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 on the extent of GnRH agonist-induced gonadotrope desensitization. Design: Prospective and controlled. Setting: Primate Research Center. Participants: Six reproductive age cycling female baboons (Papio cyanocephalus anubis). Interventions: The animals were divided into two groups. Group A received a total of 19 pulses of 0.83 μg/kg leuprolide acetate (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 identical 19 pulses of LA while continuing Nal-Lys therapy. Main Outcome Measures: Characterization of the gonadotropin response was done by col lecting serum samples at 15, 0, 15, 30, 60, 90, 120, 240, and 480 minutes relative to the injection of the LA. Results: After equivalent baseline 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 response 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 reduces the extent of gonadotrope desensitization in response to the administration of repetitive pulses of GnRH agonist.