In the months since the Supreme Court overturned Roe v. Wade, demand for medication abortion has soared. The method already accounted for more than half of all abortions in the United States before the Court’s decision; now reproductive-rights activists and sites such as Plan C, which shares information about medication abortion by mail, are fielding an explosion in interest in abortion pills. As authorized by the FDA, medication abortion consists of two drugs. The first one, mifepristone, blocks the hormone progesterone, which is necessary for a pregnancy to continue. The second, misoprostol, brings on contractions of the uterus that expel its contents. The combination is, according to studies conducted in the U.S., somewhere between 95 percent and 99 percent effective in ending a pregnancy and is extremely safe.
The second drug, misoprostol, can also safely end a pregnancy on its own. That method has long been considered a significantly less effective alternative to the FDA-approved protocol. But a growing body of research has begun to challenge the conventional thinking. In situations where people use pills to end a pregnancy at home, studies have found far higher rates of success for misoprostol-only abortions than were found in clinical settings. One recent study in Nigeria and Argentina showed misoprostol-only abortion to be 99 percent effective.
Even before new restrictions began to ripple across the U.S., mifepristone—often referred to as “the abortion pill”—was tightly controlled by the FDA, which requires that the drug be dispensed only by doctors certified to prescribe it and only to patients who’ve signed an agency-approved agreement. As efforts to ban that drug intensify, the relative availability of misoprostol, which can be obtained at pharmacies in every state and prescribed by any doctor, could make misoprostol alone a more common option for women seeking abortions, legally or clandestinely.
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Already, the Austria-based nonprofit Aid Access, which helps women in the U.S. order pills through the mail, helped thousands of women procure misoprostol-only regimens in the first months of the coronavirus pandemic, when shipments of mifepristone were disrupted. At least one U.S. abortion provider, Carafem, has been offering its patients a misoprostol-only option for close to two years, and other reproductive-health groups are now considering offering the same regimen. This approach follows a path that has been well established in places around the world, where mifepristone has been scarce or unavailable, but in the U.S., it represents a real shift in abortion provision.
If in the past mifepristone has garnered the bulk of attention from politicians and the public in the U.S., that focus may owe in part to an oft-told story about the origins of “the abortion pill” and its lone inventor, the renowned French researcher Dr. Étienne-Émile Baulieu. The reality is that of the two drugs, misoprostol has always mattered more.
For his work on mifepristone, Baulieu won one of the most prestigious prizes in medicine, whose recipients tend to be discussed as candidates for a Nobel Prize, and received France’s Legion of Honor. A lengthy profile in The New York Times Magazine called him “a different kind of scientist.” And though the chemists George Teutsch and Alain Belanger actually synthesized the compound, Baulieu became, to American audiences, “the father of the abortion pill.”
Yet mifepristone is not, by itself, a highly effective abortifacient. Taken alone, the drug ends a pregnancy only about two-thirds of the time, which is why it has always been administered in combination with a prostaglandin—a drug that mimics the function of hormones that promote menstrual cramping and inflammation.
For years, doctors in Europe had been administering mifepristone with a prostaglandin called sulprostone. The combination was nearly 100 percent effective, but required multiple in-person visits to a clinic or hospital because sulprostone could only be given by injection. “Everyone had been looking for a prostaglandin that didn’t have to be either injected or kept frozen,” says Beverly Winikoff, the founder of Gynuity Health Projects, whose research on medication abortion helped win FDA approval in the United States.
In Brazil, women had already found one. No individual, or individuals, have ever been widely credited for that discovery, the way Baulieu is credited for mifepristone. But scholars agree that the practice began in the country’s impoverished northeast soon after the drug went on the market in 1986.
Manufactured by G.D. Searle & Company, misoprostol was developed to treat stomach ulcers. To women in Brazil, where abortion was and remains severely restricted, the warning on the label, to avoid taking the drug while pregnant, advertised its potential as an abortifacient. And when they found the drug safer and more effective than other clandestine methods, misoprostol’s popularity exploded. (To state the obvious, no one should interpret drug warnings for pregnant people as covert advertisements for effective abortion alternatives.)
Soon, doctors in Brazil reported seeing fewer women with severe abortion-related complications, and Brazilian researchers began documenting the drug’s off-label use. The first such study appeared in a 1991 letter to the editor of The Lancet: Helena Coelho and her colleagues at the University of Ceara had found that knowledge of misoprostol’s capacity to induce abortion had “spread rapidly” among both women and pharmacy personnel. But it had also reached government officials, who limited sales to authorized pharmacies and, in one state, banned misoprostol entirely.
Read: Women in the U.S. can now get safe abortions by mail
That same year, Baulieu, the French researcher, announced that he had devised a simpler way to use mifepristone—by combining it with misoprostol, which, unlike sulprostone, could be taken by mouth. Writing in The New England Journal of Medicine, Baulieu did reference misoprostol’s use in Brazil, but only as an example of what not to do. Citing anecdotal reports of cranial malformations in infants exposed to misoprostol in utero, he and colleagues claimed that administering misoprostol alone would risk “embryonic abnormalities,” adding that G.D. Searle “strongly disapproved” of the practice.
The reports of cranial anomalies were never confirmed. But Searle did take pains to prevent the use of misoprostol for abortion, at one point publicly warning doctors in the U.S. against administering the drug to pregnant women. Over time, researchers established other important uses for misoprostol, such as treating miscarriage and preventing postpartum hemorrhage. Yet during the lifetime of its patent, the company refused to research or register the drug for any reproductive-health indication.
Meanwhile, Brazilian newspapers had seized on the dangers that Baulieu had cited, fueling fears that failed abortions would create “a generation of monsters.” That in turn provided Brazilian authorities with a public-health rationale for regulating misoprostol as a controlled substance, the “possession or supply” of which carries penalties even more punitive than those for drug trafficking. But through informal networks, feminist activists continued helping women access both misoprostol and information about how to safely use it at home. More than three decades later, experts now credit Brazil as the birthplace of self-managed medication abortion.
In the past few years, researchers have more formally documented what these informal networks established. In clinical trials, medication abortion with misoprostol alone was effective in completing first-trimester abortion roughly 80 percent of the time. As a rule, “We think about clinical-trials data as the gold standard,” says Caitlin Gerdts, a vice president at Ibis Reproductive Health and a senior author on the study in Nigeria and Argentina. Yet when researchers have examined misoprostol’s use in nonclinical settings, they have found far higher rates of success, with 93 to 100 percent of participants reporting complete abortions using only misoprostol. Given the many studies showing high effectiveness in self-managed settings, Gerdts says, “I think it’s time to reconsider the idea of the clinical trials data as being paramount.”
One reason for the greater effectiveness of misoprostol alone in studies of self-managed abortion may have to do with how the studies were designed. “The problem with clinical trials is that often when we ask somebody to follow up in a week or two weeks, the body hasn’t had enough time to expel all of the products of conception,” says Dr. Angel Foster, a health-science professor at the University of Ottawa, whose work on the Thailand-Myanmar border was the first to rigorously investigate the effectiveness of misoprostol alone for abortion outside a formal health system. “If there’s a smudge on an ultrasound, it’s not that there’s a continuing pregnancy—it’s just debris. But rather than let the uterus absorb it or expel it, we do an evacuation procedure and we count it as a failure.” In studies of self-managed abortion, she says, the follow-up period tends to be longer—three or four weeks—and surgical intervention may not always be an option.
“I do think because of the way it’s been treated in clinical trials, misoprostol has been defined as much less effective than we now believe it to be,” Foster says. “We talk about mifepristone as ‘the abortion pill,’ but I think it’s more appropriate to think of it as a pretreatment or an adjunct therapy. Because it’s really the misoprostol that’s doing the lion’s share of the work.”
Elizabeth Raymond, a senior medical associate at Gynuity and the lead author of a systematic review of clinical trials on the use of misoprostol alone for early abortion, acknowledges that the clinical studies may have been too quick to intervene. But she says the shorter follow-up period was not without reason. Using ultrasound and a blood test to measure the amount of hCG, or human chorionic gonadotropin, doctors can diagnose a complete abortion “quite quickly, certainly within one or two weeks,” she says, “and the researchers wanted to do the assessments as soon as reasonable. They saw no sense in delaying.” Raymond suspects that misoprostol alone isn’t quite as effective as reported in the study in Nigeria and Argentina, in part because that study relied on its subjects to self-report whether the abortion was complete. “I think it’s an intriguing study, and it’s true that misoprostol alone is more effective than we thought,” she says, “but I think the general feeling is, if you can get both drugs, you should do that. The combination is more effective, and it may cause less cramping and bleeding.”
Those side effects aren’t a safety concern, says Dr. Julie Amaon, the medical director of Just the Pill, which delivers abortion medication to people in Wyoming, Montana, Colorado, and Minnesota. “But it’s something to keep in mind,” she says, adding that anyone self-managing an abortion at home should adhere to the WHO-recommended protocol and follow up with a doctor, whether in person, by phone, or by text, to ensure that the process is complete. In the U.S., the FDA has approved only the two-drug regimen; although the WHO’s recommendations also suggest a preference for medication abortion with both drugs, that agency does recommend misoprostol-only abortion “in settings where mifepristone is not available.”
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Right now, lawmakers across the U.S. are working to put both drugs out of reach. Fourteen states now fully or partially ban both mifepristone and misoprostol. Of the two drugs, though, misoprostol is still more easily obtained, either by prescription in pharmacies or via nonprofit groups in the U.S. and overseas. The Biden administration has said that it intends to maintain access to medication abortion, but so far has not acted to ease the stricter regulations on mifepristone. As long as those restrictions remain in place, ending a pregnancy with misoprostol alone could become a more common choice for people with few options.
According to the Guttmacher Institute, a reproductive-health-research group that supports abortion rights, though the rate is difficult to measure, in the past self-managed abortions probably haven’t occurred in the U.S. on a large scale. But as conditions in red states come to resemble those in Brazil, the practice could become more and more common. In this way, says Mariana Prandini Assis, a Brazilian social scientist who has written extensively on abortion, the fall of Roe may well lead to the normalization in America of self-managed abortion with pills—a choice once thought of as a last resort or an act of desperation. For that reason, she says, the Brazilian women who pioneered the use of misoprostol for abortion should be considered the “other inventors of ‘the abortion pill.’”
