Association between 20 medications and erectile dysfunction: Results from a cross-sectional study and Mendelian randomization analysis

Abstract

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.

Keywords: Mendelian randomization; NHANES; cross-sectional study; erectile dysfunction; medication use.

Figure 1.

The specific process of this study.

Figure 2.

Multivariate logistic regression analysis of the relationship between medication use and erectile dysfunction in national health and nutrition examination survey (NHANES) 2001 to 2004.Only the findings with significant association (P < .05) are shown in the figure. “No PSM” is the result of weighted multivariate logistic regression analysis before propensity score matching (PSM) and the rest of the weighted multivariate logistic regression analysis after PSM.

Figure 3.

The nonlinear relationship between days of drug use and ED risk was analyzed by weighted restricted cubic spline (RCS). (A) Agents acting on the renin-angiotensin system; (B) calcium channel blockers; (C) drugs for peptic ulcer and GORD; (D) drugs used in diabetes; (E) HMG CoA reductase inhibitors; (F) immunosuppressants.

Figure 4.

Five MR methods were used to analyze the association between 20 medication uses and ED risk. Results with a significant result (P < .05) were indicated by *. ED = erectile dysfunction, MR = Mendelian randomization.

Figure 5.

Meta-analysis of MR results from 2 datasets. (A) Drugs used in diabetes; (B) antithrombotic agents; (C) calcium channel blockers; (D) agents acting on the renin-angiotensin system; (E) HMG CoA reductase inhibitors; (F) salicylic acid and derivatives. HMG CoA = 3-hydroxy-3-methylglutaryl coenzyme A, MR = Mendelian randomization.