Causal associations between prostate diseases, renal diseases, renal function, and erectile dysfunction risk: a 2-sample Mendelian randomization study

Abstract

Abstract Background Previous observational studies have found a potential link between prostate disease, particularly prostate cancer (PCa), and kidney disease, specifically chronic renal disease (CKD), in relation to erectile dysfunction (ED), yet the causal relationship between these factors remains uncertain. Aim The study sought to explore the potential causal association between prostate diseases, renal diseases, renal function, and risk of ED. Methods In this study, 5 analytical approaches were employed to explore the causal relationships between various prostate diseases (PCa and benign prostatic hyperplasia), renal diseases (CKD, immunoglobulin A nephropathy, membranous nephropathy, nephrotic syndrome, and kidney ureter calculi), as well as 8 renal function parameters, with regard to ED. All data pertaining to exposure and outcome factors were acquired from publicly accessible genome-wide association studies. The methods used encompassed inverse variance weighting, MR-Egger, weighted median, simple mode, and weighted mode residual sum and outlier techniques. The MR-Egger intercept test was utilized to assess pleiotropy, while Cochran’s Q statistic was employed to measure heterogeneity. Outcomes We employed inverse variance weighting MR as the primary statistical method to assess the causal relationship between exposure factors and ED. Results Genetically predicted PCa demonstrated a causal association with an elevated risk of ED (odds ratio, 1.125; 95% confidence interval, 1.066-1.186; P < .0001). However, no compelling evidence was found to support associations between genetically determined benign prostatic hyperplasia, CKD, immunoglobulin A nephropathy, membranous nephropathy, nephrotic syndrome, kidney ureter calculi, and the renal function parameters investigated, and the risk of ED. Clinical Implications The risk of ED is considerably amplified in patients diagnosed with PCa, thereby highlighting the importance of addressing ED as a significant concern for clinicians treating individuals with PCa. Strengths and Limitations This study’s strength lies in validating the PCa-ED association using genetic analysis, while its limitation is the heterogeneity in study results. Conclusion The results of this study suggest a potential link between PCa and a higher risk of ED.