Association between total testosterone/sex hormone-binding globulin and stress urinary incontinence: A Mendelian randomization study

Background: Observational studies have reported associations between total testosterone and sex hormone-binding globulin (SHBG) with stress urinary incontinence (SUI). However, the causal relationship between total testosterone, sex hormone-binding globulin, and SUI remains unclear. Method Two-sample Mendelian randomization (MR) was performed using genome-wide association study (GWAS) data for total testosterone from 425,097 individuals and sex hormone-binding globulin from 214,989 individuals, along with summary statistics of GWAS for SUI from 463,010 individuals. Instrumental variables (IVs) were selected using 73 single nucleotide polymorphisms (SNPs) for total testosterone and 78 SNPs for sex hormone-binding globulin. Various MR methods, including inverse variance-weighted, MR-Egger regression, weighted median, and weighted mode, were employed to assess the causal relationship between total testosterone, sex hormone-binding globulin, and SUI. Sensitivity analyses were conducted using heterogeneity tests, pleiotropy tests, and leave-one-out sensitivity tests to validate the robustness of the data. Results Mendelian randomization analysis showed a significant association between total testosterone and SUI in IVW (OR = 0.9967; 95% CI:0.9945–0.9989, p  = 0.0035), but no evidence of an effect of total testosterone on SUI was found in other methods. MR-Egger (OR = 0.9992, 95% CI: 0.9948–1.0037, p  = 0.7463), weighted median (OR = 0.9990, 95% CI: 0.9954–1.0026, p  = 0.5549). Additionally, in IVW (OR = 0.9988, 95% CI: 0.9979–0.9997, p  = 0.0094), a causal relationship between sex hormone-binding globulin and SUI risk was also observed. However, no evidence of an effect of sex hormone-binding globulin on SUI was found in other methods. MR།Egger (OR = 0.9997, 95% CI: 0.9979–1.0014, p  = 0.7334), weighted median (OR = 0.9992, 95% CI: 0.9978–1.0006, p  = 0.2793). Conclusion The results of this study provide support for a causal relationship between total testosterone, sex hormone-binding globulin, and SUI. Higher levels of total testosterone and sex hormone-binding globulin are associated with a decreased risk of SUI. Additionally, the study's outcomes suggest the potential for improving or mitigating the severity of stress urinary incontinence through supplementation with total testosterone and sex hormone-binding globulin.