Pathogenesis of Endometriosis and Uterine Fibroids

Abstract

To evaluate the long-term effects of treatment with RU486 and to test its efficacy in endometriosis, a 3-month trial was conducted to evaluate the effects of daily administration (100 mg/day or ~2 mg/kg/day) on the functional activity of the reproductive axis, as well as implants, in patients with symptomatic pelvic endometriosis. All women became amenorrhoeic and acyclic. However, ovarian suppression was incomplete. In 24 h sampling studies, mean lutdnizing hormone (LH) and LH pulse amplitude were increased without a change in LH pulse frequency. Additionally, an antiglucocorticoid effect was demonstrated. Treatment resulted in improvement in pelvic pain in all subjects without significant changes in the extent of disease as evaluated by laparoscopy. We also attempted to reduce the growth of uterine fibroids by using 50 mg/day of RU486 for 3 months in 10 patients. Myoma size decreased-22% at 4 weeks, 39% at 8 weeks and 49% at 12 weeks. Serum concentrations of LH, androstenedione and testosterone increased in the first 3 weeks of treatment and then returned to baseline. In conclusion, daily administration of RU486 resulted in ovarian inhibition and menstrual acyclicity and in an improvement in the pain associated with pelvic endometriosis and decreased the size of uterine fibroids. This ovarian inhibition was achieved without oestrogen deprivation and may provide a novel long-term approach to the treatment of ovarian steroid-dependent disease processes.