THE EFFECTS OF CHRONIC COCAINE SELF-ADMINISTRATION ON THE MENSTRUAL-CYCLE IN RHESUS-MONKEYS

Clinical studies suggest that cocaine disrupts reproductive function, but because cocaine abusers often abuse opiates and alcohol, it has be en difficult to determine the contribution of cocaine alone. The effec ts of chronic cocaine self-administration on menstrual cycle duration and basal levels of progesterone were examined in eight female rhesus monkeys and compared with the effects of occasional administration of single cocaine doses (0.4 or 0.8 mg/kg) in six otherwise drug-free con trols. All monkeys had normal ovulatory menstrual cycles before cocain e exposure. Monkeys self-administered cocaine (0.10 mg/kg/injection) a nd food (1 gm banana pellets) in 4 daily sessions on a second-order sc hedule (fixed ratio 2 [variable ratio 16:S]). Cocaine intake was limit ed to 8 mg/kg/day. During the first cocaine exposure (256-776 days), m onkeys self-administered 3.51 (+/-0.77) to 7.41 (+/-0.27) mg/kg/day. D uring the second cocaine exposure (103-623 days), monkeys self-adminis tered 6.18 (+/-0.77) to 7.41 (+/-0.27) mg/kg/day. In these prospective longitudinal studies, 48% of the menstrual cycles were of abnormal du ration in the cocaine self-administration group, whereas only 6% of th e menstrual cycles were abnormal in the control group. There were 19 e pisodes of amenorrhea (61-190 days of no menses). During cocaine self- administration, approximately one-third of the menstrual cycles were a novulatory with low mid-luteal progesterone levels of 2.04 (+/-0.6) to 4.13 (+/-0.5) ng/ml. Over 25% of menstrual cycles were anovulatory du ring cocaine withdrawal with mid-luteal progesterone levels below 5 ng /ml. These data indicate that chronic cocaine exposure can disrupt the menstrual cycle in rhesus monkeys and that menstrual cycle abnormalit ies often persist during cocaine withdrawal. These data are consistent with clinical studies and reports of cocaine-induced disruption of th e estrous cycle in rodents.