By SUSAN IPAKTCHIAN

Publishing the results of a nearly seven-year Women's Health Initiative study dealing with estrogen therapy is bittersweet for Marcia Stefanick, PhD, professor (research) of medicine at the Stanford Prevention Research Center and chair of the WHI national steering committee.

While Stefanick is pleased that the results provide clear evidence that initiating unopposed estrogen therapy for women in their 60s and 70s is not beneficial, she's disappointed that a decision to end the study a year early means that answers aren't as precise for women in their 50s.

"I think it puts exactly the same questions back on the table that were there when we started the trial for women in their 50s," Stefanick said. "We probably could have answered them if we had been given the full eight years."

The estrogen therapy tria l-- involving nearly 11,000 women nationally between the ages of 50 and 79 who had undergone a hysterectomy -- was halted at the end of February because of concerns that estrogen increased the risk of stroke while offering no protection against heart disease. The initial study results are published in today's issue of the Journal of the American Medical Association.

Graph: Courtesy of Marcia Stefanick

Although the primary purpose of hormone therapy is to help relieve the effects of menopause, observational studies and other evidence over the years have suggested that hormones might prevent heart disease and bolster the overall health of older women. The WHI study wanted to answer those questions definitively.

Overall, the results show that the estrogen used in the study, known as conjugated equine estrogen, doesn't appear to have any effect on the risk of heart attacks, colorectal cancer or deaths. The study showed a 39 percent increase in the risk of stroke, going from 32 strokes per 10,000 women among those taking a placebo to 44 strokes per 10,000 women among those on estrogen. The one clear benefit of estrogen was in a decreased risk of hip fracture. Two areas in which estrogen's effect is uncertain are breast cancer and blood clots. Although fewer women on estrogen developed breast cancer, researchers said the result was not statistically significant.

But when the results are broken down by age group, Stefanick said, the findings aren't as clear-cut for women in their 50s. For them, estrogen appears to reduce the risk of heart disease and the overall picture suggests benefit.

"For women in their 60s and 70s, I think the message is pretty clear that initiating hormones is not beneficial for preventing heart disease or for their overall health," Stefanick said. "But for women in their 50s who have had a hysterectomy, this study does suggest some benefit. We would have had better information if we could have continued the trial for another year."

The decision to halt the trial was made by the National Institutes of Health. Although none of the previously established boundaries for stopping the study was crossed, the NIH felt that the increased risk of stroke was not acceptable in healthy women in the absence of any benefit to heart disease. While Stefanick acknowledged that concern, she was unclear as to whether it outweighed the benefit of continuing the trial for another year to give women more precise answers about the balance of risks and benefits of estrogen.

"We're in the unfortunate position of having stopped the trial because of the risk of stroke, which occurred primarily in women in their 60s and 70s," she said. "The study came up short for women in their 50s."

Stefanick said the early end of the trial also makes it difficult to know how long women can safely continue taking estrogen. In the findings related to heart disease, the results showed that women on estrogen had more heart attacks in the initial years but Stefanick said this effect diminished over time in a significant way.

"While we would encourage older women not to initiate hormone use, there's nothing from this study to suggest that they should stop taking it if they've already been on it for up to seven years," she said.

For women in their 50s who are contemplating whether to initiate estrogen, Stefanick said they should discuss their questions with their physicians. "There's certainly good evidence that it's not harmful for women in their 50s who have had a hysterectomy and would only take estrogen for at least seven years."

The message for all women and their physicians is that hormone therapy should be used for relief of hot flashes and other symptoms related to menopause and not as a method of preventing disease, Stefanick said. The Food and Drug Administration recommends that women use the lowest hormone dose needed to achieve treatment goals and limit the duration of the therapy.

Stefanick said she and the other WHI investigators will continue analyzing the data in the coming months and will publish more detailed results in the fall. The study also has received funding to continue tracking clinical outcomes in the women through 2010.

WHI was launched in 1991 to examine the most common causes of death, disability and impaired quality of life in postmenopausal women. The 15-year, multimillion-dollar effort involves more than 161,000 women nationwide.

In addition to the study of estrogen and an earlier study of the combination of estrogen and progestin, the study has arms examining the role of a low-fat diet in reducing breast and colon cancer; the role of calcium and vitamin D in fracture prevention; and an observational study to identify disease predictors. Those arms are continuing.

In 2002, the arm dealing with the estrogen-progestin combination was halted because of evidence that the participants experienced a greater risk of breast cancer, heart attack, stroke and blood clots.