Evidence for increased dopaminergic and opioid activity in patients with hypothalamic hypogonadotropic amenorrhea.

Abstract

The functional activity of endogenous opioids and dopamine (DA) was assessed by analyzing gonadotropin and prolactin responses to DA receptor antagonist (metoclopramide) and the opioid receptor antagonist (naloxone) in selected patients with hypothalamic hypogonadotropic amenorrhea and in normal cycling women. 8 amenorrheic and 9 normal women during the low estrogen (early follicular) phase of menstrual cycle were studied. Simultaneous blood sampling and agent infusion was performed via 2 indwelling catheters after an overnight fast. Those receiving metoclopramide (10 mg intravenous bolus) and those receiving naloxone (1.6 mg/h for 4 hours) had blood samples withdrawn at various intervals. The 8 amenorrheic patients weighed significantly less (P .01) and had significantly lower mean basal serum luteinizing hormone (LH) (P .0001) and prolactin (P .01) than normal women. Metoclopramide administered to normal women induced no significant changes in pituitary gonadotropin levels. In contrast, 4 of 8 hypogonadotropic amenorrhea patients responded to metoclopramide with a significant mean net change of LH (P .05); a concomitant rise in follicle stimulating hormone (FSH) was also seen but was not statistically significant. The other 4 showed no response, as in normal women. Prolactin response to metoclopramide was reduced uniformly in all 8 patients, independent of LH responders or nonresponders. Naloxone in normal women showed no response. However, a clear increment of mean LH in response to naloxone was observed in the same 4 hypogonadotropic amenorrhea patients who also responded to metoclopramide. Mean LH nearly doubled; FSH levels showed no significant changes. Those other 4 patients who had no response to metoclopramide also had no response to naloxone. The 4 LH nonresponders with significantly (P .01) lower mean basal prolactin levels compared with normal women showed greater than l00% increase in prolactin levels by Hour 3 of naloxone infusion; in contrast, the LH responders showed no changes in prolactin levels in response to naloxone infusion.