Perioperative Testosterone Supplementation Improves Short-Term Outcomes of Anterior Urethroplasty in Hypogonadal Models: Insights From a Preclinical Rabbit Study

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.