Effect on corpus luteum function of luteal phase administration of a potent gonadotropin-releasing hormone analog (nafarelin).

Fourteen women with ovulatory menstrual cycles were treated with a superactive agonistic analog of gonadotropin-releasing hormone (6-D-[2-naphthyl]-alanyl)-GnRH (nafarelin). Eight of the women received a single subcutaneous injection of nafarelin during the luteal phase at a dosage of 2, 5, or 100 micrograms for determination of the dose-response and pharmacokinetic characteristics of the drug. All doses stimulated the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Maximal release was obtained with the 5-micrograms dose (mean +/- standard deviation: delta LH = 297 +/- 75 mIU/ml; delta FSH = 29 +/- 7 mIU/ml), and there was no greater release of gonadotropin with the 100-micrograms dose. To investigate the contraceptive potential of nafarelin as a luteolytic agent, six of the women were treated with 100 micrograms of analog by daily injection for 10 days, beginning either 2 to 3 days or 5 to 7 days after ovulation. Gonadotroph desensitization or down-regulation developed within 24 hours, but serum concentrations of LH and FSH did not fall below normal values during treatment. There were no significant changes in mean estradiol or progesterone concentrations. There also was no change in mean length of the luteal phase (13.7 +/- 2.1 days [control] versus 13.6 +/- 1.4 days). Thus, nafarelin, like other superactive analogs of GnRH, does not appear to be clinically useful as a luteolytic agent in contraceptive development.