Induction of ovulation and fertility in amenorrheic women by pulsatile low-dose gonadotropin-releasing hormone

In functional hypothalamic amenorrhea, anovulation is associated with low or apparently normal gonadotropin levels and normal prolactin levels, without evidence of structural pituitary or hypothalamic lesion. The demonstration of reduced LH pulsatility and inappropriately low FSH, despite normal or increased pituitary responsiveness to GnRH, suggests that the syndrome results from deficient hypothalamic secretion of GnRH. The aim of the present study was to develop a method of physiological GnRH replacement, using the safe and convenient subcutaneous route, in order to restore normal reproductive function in patients with clomiphene-unresponsive hypothalamic amenorrhea. The authors studied 1 patient with primary amenorrhea, 11 with secondary amenorrhea, and 2 with oligomenorrhea. A peristaltic pump delivered 5–15 μg of GnRH at intervals of 90 minutes. A total of 36 cycles of treatment were performed in the 14 patients. Hormonal and ultrasound evidence of ovula-tton (pregnanediol glucuronide, 4 μmol or more per day (Fig. 1); disappearance of follicle 19 mm or more in diameter) was observed in 30 (83 per cent) of the cycles and was followed by normal luteal function (peak pregnanediol glucuronide, 7 μmol or more per day; luteal phase duration, 12 days or more) in 24 of the ovulatory cycles (80 per cent). Pregnancy was confirmed after 13 (54 per cent) of these cycles in 11 women.