Abstract
Background: Benign prostatic hyperplasia (BPH) gives rise to benign prostatic enlargement owing to unregulated hyperplasia of the epithelial and fibromuscular components within the transition zone and periurethral area. Vitamin D is a pleiotropic steroid hormone with functions that encompass the modulation of calcium and phosphate metabolism and the preservation of skeletal health, but prospective evidence in BPH is unclear. Methods: We analyzed data from 195,074 participants in the UK Biobank (recruited 2006-2010) with valid vitamin D measurements and without prevalent BPH. Serum vitamin D was measured using the chemiluminescent immunoassay approach (units: nmol/L). Incident BPH cases were identified through linkage to hospital, primary care, and death registry records until 2022. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Vitamin D was modeled as both a continuous variable and in quartiles. Dose-response relationships were examined using restricted cubic splines, with thresholds determined by maximally selected rank statistics. Subgroup and sensitivity analyses assessed robustness. Results: Over a median follow-up of 13.3 years, 21,168 incident BPH cases were documented. Lower serum vitamin D was associated with an increased risk of BPH. Multivariable-adjusted HRs (95% CIs) were calculated for participants grouped by serum 25-hydroxyvitamin D (25(OH)D) quartiles, yielding values of 1.00 (reference), 0.95 (0.91, 0.99), 0.94 (0.90, 0.98), and 0.95 (0.91, 0.98) for the first to fourth quartiles, respectively. Each 1-standard deviation (SD = 20.9) increase corresponded to a 2% lower risk (HR = 0.98, 95% CI: 0.97-0.99). Restricted cubic spline analysis revealed a progressive decrease in risk with evidence of nonlinearity, which may exist due to saturation effect. Conclusions: Based on large-scale prospective cohort data from the UK Biobank, this study validates that serum 25(OH)D levels are inversely associated with BPH risk.