Nk. Mello et al., THE EFFECTS OF CHRONIC COCAINE SELF-ADMINISTRATION ON THE MENSTRUAL-CYCLE IN RHESUS-MONKEYS, The Journal of pharmacology and experimental therapeutics, 281(1), 1997, pp. 70-83
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.