Mechanism of anovulation in hyperprolactinemic amenorrhea determined by pulsatile gonadotropin-releasing hormone injection combined with human chorionic gonadotropin

Abstract

Objective: To clarify the mechanism of anovulation in hyperprolactinemic anovulatory women by subcutaneous (SC) pulsatile GnRH injection.

Design: Prospective clinical study.

Setting: Studies were made on at the Department of Obstetrics and Gynecology, the University of Tokushima, School of Medicine.

Patients: Six hyperprolactinemic (group 1) and 7 normoprolactinemic (group 2) anovulatory patients were studied.

Interventions: After examinations of pulsatile secretion of LH, the GnRH test, thyrotropin-releasing hormone test and estrogen test, pulsatile GnRH treatment (20 micrograms/2 hours SC) was performed. Two protocols were tested on each patient. In the non-hCG protocol, GnRH treatment was continued until ovulation. In the hCG protocol, 5,000 IU of hCG was injected to induce ovulation when follicles were fully mature.

Main outcome measure: The rates of follicular maturation and ovulation, serum E2 and P in the two groups.

Results: Pulsatile LH secretion was impaired in both groups. LH release 48 hours after estrogen injection was impaired in group 1 but not in group 2. Follicles matured on pulsatile GnRH treatment in all cycles in both groups. However, with the non-hCG protocol, ovulation occurred in only 17% of group 1, but in 89% of group 2. With the hCG protocol ovulation occurred in all cycles in both groups.

Conclusions: The main cause of anovulation is impaired gonadotropin pulsatility and derangement of the estrogen-positive feedback effect on LH secretion in hyperprolactinemic patients, their ovarian response to gonadotropin being well maintained. Subcutaneous pulsatile GnRH therapy combined with hCG can be used as an alternative to bromocriptine treatment for induction of ovulation in these patients.