Yang Xiuli, Zheng Xiaochun, Zhang Miaomiao, Huang Jinlong, Huang Ping, Wang Jiangfeng
Center 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.
School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, People's Republic of China.
Clin Epidemiol. 2024 Sep 11;16:617-630. doi: 10.2147/CLEP.S470959. eCollection 2024.
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.
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.
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.
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.
药物性乳腺增生显著影响患者健康和生活质量。本研究旨在对美国食品药品监督管理局不良事件报告系统（FAERS）数据库中的乳腺增生报告及最常相关的药物进行探索性分析。
对2004年1月至2023年12月期间的FAERS进行了全面分析。利用报告比值比（ROR）进行不成比例分析及后续敏感性分析，以确定可能与乳腺增生相关的药物。采用逻辑回归分析评估潜在风险因素。使用威布尔形状参数（WSP）检验评估与乳腺增生相关的前几种药物的发病时间特征。
该研究确定了30265例乳腺增生病例，主要与神经系统药物相关，占病例的85.50%。值得注意的是，利培酮占总病例的80.81%。在165种有≥5例乳腺增生病例的药物中，利培酮（ROR 602.38，95%可信区间585.07 - 620.20）、度他雄胺（ROR 17.18，95%可信区间15.55 - 18.89）、螺内酯（ROR 15.8，95%可信区间13.99 - 17.83）和帕利哌酮（ROR 7.16，95%可信区间6.55 - 7.84）显示出最强信号。在不成比例的敏感性分析中，观察到意外关联，如孟鲁司特（n = 21，ROR 1.94，95%可信区间1.26 - 2.98）。逻辑回归分析表明，与儿科患者相比，成人利培酮诱发乳腺增生的风险显著较低（比值比0.12，95%可信区间0.09 - 0.15），且体重较高的患者比体重较低的患者风险更高（比值比5.24，95%可信区间3.62 - 7.76）。WSP检验表明，前10种常见药物诱发的乳腺增生往往呈早期失效模式。
从FAERS中提取了与乳腺增生相关的药物排名和信号强度。研究了与乳腺增生相关的前10种药物的年龄分布和发病时间分布，这有助于准确临床识别药物性乳腺增生。
