Abstract

PIP: The development of the antiprogestin RU-486, and its current use in France and the UK, potential other application, politics in the US, and future are presented. Ru-486, as commonly known by its company code name, rather than its generic name mifepristone, is an analogue of a progestin used in oral contraceptives, with an added chemical group that allows it to link up with the progesterone receptor, but prevents progesterone's effects. It was approved in France in 1988, and has been used for early abortion up to 7 weeks LMP on 80,000 women. French women, after an initial diagnostic appointment, take 3 200 mg tablets of RU-486, then 36-48 hr later return for a Sulprostone (prostaglandin) injection, and are checked up 4-6 weeks later. About 96% abort completely. Some have nausea, vomiting, or pain. Bleeding averages 9 days, and 1% require treatment for bleeding. 2 cardiovascular events and 1 heart attack have been associated with the prostaglandin, now contraindicated in smokers or women 35. In England, RU-486 abortions began in late 1991, for pregnancies up to 9 weeks, using a gentler prostaglandin, Gemeprost, in a vaginal suppository. Only company-trained doctors may order the drug. Research continues on lower doses of RU-486, other prostaglandins, and effects on the fetus if abortion fails. While there is no known basis for a teratogenic effect of the antiprogestin, strong uterine contractions brought on by prostaglandins, such as misoprostol, as abused for illegal abortion in Latin America, may cause birth defects. RU-486 is expected to be useful for inducing labor, dilating the cervix, emergency contraception, pre-surgical management of Cushing's syndrome, brain cancers with profesterone receptors, among other conditions. Several of the 400 or so antiprogestins known are being tested clinically, notably HRP 2000 by WHO. Political controversy is so intense in the US that Roussel, the maker of RU-486, has no intention of marketing it, and even research supplies are unreliable. Meanwhile, pro-choice groups are innovating ways to test and market antiprogestins legally, perhaps inside state lines. It is expected that a suitable prostaglandin, misoprostol, licensed for peptic ulcer, will be available soon, and even RU-486 will become generic by 1998 when its patent expires.