It was 10 years ago this month that the National Institutes of Health prematurely terminated one part of the Women’s Health Initiative—a milestone, multi-year study of health problems facing older women. In 2002, the NIH halted the section of the study focusing on the combination of the hormones estrogen and progestin because preliminary results seemed to indicate that it increased the risk of heart problems and breast cancer. It was the first of several findings which, as The New York Times’s Tara Parker-Pope has written, have left some women “feeling frustrated, betrayed and whipsawed by what often seem to be contradictory headlines. And they have fueled cynicism about the medical establishment’s treatment of women.”
On this unusual anniversary, Dr. Wulf H. Utian, founding executive director of the North American Menopause Society and professor emeritus at Case Western Reserve University, takes another look at the Women’s Health Initiative, the decision to halt the study involving estrogen and progestin, and what it has meant for our generation of women. —Ed.
A firestorm in women’s health erupted on July 9, 2002, when the National Institutes of Health prematurely terminated one arm of its Women’s Health Initiative Study (WHI) because, as it stated, “on balance the harm was greater than the benefit.”
The WHI study had been planned largely by cardiologists and epidemiologists to confirm earlier research showing a heart-protective effect of postmenopausal hormonal therapy (PHT). But initially, there was no input from women’s health experts. The study was never designed to investigate menopause itself.
When the WHI began, clinical use of postmenopausal estrogen and progestin therapy had been mostly limited to treating menopause-related symptoms in women between the ages of 40 and 60, and for prevention of bone fractures. There was a growing tendency to prescribe hormones for prevention of cardiovascular disease. But in the study, women up to 79 years of age were started on hormones—something unusual in clinical practice.
Broken into age groups, the absolute risks in the populations studied are quite revealing. In women under the age of 60, estrogen compared to placebo showed fewer cases of chronic heart disease, strokes, diabetes, breast cancers, fractures, and deaths. The only increased adverse event was blood clots, which was low enough in the 50-to-60-year-old group to yield fewer than one additional case per 1,000 women per year, and which caused no increase in mortality in any age group. Even more striking, the data shows a significant risk reduction of chronic heart disease in women on estrogen and progestin therapy who were less than 10 years beyond menopause.
But, as The New York Times noted, the NIH’s announcement in 2002 “prompted women to abandon the treatment in droves.” And while the WHI data for early-menopausal woman clearly demonstrates that benefits outweigh risks, women themselves remain fearful of postmenopausal hormone therapy. Ironically, current recommendations for postmenopausal use of hormone therapy are virtually back to where we started. For example, The North American Menopause Society (NAMS) concludes: “Recent data support the initiation of hormone therapy around the time of menopause to treat menopause-related symptoms and to prevent osteoporosis in women at high risk of fracture.”
Questions remain as to why the WHI investigators did not analyze and present the July 2002 data in 10-year subsets, and how the results would have been interpreted differently if they had. In an article headlined “How NIH Misread Hormone Study in 2002,” the lead WHI author told The Wall Street Journal that “Our main job at the time was to turn around the prevailing notion that hormones would be useful for long-term prevention of heart disease. That was our objective. This was a worthy objective which we achieved.” But this explanation doesn’t make sense when we consider that the catalyst for the WHI study itself was other research showing that starting postmenopausal hormone therapy at a younger age had a protective effect.
We now face two issues: Has women’s health after menopause been helped or harmed by the way these findings were presented? And if harmed, what needs to be done to put things right? The real story of the WHI may turn out to be the damage wrought on younger peri- and early postmenopausal women who discontinued their therapy by the millions and are now several years beyond menopause and off hormones. Not only did they suffer through menopause-related symptoms, but they may have lost the opportunity to be protected from heart disease—the single biggest killer of women over 50—and osteoporosis, one of the major causes of long-term disability.
At the very least, an independent re-examination of the major WHI publications should be done to determine whether their data justified their conclusions. An invaluable body of information was amassed in this historic study. It should be put to its most effective use in benefiting the women for whom it was intended.
Click here for the full text of Dr. Utian’s published comments.