Pubertal induction in prepubertal males with hypogonadotropic hypogonadism: testosterone or gonadotropins?

Pubertal induction in males with hypogonadotropic hypogonadism (HH) remains challenging. Various treatment strategies using testosterone or gonadotropins have been developed; however, the optimal approach for initiating and sustaining puberty remains uncertain. A comprehensive PubMed search was conducted in July 2024 using the keyword "puberty induction in males" for studies published between January 2004 and July 2024. The inclusion criteria were publication in English including male patients under 18 years of age with HH. Animal studies, adult cohorts, and non-HH groups were excluded. Of the 134 retrieved records, 18 met the inclusion criteria and were analyzed for therapeutic regimens, efficacy, and outcomes. Both testosterone- and gonadotropin-based therapies effectively induced puberty in males with HH. Intramuscular testosterone esters remain the most commonly used approach because of their accessibility and cost-effectiveness, whereas newer long-acting transdermal formulations offer improved tolerability. Gonadotropin-based regimens, including human chorionic gonadotropin, alone or in combination with follicle-stimulating hormone, demonstrated effective virilization and increased testicular growth and spermatogenesis, suggesting potential benefits for future fertility. However, treatment protocols vary widely and no standardized guidelines are currently available. Pubertal induction in HH should aim to mimic physiological puberty and consider psychological and somatic well-being as well as future fertility potential. Although testosterone effectively promotes virilization, gonadotropin therapy enhances testicular development and spermatogenesis. Their formulations, dosages, treatment durations, and modes of administration show considerable heterogeneity. Further multicenter studies are required to establish optimal regimens and clarify long-term fertility outcomes associated with different therapeutic strategies.