RU486: pharmacology and potential use in the treatment of endometriosis and leiomyomata uteri

Abstract

More than a decade after the serendipidous discovery of RU486, numerous antiprogestins have been synthesized and studied. Interest in how antiprogestins exert their antagonist effect has led to novel information about the molecular mechanisms of progesterone action. The pivotal role that progesterone plays in reproductive biology has led to research in many areas where a potential role for these compounds may be found in health and disease. RU486 has been shown to relieve pelvic pain associated with endometriosis and to decrease American Fertility Society endometriosis scores. Uterine leiomyomata show a significant reduction in size after administration of RU486 for 3 months. Although much research remains to be carried out, RU486 appears promising as alternative therapies for these diseases.

PIP: More than a decade after the discovery of RU-486, numerous antiprogestins have been synthesized. Interest in the antagonist effect of antiprogestins has revealed novel information about the molecular mechanisms of progesterone action owing to the pivotal role that progesterone plays in reproductive biology. RU-486 side effects include hot flashes and transient increases in liver transaminases. Generalized cystic changes in the endometrium have been demonstrated consistent with a chronic unopposed estrogen effect. RU-486 has been shown to relieve pelvic pain associated with endometriosis and to decrease American Fertility Society endometriosis scores. Since uterine leiomyomas appear to be ovarian steroid dependent, it was attempted to reduce the growth of uterine fibroids by using low-dose (50 mg/day or approximately 1 mg/kg/day) RU-486 for 3 months in 10 patients. 10 patients were studied at a 25 mg daily dose for 3 months and 7 patients received 5 mg daily for the same length of time. Additionally, leiomyomata and myometrium of 5 patients treated with 50 mg daily of RU-486 and 5 untreated patients in the follicular phase of the cycle were examined immunohistochemically using antibodies recognizing estrogen receptor protein and progesterone receptor protein. Myoma size decreased approximately 22% at 4 weeks, 39% at 8 weeks, and 40% at 12 weeks. It has been shown, for the first time, that an antiprogesterone which induces acyclicity also induces a decrease in size of leiomyomata. Additionally, a small randomized study attests to the probable efficacy of RU-486 in the treatment of leiomyomata. This decrease in size is seen in the face of follicular phase levels of estrogen, and data suggest that the decrease may be mediated through its antiprogestin properties. RU-486 appears promising as a safe and well-tolerated alternative therapy for these diseases. Further investigation of the endometrial effects of RU-486 must be conducted if RU-486 is to be used for longer than 3-6 months.