Inhibition of ovulation in women by intranasal treatment with a luteinizing hormone-releasing hormone agonist

Abstract

The potent and long-acting stimulatory luteinizing hormone-releasing hormone LRH analogue D-Ser(TBU) 6-EA 10-LRH was administered intranasally once daily in doses of between 87–600 μg to 39 normally ovulating women over 26–35 days. All the 8 women who were treated with daily intranasal doses of 87 or 174 μg, had signs of follicular growth during the treatment and 6 of them had raised premenstrual progesterone levels in blood. The progesterone values were low during 4 of the 6 presumptively ovulatory cycles, indicating defective corpus luteum function. Three out of 5 women treated with 348 μg daily had anovulatory cycles and the other two very low progesterone values, indicating insufficient luteal function. Anovulation occurred in all but 2 of the 26 women who received 400 or 600 μg of the analogue intranasally. None of the women had dysfunctional uterine bleeding. Ten of the 26 women treated with 400 or 600 μg daily, did not have any bleeding during the five-week study period. The remaining 16 women experienced a menstrual-like bleeding after 26 days on average (range 21–34 days). Thirty-two of the 39 women have discontinued intranasal treatment with the analogue and all of them ovulated within 4 weeks after discontinuation. The results suggest that it might be possible to use intranasal administration of the stimulatory LRH analogue D-Ser(TBU) 6-EA 10-LRH to control fertility.