In a teleconference Monday she cited a 45 percent "significant" reduction for heart attack and coronary heart disease. By contrast, in older study participants, there was no sign of reduced risk, she said.

"It may be different outcomes depending on age and the amount of time since menopause," she said, adding that HRT should not be used to prevent heart problems but rather to prevent menopausal symptoms. The KEEPS study will help determine if there is heart benefit for younger women.

The just-reported research shows a striking benefit, according to Dr. S. Mitchell Harman, director and president of the Kronos Longevity Research Institute and lead principal investigator of the clinical trial, which has already begun enrolling participants.

KEEPS is a randomized, controlled, double-blind (neither patients nor doctors know who is getting the hormone or the placebo) trial that will provide prospective information on the risks and benefits of early menopausal hormone therapy as it relates to atherosclerosis.

Harman said one explanation for the difference in findings may be that even in the decade after menopause, women may develop a significant amount of plaque, although there's no evidence of heart disease. Their research showed that, by their mid-60s, 35 to 40 percent of women have arterial disease that could cause a heart attack. It is possible, they theorize, that you can't prevent disease that's already present and therefore the timing of the estrogen therapy is important.

Animal studies in monkeys have suggested that HRT is good when started early and ineffective if started later, Harman said.

To enroll in KEEPS, women must have passed through natural menopause (no hysterectomy) within the past three years and be 42-58. Women who smoke more than a half-pack a day, have diabetes or a history of heart disease are not part of the study. Enrollees will be randomly assigned to one of three arms: One group will receive low-dose Premarin, one group will receive a low-dose estrogen skin patch and one group will be given a placebo. All participants will use a patch and a pill, but either or both will be a placebo to mask who is getting what, Brinton said.

Part of the difference in risks and benefits may be the form of estrogen taken. Taking estrogen by mouth seems to increase clotting factors, for instance, compared to a skin patch. The study will look at quality of life and cognitive function, as well as various measures of vascular function, cholesterol, triglycerides, circulation, bone density and joint space maintenance, moods, body fat and more — "anything and everything related to estrogen and its benefits or risks," Brinton said.

Some sections will be optional. The endpoint to determine atherosclerosis will be an ultrasound examination at the beginning, middle and end to see carotid wall thickness. Manson said the women with the lowest amount of atherosclerosis at the time they started the hormone therapy seemed to have the best outcomes in the recent research — a window of opportunity to relieve menopause symptoms without increasing risk of heart problems. Funding for the trial, Harman noted, comes from a private foundation, with no connection to any pharmaceutical company. The centers were chosen through competitive bid.

Highlights in recent research involving younger women were a 45 percent lower risk of having angioplasty or bypass in women using estrogen compared to placebo. For combined major coronary events including heart attack, death, coronary bypass and angioplasty, risk was 34 percent lower.

Women interested in the clinical trial at the U. can call 801-585-0374 or toll-free 866-807-4517.

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E-mail: lois@desnews.com