To investigate whether perioperative androgen supplementation could improve surgical outcomes of anterior urethroplasty, particularly in hypogonadal patients, we evaluated the effects and mechanisms of systemic androgen supplementation at different doses in a castrated New Zealand rabbit model of bulbar urethroplasty.

Fifteen castrated and five non-castrated adult male New Zealand rabbits were randomized into four groups: non-castrated control, castrated control (0 mg/kg), physiological dose (2.5 mg/kg), and supraphysiological dose (5 mg/kg) of testosterone propionate. All rabbits underwent bulbar urethroplasty via end-to-end anastomosis and were sacrificed one month postoperatively. Plasma testosterone levels, urethrograms, gross specimens, histopathological data, immunofluorescence, and transcriptomic profiles were assessed and compared among the groups.

Plasma testosterone levels in the castrated control group (5.88 ± 0.19 nmol/L) were significantly lower than those in the physiological dose group (7.56 ± 0.53 nmol/L), supraphysiological dose group (8.98 ± 0.35 nmol/L), and non-castrated control group (7.30 ± 0.29 nmol/L; P <.0001). One month postoperatively, androgen supplementation significantly increased urethral lumen diameter, urethral circumference, androgen receptor, and CD31 expression compared to the castrated control group (P <.001). Transcriptomic analysis revealed upregulation of angiogenesis-related genes and suppression of fibrosis-related genes in the androgen-supplemented groups, along with modulation of inflammatory, proliferative, and metabolic pathways.

Perioperative androgen supplementation increases urethral lumen diameter, enhances peri-urethral vascularization, and suppresses short-term fibrosis-related gene expression, thereby improving outcomes of bulbar urethroplasty in hypogonadal rabbits. However, the long-term effects and clinical applicability of systemic androgen supplementation warrant further investigation.