Dissociating antifertility effects of GnRH-antagonist from its adverse effects on mating behavior in male rats.

Antagonist analogues of gonadotropin-releasing hormone (GnRH-A) alone inhibit spermatogenesis in experimental animals, but concomitant decline in serum testosterone leads to abolition of mating behavior. We assessed if the antifertility effects of GnRH-A could be dissociated from its effects on mating behavior by combining it with a small dose of androgen. Seven groups of six adult male Wistar rats were treated for 70 days as follows: I) controls, II) GnRH-A alone (250 micrograms/day), III) GnRH-A + 0.05 mg testosterone enanthate (TE), IV) GnRH-A + 0.15 mg TE, V) GnRH-A + 0.50 mg TE, VI) GnRH-A + 1.50 mg TE, and VII) GnRH-A alone (recovery group). Testes, prostate, and seminal vesicle weights were markedly reduced by GnRH-A treatment alone. Doses of TE required to maintain prostate and seminal vesicle weights were between 0.15 and 0.50 mg. Testis weights were not restored to normal even by the highest dose of TE. Intratesticular sperm counts were markedly decreased by GnRH-A treatment and restored only at the highest dose of TE (1.50 mg). Five out of six animals in group II, six out of six animals in group III, and one out of six in group IV were azoospermic. When mated with normal females, all animals in groups I and VI were fertile, all animals in groups II, III, and IV were infertile, whereas only four out of six animals in group V were fertile. All measures of mating behavior were impaired by GnRH-A treatment and restored by the smallest dose of TE (0.05 mg).(ABSTRACT TRUNCATED AT 250 WORDS)