There are very limited data from a few small studies on the use of antiprogestins in the treatment of uterine leiomyomas. In these studies, mifepristone at doses ranging from 5 to 50 mg/day for three months produced a marked decrease in leiomyoma volume. Side effects were limited and promptly resolved after discontinuation of the drug. Importantly, estrogen levels were maintained in a range sufficient to prevent bone loss as measured in the spine and hips. At the highest dose studied (50 mg/day), however, antiglucocorticoid effects were observed.

These early studies on the use of antiprogestins in the treatment of both endometriosis and uterine leiomyomas appear promising; however, larger studies than those currently available are required to establish the long-term efficacy and safety of these drugs for such purposes. In particular, efforts should be made to determine whether antiprogestins improve fertility as compared to other available regimens. As with many areas of antiprogestin research, substantial additional studies are also needed to elucidate the molecular mechanism of action of antiprogestins in the treatment of these diseases. Understanding the mechanism of action of these compounds is critical and might provide leads for future therapeutic uses. In particular, the noncompetitive "antiestrogenic" properties reported in some studies should be characterized, especially as they relate to defining potential long-term side effects of these therapies.

Recommendation No. 13. The committee recommends further studies to determine the minimal effective dose of mifepristone and other antiprogestins for the treatment of endometriosis and uterine leiomyomas. Measures of outcome should not be limited to pain relief alone, but should also address the likelihood of improving fertility. Once such studies are completed, randomized clinical trials should be undertaken to compare the safety and efficacy of mifepristone and other antiprogestins with current therapies for the treatment of endometriosis and uterine leiomyomas.

Recommendation No. 14. The committee recommends additional research to elucidate the antiestrogenic property of mifepristone and other antiprogestins. Research models should include endometrial cultures, explants, and in vivo systems. It is also important to clarify the molecular events involved and, in all such investigations, to characterize whenever possible the steroid-receptor status of the endometriotic and fibroid tissues under study.

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