Testosterone Use in Adolescent Males

Current Practice and Unmet Needs

Maria Vogiatzi; James P. Tursi; Jonathan S. Jaffe; Sue Hobson; Alan D. Rogol


J Endo Soc. 2021;5(1) 

In This Article

Testosterone Formulations: Pediatric Applications and Regulatory Perspectives

Since the initial reports of T synthesis in the 1930s,[55] numerous T formulations have been introduced, but the only products that currently have a pediatric indication in the United States are intramuscular (IM) TE injections and implantable subcutaneous T pellets.[23–25] Both are approved to stimulate puberty in "carefully selected males with clear evidence of delayed puberty".[23] TE and T pellets were approved in 1953 and 1942, respectively, before the passage of the 1962 Kefauver-Harris Drug Control Act, which requires that approved drugs be both efficacious and safe.[23] Although both formulations remain approved, it is unlikely that evidence supporting their efficacy and safety aligns with current standards for FDA approval of drugs for children and adolescents.

Additional IM formulations (T propionate and cypionate) were introduced in the 1950s, oral testosterone undecanoate (TU) was developed in the 1980s, transdermal patches were first marketed in the 1990s, and topical gels, buccal patches, and a long-acting IM preparation of TU were initially marketed in the 2000s.[22,55] More recent introductions include a nasal T preparation in 2016,[22,56] a weekly TE depot delivered subcutaneously via an autoinjector in 2018, and an oral TU formulation in 2019.[22,57]

All TRT products approved after 1953 target adults, and their safety and efficacy in boys younger than 18 have not been established.[23] For newer agents, the labeling warns that improper use of T in adolescents has been associated with bone age acceleration and premature closure of epiphyses.[23] Because these formulations were designed for adults, dosing is not flexible or easily titrated, which is essential for therapy in adolescents, especially to initiate pubertal maturation. Certain preparations are not available globally.[58] For example, oral TU, which has been used successfully in boys with CDGP,[59,60] is available in Europe. TU was not available in the United States until 2019, when it was FDA approved for men,[61] whereas T pellets are still available in the United States and Australia.