Albion Monitor /Features

Seeking Approval

by Karen Hawkins and Jeff Elliott

Rather than providing evidence of the drug's hazards or safety, poor controls over many studies only blurred the picture

It's probably safe to assume that the scientists for Upjohn were frustrated by 1992. For fifteen years, the company had been trying to get Depo Provera approved as a contraceptive in the United States. The FDA had announced its intention to approve the drug in both 1973 and 1976, then backed away. One reason why the FDA's retreated may have been the slashing testimony of Dr. Sidney Wolfe, director of Public Citizen's health research group in Washington. In 1975 he told the FDA,
Depo Provera is indicated for a patient who "refuses or is unable to accept the responsibility demanded by other contraceptive methods, or is incapable or unwilling to tolerate the side effects of conventional oral contraceptives..." Read this in shorthand: the poor, who often lack sufficient contraceptive education or access to contraceptives, and the mentally retarded. To submit the relatively helpless to Depo Provera without a substantiated clear demonstration of cancer safety, would, in our view, be an outrage..." [emphasis his]
But in those years before Depo was finally approved by the FDA, it was given to women in Nigeria, Costa Rica, Thailand, India, and elsewhere in the Third World. The clinical trials using these women provided Upjohn with thick stacks of reports, but the results were hard to interpret. Depo seemed to cause increased rates of liver cancer in Kenya, but not in Thailand. Children born to Thai women who used the injectible contraceptive sometimes had extra or missing fingers, but this was not reported in other countries. Rather than providing evidence of the drug's hazards or safety, it seemed like the poor controls over many of these studies only blurred the picture more.

Many of these small studies suggested that the chemical appeared to be a carcinogen. Also worrisome were reports from India and New Zealand that it caused decreased bone mass in adolescent girls, to whom it was often given, which could logically result in early onset of osteoporosis.

Over half the 13,000 women in the study were lost to followup due to sloppy record keeping

In the West, tests began using beagles and Rhesus monkeys. In both cases, the studies showed Depo to cause cervical, ovarian, or breast cancer. This was another damning point in Dr. Sidney Wolfe's testimony; all chemicals found to cause cancer in humans also cause cancers in some animals.

The FDA appeared to agree with Wolfe. The agency had withdrawn a pill form of Depo in 1970 precisely because of the tumors developed by animals. A member of the FDA's Bureau of Drugs also testified at an agency Depo hearing, "...Animal data for this drug is more worrisome than any other drug we know of that is to be given to well people."

Upjohn and Depo advocates countered that these animals were not appropriate; beagles are known to be susceptible to certain cancers. But this was the first time that Rhesus monkeys had ever been found to have some of the cancers that they developed after exposure to Depo.

Besides dogs and monkeys, one study was also underway in the U.S. on women, at the Grady Medical Center in Atlanta. The study began in 1968, and for 11 years, no annual reports were filed with the FDA, as required. In 1978, investigators were finally sent to Grady, because there was "something funny going on."

They found that data collection was questionable, consent forms and protocol were absent; that those women whose consent had been obtained at all were not told of possible side effects. Women whose known medical conditions indicated that use of Depo would endanger their health were given the shot. Several of the women in the study died; some of cancer, but some for other reasons, such as suicide due to depression. Over half the 13,000 women in the study -- most of them recipients of public health care -- were lost to followup due to sloppy record keeping.

Although the Grady study has been discredited, the Black Women's Health Project's (BWHP) still is trying to recoup the data lost. Julia Scott of the BWHP feels that it is crucial to examine this evidence; the researchers at Grady never examined the link between depression and Depo, although some of the women who were part in the experiment were treated by Grady psychiatrists for depression. This links to reports in BWHP's registry of Depo users, which, although composed of only anecdotal data, has documented common side effects such as suicidal depression, pronounced weight gain, cysts, and cancer in young women.

Any "international panel of experts" called on to testify about Depo is hardly impartial

But the FDA pays far less attention to things that cause depression and weight than drugs that might cause the "Big C," and much of their 25 years of resistance to Depo's approval comes from those animal tests that showed cancerous effects.

The cancer questions were resolved -- or at least, to the FDA's satisfaction -- by the studies done by the World Health Organization (WHO). Published in 1991, these were the most comprehensive studies ever; and found were no increased risk for liver, ovarian, or cervical cancers. Depo even had a beneficial effect for endometrial cancer, according to the WHO reports.

WHO did find it doubled the risk for breast cancer in the first five years that the woman used the drug. But the evidence suggested that it only speeded up the growth of existing tumors, rather than turning normal cells cancerous.

Armed with these studies, Upjohn again applied to the FDA in 1992. Testifying against approval were the National Women's Health Network (NWHN), along with the Black Women's Health Project and the National Latina Health Organization. NWHN called it a "questionable drug contained within a problematic delivery system" and opposed FDA approval as "premature and ill-advised."

They presented studies from Costa Rica, New Zealand, and the WHO breast cancer results, and won a concession from representatives from Upjohn, agreeing that more study was definitely required, especially among "high-risk" populations.

Belinda Cowan of NWHN pointed out that any "international panel of experts" called on to testify about Depo is hardly impartial, since they generally are in the employ of organizations such as International Planned Parenthood and the World Health Organization, groups which have been using Depo for years, and their jobs would be at stake if they were to advise the FDA that Depo was safe for the "Third World," but not for the United States.

But after a quarter century of opposition, the FDA finally approved Depo for use in the United States, making it about the 90th country where the drug could be used.

What about those monkeys and beagles that developed cancer? The FDA made another decision in 1992: it changed its requirements, no longer demanding that contraceptive hormones be tested on beagles.

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Albion Monitor May 5, 1996 (http://www.monitor.net/monitor)

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