The Stimulatory and Down-Regulatory Effects of a Gonadotropin-Releasing Hormone Agonist in Man*

Abstract

Synthetic long-acting agonistic analogs of GnRH both stimulate and paradoxically inhibit gonadotropin secretion in male animals and humans. To characterize the stimulatory and down-regulatory effects of such a superactive GnRH analog in man, either 10 or 100 µg D-(Nal₂)⁶GnRH were administered sc to two groups of seven normal men for 10 days. Serum LH, FSH, and testosterone were determined daily before analog injection and 1, 2, 4, 6, 8, 12, 16, and 24 h after analog injection on days 1 and 10. Both doses of analog led to initial increases in LH, FSH (peak, days 2–3), and testosterone (peak, days 3–4), but by day 10 of analog administration, serum levels of LH, FSH, and testosterone returned to pretreatment levels. The integrated 24-h responses above baseline of serum LH and FSH to both doses of GnRH analog were significantly decreased on day 10 compared to day 1 (P < 0.05). The integrated 24-h responses of serum testosterone to both doses of agonist were not significantly decreased on day 10 of agonist treatment compared to those on day 1 (P > 0.2). Integrated serum testosterone responses above baseline in response to 3000 IU hCG administered 2 weeks before analog treatment and 24 h after the last analog injection were not different (P > 0.2) GnRH agonist treatment resulted in proportionate stimulation of LH, FSH, and testosterone consistent with a predominant pituitary effect of the analog at these doses given for 10 days. The stimulatory effects of daily GnRH agonist treatment in men are transient with some down-regulatory effects evident after 10 days of treatment. (J Clin Endocrinol Metab58: 1084, 1984)