Effects of tadalafil on endothelial, angiogenic, metabolic, and microRNA biomarker profiles in sexually active men...

Benign prostatic hyperplasia (BPH) is increasingly linked to endothelial dysfunction, angiogenic activation, chronic inflammation, and metabolic dysregulation. This randomized controlled trial evaluated the dose-dependent effects of tadalafil on circulating endothelial, angiogenic, metabolic, and microRNA biomarkers implicated in BPH. A total of 306 sexually active men with BPH/LUTS and erectile dysfunction were randomized equally to placebo, tadalafil 2.5 mg, or tadalafil 5 mg daily for 12 weeks. Baseline demographic, clinical, biochemical, and molecular characteristics were comparable across groups. Tadalafil produced significant, dose-dependent improvements across multiple mechanistic domains. Both doses reduced circulating ANGPTL2, E-selectin, MMP-7, and PECAM-1, while increasing eNOS levels (p < 0.0001). Lipid metabolism improved, with favorable shifts in the Atherogenic Index of Plasma (AIP), decreasing from 0.65 in the placebo group to 0.62 with 2.5 mg and 0.50 with 5 mg tadalafil (p < 0.0001). Tadalafil also modulated microRNA expression, increasing hsa-miRNA-486-3p and decreasing hsa-miRNA-181a-5p in a dose-dependent manner (p < 0.0001). Clinical outcomes paralleled biomarker changes. Both tadalafil doses improved IPSS scores, with the greatest symptom relief at 5 mg. Biomarker-symptom correlations were strong, including ANGPTL2 (r = 0.6806-0.766), PECAM-1 (r = 0.892-0.896), eNOS (r = -0.655 to -0.824), hsa-miRNA-486-3p (r = -0.707 to -0.880), and HDL (r = -0.833 to -0.855). Tadalafil was well tolerated, with no treatment-related discontinuations. Tadalafil was associated with dose-dependent changes in endothelial, angiogenic, metabolic, and microRNA biomarkers. Because the study enrolled sexually active men with BPH/LUTS and erectile dysfunction, findings may not be generalizable to all men with BPH.