Does constant infusion of gonadotropin-releasing hormone agonist lead to greater suppression of gonadal function in man than its intermittent administration?

Constant infusion of gonadotropin-releasing hormone agonist (GnRH-A) in the rhesus monkey leads to far greater suppression of spermatogenesis than its intermittent administration. To assess whether administration of GnRH-A by constant subcutaneous infusion will also lead to greater inhibition of gonadal function, we administered either 20 or 200 micrograms of D(Nal2)6GnRH (GnRH-A) to two groups of normal male volunteers, either by a single daily injection or constant subcutaneous infusion through a portable infusion pump, for 28 days. Basal and integrated luteinizing hormone (LH), follicle-stimulating hormone, and testosterone (T) responses were not significantly different between the two methods of GnRH-A administration at either the 20- or 200-microgram dose, even though subjects in the constant infusion group showed more consistent inhibition of basal and 24-hour integrated T concentrations. Significant decline in serum T in both groups occurred in the face of little or no decline in serum LH. It is concluded that the effects of constant infusion of GnRH-A in man are not as striking as those reported in the rhesus monkey and that the antigonadal effects of GnRH-A in man are complex and cannot be explained on the basis of down-regulation of pituitary gonadotropin secretion alone--additional mechanisms may be operative.