Low dose pulsatile gonadotropin-releasing hormone in anorexia nervosa: a model of human pubertal development

Patients suffering from anorexia nervosa were studied to determine whether gonadotropin-releasing hormone (GnRH) could induce the hormonal changes which occur during normal puberty. Three amenorrheic patients were studied at low body weight (less than 70% ideal BW). All three patients were prepubertal, as evidenced by immature LH and FSH responses to a standard GnRH test (2.5 micrograms/kg BW) and the absence of spontaneous LH peaks both during the day and during sleep. Low doses of GnRH (0.025--0.05 microgram/kg), aimed at producing peak plasma GnRH values of approximately 200 pg/ml, were given by iv bolus injection every 2 h for 5 days. Plasma responses of FSH, LH, and estradiol were measured by RIA. Preinjected FSH values rose rapidly to plateau (range, 15--30 mIU/ml) on the second to third day before falling despite the continued administration of GnRH. In contrast, plasma LH and estradiol increased gradually throughout the 5 days of injections. Acute FSH responses to GnRH initially exceeded those of LH but subsequently decreased, whereas LH increments increased progressively after the first 36 h of injections. The 5 days of low dose GnRH pulses induced maturation of the hormone responses to the standard GnRH test, so that LH release exceeded that of FSH at the completion of the study. These changes in the patterns of FSH and LH secretion are similar to those seen during normal puberty in girls and during the follicular phase of the menstrual cycle. The results demonstrate a changing pattern of pituitary response to physiological administration of GnRH and indicate that the changes in gonadotropin secretion during normal puberty are consistent with the effects of the single decapeptide GnRH.