Alternate‐day GnRH therapy for ovarian hypofunction induced by weight loss: treatment of six patients who remained amenorrhoeic after weight gain

Summary objective Body weight loss has an adverse effect on the pituitary-ovarian function, and no restoration of the function occurs in 20–30% of patients even after the recovery of body weight. In the present study, the efficacy of alternate-day GnRH therapy was investigated in six patients whose pituitary-ovarian function had not recovered at 15 months to 6 years after the recovery of body weight. DESIGN Synthetic GnRH (100 μg) was injected intramuscularly on alternate days for a total of 12 doses. On the completion of GnRH administration the efficacy of clomi-phene-human chorionic gonadotrophin (hCG) therapy was evaluated. A GnRH loading test and evaluation of LH secretion patterns were also performed to investigate the changes in hypothalamic-pituitary-ovarian function secondary to GnRH treatment. RESULTS All six patients ovulated in response to clomiphene-hCG therapy after 1–3 courses of GnRH treatment. The ovulatory response to clomiphene-hCG continued during follow-up periods of 5 months to 5 years. The initial hormonal change induced by GnRH treatment was a rise in the basal serum FSH level and a return of the FSH response to GnRH loading. This was followed by an increase in serum LH and the return of LH response to GnRH loading. In all six patients, pulsatile LH secretion was absent before starting GnRH treatment. GnRH treatment produced LH pulses in five of the six patients, although the pulse frequency was less than that in normally cycling women. A further increase in the pulse frequency was observed during clomiphene therapy. CONCLUSIONS Alternate-day GnRH administration is effective in inducing responsiveness to clomiphene in patients with anovulation secondary to weight loss.