Regression of Uterine Leiomyomata in Response to the Antiprogesterone RU 486

摘要

Uterine leiomyomata are steroid hormone-dependent tumors that are common in reproductive-age women. Some series have found leiomyomata in up to 20 per cent of women over 30 years of age. These tumors represent the most frequent indication for operative procedures in women of reproductive age. Receptors for both estrogen and progesterone have been identified in leiomyomata.RU 486 is a synthetic steroid with both antiprogesterone and antiglucocorticoid activities. Long-term administration of RU 486 relieves pelvic pain in women with endometriosis. Because leiomyomata and endometriosis share a dependence on ovarian steroids, the authors hypothesize that RU 486 might have an inhibitory effect on the growth of leiomyomata.Ten normal women between the ages of 18 and 45 years with symptomatic uterine leiomyomata were recruited for the study. Each received 50 mg of RU 486 daily for a period of 3 months. Baseline ultrasound examinations were obtained and were repeated monthly throughout treatment to measure leiomyomata volume. Hormonal concentrations were measured by radioimmunoassay. Myomectomy or hysterectomy was performed in 6 of the 10 patients at the end of treatment. Leiomyomata and myometrial tissue was obtained for immunohistological analysis.All patients became amenorrheic during treatment. Myoma volume decreased by 22 per cent at 4 weeks, by 40 per cent at 8 weeks, and by 49 per cent after 12 weeks, compared with pretreatment measurements (Fig. 1). Serum LH levels doubled during the first 3 weeks of treatment, with concomitant rises in serum androstenedione and testosterone. These elevated hormone levels had returned to baseline in 4 weeks and remained there throughout treatment. Rises in cortisol and serum dehydroepiandrosterone sulfate were seen at 12 weeks, suggesting an antiglucocorticoid effect of RU 486 (Fig. 2).Progesterone-receptor, but not estrogen-receptor, immunoreactivity was reduced in both the myomas and myometrium after RU 486, compared with tissues from untreated patients. This immunohistochemical finding suggests that regression of tumors may be obtained through a direct antiprogesterone effect.