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

Abstract

Objective: To evaluate the effect of daily low-dose follicular-phase cocaine administration on menstrual cyclicity, ovulation rates, corpus luteum function, and hormone levels in rhesus monkey.

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 cathers for measurement of serum gonadotropins and ovarian steroids. Daily vaginal swabs were obtained to determine onset of menses. Laparoscopy was performed 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 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.