Cocaine impairs ovarian response to exogenous gonadotropins in nonhuman primates

Objective: Determine whether cocaine directly impairs ovarian steroid production and ovulation. Methods: Normally cycling adult female rhesus monkeys received daily intravenous normal saline (control; n = 8) or cocaine (4 mg/kg; n = 8) through the follicular phase. Monkeys were injected daily with human menopausal gonadotropin (hMG; Pergonal) at a dose of 6 IU/kg intramuscularly beginning on cycle day 2. Daily blood samples were obtained, and serum estradiol (E₂) and progesterone (P₄) were measured by radioimmunoassay. When serum levels of E₂ declined, plateaued, or exceeded 600 pg/mL, laparoscopy was performed to count the number of follicles. If no new corpus luteum was present, monkeys were injected intramuscularly with 1000 IU of hCG. Laparoscopy was repeated 2 days later to document the number of ovulatory stigma. Results: During ovarian stimulation, cocaine-treated monkeys required an average additional 1.5 days of hMG injections (P = .01), and this resulted in a greater total dose of hMG compared with control monkeys (351 ± 16 IU versus 297 ± 15 IU [mean ± standard error of the mean], P = .03). For spontaneous and hCG-triggered ovulation, the number of ovulatory stigma was significantly lower (P < .003) in the cocaine-treated versus control monkeys (16 versus 31). Peak E₂ levels were significantly (P = .05) lower in cocaine-treated monkeys compared with controls. Luteal phase P₄ levels were lower in the cocaine-treated monkeys, but the difference was not statistically significant when compared with controls. Conclusion: Cocaine impaired ovarian responsiveness to exogenous gonadotropins and decreased ovulatory stigma in nonhuman primates. These findings suggest that cocaine has direct ovarian effects.