Testosterone is increasingly prescribed to middle aged and older men, but the safety of this treatment has been called into question, and the possible risk of prostate cancer is unknown. We treated Wistar Cpb: WU rats chronically via slow-release Silastic implants with doses of testosterone that increased circulating levels in a dose-related fashion with or without a preceding single injection of the carcinogen N-nitroso-N-methylurea (MNU). Without MNU, testosterone induced prostate carcinomas in 10%-18% of rats, and after MNU injection, testosterone treatment caused prostate cancer in 50%-71% of rats with a very steep dose response, producing a 50% prostatic tumor incidence even at a testosterone dose that did not elevate circulating testosterone levels. Prostate cancers did not occur in rats given MNU or no treatment, whereas testosterone alone induced a low incidence of prostate cancer and increased the number rats bearing tumors at other sites, particularly malignant tumors. Thus, testosterone was shown to be a weak complete carcinogen and a strong tumor promoter for the rat prostate in this study. These findings have potential significant public health implications for the use of testosterone therapy in men.
