基于FAERS的未成年人使用3种常见促性腺激素释放激素激动剂的安全性评价

Safety Evaluation of Three Common Gonadotropin-Releasing Hormone Agonists in Minors Based on FAERS

关键词:  促性腺激素释放激素  FAERS数据库  不良事件信号

Key words:  GnRH  FAERS database  adverse event signal

摘要:

目的 本研究旨在利用美国食品和药物管理局不良事件报告系统（FAERS）评估未成年人（<18岁）使用促性腺激素释放激素（GnRH）激动剂——亮丙瑞林、曲普瑞林和组氨瑞林的安全性，识别潜在安全信号，为临床实践提供证据。方法 从2004年第一季度至2025年第一季度，提取FAERS数据库中18岁以下人群使用亮丙瑞林、曲普瑞林和组氨瑞林的报告。采用报告比值比（ROR）和比例报告比（PRR）等方法，基于系统器官分类（SOC）和首选术语（PT）分析不良事件（ADEs）的频率、强度及时间分布，并探讨给药途径的影响。结果 共纳入590,539份报告，其中亮丙瑞林2,288份、曲普瑞林742份、组氨瑞林408份。女性报告占比显著高于男性（亮丙瑞林81.5%，曲普瑞林80.7%，组氨瑞林78.0%）。主要SOC包括“全身性疾病及给药部位各种反应”和“各类损伤、中毒及操作并发症”。新发现信号包括骺滑脱（亮丙瑞林ROR=28.67，曲普瑞林ROR=39.42）和步态无力。严重ADEs（如癫痫发作48例、死亡20例）提示需关注罕见但严重后果。ADE多集中于给药后的前500天内，且亮丙瑞林发生率最高。给药途径分析显示，皮下注射与操作并发症相关，肌肉注射与局部反应相关。结论 亮丙瑞林、曲普瑞林和组氨瑞林在未成年人中显示出不同的安全性特征，注射部位反应、操作并发症及骨骼相关信号需特别关注。女性及治疗初期风险较高，建议加强监测。未来需前瞻性研究验证长期安全性，为儿科及性别确认治疗提供指导

Abstract:

OBJECTIVE The purpose of this study is 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), 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, trioreptlin, and histrelin use 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 590,539 reports were included, with 2,288 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 seizures of and 20 deaths) indicated the need to pay attention to rare but severe consequences. ADEs are mostly concentrated within the first 500 days after administration, and leuprorelin has 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 exhibited different safety profiles in minors. Injection-site reactions, procedural complications, and skeletal-related signals require particular attention. Females and the early treatment period were 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.