Causal association between statin use and erectile dysfunction: a 2-sample Mendelian randomization study

The impact of statins on erectile dysfunction (ED) remains a subject of intense clinical debate. Previous observational studies have yielded inconsistent results and are often limited by confounding factors and reverse causation.

To investigate the causal relationship between statin use and ED risk through a 2-sample Mendelian randomization (MR) analysis of genome-wide association study summary data from the UK Biobank and FinnGen. Genetic variants for general statins and specific types (atorvastatin, simvastatin, and rosuvastatin) were utilized as instrumental variables. The primary effect was estimated using the inverse variance weighted (IVW) method. Sensitivity analyses, including MR-Egger, weighted median, and MR-PRESSO, and leave-one-out analyses, were conducted to ensure the robustness of the findings, alongside the MR Steiger directionality test to validate causal orientation.

IVW analysis demonstrated that general statin use is associated with a higher risk of ED (OR = 1.064; 95% CI, 1.011-1.119; P = .018). Subgroup analysis revealed that lipophilic statins significantly increased ED risk: atorvastatin (OR = 27.892; 95% CI, 1.912-40.977; P = .015) and simvastatin (OR = 4.948; 95% CI, 1.598-15.319; P = .006). In contrast, no causal relationship was found for hydrophilic rosuvastatin (P = .428). Sensitivity analyses confirmed the absence of horizontal pleiotropy and heterogeneity. The MR Steiger directionality test confirmed that the causal direction from statin use to ED was robust. Additionally, the leave-one-out analysis demonstrated that the overall results were not driven by any single SNP.

Statin use, particularly atorvastatin and simvastatin, causally increases the risk of ED, whereas rosuvastatin appears to have a neutral effect.