What the Women's Health Initiative hormone replacement treatment study
really says
(Published July 15, 2002)

Since 1980, the incidence of coronary disease, the leading cause of death in the United States, has actually increased in women even though the overall coronary mortality has been decreasing since the late 1960s. Since 1984 in Americans over age 60, more women die of heart disease than men.

Last week the National Institutes of Health prematurely stopped part of the long awaited Women's Health Initiative project designed to answer the question of whether combination hormone replacement therapy would reduce heart disease in previously healthy women. In previous columns, I have addressed the issue of women who already had heart disease when I reviewed the Heart Estrogen/progestin Replacement Study (HERS) and Estrogen Replacement and Atherosclerosis (ERA) trial, both of which suggested that hormone therapy to prevent further disease was not beneficial. The theory and utility of clinical trials to answer these questions has also been addressed in previous columns.

The Women's Health Initiative (WHI) is a well designed clinical trial, with this arm involving 16,608 women aged 50-79 years followed for an average of 5.2 years. From these results, we now have evidence that even in healthy women who still have their uterus, combination estrogen-progestin treatment to prevent heart disease is a false hope. Indeed, the investigators found an increased risk of breast cancer (+26%), heart attacks (+29%), strokes (+41%) and blood clots (+113%). Even though a reduced risk of hip fractures (-34%) and colorectal cancer (-37%), the increased risks likely outweigh benefits. Besides, there are other medications like Fosamax and Actonel that may protect the bones, as well as drugs like raloxifene, a selective estrogen receptor modulator, that may benefit the perimenopausal symptoms without the increased cardiovascular and cancer risks. Even though those assertions are still unproven alternatives, they are probably safer.

This trial corroborates earlier data from HERS and ERA in menopausal women with extant cardiovascular disease, but now extends it to primary prevention (ostensibly healthy women). As recently as 1996, two of three surveyed American physicians said they recommended hormone replacement therapy for their post-menopausal women patients to prevent coronary heart disease. The WHI data should stop the practice of routine prescription of hormone replacement therapy to prevent cardiovascular disease.

Remember that these data are only applicable to women without hysterectomies and on combination estrogen/progestin medication. It is unknown if hormone patches are safer. Data on women who have had hysterectomies on estrogen alone is pending. That arm of the Women's Health Initiative involving over 10,000 women was not stopped, which suggests that no definite harm has been demonstrated, but similarly no clear benefit has been shown.

Although critics will argue that these data are not definitive, these nonetheless are likely best data to ever become available due to the size and prohibitive cost of doing such a large clinical trial. If the British Medical Research Council's Women's International Study of Long Duration Oestrogen after Menopause (WISDOM) corroborates these conclusions, the final nail in the “hormone replacement treatment for heart disease prevention” coffin will be in place.

Conclusions I think we can reach at this time are as follows:

Menopausal women with a uterus taking combination therapy should talk to their doctors about whether they should continue. They should not continue the therapy with the primary intent to prevent cardiovascular disease.

Menopausal women with a uterus NOT taking combination therapy should address the prevention of heart disease, osteoporosis and the perimenopausal syndrome with proven treatments other than oral hormone replacement drugs. And the latest recommendations of the National Cholesterol Education Program have emphasized that statin class drugs should be the mainstay of prevention strategies in eligible patients. Furthermore, we now know that women benefit more than men in the statin trials for both primary and secondary prevention of heart disease.

Menopausal women without a uterus on estrogen therapy alone without heart disease can continue until the follow-up date from that arm of the Women's Health Initiative become available. A previous clinical trial in women with known heart disease showed no benefit from estrogen alone, but did not have the statistical power for definitive proof.

Hormone replacement therapy may still be considered for non-cardiac indications, but now more than ever, consultation with your physician is even more important to make that individual decision.



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