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Chronic naltrexone treatment induces desensitization of the luteinizing hormone pulse generator for opioid blockade in hyperprolactinemic patients.

The aim of this study was to assess the possibility that ovulation might be induced in seven amenorrheic hyperprolactinemic women by treatment with naltrexone (50 mg/day) for 4-5 weeks. None of the patients ovulated. Increases in LH levels, LH area under the curve, FSH levels, and the number of LH pulses per 6 h were observed in all patients, 2-8 h after the beginning of naltrexone administration. However, all of these parameters had returned to the pretreatment range on day 7. The LH area under the curve, LH levels, FSH levels, and the number of LH pulses per 6 h on day 1 were significantly higher compared to the values on either day 0 (basal levels) or day 7. These data show that long term opioid receptor blockade induces desensitization of the hypothalamic-pituitary unit for the effects of opioid receptor blockade. Due to the induced desensitization, naltrexone is not an effective drug for ovulation induction in hyperprolactinemic patients.