The relationship between autoimmune diseases (ADs) and male reproductive health is easily neglected. Epidemiological studies indicated that multiple ADs may adversely affect male reproductive health. This study aimed to explore the causal relationship between ADs and erectile dysfunction (ED), abnormal spermatozoa, and sex hormones using Mendelian randomization (MR) analysis.

We selected 12 common ADs as exposures, with outcomes including ED, abnormal spermatozoa, and sex hormones. The selection of instrumental variables was based on summary statistics from European GWAS studies. A combination of multiple methods was performed for MR analysis of the above data, with the inverse-variance weighted method being the main method. We also conducted several sensitivity analyses to verify the reliability of the results.

Inflammatory bowel disease (IBD) and Crohn's disease (CD) were associated with an increased risk of ED (IBD, OR: 1.101, 95% CI: 1.016-1.194, P = 0.019; CD, OR: 1.086, 95% CI: 1.012-1.165, P = 0.022). Asthma was positively causally related to abnormal spermatozoa (OR: 1.270, 95% CI: 1.045-1.545, P = 0.017), but negatively causally related to total testosterone (β: -0.042, 95% CI: -0.057 - -0.027, P < 0.001). Detection of sensitivity analysis supported findings related to ED and abnormal spermatozoa.

This study supported the role of IBD and CD in ED. Asthma was also found to be associated with abnormal spermatozoa, and possibly affected total testosterone levels in the process. Our results contributed to targeted prevention and treatment of the above diseases and promoted male reproductive health.