Drug-Induced Gynecomastia: Data Mining and Analysis of the FDA Adverse Event Reporting System Database

Xiuli Yang,1 Xiaochun Zheng,1 Miaomiao Zhang,1,2 Jinlong Huang,1,2 Ping Huang,1,* Jiangfeng Wang1,3,* 1Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 2School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Pharmaceutical Services, Ipharmacare Ltd, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ping Huang; Jiangfeng Wang, Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, 158 Shangtang Road, Gongsu District, Hangzhou, Zhejiang, 310014, People’s Republic of China, Email [email protected]; [email protected]: Drug-induced gynecomastia significantly affects patient health and quality of life. This study aimed to perform an exploratory analysis of gynecomastia reports and the most commonly associated medications within the FAERS database.Patients and Methods: A comprehensive analysis of the FAERS from January 2004 to December 2023 was conducted. Disproportionality analysis and subsequent sensitivity analysis were performed to identify drugs potentially associated with gynecomastia, utilizing the reported odds ratio (ROR). Logistic regression analysis was employed to assess potential risk factors. The Weibull shape parameter (WSP) test was used to assess the time-to-onset characteristics of the top drugs associated with gynecomastia.Results: The study identified 30,265 cases of gynecomastia, primarily associated with nervous system drugs, accounting for 85.50% of cases. Notably, risperidone accounted for 80.81% of the total cases. Among the 165 agents with ≥ 5 cases of gynecomastia, the strongest signals were exhibited by risperidone (ROR 602.38, 95% CI 585.07– 620.20), dutasteride (ROR 17.18, 95% CI 15.55– 18.89), spironolactone (ROR 15.8, 95% CI 13.99– 17.83), and paliperidone (ROR 7.16, 95% CI 6.55– 7.84). In the sensitivity analysis of disproportionality, unexpected associations were observed, such as montelukast (n = 21, ROR 1.94, 95% CI 1.26– 2.98). The logistic regression analysis indicated that the risk of risperidone-induced gynecomastia was significantly lower in adults compared to pediatric patients (OR 0.12, 95% CI 0.09– 0.15) and in patients with higher body weight than in those with lower body weight (OR 5.24, 95% CI 3.62– 7.76). The WSP test showed that gynecomastia induced by most of the top 10 common agents tends to occur in an early failure mode.Conclusion: The rankings and signal strengths of drugs associated with gynecomastia were extracted from the FAERS. The age distribution and time-to-onset distribution of the top 10 drugs linked to gynecomastia were investigated, which can facilitate accurate clinical recognition of drug-induced gynecomastia.Keywords: drug-induced, gynecomastia, FAERS, risperidone, time-to-onset