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TUESDAY, March 2 (HealthDayNews) -- U.S. health officials are halting a third portion of a landmark hormone replacement therapy trial.

The National Institutes of Health on Tuesday was expected to pull the plug on the estrogen-only segment of the Women's Health Initiative (WHI), a major 15-year research program on postmenopausal women, because the data suggests estrogen on its own has no impact either way on heart disease.

While that was the main focus of the study, it reportedly found instead that estrogen alone appears to increase the risk of stroke. On the plus side, it also found that estrogen alone did not appear to increase the risk of breast cancer while decreasing the risk of hip fracture.

"The increased risk of stroke with estrogen alone outweighs any benefits found in the study," says a U.S. Food and Drug Administration statement announcing the NIH action.

The FDA will now assess these latest results to determine whether additional label changes for hormone replacement therapy (HRT) are needed, the statement added.

The trial, cut short one year shy of its eight-year run, involved 11,000 healthy postmenopausal women who had had their uteruses removed in a hysterectomy. Women without uteruses can take estrogen alone; those who have a uterus increase their risk of uterine cancer if they don't take progestin to counteract the effects of estrogen.

The women in the estrogen-only portion of the trial were taking Premarin, 0.625 mg of conjugated equine estrogens, daily, according to the NIH website.

The latest trial halt followed two earlier endings of high-profile WHI studies involving combination hormone therapy, estrogen plus progestin. In July 2002, the first study was halted because of an unexpected increased risk of breast cancer, heart disease, stroke and blood clots. There was also a decreased risk of hip fracture and colon cancer, but that was not enough to merit continuation of that study.

In May 2003, the memory arm of the WHI was stopped when data showed an increased risk of dementia in women aged 65 and older who took the combination therapy.

And the litany of bad news about HRT trials is not limited to the United States.

In October 2002, a major British trial evaluating hormone therapy was also stopped after elevated risks of breast cancer appeared. Last month, a Swedish HRT study on women who have had breast cancer was halted because the risks of a recurrence of cancer were judged to be too great.

But expert reaction to the newest cutoff was cautious.

"This is not anywhere as exciting or alarming as the last halting of the study [the July 2002 one]," says Dr. Mary Jane Minkin, a clinical professor of obstetrics and gynecology at Yale University School of Medicine.

And despite the latest findings, Minkin sees no reason to universally stop hormone therapy for menopausal women.

"The key thing to remember with any of these studies is that they were not studying women going through menopause," she says. "The average age of women in the WHI is 63 years old upon initiation of therapy, much older than menopausal, and they're not the world's healthiest. These are not typical women going through menopause."

"Is this relevant at all to my patients going through menopause, and the answer is I don't know," she continues. "Does this make me more worried? No. What my patients are really worried about is breast cancer and what they're going to be interested in is this didn't show increased risk of breast cancer."

She says she would like to know exactly how much of an increased risk of stroke was seen, too.

Also unanswered are questions about what form of estrogen is problematic. This study looked only at oral estrogen, leaving open the possibility that hormone patches might be better.

As the disturbing evidence keeps accumulating, the FDA has been working with manufacturers of hormone therapies to update product labeling.

While these products are still available, the FDA advises women and their health-care providers to discuss the benefits and risks of HRT. The agency is also reminding people that hormone therapy has never been approved for preventing heart disease or memory conditions such as Alzheimer's. Hormone products should only be used for the relief of moderate to severe postmenopausal symptoms such as hot flashes, the agency says. And, it adds, products should also be used at the lowest dose and for the shortest duration possible.

Minkin thinks individualized decisions are the way to go.

"Does this scare me? No. Is this going to tell me to tell my patients who are using estrogen and/or progestin you've got to stop? No," she says. "It's got to be evaluated on a case-by-case basis. You have to take into account each patient's risk profile and what the symptoms are."

More information

The U.S. Food and Drug Administration has more on menopause and hormones. The National Institutes of Health has more on the Women's Health Initiative.

(SOURCES: Mary Jane Minkin, M.D., clinical professor, obstetrics and gynecology, Yale University School of Medicine, New Haven, Conn.; March 1, 2004, U.S. Food and Drug Administration statement)

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