Estrogen trials -- and errors


HOW do medical researchers go about testing promising therapies?

Generally, they call for volunteers. They give the volunteers a form that lays out the possible advantages and disadvantages of the new treatment. Anyone who agrees to participate signs on the dotted line to signify his or her "informed consent."

It's not an empty phrase. Informed consent says that the people participating in the trial are there because they freely choose to be. It says the trial is ethical. So if a consent form misrepresents the risks involved, it calls the entire process into question.

This month, the National Institutes of Health began enrolling volunteers in a hormone-replacement study by the Women's Health Initiative, a federal research project.

Eventually, 25,000 women are to participate in the study, which is supposed to show whether taking estrogen, alone or with progesterone (a second female hormone), lowers the risk of heart disease and osteoporosis, as suggested by studies over the last decade.

But unlike people with diseases such as AIDS or drug-resistant forms of tuberculosis, who have much to gain from a new drug trial, the women signing up for the hormone study are not sick.

The volunteers, all women aged 50 to 79, will be taking hormone supplements on the chance that this will keep them from getting sick sometime in the future.

Unfortunately, they could also be putting themselves at risk -- not of heart disease or broken bones but of cancer.

The 10-page consent form for the NIH study evaluates the risks of hormone use, including the possibility of cancer of the endometrium (the lining of the uterus) and cancer of the breast.

It says that "in rare cases" taking estrogen may cause endometrial cancer and "more rarely" may increase the risk of breast cancer.

These phrases are false reassurance. Since 1975, there has been compelling evidence linking use of estrogen-replacement therapy to endometrial cancer in menopausal women.

The NIH protocol -- the study description to be read by the people running the trials but not part of the consent form -- says the chance a woman taking estrogen will get endometrial cancer rises "4-to-10-fold over six years of treatment with estrogens and may persist for some years following the cessation of treatment."

What about cancer of the breast? In April 1991, the Federal Centers for Disease Control in Atlanta compared 16 studies on the effect of estrogen replacement therapy on the risk of breast cancer and found "a small but statistically significant increase in breast cancer risk due to long-term estrogen use."

It added, "This small increase in risk represents a large number of preventable breast cancer cases."

NIH acknowledges this apparent risk in its protocol, which -- based on studies conducted over the last 18 years -- describes the overall increase in risk of breast cancer as 7 percent higher among women who have ever taken estrogen.

For women who take estrogen for at least 10 years, it is 20 percent higher, for 15 years, 30 percent higher.

The hormone study is scheduled to run for 12 years. The National Women's Health Network, a nonprofit organization, predicts that by the time it ends there will be at least 120 cases of endometrial cancer among women who would have remained healthy if they hadn't joined the hormone trial.

Experts and activists may argue over whether this is reason enough to stop the hormone-replacement study. Many doctors believe that for menopausal women the potential benefits of estrogen supplements outweigh the risks.

What is not debatable is whether women in the study should get an honest evaluation of the hazards. Before even one woman puts her name on the form and her body on the line, the NIH consent form ought to be revised to show the real risks of estrogen.

Otherwise, the government will be running tests on women who have not truly consented to their fates.

Carol Ann Rinzler is author of "Estrogen and Breast Cancer: A Warning to Women."

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