Combined effects of Depo-Provera and Fadrozole on the sexual behavior of intact male cynomolgus monkeys (Macaca fascicularis).
Our previous studies showed that treating castrated, testosterone-treated male cynomolgus monkeys with Depo-Provera (medroxyprogesterone acetate, MPA) decreased ejaculatory performance and also measures of male sexual motivation by about 40%. Similarly, treating castrated, testosterone-treated males with the nonsteroidal aromatase inhibitor, Fadrozole, decreased ejaculatory performance and male sexual motivation again by about 40%. These behavioral decrements are, of course, mediated by totally different mechanisms. We have therefore hypothesized that both unchanged T and E2 might be important for the control of sexual behavior in this male primate, and the present study examined the consequences of administering Fadrozole at a dose of 0.25 mg/kg/day to intact male cynomolgus monkeys being treated with 40 mg/week MPA. Intact males were each tested with an ovariectomized, E2-treated female partner (i) before treatment, (ii) during treatment with MPA alone, and (iii) during treatment with MPA and either Fadrozole or water administered SC by osmotic minipumps. As in previous studies, MPA significantly decreased plasma T levels and sexual behavior. But additional treatment with Fadrozole resulted in a rapid increase in plasma T levels although causing a further decline in sexual behavior. Results supported the view that both unchanged T and its aromatized product are important for ejaculatory activity and sexual motivation in the primate. Fadrozole's effect on plasma T may have been due to the elimination of the negative feedback of E2 on the hypothalamic-pituitary-gonadal axis.
Zumpe
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Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322.
Michael
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RP
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004542:Ejaculation / Q000187:drug effects; D004958:Estradiol / Q000097:blood; D017316:Fadrozole / Q000494:pharmacology*; D005246:Feedback; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D007260:Infusion Pumps; D007989:Libido / Q000187:drug effects; D007986:Luteinizing Hormone / Q000097:blood; D008252:Macaca fascicularis; D008297:Male; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D012931:Social Environment; D013737:Testis / Q000187:drug effects; D013739:Testosterone / Q000097:blood
D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D017258:Medroxyprogesterone Acetate; D017316:Fadrozole