ANTIPROGESTIN AND OR GONADOTROPIN-RELEASING-HORMONE AGONIST FOR ENDOMETRIOSIS TREATMENT AND BONE MAINTENANCE - A 1-YEAR PRIMATE STUDY/

The fact that RU 486 curtailed estrogen-induced endometrial proliferat ion in primates and relieved pelvic pain in women with endometriosis i s the reason for continuing research on antiprogestins. Thirty-two adu lt female cynomolgus monkeys demonstrating menstrual regularity had su rgery for the induction of endometriosis. After lesion staging, four t reatment groups (n = 8), each of 1-yr duration, were made. Group I rec eived combination/sequential therapy with depot GnRH agonist (GnRH-a) for 3 months, followed by weekly RU 486 for 9 months. Group II receive d weekly RU 486, group III received monthly GnRH-a, and group IV serve d as a vehicle control. A staging laparotomy was performed every 3 mon ths to assess the area of peritoneal endometriosis (square centimeters ) and the thickness of in situ endometrium. Bone density was measured serially by dual x-ray absorptiometry. Serum was collection weekly. Me an (+/- se) serum estradiol levels were lower after GnRH-a (77.1 +/- 2 .6 pmol/L) than after RU 486 (231 +/- 12 pmol/L) treatment and lower t han those in untreated cycling controls (231 +/- 13 pmol/L). GnRH-a pr oduced significant atrophy of endometriotic plaques within 3 months of therapy; this lesion reduction was sustained with RU 486. Both GnRH-a and RU 486 alone produced profound thinning of ectopic and eutopic en dometrium throughout 1 yr of continuous therapy. Bone density decrease d significantly after 6 months of GnRH-a alone (P < 0.05), without sig nificant changes in the other groups. After RU 486 treatment, there we re no significant changes in testosterone, androstenedione, sex hormon e-binding globulin, or cortisol. Like GnRH-a, long term antiprogestin therapy produced a reduction in the volume of pelvic endometriotic les ions as well as atrophy of in situ endometrium; however, RU 486 allowe d maintenance of tonic ovarian estradiol secretion, suggesting that ef ficacious endometriosis therapy can be sustained long term without the sequelae of hypoestrogenism, specifically bone density loss.