目的 使用美国食品药品监督管理局不良事件报告系统（FAERS）中来自真实世界的数据，分析阿托伐他汀与生殖相关不良反应之间的统计学关系，并采用孟德尔随机化来评估潜在的因果关系，为临床安全用药提供参考。方法 收集FAERS数据库中阿托伐他汀引起生殖相关不良反应的报告。采用报告比值比法（ROR）、比例报告比值比法（PRR）和贝叶斯置信区间传播神经网络法（BCPNN）检测阿托伐他汀的高危生殖相关不良反应信号。将数据库中检测到的能够引起生殖不良反应的阿托伐他汀作为暴露因素，阿托伐他汀引起的不同生殖不良反应作为结局因素，采用两样本孟德尔随机化评价其之间的因果关系。结果 最终在数据库中新发现300例阿托伐他汀相关的11种生殖不良反应，其中男性占比最多（231例，77.0%），主要发病年龄集中在60～79岁（111例，37.0%），2019年上报的不良反应最多（47例，15.7%），主要上报欧洲国家为英国（189例，63.0%），上报生殖不良反应最多的是勃起功能障碍（163例，54.3%），检测信号强度最高的生殖不良反应是盆底肌无力，ROR为28.44[95%置信区间（CI）： 12.78～63.31]，报告显示在用药0～30 d发生生殖不良反应最多（29.25%），且男性患者（ROR＝9.71）较女性患者（ROR＝6.74）生殖不良反应的风险更高，80岁以上患者风险最高（ROR＝16.47）。对阿托伐他汀和检测到的生殖不良反应进行两样本孟德尔随机化分析，发现阿托伐他汀和勃起障碍得到阳性结果，逆方差加权法（IVW）显示比值比（OR）值为23.914（95% CI： 1.570～64.249，P＝0.022＜0.05），证明阿托伐他汀的使用与勃起障碍之间存在因果关系。结论 通过药物警戒分析显示阿托伐他汀与生殖相关不良反应之间存在显著的统计学关联。通过孟德尔随机化分析表明阿托伐他汀的使用与勃起障碍之间存在因果关系。这些研究结果提示在使用阿托伐他汀治疗心血管疾病时需要考虑潜在生殖相关不良反应。

Objective To use real-world data from the US Food and Drug Administration Adverse Event Reporting System (FAERS), the statistical relationship between atorvastatin and reproductive adverse reactions was analyzed, and Mendelian randomization was used to evaluate potential causality, so as to provide reference for clinical safety of drug use. Methods The FAERS database of reproductive-related adverse reactions caused by statins was collected. Reporting Odds Ratio (ROR), Proportional Reporting Ratio, (PRR) and Bayesian Confidence Propagation Neural Network (BCPNN) were used to detect signals of high-risk reproduction-related adverse effects of atorvastatin. Atorvastatin, which can cause adverse reproductive reactions detected in the database, was taken as the exposure factor, and different adverse reproductive reactions caused by atorvastatin were taken as the outcome factor, and the causal relationship between them was evaluated by using two-sample Mendelian randomization. Results Finally, 300 new cases of 11 kinds of adverse reproductive reactions related to atorvastatin were found in the database, of which males accounted for the most (231 cases, 77.0%), and the main age of onset was concentrated in 60—79 years old (111 cases, 37.0%), and the most adverse reactions were reported in 2019 (47 cases, 15.7%). The main reported European country was the United Kingdom (189 cases, 63.0%), the most reported reproductive adverse reaction was erectile dysfunction (163 cases, 54.3%), and the highest detected signal intensity was pelvic floor muscle weakness, with a ROR of 28.44 (95% CI: 12.78—63.31), reported that reproductive adverse reactions occurred most (29.25%) at 0—30 d of administration, and male vaccinators (ROR = 9.71) had a higher risk of reproductive adverse reactions than female vaccinators (ROR = 6.74), with the highest risk in patients over 80 years of age (ROR = 16.47). A two-sample Mendelian randomization analysis was performed for atorvastatin and detected reproductive adverse reactions, and a positive result was found for atorvastatin and erectile dysfunction. Inverse variance weighted method (IVW) showed an odds ratio (OR) value of 23.914 (95% CI: 1.570—64.249, P = 0.022 < 0.05), demonstrating a causal relationship between atorvastatin use and erectile dysfunction. Conclusion Pharmacovigilance analysis showed a statistically significant association between atorvastatin and reproduction-related adverse reactions. A causal relationship between atorvastatin use and erectile dysfunction was demonstrated by Mendelian randomization analysis. These findings suggest that potential reproduction-related adverse effects need to be considered when using atorvastatin for cardiovascular disease.

R969.3

郑州市医疗卫生领域科技创新指导计划项目（2025YLZDJH158）