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  • Title: Mifepristone: a potential contraceptive.
    Author: Heikinheimo O, Archer DF.
    Journal: Clin Obstet Gynecol; 1996 Jun; 39(2):461-8. PubMed ID: 8734010.
    Abstract:
    Use of standard estrogen-progestin contraception remains problematic in several subgroups of patients (e.g., those in whom exogenous estrogens are contraindicated, such as survivors of hormone-dependent cancer, or patients with endometriosis or uterine fibroids). In addition, the postcoital contraception, even if already available, remains at least underused. Additionally, continuous intake of contraceptive steroids is under increasing scrutiny. Would antiprogestins, and specifically the applications of mifepristone such as the ones reviewed in this article offer significant improvements at such problematic occasions? The most attractive novel contraceptive application of mifepristone is that of emergency postcoital contraception after unprotected intercourse. In addition, various options in the endometrial category, specifically those requiring drug administration only during a limited time, might be used in the future. Mifepristone might offer contraceptive and therapeutic relief to patients suffering from endometriosis or uterine fibroids, both conditions that have been shown to benefit from mifepristone therapy. However, the use of mifepristone in contraceptive preparations that are widely available would pose an additional problem of possible misuse of the compound, the reason for currently limiting access to mifepristone. However, such risk should be easily avoidable in the case of postcoital contraception in which only one dose of mifepristone is needed. Regarding the future of mifepristone, and more broadly that of antiprogestins in contraception, the authors believe that they will have a place in the future contraceptive armament. As already emphasized, the strongest clinical areas are those of immediate postcoital and endometrial contraception. Additional studies evaluating parenteral modes of administration, the long-term endometrial effects, and safety and metabolic effects of prolonged antiprogestin administration are needed before mifepristone can be considered a part of the contraceptive arena. The evaluation of mifepristone (RU-486) as a potential contraceptive has entailed three strategies: endocrine, endometrial, and postcoital. Both animal and human studies have indicated that continuous preovulatory administration of RU-486 (at least 2 mg/day) inhibits ovulation, presumably through its perturbation of the hypothalamo-pituitary-ovarian axis and disruption of normal folliculogenesis. However, the return of menses after RU-486 termination is unpredictable. Early luteal phase or continuous RU-486 administration eliminates this side effect and delays endometrial maturation. On the other hand, late luteal phase administration of a high single dose is associated with failure rates of 3-16%. The use of RU-486 for immediate postcoital contraception lengthens the subsequent menstrual cycle, but is highly effective and well tolerated. At present, the immediate postcoital and endometrial strategies appear most promising. Urged is further research evaluating parenteral modes of administration, the long-term endometrial effects, and the safety and metabolic effects of prolonged antiprogestin use.
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