long-term administration of low-dose antiprogestins. However, data derived from a number of therapeutic studies of mifepristone to treat endometriosis, leiomyomas, meningiomas, and Cushing's syndrome suggest that long-term use of this compound would inhibit ovulation and induce consistent amenorrhea (lack of menstrual bleeding). Toxicity experienced by women in these various studies was minimal except at the highest doses. Furthermore, the antiglucocorticoid activities of the compound were not manifest at low doses (less than 25 mg/day), even though doses as low as 2 mg/day were effective at inhibiting ovulation.

Recommendation No. 4. Clinical research should be undertaken promptly to evaluate the efficacy and safety of mifepristone and other antiprogestins as low-dose contraceptives. Such research should address, among other issues,

  1. mechanisms of contraceptive action

  2. the effectiveness of various regimens in preventing pregnancy (e.g., continuous versus cyclic administration, possibly with the addition of other hormones)

  3. the lowest effective dose to prevent pregnancy for each regimen

  4. potential short- and long-term toxicities affecting bone (osteoporosis), lipids (alteration in profile), endometrium (histologic changes), ovary (cyst formation), and brain (mood); and

  5. benefits and risks, both contraceptive and noncontraceptive, of antiprogestin contraception relative to other hormonal contraception.

Post-Coital Contraception

A post-coital contraceptive is a pill or other method that can be used to reduce the chance of undesired pregnancy after unprotected intercourse around the probable time of ovulation (midcycle). In the United States, the most common post-coital approach (termed the ''morning-after pill") involves a combination oral contraceptive containing both a synthetic estrogen and a progestin. Although the regimen is not 100 percent efficacious, currently available oral contraceptives reduce the risk of pregnancy by at least 75 percent after unprotected midcycle sexual intercourse. Unfortunately, the relatively high amount of estrogen used results in side effects such as nausea and vomiting, and a 25 percent failure rate is highly undesirable.

Because of the critical role progesterone plays in early transformation of the uterus, and its possible roles in ovulation and tubal transport, it



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