Androgen Supplementation in Rats Increases the Inflammatory Response and Prolongs Urethral Healing

• Published in: Urology (Ridgewood, N.J.) Vol. 85; no. 3; pp. 691 - 697
• Main Authors: Hofer, Matthias D, Cheng, Earl Y, Bury, Matthew I, Xu, Wei, Hong, Seok Jong, Kaplan, William E, Sharma, Arun K
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2015
• Subjects: Androgens - pharmacology; Animals; Inflammation - chemically induced; Male; Rats; Rats, Sprague-Dawley; Testosterone - pharmacology; Time Factors; Urethra - drug effects; Urology; Wound Healing - drug effects
• ISSN: 0090-4295; 1527-9995
• DOI: 10.1016/j.urology.2014.11.025

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.