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
buserelin (200 micrograms/12 h or 400 micrograms/24 h) was given intranasally 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
buserelin. 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 E2 levels were higher during the administration of 200 micrograms/12 h compared to 400 micrograms/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 micrograms/12 h than with 400 micrograms/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.