Influence of Continuous Gonadotropin-Releasing Hormone (GnRH) Agonist Treatment on Luteinizing Hormone and Testosterone Secretion, the Response to GnRH, and the Testicular Response to Human Chorionic Gonadotropin in Male Rhesus Monkeys*

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Abstract
Five adult male rhesus monkeys were continuously infused for 56 dayswith 25 μg/day of GnRH agonist (Wy- 40972; Ag) using an implanted osmotic pump. Bioassayable serum levels of LH were elevated 8-fold on the second day of Agtreatment and then declined precipitously to below pretreatment levels by day 15.Serum levels of testosterone (T) changed similarly during Ag treatment, except that the fall in serum LH levels preceded the decline in serum levelsof T by at least 2 days. Ag administration also eliminated the diurnal variation inserum LH and T. GnRH administration (50 μg) induced a 13- to 20-fold rise in serum LH and a 3- to 7-fold increase in serum T incontrol monkeys. After 4 weeks of Ag administration, none of the animals responded to GnRH. Both control and experimentalmonkeys had a rise in serum T in responseto hCG after 7 weeks of Ag treatment. Basal levels of LH and T returned to normalby 12 days posttreatment, and the serum LH and T responses to GnRH were normal 19days posttreatment. These results indicate that 1) continuous administration of Ag is an effective method of inducing antifertility effects in male rhesus monkeys; 2) pituitary desensitization is a major factor involved in Ag-induced gonadal dysfunction in this species; and 3) the method of administration may be the critical factor in determining the effectiveness of GnRH agonists.

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