Presumed Benefits of Hormone-Replacement Therapy May Have Caused Harm, Wake Forest Physician Writes in New England Journal of Medicine

August 12, 2003

The medical community learned some hard lessons in women’s health care with the results of a massive study on postmenopausal hormone therapy, writes Wake Forest University Baptist Medical Center cardiologist David M. Herrington, M.D., M.H.S.

Despite years of belief in hormone replacement therapy (HRT) as a means of improving the cardiovascular health of women, results of the Women’s Health Initiative reported last summer indicate that HRT might even increase cardiovascular risk.

In the Aug. 7 edition of The New England Journal of Medicine, Herrington, professor of internal medicine-cardiology at Wake Forest University School of Medicine, states that the belief that hormone replacement therapy might reduce a woman’s risk of coronary heart disease contributed considerably to its widespread use.

“The simple and intuitively appealing concept that replacing estrogen lost during menopause would be beneficial was easy for both patients and physicians to believe,” Herrington writes. “This fact, coupled with impressive indirect evidence of a cardio-protective effect and growing awareness of the need for effective means to treat and prevent heart disease in women, made for a nearly unshakable belief in the benefits of hormone therapy”

However, as early as 1998, Herrington reports, results from a series of randomized clinical trials clearly demonstrated that hormone therapy did not slow the progression of heart disease or prevent heart disease in healthy women. According to Herrington, such reports were heavily criticized and in some cases disregarded.

“The lesson is that belief, no matter how sincerely held, is no substitute for proof in the form of adequately designed randomized clinical trials when it comes to medical interventions,” writes Herrington, “especially long-term interventions that are being contemplated for widespread use in order to prevent disease.”

Researchers also learned that while HRT may have lowered the levels of low-density lipoprotein (LDL) cholesterol and increased the level of high-density lipoprotein (HDL) cholesterol in women, both usually considered beneficial, this did not affect the development or progression of coronary disease.

“The lesson is that an association between a factor and the risk of a disease does not guarantee that drug-induced changes in that factor will produce corresponding change in the risk,” Herrington wrote. “Nor is such an association a guarantee that there will not be other unanticipated adverse effects that might offset real benefits…”

However, Herrington concludes that HRT research may one day produce beneficial results.

“We may yet discover how to manipulate selected features of estrogen biology in ways that will be useful for the treatment and prevention of cardiovascular disease and, more broadly, for the advancement of public health.”

Herrington wrote the perspective article, titled, “From Presumed Benefit to Potential Harm—Hormone Replacement and Heart Disease,” with Timothy D. Howard, Ph.D., assistant professor of pediatrics- medical genetics at the Wake Forest Center for Human Genomics.


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