Alcohol self-administration by female macaque monkeys: a model for study of alcohol dependence, hyperprolactinemia and amenorrhea.

Chronic alcohol dependence produces persistent amenorrhea in alcoholic women and female Macaque monkeys but the mechanism is unknown. In one amenorrheic alcohol-dependent monkey, prolactin levels increased from 16.5 to 63 ng/ml during chronic, high-dose alcohol self-administration (3.4 g/kg/day) and immunocytochemical examination of the anterior pituitary showed apparent hyperplasia of the lactotrophs. These data suggested that hyperprolactinemia might contribute to alcohol-induced amenorrhea. Four amenorrheic cycles (85-194 days) from two other alcoholic female monkeys that self-administered an average of 2.97 to 4.4 g/kg/day of alcohol were also studied. Each monkey became amenorrheic during the first menstrual cycle that alcohol was available. One monkey developed galactorrhea during a 97-day amenorrheic cycle when alcohol self-administration averaged 3.35 g/kg/day. Although prolactin levels were intermittently elevated above 20 ng/ml, average levels during these amenorrheic cycles (14.7 +/- 1.8 to 19.6 +/- 1.5 ng/ml) did not differ significantly from prolactin levels during normal ovulatory menstrual cycles when no alcohol was available (19.7 +/- 0.36 ng/ml). There was a negative correlation between daily alcohol dose and prolactin levels (p less than .01). High-dose alcohol self-administration was often associated with low normal prolactin levels, but a relative fall in alcohol dose was usually associated with elevated prolactin levels. These data suggest that both alcohol intoxication and relative alcohol withdrawal may alter basal prolactin levels. LH levels were significantly lower during amenorrheic cycles (16.9 +/- 1.2 to 24 +/- 1.4 ng/ml) than during nonalcohol control cycles (28 +/- 1.2 to 30 +/- 2.2 ng/ml) (p less than .001). These data are consistent with clinical data that suggest that hypothalamic amenorrhea is associated with suppression of gonadotropin secretory activity.