A Sept. 6 Health article about emergency contraception incorrectly stated that combination oral contraceptives may increase the risk for endometrial cancer. The drugs are thought to protect against that form of cancer. (Published 9/8/2005)

The Food and Drug Administration (FDA) decision to defer a ruling to allow over-the-counter (OTC) sales of the emergency contraception drug Plan B has generated debate over the agency's independence from political pressure.

But opponents of broader access to the so-called morning-after pill often cite safety issues as a primary concern. They say there is no research in adolescents showing safety of the treatment, which consists of high doses of the hormone progestin.

Some opponents say use of the pills leads to higher incidence of sexually transmitted infections (STIs) and promiscuous behavior, which can carry its own dangers. A Swedish study published in 2002 reported that STIs were on the rise among adolescents who had OTC access to emergency contraception and other forms of contraception.

Groups opposing OTC status include the American Association of Pro-Life Obstetricians and Gynecologists and Concerned Women for America, a public policy organization. Since birth control pills, which contain lower doses of progestin, are available only by prescription, said Wendy Wright, senior policy director of Concerned Women for America, "it's crazy that we're even discussing that the high dose of the drug be available without a prescription."

Most research conducted on Plan B does not substantiate these safety concerns. Several mainstream medical groups, including the American Academy of Pediatrics and the American Medical Association, issued statements in support of Plan B, emphasizing that the drug is safe and effective.

An opinion piece to be published in the Sept. 22 New England Journal of Medicine points out that the FDA has not cited any data supporting safety concerns, and that the agency's advisory committee, including those who subsequently voted against OTC access for Plan B, "acknowledged its appropriate safety earlier at the December 2003 meeting, when the committee voted 28 to 0 that the drug was safe."

What has stalled FDA approval of the drug for over-the-counter (OTC) sale is controversy over whether Plan B should be sold without a prescription to those ages 16 and under. Plan B was approved by the FDA in 1999 as a prescription-only medication. But in 2003, the FDA advisory panel voted to allow Barr Laboratories to sell the drug over the counter. Because the pills must be taken soon after unprotected intercourse to prevent pregnancy, the panel said, barriers to access must be low.

A study published in the journal Obstetrics and Gynecology this month suggests the treatment is safe for adolescents and younger women.

The analysis, which draws on information derived from an earlier randomized controlled trial, reports the experiences of 2,117 young women given access to Plan B, either directly (they were given three packets of Plan B in advance), through a pharmacy (where they could get Plan B for free and without a prescription) or at a clinic (where they had to see a doctor to get the drug).

"We didn't find, with regard to health issues, that younger women were any different than older women," said study co-author Philip Darney, chief of obstetrics and gynecology at San Francisco General Hospital and a professor at the University of California, San Francisco.

While the study looked mostly at the behavioral effects of different levels of access to Plan B, it also monitored STIs. Researchers reported finding that level of access had no effect on STI rates. The study also found that sexual behavior was not riskier among those who had pharmacy or direct access to the drug than among those who saw a doctor to obtain it.

Plan B contains a high dose of a synthetic form of progestin, which has been used in birth control pills for more than three decades -- both in progestin-only formulations and in combination with estrogen, another female hormone. (The combination pill, especially in formulations stronger than those currently on the market, is associated with increased risks of nausea, vomiting and blood clots in the legs and lungs. The combination pills may also increase the risk of breast cancer, liver tumors and endometrial cancer. It is not known if progestin-only contraceptives increase risk for those conditions.)

Progestin works by preventing the release of an egg from an ovary, and it may also "prevent the union of sperm and egg (fertilization)," according to an FDA statement listing common questions and answers about Plan B. If fertilization occurs, Plan B "may prevent a fertilized egg from attaching to the womb (implantation). If a fertilized egg is implanted prior to taking Plan B," the drug will not prevent pregnancy.

Plan B "reduces the risk of pregnancy following a single act of unprotected sex from about 8 [percent] down to 1 [percent]," according to Plan B's label. Barr, the drug's maker, advises women to take the first of two tablets within 72 hours of unprotected sex; the second tablet should be taken 12 hours later.

Wright said her group opposes OTC emergency contraception because the pill would have side effects similar to those found in birth control pills.

"Any of the complications you can have [with birth control pills], you obviously could have with" Plan B, Wright said. She cites the need for a doctor to evaluate a woman's health and medical history before writing a prescription. Women should not take Plan B if they have undiagnosed, unusual vaginal bleeding or a sensitivity to progestin.

Supporters say Plan B's safety is well established. "There's never been an adverse medical event in any age group" using Plan B, said Vivian Dickerson, immediate past president of the American College of Obstetricians and Gynecologists (ACOG). "The risks are virtually nil . . . and that is not based on age of the patient."

Traditional progestin-only birth control pills increase risk for tubal pregnancies -- when a fertilized egg implants outside the uterus, and the fetus and placenta start to form there, most often inside of a fallopian tube. It is not known if Plan B increases this risk, according to the drug's label, which adds that women who experience severe abdominal pains should see a doctor immediately because that can be a warning sign of tubal pregnancies.

Plan B's label advises that women may experience heavier or lighter bleeding than normal soon after taking it. After taking the drug, 87 percent of women get their next period within a week of when it was expected, the label states.

Birth control pills are intended for extended use, while Plan B is meant for one-time or episodic use. But Plan B doesn't pose major risks to those who use it more than once, experts said. The drug "can be used multiple times because it's safe" in each use, said Scott Spear, chair of the national medical committee for the Planned Parenthood Federation of America.

Barr officials say the pill offers other safety advantages. "I think what you have to compare [Plan B's safety] to is [the safety of] pregnancy," said Carole S. Ben-Maimon, president and chief operating officer of Duramed Research Inc., an arm of Barr Laboratories. Pregnancy "obviously carries significantly more risks than Plan B," she said.

ACOG estimates that making emergency contraception widely available OTC could prevent about 2 million pregnancies annually (half of all unintended pregnancies in the United States) and about 500,000 abortions per year.

Still, if clinicians see a woman repeatedly relying on the Plan B as a primary form of birth control, "we want to have a conversation about finding something that might be more reliable and more effective for her," Spear said.


Plan B consists of two pills containing high doses of the hormone progestin.