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The effects of estradiol (E2) administered by a transdermal system on the induction of hypothalamic opioid activity was examined in 18 postmenopausal women. Women were given 25, 50, 100, or 200 micrograms/d dosages of E2 for 28 days each. Naloxone at a dosage of 2 mg/h was infused intravenously for 4 hours, and serum was obtained every 15 minutes for 6 hours. With increasing doses, rises of serum E2 and estrone were elicited across the range seen in premenopausal women. A stepwise reduction of luteinizing hormone (LH) levels was observed with increasing dosages of E2. The naloxone infusions resulted in significant increases of LH when E2 was being given but not during the pretreatment studies. These data indicate E2, in physiological concentrations, induces hypothalamic opioid activity.
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