Age is Important in HRT Use

Five years ago this summer, the National Institutes of Health stopped a major portion of the Women's Health Initiative, a large and ambitious study to address the most common causes of death, disability, and impaired quality of life in post-menopausal women.

One part of the project sought to determine whether hormone therapy has a positive or negative impact on cardiovascular disease, cancer, and osteoporosis.

The estrogen-plus-progestin hormone-therapy trial for women with their uteruses intact was stopped in July 2002 after investigators found that the associated health risks of the combination hormone therapy outweighed the benefits.

Less than two years later, in March 2004, the National Institutes of Health announced that it had stopped another portion of the initiative—the estrogen-alone hormone-therapy study for women who have had a hysterectomy—in the interest of safety after careful consideration of preliminary data and an average follow-up of nearly seven years.

Questions Remain

The abrupt end to the studies and news stories that followed left many patients confused or scared. Questions still remained about the safety and efficacy of hormone therapy, about who could take it, and for what purpose and what duration.

• the risks and benefits of estrogen-alone hormone therapy;
• long-term risks for short-term use of hormone therapy;
• the appropriate timing of hormone-therapy use in relation to a woman's onset of menopause; and
• the effects for women who take hormone therapy well after menopause has ended.

The medical community has learned more about hormone therapy since the Women's Health Initiative trials were stopped.

A study published in July's British Medical Journal confirmed that hormone-replacement therapy should not be prescribed for preventing chronic conditions, such as heart disease, in older women who are well past menopause.

That same study, however, concluded that hormone therapy may be a safe, short-term option for younger women in early menopause to relieve symptoms and improve quality of life.

"If the woman is healthy and has no risk factors, low-dose hormone-replacement therapy use for a short period of time should confer a small risk to her health," says Dr. Helen Roberts, a senior lecturer of women’s health issues at New Zealand's University of Aukland.

Roberts, who wrote an accompanying editorial to the British Medical Journal study, also said women with risk factors, such as a previous heart attack, stroke, blood clots, breast cancer or high risk of cardiovascular disease, should not use hormone therapy.

Although confusion about hormone therapy persists, this study solidifies some thinking on the issue. Short-term use of hormones in healthy women going through early menopause may not pose serious health risks.

Long-term use of hormone therapy to prevent chronic diseases in older women, who begin the therapy many years after menopause, may actually increase their risk of blood clots and heart disease, and should be discouraged.

A limitation of the Women's Health Initiative is that it primarily studied women who began taking hormone therapy long after they had passed menopause. Researchers are still trying to determine the effects of taking hormone therapy for long periods of time if the treatment begins in the early stages of menopause.

More Research Is Needed

Some data suggests the health risks are lower for these women, but more studies are needed.

"There has been mounting evidence that a woman's age and amount of time since onset of menopause influence her health outcomes on estrogen, particularly her risk of heart disease," says Dr. JoAnn Manson, chief of preventive medicine at Brigham and Women's Hospital in Boston, professor at Harvard Medical School, and a Women’s Health Initiative principle investigators.

"We've recently reported in April of 2007 that when you combine the findings from the estrogen plus progesterone trial and the estrogen alone trial, there is a suggestion of a lower risk of heart disease in the women who were less than ten years since onset of menopause."

By contrast, Manson's analysis shows an increased risk of heart disease for women who were more than 20 years past menopause.

Manson's research team reported in June's New England Journal of Medicine that women who were in their 50s in the estrogen-alone trial tended to have less coronary artery calcium, if they received estrogen compared to placebo.

"Coronary artery calcium is a marker for plaque build-up in the arteries, hardening of the arteries and it's a strong predictor of future risk of cardiovascular, of coronary heart disease," Manson says. "So these results lend support to the theory that estrogen may slow early stages of atherosclerosis."

As research continues, taking hormone replacement therapy is an individual decision for women that depends on many factors. Women should speak with their health care providers about the potential benefits and risks that may be relevant to them as individuals.

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