to 25 mg/day, the decrease of leiomyoma volume was virtually identical to that observed with the 50-mg dose. Further decreasing the dose to 5 mg/day was less effective, with an overall reduction of tumor volume by 25 percent. There was a decrease of immunostaining for PR but not for ER in leiomyomas treated with RU 486.
In all studies, amenorrhea with early to midfollicular range of estradiol levels was induced, and no change in bone mineral density was noted. Ovulatory cycles resumed four to six weeks after completion of treatment. Side effects were observed, which included atypical hot flushes, mild elevation of serum transaminase, and antiglucocorticoid effects at higher doses. Thus, an antiprogesterone may provide a novel mode of long-term (years) medical management for pelvic endometriosis and uterine leiomyomas. Future studies of lower doses and correlation of individual responses with the status of steroid hormone receptors, growth factors, anatomical sites, and vascularity may be helpful in predicting maximal responses of individual patients.
Pelvic endometriosis and uterine leiomyomas (fibroids) are the two most common disorders in women during reproductive age. Infertility, pelvic pain, and uterine bleeding are major clinical manifestations, and hysterectomies are frequently resorted to. Although their pathogeneses are unclear, both conditions are ovarian steroid dependent, and tumors are endowed with receptors for estrogen (ER) and progesterone (PR). The rationale for inducing regression of these tumor growths with an antiprogestin was formulated soon after the demonstration of the ability of RU 486 to interrupt early pregnancy in women (Baulieu, 1989). It was followed by a series of short-term studies showing the effectiveness of RU 486 in inhibiting ovulation, inducing luteolysis, and disrupting endometrial integrity in normally ovulatory women (Schaison et al., 1985; Liu et al., 1987; Garzo et al., 1988; Luukkainen et al., 1988; Roseff et al., 1990). Concurrently, clinical trials were conducted to determine the beneficial effect and safety of long-term daily administration of RU 486 in patients with endometriosis and fibroids.
Endometriosis is a common disease, affecting as many as 1 in 15 women of reproductive age (Barbieri, 1990). The incidence is much higher among women with infertility (25 percent; Jones and Rock, 1976). In this condition, functioning endometrial gland and stroma have migrated outside the uterine cavity. These ectopic endometriotic