Unraveling the Pathways Linking Sleep Disturbance and Vasculogenic Erectile Dysfunction: The Dominant Role of Inflammation and Testosterone Mediation

BACKGROUND: Poor sleep quality is associated with erectile dysfunction (ED), but the underlying mechanisms remain unclear. Given that systemic inflammation and testosterone levels are key factors in vascular health, this study investigates whether inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6], neutrophil-to-lymphocyte ratio [NLR], and platelet-to-lymphocyte ratio [PLR]) and total testosterone (TT) mediate the relationship between sleep quality and erectile function in vasculogenic ED patients. METHODS: A total of 167 vasculogenic ED patients and 112 age-matched controls were recruited. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), and erectile function was evaluated using the International Index of Erectile Function-5 (IIEF-5). Inflammatory biomarkers and TT levels were measured, and principal component analysis (PCA) was applied to derive an inflammatory load score. Serial mediation analysis (PROCESS Model 6) was performed to examine whether inflammation and testosterone mediate the effect of sleep quality on erectile function, adjusting for potential confounders, including age, body mass index (BMI), smoking, triglycerides (TG), and total cholesterol (TC). RESULTS: Patients with vasculogenic ED had poorer sleep quality (p < 0.001), lower TT levels (p < 0.01), and higher inflammatory biomarker levels (p < 0.01) than controls. Correlation analysis showed PSQI was positively correlated with inflammation (β = 0.371, p < 0.001) and negatively correlated with TT (β = -0.206, p < 0.01) and IIEF-5 (r = -0.437, p < 0.001). Mediation analysis revealed: Inflammatory biomarkers (hs-CRP, IL-6, NLR, and PLR) significantly mediated the association between sleep quality and ED, with hs-CRP showing the highest effect (β = -0.133, p < 0.001), accounting for 21.73% of the total effect. Testosterone also played a mediating role (β = -0.055, p < 0.01), contributing to 8.99% of the total effect. After combining inflammatory biomarkers into a PCA-derived score, the mediation effect of inflammation increased to 38.60%, whereas the testosterone pathway weakened. CONCLUSIONS: This study provides novel evidence that inflammation is a key mediator linking poor sleep quality to vasculogenic ED, while decreased testosterone levels play a secondary but still significant role.