Effect of a potent GnRH antagonist and testosterone propionate on mating behavior and fertility in the male rat.

Daily treatment with 1 mg of the GnRH antagonist [Ac-delta 3-Pro1,pC1-D-Phe2,D-Trp3,6,N alpha MeLeu7]-GnRH abolished mating behavior and disrupted spermatogenesis in male rats within 2 weeks. This was accompanied by a sharp decrease in plasma testosterone (T) levels as well as sexual organ weights while body weight remained normal. Following cessation of treatment, T levels returned to control values within 5 days, while sexual organ weights were still slightly depressed after 6 weeks. In rats having been treated for either 2 weeks or 4 months, mating behavior and fertility were restored between the 4th and 8th week after the last injection. Antagonist-treated animals who concomitantly received high doses of exogenous testosterone were sexually active as well as fertile, while lower doses of testosterone maintained sexual activity but not fertility. These data indicate that GnRH antagonists may be used to control male fertility.