Exploring the causal associations between obesity indicators and male reproductive diseases: new evidence from Mendelian randomization.

BACKGROUND: The objective of this study was to investigate potential causal associations between indicators of obesity and male reproductive disorders using Mendelian randomization (MR) analysis. METHODS: Based on summary data from the GWAS, we conducted MR analyses. Univariable MR analysis was performed to estimate the association between three obesity indicators and five male reproductive diseases. Multivariable MR analysis was conducted to account for pleiotropy observed in univariable MR analysis by including a set of covariates. RESULTS: Univariable MR analysis revealed suggestive associations between waist-to-hip ratio (WHR) and testicular dysfunction (OR = 0.32, 95% Cl: 0.11-0.99, PIVW = 0.049), body mass index (BMI) and erectile dysfunction (OR = 1.28, 95%CI 1.12-1.45, PIVW = 1.84 × 10-4). Multivariate MR analysis indicated after controlling for potential confounders, waist-to-hip ratio was suggestively associated with the decreased risk of testicular dysfunction (OR = 0.23, 95% Cl: 0.08-0.67, PIVW = 0.008). Nevertheless, multivariate MR analysis also showed that body mass index was suggestively associated with the increased risk of erectile dysfunction (OR = 1.22, 95% Cl: 1.06-1.40, PIVW = 0.006). Sensitivity analyses confirmed that these results were reliable. CONCLUSION: Our two-sample MR analysis suggests generalized obesity in was suggestively associated with the increased risk of erectile dysfunction, while central obesity obesity is associated with an decreased risk of testicular dysfunction.