Forty-seven woman volunteers used a new highly potent stimulatory analog of the hypothalamic gonadotropin-releasing hormone (GnRH) for contraception. The superagonist nafarelin acetate, D-Nal(2)6-GnRH, was administered intranasally in one daily dose of 125 micrograms to 25 women and 250 micrograms to 22 women. Ovulation was consistently inhibited during 261 of 262 treatment months. No pregnancy occurred during 222 months in which no additional contraceptives were used. The mean plasma estradiol level after 6 months of treatment was 162 pmol/l. The predominant bleeding pattern was oligomenorrhea. Three women on the lower dose and six women on the higher dose discontinued the trial prematurely, mainly because of hot flushes. No serious side effects were reported. Ovulatory menstruations returned after a median time of 43 days after discontinuation of therapy. Daily intranasal nafarelin treatment for inhibition of ovulation proved to be an effective and rapidly reversible method of contraception.
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