BACKGROUND: The causal association of insomnia with multiple urological and reproductive conditions still lacks clarity. Our aim was to assess this relationship by examining impact of insomnia on 10 urological and reproductive conditions using Mendelian randomization (MR) designs. METHODS: Summary statistics for insomnia and 10 urological and reproductive conditions were acquired from the UK Biobank, 23andMe, FinnGen, and genetic consortia. Inverse variance weighted approach was utilized as the main MR analysis. Sensitivity analyses were performed employing MR-PRESSO (Pleiotropy Residual Sum and Outlier), maximum likelihood, MR-Egger, and weighted median methods to examine the robustness of the estimates. RESULTS: Genetically determined insomnia showed an elevated risk of cystitis [odds ratio (OR) =1.81
95% confidence interval (CI): 1.47-2.24
P<
0.001], and prostatitis (OR =3.53
95% CI: 1.73-7.18
P<
0.001) after Bonferroni correction. Suggestive evidence of an association was found between insomnia and a heightened risk of prostate cancer (OR =1.30
95% CI: 1.00-1.67
P=0.046), alongside a decreased risk of bladder cancer (OR =0.48
95% CI: 0.26-0.90
P=0.02). No causal effects were observed for kidney cancer, kidney and ureter calculus, neurogenic bladder, benign prostatic hyperplasia (BPH), male infertility, or female infertility. CONCLUSIONS: Findings support insomnia as a potential causal risk factor for cystitis and prostatitis. This highlights insomnia as an important target for reducing the risk of these diseases.