Cocaine Impairs Follicular Phase Pulsatile Gonadotropin Secretion in Rhesus Monkeys

Abstract

Objective: To assess cocaine's effect on follicular phase pulsatile gonadotropin secretion in normally cycling rhesus monkeys.

Methods: Sixteen monkeys were paired by body weight and randomized to receive intravenous saline (n = 8) or cocaine (4 mg/kg, n = 8) daily on cycle days 2 to 14. Monkeys were chronically cannulated to allow frequent blood collections without anesthesia. Blood samples were obtained every 15 minutes for 8 hours in early (EFP; cycle days 1 to 5); mid- (MFP; cycle days 6 to 10), and late (LFP; cycle days 11 to 15) follicular phase. Plasma concentrations of LH, FSH, and estradiol-17β (E₂) were determined by radioimmunoassay. Pulses were identified by cluster analysis. Statistical differences were determined by analysis of variance (ANOVA) and Sidak's multiple comparison test.

Results: Seven out of eight monkeys in the control group demonstrated timely ovulation. Only one monkey in the cocaine-treated group ovulated. Similar gonadotropin pulse intervals (7 to 90 minutes) were observed throughout the follicular phase in both the controls and cocaine-treated monkeys. LH and FSH pulse amplitudes increased significantly from the EFP/MFP to the LFP in controls. In cocaine-treated monkeys, gonadotropin pulse amplitudes remained at EFP/MFP levels throughout the study period. The mean gonadotropin pulse amplitude and the mean E₂ levels in the LFP were significantly greater in controls as compared with cocaine-treated monkeys (P < .001).

Conclusion: These findings demonstrate that cocaine suppresses the normal increase in LH and FSH pulse amplitude seen in the LFP. Further studies are in progress to determine the mechanism of cocaine's disruption of the hypothalamic-pituitary-ovarian axis.