Androgen supplementation in rats increases the inflammatory response and prolongs urethral healing

Hofer, M. D.; Cheng, E. Y.; Bury, M. I.; Xu, W.; Hong, S. J.; Kaplan, W. E.; Sharma, A. K.

Urology. 2015 Mar 4; 85(3):691-7

Abstract

OBJECTIVE: To describe the effects of androgens on urethral wound healing, we compared the urethral healing process in castrated Sprague-Dawley rats with and without testosterone supplementation. METHODS: Of 30 castrated male Sprague-Dawley rats, 15 received testosterone cypionate (3 mg/kg; T+ rats). All rats underwent an urethroplasty procedure and were sacrificed at postoperative days 5, 10, and 20. Neutrophils, macrophages, vessels, myofibroblasts, Ki67+ cells, collagen, and cytokines were quantified with immunofluorescence and real-time polymerase chain reaction. RESULTS: Penile length was significantly increased in T+ rats (21.8 vs 13.25 mm; P <.001) and operative time decreased (20.8 vs 23.3 minutes; P <.017). On day 5, T+ rats showed elevated neutrophil (727.4 vs 30.75 per high power field; P = .051) and macrophage counts (1295.8 vs 481.5 per high power field; P = .051) compared with those of T- rats. This elevation persisted throughout day 10 (291.7 vs 34; P = .002 and 1283.7 vs 110.2; P = .005) and day 20 (252.7 vs 12.2; P <.001 and 1672.7 vs 115.2; P <.001) reflecting increased and prolonged inflammation. Myofibroblasts were decreased in T+ rats on day 5 (215.7 vs 808.3; P <.001) and increased by day 10 (1490.1 vs 263.0; P = .001) and day 20 (1964.0 vs 210.0; P <.001) consistent with a delayed onset but with prolongation of the proliferative phase. Limitations include the use of castrated rats, which may have been exposed to androgens before castration. CONCLUSION: Testosterone supplementation leads to an increased inflammatory response and myofibroblast proliferation accompanied by prolonged inflammatory and proliferative phases. These novel findings suggest a delayed and possibly impaired urethral healing in the presence of excessive androgens.

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