Suppression of spermatogenesis in a nonhuman primate (Macaca fascicularis) by concomitant gonadotropin-releasing hormone antagonist and testosterone treatment.
The effects of concomitant testosterone (T)-supplementation on gonadotropin-releasing hormone (GnRH) antagonist-induced testicular regression in cynomolgus monkeys (M. fascicularis) were investigated. Four adult monkeys were infused via osmotic minipumps with daily amounts of 2 mg of a potent GnRH antagonist (N-Ac-D-Nal(2)1, D-pCl-Phe2, D-Trp3, D-hArg (Et2)6, D-Ala10)-GnRH (RS-68439) for a period of 104 days. Androgen substitution was provided via T-filled Silastic capsules implanted at initiation of GnRH antagonist treatment. Within 1-4 days of GnRH antagonist administration, serum concentrations of bioactive LH became undetectable. The implants maintained serum T at 50-80% of pre-treatment levels. Sperm production decreased in three out of four monkeys. One animal became azoospermic by the 13th week of treatment and the ejaculates of two other monkeys contained less than 5 X 10(6) sperm. In the fourth monkey, spermatogenesis was less affected. Testicular histology, judging from biopsies at termination of GnRH antagonist treatment, was typical of the hypogonadotropic status in 3 of the 4 monkeys. The most affected tubules contained only spermatogonia and Sertoli cells. Although comparison with GnRH antagonist treatment alone in a previous study indicated a delay of spermatogenic inhibition with testosterone, the present study confirms the potential of GnRH antagonist for male fertility regulation.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood; D008251:Macaca / Q000502:physiology*; D008252:Macaca fascicularis / Q000502:physiology*; D008297:Male; D010906:Pituitary Hormone-Releasing Hormones / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012661:Semen / Q000032:analysis; D013076:Sperm Count / Q000187:drug effects; D013081:Sperm Motility / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013739:Testosterone / Q000097:blood / Q000494:pharmacology*
D010906:Pituitary Hormone-Releasing Hormones; C043699:detirelix; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone