatric endocrinologists when desired by parents of children with severe intellectual disability.…”

Trans Dermal Testosterone Compared to Intramuscular Testosterone for Young Males with Delayed Puberty: A PRISMA Guided Systematic Review

“…[19][20][21] Earlier short acting esters of TE like Sustanon ® , were used as IM preparations that have been used for many years for the treatment of pubertal TE deficiency. 22 Studies report the safety and efficacy of short-term use of TE Enanthateor oral TE undecanoate in inducing puberty and increasing growth in young males with CDGP. 23,24 Though the long-term safety and efficacy of Transdermal testosterone therapy (TRT) for puberty completion and maintenance have not been established, reliable evidence on the use of Transdermal testosterone (TT) for adolescent boys to induce and maintain puberty are emerging.…”