Global stagnation and misaligned priorities in BPH drug development: a 25-year landscape analysis of clinical trial registries

Pharmacological innovation for benign prostatic hyperplasia (BPH) has stagnated. As disease burden rises, whether trial activity is addressing disease-modifying therapy remains unclear, while the published literature captures only reported successes. We reviewed BPH drug trial registrations in ClinicalTrials.gov and ChiCTR (2000-2025), standardized design, phase, status, mechanism, and result-reporting variables, and analyzed 224 eligible trials. Of these, 211 were non-ongoing, but only 55.0% had publicly available results. Among 43 studies targeting prostate volume reduction, 25 (58.1%) reported results and 12 (48.0%) showed efficacy; among 137 targeting volume-independent symptom improvement, 82 (59.9%) reported results and 63 (76.8%) showed efficacy. Classical mechanisms, including α1-adrenergic antagonists (24.6%) and 5α-reductase inhibitors (8.5%), dominated Phase III/IV trials (51.9% and 61.1%), whereas emerging mechanisms were concentrated in Phase I/II trials, accounting for 20.0-50.0% of early-phase research. Most trials evaluated single agents (78.6%), while combination and head-to-head studies were uncommon. Industry sponsorship predicted result disclosure (OR 6.67; P < 0.001); mechanism was associated with reporting overall (P = 0.02) and borderline in Phase III (P = 0.05); enrollment ratio was associated in Phase II (OR 13.97; P = 0.04). BPH drug development remains trapped in symptomatic relief, with limited disease modification and substantial hidden failure, requiring greater priority for disease-modifying mechanisms, transparency, and societal and industry investment.