3-Month Contraceptive Shot Approved by FDA

The Food and Drug Administration on Thursday approved Depo-Provera, a highly effective but controversial contraceptive that provides three months of protection against pregnancy with a single injection.

Manufactured by the Upjohn Co. of Kalamazoo, Mich., it will be marketed under the name Depo-Provera Contraceptive Injection and will be available from physicians and clinics in the United States in January.

“This drug presents another long-term effective option for women to prevent pregnancy,” FDA Commissioner David A. Kessler said in a statement. “As an injectable, given once every three months, Depo-Provera eliminates problems related to missing a daily dose.”

The move was applauded by Planned Parenthood Federation of America officials, who said they were “gratified that the FDA has recognized the mounting worldwide evidence that (Depo-Provera) is effective and safe.” But some critics expressed concern that the approval was premature and that the drug’s safety had not been proved.

Depo-Provera was developed in the 1960s and already is sold in more than 90 countries--including the United Kingdom, Germany, France, New Zealand, Norway, Belgium and Sweden. It has been taken by an estimated 30 million women worldwide and is believed to be in use now by 8 million to 9 million women.

Injected in the arm or buttocks every 12 weeks, it has proven 99% effective in preventing pregnancy. A patient who wishes to become pregnant should simply stop the injections, the FDA said. Its cost is estimated at $120 a year, an amount considered modest for a contraceptive.

Depo-Provera contains the drug medroxyprogesterone acetate, a synthetic hormone similar to the natural hormone progesterone. It inhibits ovulation by suppressing the hormones secreted by the pituitary gland that stimulate the release of a mature egg. Because Depo-Provera contains no estrogen, it can be taken by many women who cannot use oral contraceptives, including nursing mothers.

Until now, the drug had failed repeatedly to win approval in this country because of concerns raised by animal studies that it increased the risk of breast and other cancers.

But the FDA said worldwide studies and years of use had shown the overall risk of cancer, including breast cancer in humans, “to be minimal, if any.”

A series of studies conducted by the World Health Organization on more than 11,000 women has shown that the risk of breast cancer appears to be no greater than that associated with birth control pills.

The drug is the second contraceptive approved by the FDA since December, 1990, when it licensed Norplant, a fan-like arrangement of six silicone rubber capsules that is implanted under a woman’s skin. Norplant releases a hormone that prevents pregnancy for up to five years.

The agency is also deliberating approval of the vaginal condom, a pouch-like barrier device.

Unlike Depo-Provera and Norplant, which protect only against pregnancy, the female condom also would be promoted as a method for reducing the risk of sexually transmitted diseases, such as AIDS.

Early concerns about Depo-Provera arose years ago after studies showed that it caused malignant and benign breast tumors in beagles. But researchers have since concluded that beagles were not an appropriate animal model for studying the drug and the results have been discounted.

Opponents also have worried that it could be used on women against their will in institutions or other government-run facilities. Mentally retarded women or poor women who are incarcerated could be especially vulnerable, critics said.

Numerous medical, family planning and reproductive organizations--including the American Medical Assn., the Allan Guttmacher Institute and the International Planned Parenthood Federation--had urged the FDA in recent years to approve the drug.

“We believe the drug has proved itself to be very good and very safe in contraception,” said James Stacey, a spokesman for the AMA. “It may not be ideal for every patient but it’s a very effective contraceptive option. The AMA definitely welcomes another contraceptive choice for women that works and appears to be safe.”

But Dr. Sidney Wolfe, director of Public Citizen’s Health Research Group, called the FDA’s action “reckless,” saying that concerns about the drug’s potential hazards had not been resolved.

“Just because a drug has been in use for a long time doesn’t mean it is safe,” he said. “Cigarettes have been in use for a long time too. My concern is that its use will fall upon poor women who don’t have access to medical care. This is very important because some of the complications of the drug will require medical care.”

Its side effects include weight gain, absence of menstrual periods and delayed fertility once the drug is stopped. Some patients also have experienced headache, nervousness, abdominal pain, dizziness, weakness or fatigue, the FDA said.

Some studies also have shown a connection to osteoporosis and low birth weight associated with accidental pregnancies.

The FDA advised physicians who prescribe the drug to be sure that their patients are not pregnant. The drug also should not be used by women suffering from acute liver disease, unexplained vaginal bleeding, breast cancer or blood clots in the legs, lungs or eyes, the FDA said.

The FDA said the manufacturer intends to conduct further research into the question of whether the drug contributes to the development of osteoporosis.

The drug has been available in the United States for the treatment of renal and endometrial cancer.