Suppression of Follicular Maturation by Infusion of a Luteinizing Hormone-Releasing Hormone Agonist Starting during the Late Luteal Phase in the Stumptailed Macaque Monkey

Abstract

The effect of continuous administration of an LHRH agonist for 14 days on follicular estradiol secretion was studied in adult female stumptailed macaque monkeys. The infusion was started either during the early follicular phase or during the late luteal phase. Both treatments resulted in a rise in serum concentrations of LH and FSH for 2-3 days, after which time values returned to basal levels. Infusion during the early follicular phase induced a rapid rise in serum concentrations of estradiol, which declined after 7-10 days. The normal rise in serum progesterone after midcycle failed to occur, indicating that ovulation had been inhibited. Infusion “during the late luteal phase of the cycle prevented the normal rise in serum concentrations of FSH and estradiol at the end of the luteal phase, and there was no indication of follicular estradiol production during the subsequent infusion period. Removal of the minipumps after 14 days was followed promptly by normal cycles, regardless of when the infusion had been started. In a second experiment, infusion of LHRH agonist was started during the luteal phase and extended for 90 days. This resulted in marked and sustained suppression of estradiol secretion and total absence of progesterone rises. These findings show that in the monkey, a rapid and sustained suppression of estradiol production can be obtained if a long term infusion of LHRH agonist is started during the luteal phase of the cycle. Such an approach in women using infusion pumps or sustained delivery preparations may be the most effective way of achieving a medical ovariectomy for the treatment of endometriosis, leiomyomata, and other estrogen-dependent pathological conditions.