Age is important in HRT use

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

One part of the WHI 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, NIH announced that it had stopped another portion of the WHI, 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.

The abrupt end of the studies and the 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.

More information was needed about 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 WHI trials were stopped. A study published in the July 11 issue of the British Medical Journal confirmed that hormone replacement therapy should not be prescribed for the purpose of 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 Helen Roberts, M.D., M.P.H., a senior lecturer of women's health issues at the University of Aukland in New Zealand. 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 WHI 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. 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,” said JoAnn Manson, M.D., Dr.P.H., chief of preventative medicine at Brigham and Women's Hospital in Boston, professor of medicine at Harvard Medical School, and one of the principle investigators of the WHI. “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 the June 21 issue of the 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 said. “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.