Hypogonadotropic hypogonadism: hormonal responses to low dose pulsatile administration of gonadotropin-releasing hormone.

Patients with isolated gonadotropin deficiency were studied to determine whether pulsatile low dose gonadotropin-releasing hormone (GnRH) could induce the hormonal changes seen during normal puberty. Four male and two female patients with immature responses to a standard GnRH test (2.5 micrograms/kg) were given GnRH (0.025 micrograms/kg) iv every 2 h for 5 days. FSH responses varied between the sexes, and FSH concentrations in males rose continuously to 17.2 +/- 4.7 mIU/ml on day 5. In the females, FSH peaked at 13.8 and 15.8 mIU/ml on days 3-4 and then declined. The males showed increasing and the females decreasing incremental FSH responses to GnRH. LH concentrations and incremental responses to GnRH rose throughout the study in both sexes. Plasma testosterone rose slightly in the males to 0.7 +/- 0.2 ng/ml (P < 0.05), but in females estradiol increased to follicular range concentrations of 128 and 102 pg/ml. Standard GnRh tests on day 6 revealed maturation of gonadotropin responses in all patients. After termination of pulsatile GnRH, four patients were given single low dose GnRH injections on two to seven occasions over a period of 2-32 days. Initial LH responses were 2- to 14-fold greater than those seen on day 5 of pulsatile GnRH, and decreased over the next 3 weeks. FSH responses showed less initial augmentation and declined more slowly. Low dose pulsatile administration of GnRH to patients with isolated gonadotropin deficiency results in changing patterns of hormone secretion similar to those seen during puberty. Exaggerated pituitary sensitivity to GnRH may be present long after a brief period of GnRH stimulation, and may indicate previous rather than current secretion of GnRH.