A second arm of a major study has been halted when evidence emerged of possible negative effects in otherwise healthy women.

Another U.S. hormone replacement therapy study has been halted early, after researchers found estrogen-only pills have no health benefits and can increase the risk of stroke.

The National Institutes of Health instructed 11,000 post-menopausal women in the study to stop taking their pills yesterday, mirroring a similar directive issued two years ago when researchers learned during the first arm of the study that combination hormone therapy could actually lead to increased risk of heart disease, dementia and breast cancer. Estrogen-only therapy is usually used only for women without a uterus.

"This doesn't make a big change to the announcement or advice that was already given when the first arm (of the study) was stopped. Basically, one should not be using these hormones for long-term health benefits," says Dr. Donna Stewart, professor and chair of women's health at the University Health Network and University of Toronto.

The study, run by the Women's Health Initiative, found that estrogen alone has no impact on the risk of heart disease but, when used over long periods of time, it appears to increase the risk of stroke. Compared to women in the placebo group, the women taking estrogen-only therapy had eight more strokes per year for every 10,000 women.

"The NIH believes that an increased risk of stroke is not acceptable in healthy women in a research study. This is especially true if estrogen alone does not affect (either increase or decrease) heart disease, as appears to be the case in the current study," Barbara Alving, director of the Women's Health Initiative and acting director of the National Heart, Lung, and Blood Institute, said in a statement.

Estrogen-only therapy appeared to reduce the risk of hip fracture and did not increase the risk of breast cancer. The first phase of the study, involving combined estrogen and progestin therapy, ended abruptly in July, 2002, after almost six years of study, when researchers found an increased risk of breast cancer. In the end, doctors decided the risks of breast cancer, coronary heart disease, stroke and blood clots outweighed the benefits on hip fracture and colorectal cancer.

The announcement prompted thousands of women to dump their pills and suffer through the effects of menopause as confusion reigned about just who was at risk for what. Although Stewart said this might end some of the confusion about the role of estrogen versus progestin in contributing to increased health risks, it will do little to clear the confusion over whether women should stick with hormone replacement therapy.

"It certainly adds to the confusion, I'm sorry to say," says one study leader, Dr. Norman L. Lasser of the University of Medicine and Dentistry of New Jersey. "It sounds cliche to say do more studies, but I don't think we should give up on estrogens," he adds. If doctors could learn to predict who was most likely to have an estrogen-caused side effect, he says, other women could safely use it.

The Canadian Cancer Society warned women away from using HRT and the U.S. Food and Drug Administration suggested women suffering acute symptoms of menopause, such as severe hot flashes, use the lowest dose of HRT for a short period of time.