Endocrine Abstracts

JOINT1745

Introduction: Congenital hypogonadotropic hypogonadism (CHH) impairs gonadotropic axis activation during mini-puberty, puberty, and adulthood. Severely affected males may present as neonates with micropenis and/or undescended testes, while milder cases exhibit delayed or absent puberty and infertility. Mimicking gonadotropin action using central hormone agents is standard for puberty and fertility treatments. However, no consensus exists on replacement therapy for mini-puberty, with strategies ranging from testosterone application to central agents like GnRH or gonadotropins via subcutaneous injections or pumps. Central agents are thought to not only improve penile size and testicular descent, but potentially also fertility outcomes, though supporting long-term data are lacking. Variability in regimens and drug access further complicates decision-making.

Aim: This survey aimed to identify global barriers in diagnosing and managing CHH during mini-puberty, providing insights for future guidelines.

Methods: An online survey using the Jotform platform was distributed via pediatric society networks, conferences, and email snowballing between June 2024 and January 2025.

Results: A total of 153 responses from 32 countries were analyzed, with Europe (85), South America (32), and North America (24) contributing most. Most respondents were paediatric endocrinologists (94%), also acting as primary patient managers (96.7%). Referrals occurred during mini-puberty for most cases (49.7% within the first 24 weeks), though 39.9% were referred later. Diagnostic testing during weeks 4–24 was considered optimal by 78%. Next-generation sequencing was performed by 60.1%, while 27.5% lacked access, predominantly in low- and middle-income countries. Hormone treatment was offered by 79.7%, with testosterone-only regimens used by 70.5%, central agents by 9%, and both by 20.5%. Limiting factors creating barriers toward hormone prescriptions included insufficient data (64.5%) and paucity of knowledge (25.8%). Two-thirds treated 0-2 patients with either testosterone or central hormone agents in the last 12 months (n = 339 receiving testosterone, n = 111 receiving central agents). Among testosterone prescribers, intramuscular administration (64.9%) over 3 months (68%) was most common, while the most common central hormone regimen was a hCG + recombinant human FSH combination (35.1%), followed by a hCG-only regimen (24,3%) given via subcutaneous injections (69.4%) for 3 or 6 months (47,2% and 33,3%, respectively). Central agents had lower treatment adherence and were more likely discontinued (16.6%) compared to testosterone (8%).

Conclusion: Despite evidence supporting central hormone agents for fertility outcomes, testosterone remains the more commonly used treatment globally. The findings underscore the need for consensus guidelines and long-term studies, particularly on fertility outcomes.