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Revisiting hormone therapy’s risks and benefits

Hormone therapy has long been the standard treatment for relieving menopausal symptoms: hot flashes, night sweats, and vaginal dryness. Until 2002, many clinicians were also recommending it long term to prevent chronic health problems, including heart disease, stroke, and osteoporosis.

Then, in 2002, the hormonal approach to averting women’s later-life ills screeched to a halt. Researchers had to stop the Women’s Health Initiative (WHI) randomized trial of estrogen and progestin (in the form of Prempro) because the hormone combination was actually causing more heart attacks and strokes than a placebo, as well as more blood clots and breast cancer.

Two years later, the WHI’s trial of estrogen alone (Premarin), also ended early, after it became apparent that estrogen increased the rate of strokes and blood clots without conferring any benefits on the heart.

That left hormone therapy back where it started, as a short-term treatment for menopausal symptoms.

Impact and critique of the WHI

Menopausal women looking for symptom relief shouldn’t misinterpret the WHI findings. These studies were not about short-term management of menopausal symptoms. Some critics argue that the WHI results may not apply to the typical woman considering hormone therapy because most of the participants were in their 60s and 70s. Others say that the risks were overstated. Each year, for example, the women taking Prempro had only six more heart attacks per 10,000 than the women taking a placebo; among younger women, the difference was even less.

Some scientists now suggest that the cardiac risk and benefit of hormone therapy may depend on a woman’s age, particularly the age at which she starts taking hormones. This new hypothesis doesn’t change current recommendations,  but it may reassure perimenopausal and newly menopausal women who are considering short-term hormone treatment for symptom relief.

Heart risk: Is it a matter of timing?

The lack of heart benefits in the WHI contradicts findings from observational studies. In those studies, women have tended to start taking hormones closer to the onset of menopause. Researchers have observed that these women suffer fewer of the heart problems caused by atherosclerosis than women who don’t take hormones.

So why might estrogen then increase the risk of heart disease in women who start taking it at an older age? Evidence indicates that estrogen can destabilize atherosclerotic plaques that are a major source of heart disease and which are more common in older women. Estrogen appears to make plaques more vulnerable to rupture, which can result in a heart attack.

Nurses’ Health Study researchers found some support for this hypothesis in 2006 in a study undertaken to shed light on the discrepancies between the WHI results and earlier research, finding a 30% reduction in risk for heart disease among women who began hormone therapy within about four years of menopause, but little or no cardiac benefit for women who started hormones either after age 60 or 10 or more years after menopause.

A reanalysis of the WHI data turned up similar evidence that timing may be a factor. The greater the gap between onset of menopause and start of hormone therapy, the greater the risk for heart disease, especially in those with a history of hot flashes and night sweats. Stroke remained a problem, regardless of time since menopause, for women receiving either estrogen alone or combined therapy. The risk for breast cancer rose after five years in women taking combined hormones, although not in those taking estrogen alone.

What about breast cancer?

Initial results from the WHI’s estrogen-only trial indicated that estrogen alone reduced the risk for breast cancer by 23% over about seven years. The effect was not statistically significant but it was still surprising in light of the increased risk found in the combined-hormone trial after four years. So investigators decided to take a closer look. In a final report they concluded that the women taking estrogen alone were at no greater risk for breast cancer than those taking a placebo.

The difference in risk between estrogen alone versus combined estrogen and progestin is one of the unanswered questions about hormone therapy and breast cancer. In the WHI, the estrogen-only takers had undergone hysterectomy, which is different from natural menopause. Also, we don’t know yet whether the time when hormone therapy starts influences breast cancer risk in the way it does heart disease risk.

In the meantime, several groups of researchers reported in 2007 that the rate of new breast cancers began to decline in 2003, the year hormone therapy prescriptions fell off sharply.

What it means

Women in early menopause with troublesome hot flashes or night sweats can take short-term hormone therapy without increasing their risk for heart disease. Hormone therapy should be taken only for symptoms and, like any drug, for the shortest time possible and at the lowest effective dose (although we don’t know whether lower doses are actually safer).

When it comes to prevention, whether hormone therapy’s adverse effect on the heart is related to timing still needs more study. But you can reduce these risks in other ways without increasing your odds for breast cancer, blood clots, and stroke. Avoid tobacco; exercise at least 30 minutes a day; and adopt a healthy eating plan.

January 2008 update

Menopause Special Report
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Menopause: Managing the Change of Life

Menopause is no longer the obvious sign of aging it once was. Menopause: Managing the Change of Life takes a view of the whole woman and helps her sort through the latest medical findings and choose the most practical strategies for making her midlife transition as easily as possible. Read more

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