Effective, but How Safe?

The FDA considers approving a controversial contraceptive

Its advocates argue that it is the best available method of birth control: not only is the drug nearly 100% effective, but it has to be taken just four times a year. Depo-Provera has been used by 10 million women over the past 15 years in more than 80 nations, including some in Western Europe. It has been approved by the World Health Organization, the American College of Obstetrics and Gynecology and the International Planned Parenthood Federation, which has widely distributed the drug in Third World countries. Despite its popularity overseas, however, Depo-Provera is not approved as a contraceptive in the U.S. Reason: the Food and Drug Administration fears that not enough is known about the drug's long-term side effects. Last week, at the behest of the Upjohn Co., which developed and markets the drug, a special FDA-appointed panel conducted a five-day hearing to see if Depo-Provera should finally be made available to American women.

Like the birth-control pill, Depo-Provera works by disrupting the female hormonal cycle that normally leads to ovulation. The drug, which is injected, is a synthetic version of the hormone progesterone, similar to one of the two main ingredients of the birth-control pill. It does not, however, contain estrogen, and therefore does not seem to share the most serious drawbacks of the Pill: increased risk of abnormal blood clots and heart attacks. Depo-Provera can have less serious side effects that persist as long as it is in the bloodstream. Among them: weight gain, loss of sex drive, menstrual irregularities and, frequently, complete cessation of menstrual bleeding. According to Upjohn Research Manager Gordon Duncan, none of these problems are serious enough "to preclude its use as a contraceptive."

Upjohn has been haunted, however, by its own early tests of Depo-Provera in animals. In a seven-year, controlled study using beagles, two out of 16 dogs developed breast cancer. Results from a ten-year study using 52 rhesus monkeys were equally alarming: two of the animals developed cancer of the endometrium (the lining of the uterus). Upjohn's own scientists concluded in 1978 that the cancer was "likely related to treatment with Depo-Provera." Later that year the FDA refused to allow Upjohn to market the drug as a contraceptive, though it is approved for treating certain diseases.

Since then, Upjohn has challenged the validity of its own tests. According to company scientists and a number of outside experts, both beagles and rhesus monkeys are highly sensitive to progesterone and are more likely than humans to develop cancer in response to it. Depo-Provera partisans further claim that there has been no increase in the rate of cancer among women taking the drug in countries where it is approved. Says Gynecologist Elizabeth Connell of Atlanta's Emory University: "It appears to be as safe or perhaps safer than oral contraceptives or intrauterine devices."

Opponents of Depo-Provera are unconvinced. Questions raised about the animal studies are "highly conjectural," says Dr. Robert Temple, acting director of the FDA's Office of New Drug Evaluation. "The FDA does not approve animal carcinogens for prolonged use in young, healthy people." Temple also points out that it may take 20 years for cancer to show up in women taking the drug. He is joined in his concerns by a number of other government scientists and by such organizations as Consumer Advocate Ralph Nader's Health Research Group and the National Women's Health Network. The latter group has collected about 150 case histories of women who claim to have suffered ill effects from taking Depo-Provera and, according to Director Belita Cowan, it has plans to sue Upjohn.

After the panel of inquiry makes its recommendations, FDA Commissioner Arthur Hayes will face a difficult choice: deciding whether the known benefits of Depo-Provera are worth risking its possible unknown dangers. This file is automatically generated by a robot program, so viewer discretion is required.