Gonadotropins and estradiol responses to single intranasal or subcutaneous administration of a luteinizing hormone-releasing hormone agonist in the early follicular phase.

Single increasing intranasal and subcutaneous doses of a potent luteinizing hormone-releasing hormone (LH-RH) agonistic analog (D-Ser[TBU]6-des-Gly-NH2(10))LH-RH ethylamide (Buserelin) were administered on day 2 or 3 of the follicular phase in 59 normal women. Groups of five or six volunteers received intranasal doses ranging from 50 to 1300 micrograms and subcutaneous doses varying between 0.3 and 30 micrograms of the LH-RH agonist. Maximal amplitude of the serum gonadotropin response is observed at 6 hours. A sixfold increase is obtained for luteinizing hormone (LH) at a 200 micrograms intranasal dose, whereas maximal follicle-stimulating hormone (FSH) stimulation (threefold) is reached at a lower dose (100 micrograms). A 1000-micrograms dose elicits a more prolonged stimulation, levels of FSH and LH being two and five times above control levels at 11 hours. Similar response curves are obtained by the subcutaneous route, a maximal stimulation being reached at 3 micrograms for FSH and at 10 micrograms for LH. Serum estradiol levels are maximally increased at 11 hours after administration of 10 and 200 micrograms of the analog by the respective subcutaneous and intranasal routes. Twenty-four-hour response curves of gonadotropins indicate that the efficacy of the intranasal route is approximately 3% to 5% of the subcutaneous route. These observations should provide information useful in the investigation of the antifertility effects and medical treatments using an intranasal LH-RH agonist in the human being.