Testosterone-Induced Prostate Growth Is Blocked by Co- and Preadministration of Norethisterone Enanthate in Castrated Cynomolgus Monkeys

Abstract

Introduction: Prostate size and function are regulated by testosterone. However, the progesterone receptor is expressed in the primate prostate. Progestins affect the prostate by endocrine suppression, but can also act directly. Examining the role of progestins, we studied the effects of norethisterone (NET) on testosterone undecanoate (TU)-induced prostate growth in castrated macaques. Materials and Methods: Two groups (n = 6 for each group) received TU every 9 weeks. Using a crossover setting, group I received norethisterone enanthate (NETE) 3 times at 3-week intervals, while group II received placebo. After 9 weeks, placebo was administered to group I, and group II received NETE. Results: In group II, the prostate grew under TU and placebo over the first period. In group I, coadministered with NETE, the increase was lower. After the crossover, prostates of animals previously treated with NETE did not increase to normal values under placebo. Prostates of animals treated with TU and placebo in the first period shrank following NETE administration after the crossover. The long half-life of NET can explain the lack of a TU effect on animals coadministered with NETE after the crossover. Conclusions: Pre- and coadministration of NET reduces testosterone-induced prostate growth with possible implications for the treatment of benign prostate hyperplasia and hormonal male contraception.

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“…2 Testosterone converts to estradiol stimulating prostatic growth. 10 Androgenic steroid use should be considered when a muscular patient presents with symptoms or biochemical evidence of hypogonadotrophic hypogonadism. 11 There is no readily available test for androgenic steroid usage outside of elite sport.…”

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“…Moreover, the possible positive or negative effects exerted by the different progestins require special attention as has been shown in a non-human primate model that the prostate-stimulating effect of testosterone can be blocked when administered together with norethisterone (Wistuba et al, 2012).…”

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