Contraception with an LHRH agonist: effect on gonadotrophin and steroid secretion patterns

Chronic treatment with the LHRH agonist D-Ser(TBU)6-LHRH (1-9)-EA (buserelin) has been suggested as a contraceptive method since it has been shown to inhibit ovulation. To elucidate the mechanism of this paradoxical action, we investigated the pattern of gonadotrophin and steroid secretion after the daily intranasal application of 300 micrograms of the agonist. Ten volunteers with ovulatory cycles received the analogue from Day 1 to Day 22 and 5 mg norethisterone acetate from Day 16 to Day 22. Blood samples were taken on Day 1, 15, and 21 every 15 min for 6 h after the application of the agonist. LH secretion was increased nine-fold on the first treatment day as compared to Day 2 of the preceding control cycle. Thereafter, it decreased slowly but was still elevated five-fold on Day 21 of treatment. FSH release increased three-fold on Day 1 but decreased thereafter to values similar to those of the controls. During treatment with the analogue, the LH/FSH ratio changed from 1.3 (controls) to 3.8 on Day 1 and to 5.5 on Day 15 and 21 of treatment. Although the ovary retained follicular activity, ovulation was inhibited in every treatment cycle. This seemed to be due to an impairment of follicular steroid synthesis as indicated by a significant increase of 17 alpha-hydroxyprogesterone and testosterone levels for several hours after the application of the analogue. It appears that at least during the first treatment cycle of daily administration of buserelin the abolishment of pulsatile gonadotrophin release, and the abnormally increased ratio of LH/FSH secretion may possibly impair follicular maturation and thus contribute to the inhibition of ovulation.