Inflammatory index-based nomogram for risk stratification of erectile dysfunction: a cross-sectional study with dual-cohort validation and mendelian randomization analysis
Translational Andrology and Urology, 2025
Shi Z., Zhang Y., Ma S., Zhang C., Meng X., Bai J., Hu W., Du H., Yu Y., Wu Y., Han D., Gu Y., Qin W., Wang P., Guo L., Zhang K.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Rology | Pathophysiology | Plasma |  Olink Target 96 |
Abstract
Background
Erectile dysfunction (ED) diagnosis primarily relies on subjective assessments (e.g., international index of erectile function-5), lacking objective biomarkers tied to its inflammatory pathophysiology. This study had three core objectives: (I) to analyze the associations between neutrophil-lymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR) with ED; (II) to construct and validate a Least Absolute Shrinkage and Selection Operator (LASSO) regression-derived nomogram for ED risk prediction; (III) to clarify causal relationships between immune phenotypes, inflammatory cytokines, and ED via bidirectional Mendelian randomization (MR).
Methods
Using National Health and Nutrition Examination Survey (NHANES) data (2001–2004; n=3,082), we analyzed NLR and LMR associations with ED, constructed a LASSO regression-derived nomogram, validated it internally [receiver operating characteristic (ROC) analysis] and externally in a Chinese cohort (n=9,161), and performed bidirectional MR on Genome-Wide Association Study (GWAS) data (731 immunophenotypes/91 cytokines).
Results
Elevated NLR increased ED risk [odds ratio (OR) =1.15, 95% confidence interval (CI): 1.06–1.24, P=0.001], whereas higher LMR was protective (OR =0.93, 95% CI: 0.87–0.99, P=0.03). The 8-predictor nomogram (NLR/LMR included) achieved superior discrimination in NHANES [area under the curve (AUC) 0.8553 vs. 0.6101 for NLR alone] and the Chinese validation cohorts (AUC 0.7648). MR identified 25 ED-associated immunophenotypes, with C-C motif chemokine 23 (CCL23) elevating risk (β=0.13, P=0.03) and interleukin-8 (IL-8) conferring protection (β=−0.19, P=0.02), indicating divergent inflammatory mechanisms.
Conclusions
This study pioneers an inflammation-driven ED nomogram for objective risk stratification, validated across dual cohorts. It also reveals cytokine-specific inflammatory pathways in ED pathogenesis, laying a foundation for personalized ED screening and targeted therapeutic development.