{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T06:25:23Z","timestamp":1787034323122,"version":"build-2736575974"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study aimed to evaluate the safety profiles of gonadotropin-releasing hormone (GnRH) antagonists and agonists in the treatment of prostate cancer (PC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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\u201328.28; PRR = 14.33; \u03c7\n                      <jats:sup>2<\/jats:sup>\n                      = 159.30), injection site pain (ROR = 10.44, 95% CI = 6.53\u201316.71; PRR = 9.27; \u03c7\n                      <jats:sup>2<\/jats:sup>\n                      = 140.27), and injection site swelling (ROR = 10.31, 95% CI = 5.58\u201319.05; PRR = 9.63; \u03c7\n                      <jats:sup>2<\/jats:sup>\n                      = 82.72). Age-stratified analysis demonstrated that injection site reactions remained the predominant signals across age groups, while patients aged \u226565 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1895503","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:37:40Z","timestamp":1787031460000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Differences in adverse drug reactions between GnRH antagonists and agonists in the treatment of prostate cancer: a retrospective analysis using real-world data"],"prefix":"10.3389","volume":"17","author":[{"given":"Yingxun","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Urology, Shantou Central Hospital","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuwei","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Urology, Shantou Central Hospital","place":["Shantou, China"]},{"name":"Shantou Key Laboratory of Basic and Translational Research of Malignant Tumor","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqiang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Urology, Shantou Central Hospital","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Urology, Shantou Central Hospital","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shantou Central Hospital","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Urology, Shantou Central Hospital","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weinan","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Urology, Shantou Central Hospital","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanfeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, Shantou Central Hospital","place":["Shantou, China"]},{"name":"Shantou Key Laboratory of Basic and Translational Research of Malignant Tumor","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, Shantou Central Hospital","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.eururo.2020.06.002","article-title":"Differential impact of gonadotropin-releasing hormone antagonist versus agonist on clinical safety and oncologic outcomes on patients with metastatic prostate cancer: a meta-analysis of randomized controlled trials","volume":"79","author":"Abufaraj","year":"2021","journal-title":"Eur. Urol."},{"key":"B2","first-page":"8179","article-title":"Optimizing subcutaneous injection of the gonadotropin-releasing hormone receptor antagonist degarelix","volume":"23","author":"Barkin","year":"2016","journal-title":"Can. J. Urol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1210\/endrev\/bnab002","article-title":"Hormonal therapy for prostate cancer","volume":"42","author":"Desai","year":"2021","journal-title":"Endocr. Rev."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e248523","DOI":"10.1136\/bcr-2021-248523","article-title":"Late onset of pituitary apoplexy following gonadotropin-releasing hormone agonist for prostate cancer treatment","volume":"15","author":"Elshimy","year":"2022","journal-title":"BMJ Case Rep."},{"key":"B5","first-page":"48","article-title":"Androgen suppression for symptomatic disease","volume":"22","year":"2013","journal-title":"Prescrire Int."},{"key":"B6","doi-asserted-by":"publisher","first-page":"3","DOI":"10.4103\/aja.aja_22_20","article-title":"Androgen deprivation therapy and side effects: are GnRH antagonists safer?","volume":"23","author":"Freedland","year":"2021","journal-title":"Asian J. Androl."},{"key":"B7","doi-asserted-by":"publisher","first-page":"3331","DOI":"10.3390\/curroncol28050289","article-title":"Androgen deprivation therapy, hypogonadism and cardiovascular toxicity in men with advanced prostate cancer","volume":"28","author":"Gheorghe","year":"2021","journal-title":"Curr. Oncol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"5123","DOI":"10.1200\/JCO.2026.44.16_suppl.5123","article-title":"Association of cardiovascular outcomes with GnRH agonist and antagonist therapy in non-metastatic prostate cancer","volume":"44","author":"Ghiblawi","year":"2026","journal-title":"J. Clin. Oncol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1157857","DOI":"10.3389\/fendo.2023.1157857","article-title":"Adverse cardiovascular effect following gonadotropin-releasing hormone antagonist versus GnRH agonist for prostate cancer treatment: a systematic review and meta-analysis","volume":"14","author":"Gu","year":"2023","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1093\/jjco\/hyab077","article-title":"Safety and efficacy of abiraterone acetate plus prednisolone in patients with castration-resistant prostate cancer: a prospective, observational, post-marketing surveillance study","volume":"51","author":"Koroki","year":"2021","journal-title":"Jpn. J. Clin. Oncol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"639","DOI":"10.2147\/dddt.S291369","article-title":"Progress in clinical research on gonadotropin-releasing hormone receptor antagonists for the treatment of prostate cancer","volume":"15","author":"Liu","year":"2021","journal-title":"Drug Des. Devel Ther."},{"key":"B12","doi-asserted-by":"publisher","first-page":"S142","DOI":"10.4103\/ijc.IJC_65_21","article-title":"Gonadotropin-releasing hormone agonists in prostate cancer: a comparative review of efficacy and safety","volume":"59","author":"Raja","year":"2022","journal-title":"Indian J. Cancer"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1822","DOI":"10.1056\/NEJMsa0910784","article-title":"Reimbursement policy and androgen-deprivation therapy for prostate cancer","volume":"363","author":"Shahinian","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1159\/000056592","article-title":"Optimal starting time for flutamide to prevent disease flare in prostate cancer patients treated with a gonadotropin-releasing hormone agonist","volume":"66","author":"Tsushima","year":"2001","journal-title":"Urol. Int."},{"key":"B15","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1007\/s40273-016-0481-1","article-title":"Degarelix for treating advanced hormone-dependent prostate cancer: an evidence review group perspective of a NICE single technology appraisal","volume":"35","author":"Uttley","year":"2017","journal-title":"Pharmacoeconomics"},{"key":"B16","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1111\/iju.14303","article-title":"Considerations for the use of gonadotropin-releasing hormone agonists and antagonists in patients with prostate cancer","volume":"27","author":"Van Poppel","year":"2020","journal-title":"Int. J. Urol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/s40360-025-00920-4","article-title":"Post-marketing safety profile of ganirelix in women: a 20-year pharmacovigilance analysis of global adverse drug event databases (2004-2024)","volume":"26","author":"Yang","year":"2025","journal-title":"BMC Pharmacol. Toxicol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1007\/s10147-021-02070-z","article-title":"Real-world use of enzalutamide in men with nonmetastatic castration-resistant prostate cancer in Japan","volume":"27","author":"Yokomizo","year":"2022","journal-title":"Int. J. Clin. Oncol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1097\/ju.0000000000001785","article-title":"Cardiovascular events in men with prostate cancer receiving hormone therapy: an analysis of the FDA adverse event reporting system (FAERS)","volume":"206","author":"Zhang","year":"2021","journal-title":"J. Urol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1595159","DOI":"10.3389\/fpubh.2025.1595159","article-title":"Global, regional, and national prevalence of prostate cancer from 1990 to 2021: a trend and health inequality analyses","volume":"13","author":"Zhao","year":"2025","journal-title":"Front. Public Health"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1895503\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:37:41Z","timestamp":1787031461000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1895503\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,18]]},"references-count":20,"alternative-id":["10.3389\/fphar.2026.1895503"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1895503","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,18]]},"article-number":"1895503"}}