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Drug of Choice

The side effects of RU 486.

In the mid-1980s, as word of the French abortion pill rippled across the world, the new drug was greeted as a thing of awesome powers. Pro-choicers eagerly proclaimed that RU 486 would render both surgical abortion and the anti-abortion movement obsolete. If a woman suspected she was pregnant, she would go to her medicine cabinet and, in peace and privacy, swallow the pill. With this simple act she could banish the emotional, the physical, and even much of the moral trauma accompanying the decision to have an abortion. Described by its inventor, Etienne-Emile Baulieu, as a “contra-gestive'' (because it impedes gestation rather than conception), RU 486 would in effect erase the distinction between a contraceptive and an abortifacient. Anti-abortionists, horrified at the euphoria, quickly marshaled their forces against the drug, calling it a “chemical time bomb'' and a “death pill.''

The pro-choicers have sounded more sober about RU 486 over the past couple of years. Their initial hopes for the drug as “the ultimate act of reproductive privacy'' proved to be, as Bill Hamilton of Planned Parenthood puts it, “a myopic dream.'' The anti-abortionists' continual boycott threats have cowed the patent owner and sole manufacturer, Roussel Uclaf of France, and its parent company, Hoechst AG, a German multinational, into tightly restricting access to the drug. In France, the only country where RU 486 is actually available to women outside of clinical trials, each pill must be registered, and the drug is dispensed only by designated clinics, only after a pregnancy has been confirmed, and only through the seventh week. And though French doctors report impressive success with it as an abortifacient, the procedure turns out to be neither quick nor painless nor totally private. Patients are required to make four visits to a designated clinic, on the second of which they are given synthetic prostaglandin to reduce the risk of hemorrhage and help induce contractions.

But the more recent news doesn't look good for the anti-abortionists. Distribution of RU 486 will start in Great Britain within the next year. Scandinavia and the Netherlands are expected to follow soon, and Sweden has begun testing it as a once-a-month contraceptive. Spain's Ministry of Health has made an official demand for the pill, and Baulieu, who still works for Roussel, says the Soviet Union will likely be next. The World Health Organization continues its own clinical studies on RU 486 in China, India, Hong Kong, and Cuba. Perhaps most alarming of all from the anti-abortionists' point of view, RU 486 is once again being described as a miracle drug -- this time by American doctors who say it may prove just as effective in treating a range of deadly diseases as it is in terminating pregnancy. William Regelson, an oncologist at the Medical College of Virginia, declares, “If RU 486 did not have abortion associated with it, it would be considered a major breakthrough drug.''

In the August 22/29 issue of The Journal of the American Medical Association, Regelson and two co-authors describe the proven and potential uses for RU 486 in treating some kinds of breast cancer and brain tumors, Cushing's syndrome -- a terminal disease characterized by hypertension, osteoporosis, diabetes, and infections -- and even AIDS. RU 486 is known as a ``hormone antagonist'' because it prevents cells from responding to certain hormones as they normally would. It arrests the course of pregnancy by blocking the action of progesterone, without which an embryo cannot survive. Some tumors and cancers thrive on hormones as well, as do all stress-related diseases. Cushing's syndrome, for example, is caused by an excess production of cortisol, which is blocked by RU 486.

A program at the University of Southern California School of Medicine is using RU 486 in a small group of patients with a type of meningioma, or brain cancer, that cannot be cured with surgery. Martin H. Weiss, who heads the study with Stephen Grunberg, says that it is the only medical treatment that has ever been shown to work on these patients; a third of them have been responding to the treatment. George Chrousos, a senior investigator at the National Institutes of Health, who conducted a five-year study of RU 486 on Cushing's syndrome sufferers, describes “miraculous improvement'' on eight of the twelve patients in his study within weeks after treatment began. RU 486 may even be helpful to women who want to have a baby. Doctors at the University of California, San Diego, are doing a pilot study of RU 486 as a treatment for endometriosis, a common cause of infertility in women; and many believe that it could be used to induce labor in difficult deliveries, thus reducing the need for Caesarian sections.

All this sounds too good to be true, and some of it may be. The hopes that RU 486 may help AIDS patients, for example, are based on little more than informed speculation, and researchers who had hopes that it might cure glaucoma have been disappointed with the results of their animal studies. Arthur Caplan, director of the Center for Biomedical Ethics at the University of Minnesota, points out that “the rhetoric of the abortion debate has gotten the science inflamed.'' Doctors, no less than the pro-choice and anti-abortion forces, have their own interests to protect, and it's not surprising that they are among those who tend to make extravagant claims about RU 486.

Anti-abortionists, of course, are quick to downplay its curative potential -- well aware that once it is approved in the United States for other uses, doctors could legally prescribe it as an abortifacient as well, as long as abortion itself remains legal. John Willke, president of the National Right to Life Committee, says, “People are using the theoretical possibility of therapeutic use to get the drug into the country on a massive level for lethal use.'' Yet he insists that his organization objects only to studies on RU 486 as an abortifacient. “We couldn't stop the other research if we wanted to,'' he declares. 

That's true, but they can impede it. Hoechst hastily withdrew the drug in September 1988, only a month after the French government had approved it. A Roussel stockholders' meeting had been the scene of an anti-abortion protest, and the National Right to Life Committee in Washington and Catholic groups in France had issued a boycott threat against Hoechst and Roussel. Extremists proclaimed that I. G. Farben, the ancestor company of Hoechst, manufactured cyanide for Hitler's death camps. Distribution of RU 486 was resumed under orders from the French government, which owns 36 percent of Roussel Uclaf. Undeterred, the anti-abortionists kept up their boycott threats, and in December 1988 Roussel devised a set of criteria that countries have to meet before they can receive the drug: abortion must be legal and accepted by medical, public, and political opinion; prostaglandin must be available; distribution must be strictly controlled; and the patient must be required to sign a consent form declaring that if the treatment fails (as it does in up to 4 percent of women), she will have a surgical abortion. This would eliminate the possibility of babies born with defects -- an unlikely prospect, many doctors claim, since RU 486 is taken in a single dose and the drug is metabolized quickly, but one that understandably concerns the manufacturer. 

According to Roussel, the United States does not qualify for the drug -- even though abortion is legal and supported by a majority of the American public. By “accepted by public opinion,'' the company clearly means “uncontroversial'' -- a much tougher standard, which thus far essentially has given a noisy minority veto power over a major medical development. Willke vows that if RU 486 comes to the United States, he'll mount a worldwide boycott of every product made by Roussel and Hoechst, and, he warns, “It'll be a whopper.'' Hoechst AG owns two New Jersey-based companies: Hoechst-Roussel Pharmaceuticals and Hoechst Celanese Corporation, a chemical company that produces everything from carpet fibers to tire cord. Hoechst Celanese alone has annual revenues in the United States of $6 billion. American pharmaceutical companies, which could push for a license from Roussel, apparently have no intention of doing so. “Do you have any idea what would happen in the U.S. if the drug were being distributed?'' one unnamed senior executive at a drug company told The Washington Post when RU 486 was issued in France. “The market is potentially huge and the drug appears worthy. But who needs the headache?''

Some researchers who covet the new wonder drug are exasperated by Roussel's extreme caution about relinquishing it. William Regelson and his co-authors say that the threatened boycott has “largely frozen clinical trials,'' citing as evidence Roussel's cancellation of a meeting that it was to attend in April 1989 at Memorial Sloan-Kettering in New York to help the National Cancer Institute organize a multicenter study of RU 486 for treating breast cancer. Regelson says he was later told by a Hoechst employee that the company had pulled back because of the hostile political climate. Gary Hodgen, president of the Jones Institute for Reproductive Medicine, who has conducted numerous studies on RU 486 since 1982, says of Roussel and Hoechst, “They have limited access far more strictly than they did in years prior to 1989, no question about that.'' Baulieu denies these charges. It is high costs and the need for quality control, he insists, that have restricted the number of studies. And apparently not all doctors have had trouble getting the drug. Michael Kettle, who is working on the endometriosis study at San Diego, says that he and his co-workers have received active support from Roussel in their work.

On one point, at least, most people agree: Roussel's tight hold on RU 486 has crimped research in some critical areas. Since the early '80s the National Institutes of Health, which is barred from doing any abortion-related studies, has been conducting clinical trials of RU 486 for its use as a contraceptive and cellular studies on it as a possible future cure for breast cancer. However, one of NIH's most promising studies on RU 486 has come to a halt. Unlike women who use it as an abortifacient, patients with Cushing's syndrome require massive doses on a daily basis for extended periods throughout their lives. Although NIH researchers were excited by the extraordinary progress shown by the patients in the study, for whom no other medical treatment is effective, NIH decided not to continue its study in part because of concerns that it would be unable to obtain the quantities needed to sustain the patients' recovery.

One curious sign of the anti-abortionists' discomfort about RU 486 is their rhetoric. When Willke talks about the drug, he emphasizes the threat that it poses to women's health. He calls it a “chemical Dalkon Shield,'' “a powerful, poisonous steroid'' that “kills unborn babies, will injure and kill women, and will cause an epidemic of fetal deformity.'' This would seem to be a shrewd tactic. The grisly history offertility control -- DES, Thalidomide, and the early birth control pill, as well as the Dalkon Shield -- has made many women dubious about being subjected once again to an experimental drug whose long-term effects are unknown. 

But this line of attack has already been shattered by the powerful medical establishment. The American Medical Association and The New England Journal of Medicine, among others, have declared that RU 486, when properly administered, is as safe as surgical abortion -- one of the most common and least dangerous of all surgical procedures. The AMA has endorsed testing RU 486 here and is supporting efforts to convince Roussel to release it. Moreover, doctors are confident that as research continues, the drug -- like the early birth control pill -- will either be improved upon or replaced by a more sophisticated successor. NIH researchers hope that within the next several years they will have figured out the appropriate dose of RU 486 to be used as a birth control pill, perhaps taken only once or several times a month, and that it will have fewer side effects than the current pill.

Anti-abortionists should be the first to recognize the power of high-tech medicine to affect the political and ethical climate surrounding abortion. Sonograms have enabled us to peer inside the womb and detect the heartbeats of fetuses as young as six-and-a-half weeks, a development that helped to raise doubts among many whose support for abortion during the early months of pregnancy previously had been unqualified. RU 486 seems to be having precisely the opposite effect -- removing some of the moral onus from abortion. Most people -- even many in the anti-abortion rank and file -- have fewer qualms about the idea of aborting a three-quarter-inch embryo than a fetus at three months, complete with tiny fingers and toes and all of its organs. So a pill that would both enable women to have earlier abortions and result in fewer late ones would doubtless be widely seen here, as it has been in France and other countries, as a welcome medical advance. And once its other potential uses are known, and the clamor for the drug increases, the issue will become even more problematic, not least among those who believe RU 486 should be available to prolong health and save lives but have serious scruples about it as an abortifacient.

On the other hand, Willke's health warnings about RU 486 have doubtless proved effective in raising the specter of lawsuits, which scare drug manufacturers in the United States as much as anti-abortion protesters do. Ever since the Dalkon Shield disaster, pharmaceuticals and insurance companies have retreated almost entirely from the field of birth control. In fact, insurance is no longer available in this country for clinical testing of most contraceptives. And even if a U.S. drug company decided to ignore the threat of political harassment and financial vulnerability, it would first have to wind its way through the byzantine -- and politicized -- regulatory maze. After getting a license from Roussel, a company would present a protocol to the Food and Drug Administration for its own round of expensive tests on RU 486 and synthetic prostaglandin, and, finally, submit the drug application to the lengthy FDA approval process -- an even more complex procedure when two drugs are involved. The FDA, for its part, has already revealed its susceptibility to political pressure: in June 1989, at the urging of Senator Jesse Helms, Representatives Henry Hyde and Robert Dornan, and others, it banned the import of RU 486 into the United States for private use.

Limitations on birth control research, of course, mean fewer and less effective means of family planning for Americans. This only perpetuates the country's staggering rates of teenage pregnancy and abortion, both of which are among the highest in the industrialized world. A report of the National Research Council estimates that between 1.2 million and 3 million unwanted pregnancies occur in the United States each year, and that about half of the 1.5 million abortions each year are due to contraceptive failure.

Steps are being taken, though, to break the impasse. Some members of Congress, galvanized by an administration that, like its predecessor, has been more receptive to the demands of a powerful interest group than to the idea of pressing forward in controversial areas of medical research, have begun to move. In July, at the instigation of Representative Barbara Boxer of California, seventy members signed a letter urging Roussel to make RU 486 available for testing in the United States, in the hope that eventually Roussel will be convinced that the anti-abortionists represent neither the views of established medicine nor the will of the public at large. In late October the reauthorization bill for NIH collapsed after conservatives vehemently objected to several abortion-related provisions -- among them proposals for new centers to study contraception and infertility, which they claimed might lead to federal funding of research on RU 486. But this month Representative Ron Wyden of Oregon is holding a hearing on RU 486, in an attempt to smoke out the administration's position on the drug, and to raise questions about the extent to which the politics of abortion is impeding research that could save lives.

As for the pharmaceutical companies, eventually they may find the lure of profits more compelling than the fear of boycotts and litigation -- especially if RU 486 brings with it some of the health benefits that are predicted. The boycott threat could turn out to be a paper tiger: it will be hard to convince Americans not to buy a laxative made by Hoechst-Roussel Pharmaceuticals because its parent company also owns the company that produces RU 486. And Hoechst-Roussel specializes in prescription drugs rather than over-the-counter products. Even the liability conundrum is not insoluble. Many have proposed devising an insurance scheme for controversial new drugs and devices that would assure companies they would only be liable if culpable error could be proved. An insurance pool would cover unforeseen casualties.

Meanwhile, a group of physicians in San Francisco -- unwilling to wait for drug companies and the FDA -- has attempted to get the testing started themselves. Theirs would be the first trial in the United States of RU 486 with prostaglandin. (An earlier study, at the University of Southern California, examined the efficacy of the drug alone.) California's attorney general, John Van de Kamp, has proposed that the state invoke a statute that allows California to test, manufacture, and market drugs within its own borders that are not yet approved by the FDA. Three hospitals have agreed to conduct the trials, but the doctors' plan has stalled because Roussel has refused their request for the drug.

However, Baulieu, an irrepressible advocate of his invention, is confident that RU 486 will soon find its way to the United States -- and “not through the back door,'' as the Californians are proposing. “I don't see any reason to have partial distribution,'' he says. “As in the U.K., the pressure will be so strong that it will go ahead in the USA. Roussel will help when the conditions are better.'' Baulieu is advocating a joint undertaking that would include Roussel, a non-profit organization here (most likely Planned Parenthood), and a group of venture capitalists.

The anti-abortionists have raised legitimate questions about how RU 486 might be misused if it becomes a legal commodity here. What happens if a pregnant teenager gets hold of some pills in her second trimester, and thinks they'll solve her problem? Because the U.S. regulatory system is so decentralized, it will be more difficult to maintain the scrupulous controls over distribution that France has imposed. But this country would doubtless require abortion patients to undergo the same series of doctors' visits, to receive the pills and the prostaglandin only at clinics and hospitals, and to sign the same strict consent forms. And the United States isn't exactly slack about drug safety standards. RU 486 could be handled like any prescription drug that poses a threat to the fetus (such as the acne treatment Accutane, with doctors strictly screening patients and the FDA requiring detailed warning inserts along with the prescription). Or, if necessary, it could be deemed a “Class 3'' drug, like barbiturates and amphetamines, which doctors cannot prescribe without a special license, and which requires a detailed accounting on the part of physicians and pharmacists to avoid forgeries and other abuses.

There is no denying that RU 486 is an eerie drug. Even the most ardent pro-choice advocates have to ask whether there isn't a critical distinction between a contraceptive and a “contra-gestive.'' But RU 486, like abortion itself, isn't going to go away -- regardless of the restrictions that are placed on it. As more countries begin using the drug, demand for it here will increase. And if it is not approved and carefully regulated in the United States, a black market will certainly develop, with predictably unpleasant consequences. Thus Willke and his colleagues will have succeeded in creating exactly the circumstance he claims to fear the most: widespread misuse of a potent drug with possibly serious health hazards for women. 

This article originally ran in the November 26, 1990, issue of the magazine.