Endocrine Abstracts

JOINT1213

Introduction: Congenital hypogonadotropic hypogonadism (CHH) is a rare endocrine disorder caused by impaired gonadotropin secretion or action, disrupting pubertal development and reproductive function. Testosterone therapy induces secondary sexual characteristics but does not promote gonadal maturation, whereas gonadotropin therapy supports both testicular growth and function.

Aims and Methods: This study aimed to retrospectively compare auxological and pubertal outcomes in 39 male patients with isolated CHH treated with either testosterone or gonadotropins. Outcomes were assessed at four time points: T0 (treatment initiation), T1 (6–12 months), T2 (18–24 months), and T3 (attainment of adult height and after 6 months after treatment end). Testicular volume (TV) was used as a marker of gonadal maturation. Testosterone therapy was titrated to a final dose of 250 mg/month intramuscularly (or 40–60 mg/day transdermally) over two years. Gonadotropin therapy included rFSH (75 IU twice weekly) and hCG (1000–2000 IU twice weekly), with treatment durations ranging from 6 to 46 months (median: 12 months).

Results: Among the 39 patients, 16 were treated with gonadotropins, and 23 received testosterone. The median age at puberty induction was 16.2±1.5 years for the gonadotropin group and 16.7±1.8 years for the testosterone group. At each time point, gonadotropin-treated patients consistently showed a significantly higher median TV than the testosterone group. This difference, already significant at T1, increased at T2 and persisted at T3 (9.0 mL vs. 4.0 mL; P < 0.0001), confirming a sustained effect of gonadotropin therapy. Half of the gonadotropin-treated patients transitioned to testosterone after pubertal induction. In this subset, the difference in TV remained significant (11.0 mL vs. 4.0 mL; P = 0.0002). Auxological analysis revealed better adult height corrected for mid-parental height (MPH) in the gonadotropin group (SDS: 0.19 vs. -0.57; P = 0.04), indicating these patients achieved an adult height closer to their genetic potential. No significant differences were observed in other parameters.

Discussion and Conclusion: Gonadotropin therapy led to greater and sustained increases in TV compared to testosterone, even after transitioning to testosterone. This underscores its ability to promote gonadal maturation and enhance fertility potential. Additionally, patients treated with gonadotropins achieved final heights closer to their genetic potential, likely due to the more physiologically pubertal progression, which avoids premature epiphyseal closure often associated with faster initial growth seen with testosterone. Nevertheless, further studies are needed to confirm these results and explore the long-term implications, particularly for fertility outcomes.