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Reproductive Sciences
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Cocaine Impairs Ovarian Response to Exogenous Gonadotropins in Nonhuman Primates

Angela C. Thyer, MD

Thomas S. King, PhD

Arturo C. Moreno

Carlton A. Eddy, PhD

Theresa M. Siler-Khodr, PhD

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, The University of Texas Health Science Center at San Antonio, San Antonio, Texas

Robert S. Schenken, MD

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, The University of Texas Health Science Center at San Antonio, San Antonio, Texas; Department of Obstetrics and Gynecology, MSC 7836, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900

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 signficantly 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.

Key Words: Cocaine • gonadotropins • ovary

Reproductive Sciences, Vol. 8, No. 6, 358-362 (2001)
DOI: 10.1177/107155760100800609
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