Health officials are investigating whether there are any links in the cases of four California women -- at least two in Los Angeles County -- who have died since 2003 of massive infection after taking the so-called abortion pill, RU-486, and a follow-up drug.
The state and federal probe follows an announcement last month by the Food and Drug Administration, after the June death of a Sherman Oaks woman, warning doctors and patients of the potential for serious bacterial infection under certain circumstances.
At the heart of the inquiry in California are why and how the deadly infections developed and whether more women might have been harmed.
"That's something we don't have an explanation for right now," said Dr. L. Clifford McDonald, an epidemiologist with the Centers for Disease Control and Prevention, which is investigating the deaths along with the Food and Drug Administration, the California Department of Health Services and the Los Angeles County Department of Health Services.
The FDA is also working with the makers of the two drugs to see if they were contaminated with an unusual bacterium found in the bloodstream of two of the women who died. Complicating matters, neither woman showed all of the usual symptoms of an infection.
The medical mystery in California is fueling the already charged debate over the risks, rights and morality of abortion.
RU-486, prescribed under the brand name Mifeprex, was approved by the FDA in 2000 over the strong objections of many abortion opponents. In recent weeks, opponents of the RU-486 regimen have renewed their call for the passage of Holly's Law, which would take the drug off the market in the U.S., arguing that there is no way it can be administered without risk.
The proposed legislation was named after 18-year-old Holly Patterson of Livermore, Calif., the first U.S. woman to die of infection after a nonsurgical abortion in 2003. The procedure is often called a medical abortion.
"We should be just as concerned about women's safety as we are about their rights," said Wendy Wright, senior policy director for Concerned Women for America, which has been working to get the drug prohibited. "I've been stunned by the comments ... that some women have to pay the price of death so that women can have abortions."
Vicki Saporta, president of the National Abortion Federation, said such concerns were vastly overblown. "There has been no causal relationship established between the medical abortion and the subsequent infection," she said. "This is a very, very rare occurrence.... Childbirth is 10 to 13 times riskier than having an abortion, either medical or surgical."
Supporters also say the drug combination is the safest means of terminating an early pregnancy, pointing to the World Health Organization's recent listing of the drugs as essential to healthcare needs in developing countries.
Mifeprex, which is administered in a clinic or doctor's office, is taken orally up to 49 days after a woman becomes pregnant. Several days later, the drug misoprostol is given. The first drug blocks a hormone necessary for a pregnancy to continue; the second causes contractions of the uterus.
The drugs are different from emergency contraception, which is also controversial. The "morning after pill" is supposed to be taken within 72 hours of having sex. Sold under the name Plan B, it is not effective if pregnancy has already occurred, because it works by inhibiting or delaying ovulation.
About 460,000 women have taken Mifeprex safely in this country since it was approved, according to Danco Laboratories, the New York company that distributes the drug in the United States. Misoprostol, which is not a Danco product, has been in use since the mid-1980s. Though it was initially approved for prevention of gastric ulcers, it since has been prescribed for other purposes.
Outside California, other deaths have been reported in association with use of Mifeprex, and misoprostol. One occurred in Tennessee and five were reported outside the U.S., in Europe and Canada, say doctors familiar with the drugs. But only the Canadian death involved an infection.
So far, the CDC's McDonald said, just one thing ties California deaths together.
All the women who died, he said, took the follow-up drug, misoprostol, vaginally, instead of orally. It was an "off-label use," which is allowed but not specifically approved by the FDA on the basis of testing.
Cynthia Summers, Danco's director of marketing and public affairs, said that the company's sympathies were with the families of the women who have died but that no direct relationship between the drugs and the deaths has been established. In at least one Los Angeles County case, the coroner noted the use of the drugs but said the cause of death was undetermined.
"Physicians are free to prescribe FDA-approved drugs as they wish," Summers said. "Danco uses only the FDA-approved regimen in its labeling and promotional materials and does not promote any other regimens."