DIFFERENTIAL ANDROGEN RESPONSE TO ADRENOCORTICOTROPIN HORMONE STIMULATION AND EFFECT OF OPIOID ANTAGONIST ON INSULIN-SECRETION IN POLYCYSTIC OVARIAN SYNDROME

To investigate the effect of a chronic anti-opioid treatment on the ad renal steroid production in polycystic ovarian syndrome (PCOS), 20 wom en affected by PCOS were studied before and after 6 weeks of treatment with an opioid antagonist. All women had an oral glucose tolerance te st (OGTT) (75 g) on day 5 of the cycle, At 11.00 p.m. 2 mg of dexameth asone was orally administered and blood samples collected the followin g day at 7.00 a.m. Then 250 mu g of adrenocorticotrophin hormone (ACTH ) was injected i.v. and samples collected 60 min later. At this time a 6 week course of naltrexone treatment (50 mg/day orally) was started, following which the protocol was repeated on day 6-7 of the menstrual cycle. According to OGTT responses, 10 patients were classified as hy perinsulinaemic and 10 as normoinsulinaemic. No difference in baseline hormone concentrations was found, except for sex hormone-binding glob ulin, which was significantly greater in normoinsulinaemic patients (P < 0.02), The plasma concentration of all steroids after dexamethasone and ACTH administration was similar in both groups, except for andros tenedione (P < 0.02) and 17 alpha-hydroxyprogesterone (17-OHP) (P < 0. 05), which were significantly greater after ACTH injection in hyperins ulinaemic compared with normoinsulinaemic PCOS patients. Naltrexone tr eatment significantly (P < 0.001) reduced insulin response to OGTT in the hyperinsulinaemic group, while it did not affect the response in t he normoinsulinaemic group; thus at the end of the treatment the two g roups had the same insulin concentrations. Similarly, naltrexone aboli shed the difference between normoinsulinaemic and hyperinsulinaemic pa tients regarding androstenedione and 17-OHP response to ACTH. These da ta confirm that insulin may in part affect the responsiveness of the a drenal glands to ACTH, so that modifications of its plasma concentrati ons can in turn modify adrenal steroid production.