A study of more than 1 million women in Britain suggests that hormone replacement therapy (HRT) can increase the risk of dying from breast cancer, in addition to raising the risk of getting the disease.

The findings add to a growing body of evidence that hormone use may do women more harm than good, and thus may no longer be an attractive option for women seeking relief from troubling symptoms of menopause like hot flashes, moodiness, and sleeplessness.

"When the therapy was introduced, the health benefits of HRT were highlighted, but the increased risks of breast and endometrial cancer, although known, were downplayed," wrote Chris van Weel, of the University of Nijmegen in the Netherlands, in an editorial accompanying the study. Between 20% and 50% of women in western countries aged 45-70 are estimated to use hormone therapy, he said.

Based on earlier studies, HRT was believed to improve cardiovascular health, help prevent osteoporosis, and boost self-esteem, in addition to relieving menopause symptoms. It was also thought that, even if breast cancer rates did increase with therapy, the risk would only happen with long-term use, the types of cancer seen would be easy to treat, and there would be no increase in the number of women dying from breast cancer, van Weel noted.

Recent studies, however, have questioned those assumptions.

Last year, the Women's Health Initiative study was halted early because researchers found that combination estrogen-progestin hormone therapy was associated with an increased number of strokes, heart attacks, and blood clots. Other analyses of this data have found that combination HRT increases the risk of breast cancer after as little as five years of use, and that the cancers are found at a later stage, when they are more difficult to treat.

This latest study, conducted by researchers at Cancer Research UK, looked at combination therapy as well as estrogen-only therapy and other types of hormone treatment, and compared patterns of use. It was part of the Million Women Study, a project run by Cancer Research UK and Britain's National Health Service Breast Screening Program to learn about various health issues affecting women 50 and older. The results were published in The Lancet (Vol. 362, No. 9382: 419-427).

More than 1 million women aged 50-64 answered questions about their health and use of hormone therapy how long they had used it, what type (estrogen-only, estrogen-progestin combination therapy, or other types) and dose they had used, whether or not they had stopped using it (and how long ago), and whether they were already in menopause.

About half the women in the study had used hormone therapy at some point in time.

The researchers followed the women from 1996 to 2001. In that time, 9,364 women developed breast cancer, and 637 died of it.

To determine how HRT affected the incidence of breast cancer, the researchers focused their analysis on more than 800,000 women who were past menopause at the time of the study.

Among these women, those who currently used hormone replacement therapy of any kind were at greater risk of developing breast cancer. Their risk was about 66% higher than women who never used HRT. Their risk of dying from breast cancer was about 22% greater.

Using combination estrogen-progestin HRT raised breast cancer risk the most. Women using these therapies had about twice the risk of breast cancer as women who did not use HRT. Using estrogen-only HRT raised breast cancer risk by about 30%. Different brands, doses and methods of administration of each type of HRT did not appear to affect breast cancer risk.

The researchers also determined that the longer a woman used hormone therapy, the greater her risk of getting breast cancer. However, stopping hormone therapy seemed to reduce the risk fairly quickly. Women who had stopped HRT within the previous year had just a 14% greater risk of breast cancer than women who never used HRT. Women who had quit HRT five or more years previously had about the same risk as women who never used hormones.

Although the figures sound alarming, the actual increase in risk found by this study is still relatively small. Other factors, like having a family history of the disease, pose a greater risk.

The researchers said that out of 1,000 women who never use hormone therapy, 32 could be expected to develop breast cancer between the ages of 50 and 65. Using combination estrogen-progestin therapy for five years would lead to six additional cases (or 38 out of 1,000 women), while using it for 10 years would lead to 19 additional cases (or 51 out of 1,000 women).

Furthermore, the statistical results are only from one trial, and would have to be confirmed by other studies. The Women's Health Initiative, considered a more scientifically sound study, found that breast cancer incidence was about 25% higher in women who took hormones, and did not find any difference in deaths. Further results from ongoing studies will be needed to determine just how much hormone therapy may raise breast cancer risk.

Still, the findings of this latest study could potentially impact millions of women.

"Its strength is that it's a large study of over a million women with very detailed information regarding type of hormone use," said Eugenia Calle, PhD, director of analytical epidemiology for the American Cancer Society.

Estrogen-only therapy would cause less breast cancer than the combination HRT, the researchers said, but would cause more endometrial cancers if given to women who still have a uterus. The risk of endometrial cancer with estrogen-only therapy is well-documented, and for this reason, this type of HRT is generally only given to women who have had a hysterectomy.

"Comparing the risks is by no means simple, and women may well want to discuss options with their doctor," said lead researcher Valerie Beral, of Cancer Research UK, in a statement.

Calle agreed. "Because of these findings, the decision to use either (combination HRT or estrogen-only therapy) after menopause should be made by each woman and her doctor after weighing possible risks and benefits."

Van Weel, however, said there seems to be little room for hormone replacement therapy in current practice.

"HRT should be discouraged," he wrote. Women who need relief from menopausal symptoms should take HRT for no longer than three to six months, he said. And while there's no need to panic, women who are already using the hormones should stop, he added.

He called for a public information campaign urging women to talk to their doctors about the risks and benefits of hormone therapy, and the alternatives available.