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Low-Dose Follicular-Phase Cocaine Administration Disrupts Menstrual and Ovarian Cyclicity in Rhesus Monkeys

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Abstract

Objective

TO evaluate the effects of daily low-dose follicular-phase cocaine administration on menstrual cyclicity, ovulation rates, corpus luteum function, and hormone levels in rhesus monkeys.

Method

Normally cycling, drug-naive, adult rhesus monkeys were randomized to receive either 1 mg/kg of cocaine (n = 7), 2 mg/kg of cocaine (n = 7), or normal saline (n = 7) daily on cycle days 2 to 14. Daily blood samples were obtained through indwelling catheters for measurement of serum gonadotropins and ovarian steroids. Daily vaginal swabs were obtained to determine onset of menses. Laparoscopy was peformed 2 days after the midcycle estrogen peak to document ovulation. Daily caloric intakes as well as pretreatment and posttreatment weights were recorded.

Results

TWO of seven monkeys receiving 1 mg/kg per day and two of seven monkeys receiving 2 mg/kg per day of cocaine had timely ovulation and normal menstrual cycle lengths. One monkey receiving the 2-mg/kg dose ovulated on cycle day 24 and had a short luteal phase (7 days) with a mean progesterone level of 2.4 ng/mL. All seven saline-treated control monkeys ovulated normally; the mean cycle length was 29 days and all had adequate luteal phases. The difference in ovulation rates between cocaine-treated and control monkeys was statistically significant (P = .003). There were no differences in basal levels of LH or FSH between treatment groups. There were no significant differences in weight change or caloric intake among groups. One third of the subsequent menstrual cycles in cocaine-treated monkeys were of abnormal duration.

Conclusion

Daily low-dose follicular-phase cocaine administration disrupts menstrual cyclicity and folliculogenesis. This effect is independent of weight loss, caloric intake, and basal gonadotropin levels. Cocaine exposure may have a persistent effect on menstrual and ovarian cyclicity in some monkeys.

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Authors and Affiliations

  1. Departments of Obstetrics and Gynecology, Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas, 78284-7836, USA

    Daniel A. Potter MD, Michael F. Luther MS, Carlton A. Eddy PhD, Theresa M. Siler-Khodr PhD, Thomas S. King PhD & Robert S. Schenken MD

  2. Department of Research and Development, Audie L. Murphy Veterans Hospital, San Antonio, Texas, USA

    Daniel A. Potter MD, Michael F. Luther MS, Carlton A. Eddy PhD, Theresa M. Siler-Khodr PhD, Thomas S. King PhD & Robert S. Schenken MD

Authors
  1. Daniel A. Potter MD
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  2. Michael F. Luther MS
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  3. Carlton A. Eddy PhD
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  4. Theresa M. Siler-Khodr PhD
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  5. Thomas S. King PhD
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  6. Robert S. Schenken MD
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Corresponding author

Correspondence to Robert S. Schenken MD.

Additional information

Supported in part by Grant no. DA08295 from the National Institute of Drug Abuse, National Institutes of Health.

The authors thank Arturo Moreno for his technical assistance and Irma Garcia and Elsa Ortiz for their help in preparing the manuscript. The authors also thank Dr. Gordon Niswender for providing the anti-ovine LH antibody, and the National Hormone and Pituitary Program for the FSH assay reagents.

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Potter, D.A., Luther, M.F., Eddy, C.A. et al. Low-Dose Follicular-Phase Cocaine Administration Disrupts Menstrual and Ovarian Cyclicity in Rhesus Monkeys. Reprod. Sci. 6, 88–94 (1999). https://doi.org/10.1177/107155769900600207

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