New look at morning-after pills suggests debate is off target
Though the labels say the emergency contraceptives may prevent fertilized eggs from implanting in the uterus, studies say they actually block fertilization. That could alter the debate.
The New York Times
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Labels inside every box of morning-after pills, drugs widely used to prevent pregnancy after sex, say they may work by blocking fertilized eggs from implanting in a uterus. Respected medical authorities, including the National Institutes of Health and the Mayo Clinic, have said the same thing on their websites.
Such descriptions have kindled debate over abortion and contraception. Believing that a fertilized egg is a person, some religious groups and conservative politicians say disrupting a fertilized egg's ability to attach to the uterus is abortion, "the moral equivalent of homicide," as Dr. Donna Harrison, who directs research for the American Association of Pro-life Obstetricians and Gynecologists, put it. Mitt Romney recently called emergency contraceptives "abortive pills." And two former Republican presidential candidates, Newt Gingrich and Rick Santorum, have made similar statements.
But a New York Times examination has found the federally approved labels and medical websites do not reflect what the science shows. Studies have not established that emergency contraceptive pills prevent fertilized eggs from implanting in the womb, leading scientists say. Rather, the pills delay ovulation, the release of eggs from ovaries that occurs before eggs are fertilized, and some pills also thicken cervical mucus so sperm have trouble swimming.
The debate over morning-after pills and abortion probably is rooted in outdated or incorrect scientific guesses about how the pills work. Because they block creation of fertilized eggs, they would not meet abortion opponents' definition of abortion-inducing drugs. In contrast, RU-486 is an abortion pill because it destroys implanted embryos, terminating pregnancies.
The implantation idea stems from a Food and Drug Administration (FDA) decision during the drug-approval process to mention that possibility on the label — despite lack of scientific proof and objections by the manufacturer of Plan B, the pill on the market the longest. Leading scientists say studies since then provide strong evidence that Plan B does not prevent implantation, and no proof that a newer type of pill, Ella, does. Some abortion opponents said they remain unconvinced.
After being asked about this issue, ADAM, the firm that writes medical entries for the National Institutes of Health (NIH) website, deleted passages suggesting emergency contraceptives could disrupt implantation. The New York Times, which uses ADAM's content on its health webpage, updated its site. At the Mayo Clinic, Dr. Roger Harms, the website's medical editor-in-chief, said "we are chomping at the bit" to revise the entry if the FDA changes labels or other agencies make official pronouncements.
"These medications are there to prevent or delay ovulation," said Dr. Petra Casey, an obstetrician-gynecologist at Mayo. "They don't act after fertilization."
The FDA declined to discuss decisions about the implantation effect or to say whether it would consider revising labels. But spokeswoman Erica Jefferson acknowledged: "The emerging data on Plan B suggest that it does not inhibit implantation. Less is known about Ella. However, some data suggest it also does not inhibit implantation."
Ruling in Washington state
Washington state is appealing a federal judge's February ruling that supported a suit by some pharmacists that the state could not require them to dispense Plan B if they objected because of religious beliefs against abortion.
Scientists say the pills work up to five days after sex, primarily stalling an egg's release until sperm no longer can fertilize it. While many people believe sperm and egg unite immediately after sex, sperm need time to position themselves.
Controversy over emergency contraception is figuring into the presidential race and debates over the Obama administration's health-care law. Some abortion opponents and religious groups are fighting the law because it requires insurers, including those for employees of Roman Catholic institutions that oppose birth control, to cover contraceptives, including morning-after pills. While some object to contraception generally, others focus on birth-control methods that they believe cause abortions.
And some proponents of "personhood" initiatives, proposals put forward in several states to define fertilized eggs as people, say the initiatives would bar the pills if they work after eggs are fertilized.
Doctors also say some patients who are not active on abortion issues want to resolve ethical questions about whether the pills affect a fertilized egg.
While scientific and political disputes may persist even if labels change, both sides consider the wording on labels central because it summarizes scientific consensus and shapes what medical authorities say.
"FDA labeling is important to us; it's very important," said Jeanne Monahan, director of the conservative Center for Human Dignity at the Family Research Council.
Diana Blithe, a biochemist who oversees contraception research for the NIH, the federal agency for medical research, said implantation should be removed from labels. "As a scientist," she said, "I would definitely take it off of emergency contraception."
Ninety-nine percent of the U.S. emergency-contraception market consists of Plan B (approved in 1999 and now sold as Plan B One-Step) and its generic versions, Next Choice and levonorgestrel tablets. They are available without prescription for ages 17 and older. The other pill, Ella, became available by prescription only in late 2010. Emergency-contraceptive use has increased steadily, with about 12 million packages sold last year, according to IMS Health and SymphonyIRI Group, health-information and market-research companies.
European medical authorities have not placed implantation on Ella's label, and after an additional two years of scrutiny, it was approved for sale in Italy, where laws would have barred it if it could be considered to induce abortion, said Erin Gainer, chief executive of the manufacturer, Paris-based HRA Pharma.
Opponents still doubtful
Some abortion opponents said that, while emergency contraceptives' primary function may be delaying ovulation, they doubted scientists could exclude the possibility of implantation effects.
"I would be relieved if it doesn't have this effect," said Richard Doerflinger, associate director of the Secretariat of Pro-Life Activities for the United States Conference of Catholic Bishops. "So far what I see is an unresolved debate and some studies on both sides," he said, adding that because of difficulties in ethically testing the drugs on women, "it's not only unresolved, but it may be unresolvable."
Several scientists acknowledged absolute proof may be elusive; in science, as James Trussell, an emergency-contraception researcher at Princeton, said, "You can never prove the negative." But he and others said the evidence from multiple studies was persuasive.
Beginning with the 1999 approval process, the maker of Plan B — Barr Pharmaceuticals, later acquired by Teva Pharmaceuticals — asked the FDA not to list an implantation effect on the label, said people familiar with the requests.
Back then, scientific research concentrated on whether Plan B's active ingredient, a synthetic progesterone, safely and effectively prevented pregnancy, not on how it worked, said Dr. Kristina Gemzell-Danielsson, an obstetrics and gynecology professor at Karolinska Institute in Sweden, who participated in World Health Organization studies leading to FDA approval.
The FDA's description was speculative, saying Plan B "could theoretically prevent pregnancy by interfering with a number of physiological processes" followed by a long list, including ovulation and implantation.
A New York Times review of hundreds of pages of approval-process documents found no discussion of evidence supporting implantation effects.
Jefferson of the FDA said it was often difficult when a drug is approved, and even afterward, to pinpoint how it works. Citing confidentiality rules, she would not discuss why the request to omit implantation was declined.
Experts say implantation likely was placed on the label partly because daily birth-control pills, some of which contain Plan B's active ingredient, appear to alter the endometrium, the uterus lining into which fertilized eggs implant. Altering the endometrium has not been proved to interfere with implantation. But in any case, scientists say that unlike the accumulating doses of daily birth-control pills, the one-shot dose in morning-after pills does not have time to affect the lining.
"It takes time for an endometrium to change, for its cells to divide," said Susan Wood, a biochemist who, shortly after Plan B's approval became the FDA's top women's health official and later resigned, frustrated with the delay in making the pill available without prescription.
Implantation also likely wound up on the label because of what Gemzell-Danielsson called wishful thinking by some scientists, who believed if it also could block implantation, it would be even better at preventing pregnancy.
What studies found
By 2002, studies produced evidence that Plan B did not interrupt implantation.
By 2007, scientific consensus was building that morning-after pills did not block implantation.
Later, in 2007, 2009 and 2010, researchers in Australia and Chile gave Plan B to women after determining with hormone tests which women had ovulated and which had not.
None who took the drug before ovulation became pregnant, underscoring how Plan B delays ovulation. Women who had ovulated became pregnant at the same rate as if they had taken no drug at all. "No one can say that it works to inhibit implantation based on these data," said the NIH's Blithe.
In 2009-10, during discussions about making Plan B available over the counter for all ages, Teva Pharmaceuticals again asked that implantation be deleted from the label. The FDA again declined.
By this year, the International Federation of Gynecology and Obstetrics considered the research so strong that it issued a statement saying pills with Plan B's active ingredient "do not inhibit implantation."
Research on Ella, approved in 2010, is less extensive, but the FDA, Blithe and others say evidence increasingly suggests it does not derail implantation, citing, among other things, several studies in which women became pregnant when taking Ella after ovulating.
Trussell of Princeton said that if morning-after pills worked after eggs were fertilized, they would prevent pregnancy better than they do. The pregnancy-prevention rates probably are lower than scientists and pill-makers originally thought, he said.
By contrast, scientists say, research suggests the only other officially approved form of emergency contraception, the copper intrauterine device (also a daily birth-control method), can work to prevent pregnancy after an egg has been fertilized.
Despite the accumulating evidence, several abortion opponents said they remain unpersuaded. Harrison, director of research and public policy for the American Association of Pro-life Obstetricians and Gynecologists, said the Plan B studies were led by "a good researcher," but that she would prefer a study with more women and more documentation of when in their cycles they took Plan B. If studies done so far are correct, she said, Plan B's label should say it is ineffective after ovulation.
With Ella, Harrison cited a document from the European Medicines Agency (similar to the FDA) and animal studies that she said suggest the uterus lining could be altered. Blithe said the document did not demonstrate that effect, and that the animal results were not analogous to human experience.
So far, only one human study has suggested Ella's active ingredient might thin the lining in doses higher than the dose in an Ella pill. But Blithe said that study, conducted by NIH researchers, produced results too unclear or insignificant to show that effect. Most human studies suggest otherwise, she said.
Harrison also cited similarities between Ella's active ingredient and RU-486. But Dr. Anita Nelson, a professor of obstetrics and gynecology at University of California, Los Angeles, said RU-486's ingredient is given in a dose up to 20 times higher and is taken when women are up to seven weeks pregnant, long after the egg has implanted.
Steps by government agencies or medical websites to revise language about implantation already are causing controversy. Some abortion opponents recently criticized two agencies of the Department of Health and Human Services for online fact sheets that omit an implantation effect or say science undermines it.
Some critics say they wonder if those scientists and government agencies support abortion rights. Jonathan Imbody, vice president of government relations for the Christian Medical Association, wrote on LifeNews.com that the fact sheets contradict Plan B's nature and raise questions about "whether ideological considerations are driving these decisions."
Information from Seattle Times archives is included in this report.