Inhibition of 5αR2 promotes postoperative wound repair in BPH patients after TURP by alleviating fibrosis and inflammation

Postoperative wound repair after transurethral resection of the prostate (TURP) in benign prostatic hyperplasia (BPH) patients is crucial for reducing complications and promoting recovery. Androgens, particularly dihydrotestosterone (DHT), influence prostatic development and wound healing, with type II 5α-reductase (5αR2) playing a key role in DHT synthesis. In this study, the effects of type II 5α-reductase inhibitors (5-ARIs) on postoperative healing, inflammation control, and fibrosis reduction were evaluated. A double-blinded randomized clinical trial was performed to assess 87 BPH patients treated with type II 5-ARIs ( n = 47) or placebo ( n = 42) over six months. The type II 5-ARIs group presented a 55.0% lower complication rate ( P = 0.002), with reduced hematuria (0 vs 7.1%, P = 0.046) and catheter reintroduction (0 vs 9.5%, P = 0.025). An animal study using 12 beagles was performed, and molecular markers were analyzed via single-cell RNA sequencing, enzyme-linked immunosorbent assay (ELISA), and histology. 5αR2 inhibition accelerated urothelial regeneration, decreased inflammation, and reduced myofibroblast activation by 42.0% while increasing the expression of the urothelial marker uroplakin 3A (UPK3A) by 67.0%. Organoid experiments confirmed increased urothelial differentiation and reduced glandular epithelial expansion with type II 5-ARI treatment. These findings suggest that 5αR2 inhibition promotes TURP postoperative recovery in BPH patients by reducing inflammation, inhibiting fibrosis, and promoting wound repair. These findings support the use of type II 5-ARIs as potential adjuvant therapies for optimizing BPH patient postoperative outcomes.