EVALUATION OF THE IMPACT OF CONCURRENT GONADOTROPIN-RELEASING-HORMONE(GNRH) ANTAGONIST ADMINISTRATION ON GNRH AGONIST-INDUCED GONADOTROPE DESENSITIZATION

Objective: To evaluate the impact of chronic GnRH antagonist therapy o n the extent of GnRH agonist-induced gonadotrope desensitization. Desi gn: Prospective and controlled. Setting: Primate Research Center. Part icipants: Six reproductive age cycling female baboons (Papio cyanoceph alus anubis). Interventions: The animals were divided into two groups. Group A received a total of 19 pulses of 0.83 mu g/kg leuprolide acet ate (LA) on a 12-hour dosing schedule. Group B received Nal-Lys (3 mg/ kg then 1 mg/kg every other day) for 1 week and then added an identica l 19 pulses of LA while continuing Nal-Lys therapy. Main Outcome Measu res: Characterization of the gonadotropin response was done by collect ing serum samples at -15, 0, 15, 30, 60, 90, 120, 240, and 480 minutes relative to the injection of the LA. Results: After equivalent baseli ne responses, the baboons pretreated with Nal-Lys had an increased LH and FSH response to the administration of the LA. After a total of 19 pulses of the LA, the Nal-Lys-treated animals had an increased FSH res ponse in comparison to the untreated controls. This indicates that the extent of gonadotrope desensitization was reduced in the presence of the GnRH antagonist. Conclusions: The presence of GnRH antagonist redu ces the extent of gonadotrope desensitization in response to the admin istration of repetitive pulses of GnRH agonist.