The role of postoperative testosterone in repair of iatrogenic hypospadias in rabbits

Abstract

Introduction Testosterone administered preoperatively in hypospadiac children increases phallic size and improves skin vascularity. We histologically evaluated the role of postoperative testosterone in tissue remodeling in an animal model. Materials and methods Hypospadias was created in 18 rabbits and repaired with a preputial onlay graft. Animals were randomized to receive either one intramuscular (i.m.) dose of testosterone postoperatively ( n = 6), or 2 weeks of daily 1% topical testosterone ( n = 6). Control animals underwent the urethral operation, but received no testosterone ( n = 6). Penises were harvested at 2 and 5 weeks, and blindly assessed for collagen formation, re-epithelialization and fibrosis, and complications. Results Of the animals sacrificed at 2 weeks, those that received testosterone had a greater incidence of cuboidal epithelium (83%) versus controls (33%). In the 2-week group, animals receiving testosterone had increased fibrosis, periurethral and soft-tissue inflammation compared to controls. By 5 weeks, all differences in fibrosis and inflammation had resolved. No animal developed fistula or diverticulum. Of animals sacrificed at 2 weeks, 67% stained for BrdU, a DNA proliferative marker. At 5 weeks, no non-testosterone rabbit demonstrated positive staining, while 83% of those receiving testosterone were positive. There were no differences between animals that received topical and i.m. testosterone. Conclusion Administration of testosterone following hypospadias repair in rabbits changes the histologic composition of the urothelium and leads to an exaggerated inflammatory response in the supportive stroma. Such treatment may prove a useful adjunct in patients undergoing complex genital reconstruction.