Women’s Health Initiative (WHI) Study

A furor broke out in the media and in doctors’ offices In 2002 when the news came out that the most important government study of hormone replacement therapy (HRT) ever undertaken, the Women’s Health Initiative (WHI), was stopped midway through the trial because of observations that healthy women in the study who were given HRT were at much greater risk for breast cancer, heart attacks, stroke, and blood clots.

The WHI was launched in 1991 and consisted of a set of clinical trials and an observational study of 161,000 healthy postmenopausal women. The trial was designed to test the effects of postmenopausal hormone therapy, diet modification, and calcium and vitamin D supplements on heart disease, fractures, and breast and colorectal cancers.

The hormone trial had two parts: an estrogen-alone study, and an estrogen-plus-progestin study. The National Institutes of Health (NIH) stopped the estrogen-plus-progestin study prematurely in light of the disastrous findings of high rates of life-threatening chronic diseases in the treated group compared to significantly lower rates in the control group.

Women’s health groups had lobbied for this clinical trial for over a decade based on concerns about the questionable way HRT was being marketed and widely prescribed for healthy menopausal women. While HRT was considered beneficial for short-term relief of menopausal symptoms, such as hot flashes, night sweats, and loss of libido, longer-term use of HRT (5 years or longer) was commonly being prescribed for all women, not just for those with severe symptoms, when that was medically unjustified and potentially hazardous, according to the critics. It turned out the critics were right.

The results of the WHI trial confirmed that taking estrogen and progestin long-term by healthy women hugely increased women’s risks for fatal chronic diseases:

• strokes: 41%,
• heart attacks: 29%,
• blood clots: 200%,
• heart disease: 22%,
• breast and uterine cancer: 26%.

According to the WHI researchers, the study results meant that given the great numbers of women treated with HRT in the US and Canada, tens of thousands of women, were now at increased risk for deadly diseases that otherwise would have posed little threat. As a result of the interrupted WHI trial, the FDA now requires Wyeth, the manufacturer of Prempro, the drug used in the trial that combined synthetic estrogen and progestin, to include a black box warning on the drug package and promotional material.

In 2004, the NIH stopped the estrogen-only branch of the WHI study. 11,000 healthy postmenopausal women who had a hysterectomy were given estrogen pills and monitored for an average of 7 years. After careful review of the data, NIH concluded that estrogen alone does not appear to affect (either increasing or decreasing) the risk of heart disease. But at the same time, estrogen alone did seem to increase the risk of stroke. It did not appear to increase the risk of breast cancer, called an uncertain effect, and it showed a modest beneficial effect on bones with fewer hip fractures in treated women compared to untreated women in the control group.

This interrupted hormone (HRT) trial demonstrates the dangers of widespread prescribing of risky drugs to healthy people before the drugs are thoroughly tested in clinical trials. It is an egregious example of marketing trumping science in the practice of medicine.

Six years after the release of the WHI findings, the drugmaker’s ads for synthetic hormone therapy can still be found in all media. Will patients and physicians know enough about the WHI results to withstand the siren calls of the marketers? It will depend on how diligent physicians are in educating their patients. It will also depend on how women view menopause: as a natural life transition or a disorder that needs fixing. Patients will have to judge whether their symptoms are severe or manageable, and whether they and their physicians know enough about the benefits of alternative therapies, to trust their reported advantages.

According to Dr. Susan Lark, a well-known gynecologist and breast cancer researcher, relief is possible without resorting to conventional hormone therapy. To bring estrogen back into balance and get menopausal symptoms under control, Lark has had good results with a combination of diet, nutritional supplements, stress reduction techniques, and natural hormone support.

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