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Fourteen-Day Versus Twenty-One-Day Regimens of Intermittent Intranasal Luteinzing Hormone-Releasing Hormone Agonist Combined with an Oral Progestogen as Antiovulatory Contraceptive Approach^*

Endocrinology of Reproduction, Department of Obstetrics and Gynecology, St. Franqois d'Assise Hospital, Laval University Quebec, Quebec, Canada

This study was designed to determine the effect of discontinuous administration of a LHRH agonist on pituitary-ovarian function in normal women. The LHRH agonist busere-lin (200 g/12 h or 400 /g/24 h) was given intransally for four consecutive cycles for 14 or 21 days in 26 normally cycling women. Five milligrams of medroxyprogesterone acetate were given orally twice daily from days 15–21. There was a 7-day pause between each medication cycle. Blood samples were drawn(every other day for RIA of LH, FSH, estradiol (E₂), and progesterone (P).

Serum FSH increased for only a few days at the beginning of each cycle, whereas sustained elevation of serum LH occurred (during LHRH agonist administration. Serum E₂ increased rapidly and remained elevated during the administration of buser-elin. Serum P remained in the follicular phase range or increased briefly after the initiation of buserelin occasionally in the 14-day regimens. After discontinuation of buserelin, E₂ fell rapidly, and uterine withdrawal bleeding occurred. During the pause,FSH increased progressively. The patterns of gonadotropin response to buserelin were similar in the four cycles.

Based on measurement of the areas of the response curves, serum (LH and E)2 levels were higher during the administration of 200 g/12 h compared to 400 g/24 h buserelin. However, down-regulation of the pituitary-ovarian axis, as evaluated by the acute gonadotropin response to buserelin on day 14, was more pronounced with 200 g/12 h than with 400 g/24 h. Breakthrough bleeding occurred in the 14-day schedules, whereas withdrawal bleeding occurred during the pause in the 21-day schedules. The immediate cycles following buserelin administration were normal ovulatory cycles.

Intermittent LHRH agonist administration for 21 days avoided constant down-regulation of the pituitary-ovarian axis and allowed regular uterine bleeding. Combined with an appropriate P complement, it could be a useful contraceptive approach.

^* This work was supported by the Contraceptive Branch of the NIH (Contract l-HD-0-2800, to F. Labrie, A.L., and N.F.).