OPIATE ANTAGONIST TREATMENT OF OVARIAN FAILURE

One-hundred-and-thirty-eight women suffering from hypothalamic or hype randrogenic ovarian failure were treated with daily doses of 25-150 mg of the opiate antagonist naltrexone for 4-100 weeks. In patients with hypothalamic ovarian failure, treatment with naltrexone alone was fol lowed by an increase of gonadotrophins and by normalization of the men strual cycle in approximately 70% of patients. Eight of 10 patients wh o did not respond to naltrexone and had not previously ovulated in res ponse to clomiphene administration exhibited ovulatory cycles when bot h compounds were administered. Twenty-four pregnancies were achieved i n 22 women, corresponding to an overall pregnancy rate of 26%, with a cumulative pregnancy rate closely resembling that of a normal populati on. In contrast, in hyperandrogenic insulin-resistant patients, the pa ttern of gonadotrophin secretion did not seem to change dramatically d uring naltrexone treatment. However, the rise of insulin in plasma fol lowing an oral load of glucose (oGTT) was blunted considerably, result ing in normalization of previously elevated circulating insulin levels . Since the time course of plasma glucose after oGTT did not appear to be affected by treatment, this indicates an increase in insulin sensi tivity (or a decrease in insulin resistance) during naltrexone therapy . Side-effects of naltrexone treatment were negligible in patients wit h hypothalamic ovarian failure. Hyperandrogenic patients, however, did experience more intense and prolonged side-effects, such as nausea an d dizziness. In conclusion, our data demonstrate dramatic effects of t he opiate antagonist naltrexone on gonadotrophin secretion in hypothal amic ovarian failure and on insulin resistance and hyperandrogenism, s uggesting a critical role of endogenous opioids in the pathogenesis of both disorders. In addition, these findings may provide the basis for new forms of treatment.