Gonadotropin-releasing hormone agonist suppresses ovulation, menses, and endometriosis in monkeys: an individualized, intermittent regimen.
This study was designed to test the efficacy of a long-acting GnRH agonist (alpha) for inhibition of ovulation and menses in monkeys as well as suppression of mild to moderate endometriosis through an individualized, intermittent regimen. Endometriosis was surgically induced in 21 cynomolgus monkeys; ectopic tissue viability was verified histologically. GnRH alpha (leuprolide, D-Leu6-Pro9-Net-LHRH, Abbott Laboratories) was injected weekly in treatment cycle 1 (10 microgram/kg, sc; n = 15). Ovulation and menses ceased in 6 of 15 females. For the remaining 9 monkeys, the GnRH alpha dose was increased to 15 microgram/kg weekly in treatment cycle 2. Still, 4 monkeys resisted suppression; in treatment cycle 3, their regimen increased to 15 microgram/kg every fourth day. Thus, anovulation and amenorrhea was achieved in 14 of 15 monkeys within 90 days, seemingly as a result of ovarian desensitization, since GnRH alpha injections usually enhanced serum LH and FSH levels (P less than 0.05). Frequent laparotomies and daily hormonal profiles of estradiol, progesterone, FSH, and LH in serum confirmed these findings. After treatment, 12 of 15 monkeys manifested resolution of ectopic endometrial tissue; concurrently, there was no change in the severity of endometriosis in the 6 saline-injected controls. Six of 15 monkeys became pregnant within 90 days after cessation of GnRH alpha injections; 1 of 6 control females conceived. These findings may encourage consideration of clinical investigations employing individualized and/or intermittent GnRH alpha administration for the treatment of endometriosis or to achieve contraception.
D000818:Animals; D004715:Endometriosis / Q000188:drug therapy*; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016729:Leuprolide; D007986:Luteinizing Hormone / Q000097:blood; D008252:Macaca fascicularis; D008598:Menstruation / Q000187:drug effects*; D010060:Ovulation / Q000187:drug effects*; D011247:Pregnancy; D011374:Progesterone / Q000097:blood
D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D016729:Leuprolide