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The Three M's of Medical Abortion
-- Mifepristone, Methotrexate and Misoprostol Susan C. Stewart, M.D. What is medical abortion? Quite simply, it is the ending of a pregnancy using drugs rather than surgery. A conventional abortion is considered a type of surgery. Although various herbal preparations that claim to cause an abortion have long been part of folk medicine in many cultures around the world, it is only in the last 20 years that modern science has developed abortion drugs that are reliable and effective. While there are now several medical abortion drugs, as well as different ways of administering them, all of the approaches have one thing in common: they make use of one or more of three drugs: mifepristone, methotrexate and misoprostol.
Mifepristone,
A.K.A. RU-486 Progesterone is a key player in the body's early preparations for pregnancy, helping to prepare the wall of the uterus for the implantation of the embryo, or rapidly dividing fertilized egg. If the body does not provide sufficient amounts of progesterone, the embryo cannot be implanted in the uterus. When this occurs, the uterus expels the embryo by a series of muscular contractions and the pregnancy is terminated. As they investigated the use of mifepristone as an abortion drug, early researchers found that the drug's success rate in causing abortion was no better than 80%. But when they combined mifepristone with other drugs, such as misoprostol that further stimulate uterine contractions, the success rate rose to almost 90%. This combination, a technique which is called the "French Protocol," has been widely and successfully used in France, Sweden, China and the United States.1,2 The dose of mifepristone used in the French Protocol is 600 mg. Recent studies, however, have suggested that much lower doses can be just as effective and may be safer. In the U.S., the most common protocols are two variations on the French Protocol called the Population Council, or PC, Protocol and the Abortion Rights Movement, or ARM, Protocol. These are named for two large-scale studies of medical abortion that were done in the United States. A key benefit of these protocols is that they can be done very early in pregnancy. This is also an important limitation because medical abortion drugs do not work as well after the seventh week of pregnancy when other hormones and mechanisms, including the growth of the placenta (the organ formed in the uterus during pregnancy), support the pregnancy. The seventh week is up to the 49th day after the first day of the last menstrual period.3
In 1982, researchers discovered that methotrexate was an effective treatment for ectopic pregnancy. Ectopic pregnancy is a dangerous condition in which a fertilized human egg implants in the wrong place, usually in one of the two fallopian tubes that transport eggs from the ovaries to the uterus. While an ectopic pregnancy cannot produce a baby, it can threaten the health, fertility and even the life of the woman. Before methetrexate, the only treatment for an ectopic pregnancy was surgery. The surgery, unfortunately, often results in fertility problems because the fallopian tube, sometimes also an ovary or, in the worst cases, the entire uterus may need to be removed. Methotrexate doesn't interfere with progesterone but, instead, prevents the growth of the rapidly dividing cells of the developing placenta. The drug has proven to have the same effect on normal pregnancies in the uterus. Once researchers saw the potential of methotrexate as a medical abortion drug, they tried it in combination with misoprostol, usually given as a vaginal suppository. They found that the methotrexate/misoprotol combination had a 90% success rate, which was comparable to that achieved with mifepristone/misopristol.4
In the French Protocol, misoprostol is given in pill form (400 mcg) 48 hours after a woman has taken mifepristone. It is sometimes prescribed as a vaginal suppository (800 mcg) because this route can be safer and more effective, especially with pregnancies that are farther along.5 The use of misoprostol by itself for medical abortion has been studied, particularly in Brazil, where abortion is illegal and misoprostol is the easiest of the three medical abortion drugs to acquire. These studies have found that although misoprostol is about as effective as both two-drug combinations, there are many more unpleasant side effects.4,6 Among the side effects of misoprostol are diarrhea, nausea and vomiting. Some women also get hot flashes or episodes of fever. Possibly because it enters the bloodstream more gradually, misoprostol seems to have fewer side effects when given as a suppository than by mouth.5 Based on what we know today, of the three drugs we have mentioned, misoprostol is the most likely to cause birth defects. Limb and cranial abnormalities have been reported in babies born to women who remained pregnant after using misoprostol. Obviously, the newer the drug the less information is available. For instance, there is little or no evidence that mifepristone can cause any particular problem. Although in the high doses used in cancer treatment methotrexate poses a clear risk to a developing fetus, we do not know if the low dose of methotrexate used for medical abortion has a similar effect.4 It should be remembered, however, that most of the scientific data on these drugs come from studies in which women have agreed in advance to undergo a surgical abortion if medical abortion drugs fail. For this reason, it is difficult to collect enough data to determine whether these drugs will cause birth defects.
For many women, medical abortion is desirable because it enables them to avoid a surgical procedure. However, because of the possible birth defect risk discussed above, all patients are required to agree that they will have a surgical abortion if the medical abortion fails.
Mifepristone/Misoprostol In the ARM version, the woman takes mifepristone by mouth (200 mg) and two days later takes misoprostol (800 mcg) as a suppository. In both of these regimens, two-thirds of women develop cramps and bleeding and complete the abortion in the next four hours. After 24 hours, the success rate nears 90%.8 The heaviest bleeding occurs on the day misoprostol is taken. For most women, bleeding and spotting continue for about two weeks. Uterine cramps also occur and vary from extremely severe to very mild. Women usually describe the bleeding and cramps as resembling a heavier than normal menstrual period.5,9 Women having a medical abortion are normally given pain killers such as ibuprofen, acetaminophen or a stronger analgesic containing codeine. Methotrexate/Misoprostol
The political picture is less clear. In the United States, pro-life forces have focused on trying to restrict the use of mifepristone (RU-486). This is largely because the two other medical abortion drugs have been approved for other uses and are, therefore, already available. The PC and the ARM studies demonstrated the safety and efficacy of mifepristone and, despite the opposition, the drug was approved by the FDA in September of 2000. The FDA has, however, put limits on the use of RU-486 -- the medication is not sold in pharmacies but is provided directly to physicians' offices. Opponents of medical abortion continue to pursue the battle on two fronts. Upon his appointment as Health and Human Services Secretary, Tommy Thompson suggested that he might direct the FDA to reopen the approval process for RU-486. Although Secretary Thompson has since backed away from his comment in his public statements, the possibility remains that the Bush Administration may further restrict the availability of medical abortion. Meanwhile, the U.S. Congress is debating a bill that would allow RU-486 to be prescribed only by the small minority of doctors who currently perform surgical abortions and only at clinics within an hour's drive of an hospital emergency room.
References 1. Creinin MD. Medical abortion regimens: Historical context and overview. Am J Obstet Gynecol 2000; 183: S3-9. return 2. Ulmann A. The Development of Mifepristone: A Pharmaceutical Drama in Three Acts. JAMWA 2000; 55:117-120. return 3. Baird DT. Mode of Action of Medical Methods of Abortion. JAMWA 2000; 55: 121-126. return 4. Pymar HC, Creinin MD. Alternatives to mifepristone regimens for medical abortion. Am J Obstet Gynecol 2000; 183: S54-64. return 5. Newhall EP, Winikoff B. Abortion with mifepristone and misoprostol: Regimens, efficacy, acceptability and future directions. Am J Obstet Gynecol 2000; 183: S44-53. return 6. Pollack AE, Pine RN. Opening a Door to Safe Abortion: International Perspective on Medical Abortifacient Use. JAMWA 2000; 55: 186-188. return 7. Mifeprex package insert, Danco Laboratories, LLC. return 8. Schaff EA, Fielding SL. A Comparison of the Abortion Rights Mobilization and Population Council Trials. JAMWA 2000; 55: 137-140. return 9. Davis A, Westhoff C, De Nonno L. Bleeding Patterns After Early Abortion With Mifepristone and Misoprostol or Manual Vacuum Aspiration. JAMWA 2000; 55: 141-144. return 10. Kruse B, Poppema S, Creinin MD, Paul M. Management of side effects and complications in medical abortion. Am J Obstet Gynecol 2000; 183: S65-75. return 11. MacIsaac L, Darney P. Early surgical abortion: An alternative to and backup for medical abortion. Am J Obstet Gynecol 2000; 183: S76-83. return 12. Koenig JD, Tapias MP, Hoff T, Stewart FH. Are US Health Professionals Likely to Prescribe Mifepristone or Methotrexate? JAMWA 2000; 55: 155-160. return |
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