Endocrinology of gonadotropin-releasing hormone induced cycles in hypothalamic amenorrhea: the role of the pulse dose.

Objective: To find the treatment regimen giving a maximum chance of ovulation and a minimal chance of multiple follicular development in pulsatile gonadotropin-releasing hormone (GnRH) therapy in patients with hypothalamic amenorrhea.

Design: We propectively studied the endocrinology of cycles induced with 5, 10, and 20 micrograms GnRH pulse doses, randomly assigned per patient, comparing this with the endocrinology of spontaneous menstrual cycles.

Setting: All patients were treated at the Academic Hospital of the Vrije Universiteit, Division of Reproductive Endocrinology and Fertility.

Patients: Fifteen patients with hypothalamic amenorrhea were treated for one to three cycles; 14 normally cycling volunteers were studied for one cycle.

Main Outcome Measure: Number of ovulations per pulse dose; luteinizing hormone, follicle-stimulating hormone, total urinary estrogens (Es), and pregnanediol were measured per cycle day and per stimulation day.

Results: The endocrinology of all ovulatory cycles remained within the normal range. First treatment cycles showed significantly higher ovulation rates compared with subsequent cycles. Significantly more anovulation was observed in cycles with 5-micrograms pulse doses. Luteal Es were significantly higher in induction cycles compared with controls.

Conclusions: The optimum treatment regimen should be to start induction with 5 micrograms/pulse in the first cycle and to raise the dose to 10 micrograms/pulse in subsequent cycles, regardless of the outcome of the first cycle. After ovulation, the pulse interval should be changed to 240 minutes.