OBJECTIVE To evaluate the safety of gonadotropin-releasing hormone(GnRH) agonists leuprorelin, triptorelin, and histrelin in minors(<18 years old) using the US Food and Drug Administration Adverse Event Reporting System(FAERS) database, identify potential safety signals, and provide evidence for clinical practice.

METHODS From the first quarter of 2004 to the first quarter of 2025, reports of leuprorelin, triptorelin, and histrelin used in individuals under 18 years old were extracted from the FAERS database. Methods such as reporting odds ratio(ROR) and proportional reporting ratio(PRR) were used to analyze the frequency, intensity, and temporal distribution of adverse drug events(ADEs) based on system organ class(SOC) and preferred term(PT), and the impact of administration routes was also explored.

RESULTS A total of 590539 reports were included, with 2288 for leuprorelin, 742 for triptorelin, and 408 for histrelin. The proportion of female reports was significantly higher than that of males(81.5% for leuprorelin, 80.7% for triptorelin, and 78.0% for histrelin). The main SOCs included “general disorders and administration-site conditions” and “injury, poisoning, and procedural complications”. New signals identified included slipped capital femoral epiphysis(ROR=28.67 for leuprorelin, ROR=39.42 for triptorelin) and gait weakness. Serious ADEs(such as 48 cases of epileptic seizure and 20 deaths) indicated the need to pay attention to rare but severe consequences. ADEs were mostly concentrated within 500 d after administration, and leuprorelin had the highest incidence rate. Analysis of administration routes showed that subcutaneous injection was associated with procedural complications, while intramuscular injection was associated with local reactions.

CONCLUSION Leuprorelin, triptorelin, and histrelin exhibit different safety profiles in minors. Injection-site reactions, procedural complications, and skeletal-related signals require particular attention. Females and the early treatment period are at higher risk, and enhanced monitoring is recommended. Future prospective studies are needed to verify long-term safety and provide guidance for pediatric and gender-affirming treatments.