Zhao Chengyi, Qu Ling, Liu Feng
Department of Surgical Oncology, Tumor Hospital of Harbin Medical University, Harbin Medical University, Harbin, China.
Department of Gastroenterology, Tumor Hospital of Harbin Medical University, Harbin Medical University, Harbin, China.
Medicine (Baltimore). 2025 Aug 8;104(32):e43157. doi: 10.1097/MD.0000000000043157.
Previous studies on the impact of medication use on the risk of erectile dysfunction (ED) have yielded controversial results. Therefore, this study aims to explore the association between the use of 20 different drugs and the risk of ED through cross-sectional research and Mendelian randomization (MR) analysis. We analyzed 3989 participants from the 2001 to 2004 National Health and Nutrition Examination Survey. Weighted multivariable logistic regression was used to analyze the association between medication use and the risk of ED. After propensity score matching, the association between the use of 20 different medications and the risk of ED was further assessed. Weighted restricted cubic splines were applied to evaluate the nonlinear relationship between the days of medication use and the risk of ED. Then, two-sample MR analysis was conducted to investigate the causal association between medication use and the risk of ED, with inverse variance weighting as the primary analytical method. Cross-sectional findings indicated salicylic acid derivatives (OR 3.28; 95% CI 1.27-8.50) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (OR 1.34; 95% CI 1.01-1.79) were associated with higher ED risk, and that the duration of HMG CoA reductase inhibitor use had an S-shaped nonlinear relationship with ED risk (P = .0329). The results in the preliminary MR analysis further demonstrated a causal relationship between the use of salicylic acid (OR 1.23; 95% CI 1.00, 1.51) and derivatives or HMG CoA reductase inhibitors (OR 1.12; 95% CI 1.04, 1.21) and the increased risk of ED. The meta-analysis of the preliminary MR analysis and the validation analysis also confirmed this causal relationship. Our study suggests a causal association between the use of salicylic acid and derivatives or HMG-CoA reductase inhibitors and an increased risk of ED. Therefore, special caution should be exercised in applying these 2 classes of drugs to patients at high risk of ED or those already suffering from ED.
先前关于药物使用对勃起功能障碍（ED）风险影响的研究结果存在争议。因此，本研究旨在通过横断面研究和孟德尔随机化（MR）分析，探索20种不同药物的使用与ED风险之间的关联。我们分析了2001年至2004年国家健康和营养检查调查中的3989名参与者。采用加权多变量逻辑回归分析药物使用与ED风险之间的关联。在倾向得分匹配后，进一步评估20种不同药物的使用与ED风险之间的关联。应用加权受限立方样条来评估药物使用天数与ED风险之间的非线性关系。然后，进行两样本MR分析，以研究药物使用与ED风险之间的因果关联，采用逆方差加权作为主要分析方法。横断面研究结果表明，水杨酸衍生物（比值比[OR] 3.28；95%置信区间[CI] 1.27 - 8.50）和3 - 羟基 - 3 - 甲基戊二酰辅酶A（HMG CoA）还原酶抑制剂（OR 1.34；95% CI 1.01 - 1.79）与较高的ED风险相关，且HMG CoA还原酶抑制剂的使用时长与ED风险呈S形非线性关系（P = 0.0329）。初步MR分析结果进一步证明了水杨酸（OR 1.23；95% CI 1.00，1.51）及其衍生物或HMG CoA还原酶抑制剂（OR 1.12；95% CI 1.04，1.21）的使用与ED风险增加之间存在因果关系。初步MR分析的荟萃分析和验证分析也证实了这种因果关系。我们的研究表明，水杨酸及其衍生物或HMG - CoA还原酶抑制剂的使用与ED风险增加之间存在因果关联。因此，对于ED高危患者或已患有ED的患者，在应用这两类药物时应格外谨慎。
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