Differences in adverse drug reactions between GnRH antagonists and agonists in the treatment of prostate cancer: a retrospective analysis using real-world data.

PURPOSE: This study aimed to evaluate the safety profiles of gonadotropin-releasing hormone (GnRH) antagonists and agonists in the treatment of prostate cancer (PC). METHODS: A retrospective pharmacovigilance analysis was conducted using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the fourth quarter of 2024. Within-class direct comparison analyses between GnRH antagonists and GnRH agonists were performed using disproportionality methods, including the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR). Further analyses on age stratification, combination therapy, and onset time of adverse events (AEs) were conducted to explore the safety differences between GnRH antagonists and agonists. RESULTS: A total of 2,486 reports were included in the study, comprising 444 reports for GnRH antagonists and 2,042 reports for GnRH agonists. GnRH antagonists showed higher risk for injection site reactions compared with GnRH agonists, with the strongest signals observed for injection site erythema (ROR = 16.07, 95% confidence interval [CI] = 9.14-28.28; PRR = 14.33; χ2 = 159.30), injection site pain (ROR = 10.44, 95% CI = 6.53-16.71; PRR = 9.27; χ2 = 140.27), and injection site swelling (ROR = 10.31, 95% CI = 5.58-19.05; PRR = 9.63; χ2 = 82.72). Age-stratified analysis demonstrated that injection site reactions remained the predominant signals across age groups, while patients aged ≥65 years exhibited a broader spectrum of AE signals. Time-to-onset analysis revealed different temporal patterns between the two drug classes, with a higher proportion of GnRH antagonist-associated AEs occurring within 30 days after treatment initiation, whereas GnRH agonist-associated AEs were more frequently reported after 360 days. Concomitant medication subgroup analyses further identified distinct AE reporting patterns in specific treatment contexts. CONCLUSION: This pharmacovigilance study identified distinct AE reporting patterns between GnRH antagonists and GnRH agonists in PC treatment. GnRH antagonists were primarily characterized by higher risk of local injection site reactions, whereas AE profiles varied according to patient age, treatment duration, and concomitant medication exposure.