Contraception with an LHRH agonist: effect on gonadotrophin and steroid secretion patterns
Kuhl, H.; Jung, C.; Taubert, H.D.
Clinical Endocrinology 21(2): 179-188
1984
ISSN/ISBN: 0300-0664 PMID: 6432376 DOI: 10.1111/j.1365-2265.1984.tb03458.xDocument Number: 405823
Chronic treatment with the luteinizing hormone releasing hormone (LHRH) agonist D-Ser(TBU)6-(LHRH (1-9)-EA (buserelin) has been suggested as a contraceptive method since it was shown to inhibit ovulation. To elucidate the mechanism of this paradoxical action, the pattern of gonadotropin and steroid secretion after daily intranasal application of 300 mcg of the agonist was studied. 10 volunteers with ovulatory cycles received the analogue from days 1 to 22 and 5 mg norethisterone acetate from days 16 to 22. Blood samples were taken on days 1, 15, and 21 every 15 minutes for 6 hours after agonist application. LH secretion was increased 9-fold on the 1st treatment day as compared with day 2 of the preceding control cycle. Thereafter, it decreased slowly but was still elevated 5-fold on day 21 of treatment. Follicle stimulating hormone (FSH) release 3-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 17alpha-hydroxyprogesterone and testosterone levels for several hours after analogue application. It appears that at least during the 1st treatment cycle of daily administration of buserelin, the abolishment of pulsatile gonadotropin release, and the abnormally increased ratio of LH/FSH secretion may possibly impair follicular maturation and thus contribute to ovulation inhibition.