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Caution for estrogen therapy after hysterectomy

An editorial in the April 6 issue of the Journal of the American Medical Association cautions against estrogen-only hormone therapy in women who have had a hysterectomy because of longstanding evidence that it raises the risk of breast cancer.

The editorial is a response to a study in the same issue of the journal that found that estrogen-only therapy, currently used in women with menopausal symptoms who have had a hysterectomy, may decrease breast cancer risk if it is used for fewer than five years. The study found this benefit persisted even after the hormone therapy was discontinued.

But in the editorial, Graham Colditz, MD, PhD, the Niess-Gain Professor of Surgery, and Emily Jungheim, MD, of Washington University School of Medicine in St. Louis, say that while short-term use of estrogen-only therapy appears safe, the long-term consequences of that short use are unknown.

The study, by researchers at Fred Hutchinson Cancer Research Center, looked at data from the Women's Health Initiative, a large study of the risks and benefits of hormone therapy in preventing chronic disease.

The researchers found that the negative effects of hormone therapy (HT), primarily stroke, went away after the women stopped treatment. Likewise, the benefits, mainly a decreased risk of bone fracture, also disappeared. The exception, according to the authors, was that a possible decreased risk of breast cancer found in the estrogen-only group continued even after therapy ended.

But Colditz and Jungheim caution doctors to look at the larger body of evidence that contradicts this finding and shows that hormone therapy may raise the risk of breast cancer. While estrogen therapy is commonly used on a short-term basis to manage menopausal symptoms after hysterectomy, Colditz and Jungheim say questions remain about its safety, including whether there is a safe duration of use.

The Women's Health Initiative (WHI) began recruiting participants in 1993 to look at the risks and benefits of hormone therapy (HT), including estrogen-only therapy, when used to prevent chronic disease.

At that time, not only was hormone therapy standard practice in treating women with menopausal symptoms, it was thought to be beneficial for preventing age-related diseases including heart disease, bone fractures and breast and colorectal cancers.

"Back then hormone therapy was prescribed almost like a vitamin," says Jungheim, assistant professor of obstetrics and gynecology.

That practice changed drastically as the WHI study was halted early because of an increased risk of stroke and no clear benefits in other disease categories.

In their editorial, Colditz and Jungheim question whether the WHI was an appropriate population to study when asking whether estrogen-only therapy is safe for treating the symptoms of menopause, including hot flashes, mood swings and sleep disturbances.

Generally, the women in the WHI do not represent the typical woman who might be prescribed hormone therapy for menopausal symptoms today. For example, 68 percent of the women in the WHI were over age 60 when enrolled in the study, making them older than the average woman entering menopause.

And though the women were followed for 10 years after therapy stopped, the average amount of time they actively took hormones was only three and a half years. Therefore, the WHI results cannot address the risks and benefits of longer-term estrogen use, they say.

Despite the risks, Jungheim still sees a role for short-term hormone therapy in treating women with severe menopausal symptoms, especially those experiencing premature menopause.

"The symptoms women experience around the time of menopause can be significant. There may be a role for hormone therapy for some women who cannot find relief from other things," she says. "But it's worth exploring other options including medications and lifestyle changes."

Jungheim suggests women discuss their symptoms with their doctors. Together, they can review the risks and benefits of the available treatment options and arrive at a personal strategy for managing their symptoms.

Jungheim ES, Colditz GA. Short-term use of unopposed estrogen: a balance of inferred risks and benefits. Journal of the American Medical Association. Vol. 305, No. 13. April 6, 2011.

LaCroix AZ, et al. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial. Journal of the American Medical Association. Vol. 305, No. 13. April 6, 2011.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Julia Evangelou Strait | EurekAlert!
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