Supplementary Material for: Comparison of Gonadotropin and Testosterone Therapy in Adolescent males with Hypogonadotropic Hypogonadism

Introduction: Hypogonadotropic hypogonadism (HH) is characterized by insufficient gonadotropin and testosterone secretion, resulting in failure of pubertal development. This study compared the efficacy and safety of gonadotropin therapy and testosterone replacement therapy (TRT) for pubertal induction in adolescent male patients with HH.
Methods: This retrospective cohort study included 70 male patients with HH aged <18 years who were treated at a single tertiary medical center between November 2005 and December 2023. Diagnosis was based on clinical presentation, prepubertal hormone levels, and genetic evaluation. The patients received gonadotropins (n = 56) or TRT (n = 14) and were evaluated at 6-month intervals for up to 36 months.
Results: Serum testosterone levels increased significantly in both groups, with a greater rise observed in the TRT group (from 5.2 to 283.0 ng/dL in the gonadotropin group and from 5.2 to 527.5 ng/dL in the TRT group; overall p < 0.05). Height standard deviation scores improved significantly in both groups, without significant intergroup differences. Stretched penile length also increased significantly in both groups. Testicular volume increased significantly only in the gonadotropin group. Sperm were detected in 72.0% (18/25) of the patients in the gonadotropin group. In the TRT group, two patients underwent semen analysis, wherein sperm were detected. Semen analyses in both groups were performed only after completing pubertal induction and patients reached ≥19 years of age. Both patients undergoing TRT, wherein sperm were detected, received short-term gonadotropin administration in adulthood prior to testing.
Conclusion: Gonadotropin therapy and TRT were both effective and safe for pubertal induction in adolescent male patients with HH. Using TRT, a steeper increase in serum testosterone levels was achieved, whereas gonadotropin therapy uniquely promoted testicular growth, emphasizing the importance of individualized treatment strategies and long-term follow-up to optimize clinical outcomes and preserve fertility potential.