Hormone Therapy May be Most Protective in Women with Healthiest Blood Vessels

March 19, 2002

WINSTON-SALEM, N.C. – When it comes to protection against heart disease, women with the healthiest blood vessels may have the most to gain from estrogen replacement therapy, reported Mary S. Anthony, Ph.D., from Wake Forest University Baptist Medical Center in Atlanta today at the 51st annual scientific sessions of the American College of Cardiology.

In a study of monkeys, Anthony and colleagues found that animals in the earliest stages of atherosclerosis, the buildup of fatty deposits in the vessels, showed the most benefit from hormone therapy. The hormone was most effective at slowing the disease’s progression when it was given at an early stage.

“Applied to women, this means that estrogen replacement therapy may be less effective when arterial disease is advanced,” said Anthony, assistant professor of public health sciences. “This corresponds with two studies showing that in women with existing heart disease, hormone replacement does not slow the disease’s progression or prevent heart disease events.”

For the study, female monkeys were fed a high-fat diet for two years to cause atherosclerosis. The researchers then measured fatty lesions in the animals’ blood vessels and designated the animals into three groups based on their levels of vessel disease.

The ovaries of all monkeys were removed to induce menopause. For three years after menopause, half of the monkeys were treated with estrogen in doses comparable to what women typically take. The other animals got no hormone treatment. At the end of the three years, the researchers again measured fatty lesions in the animals’ vessels.

The measurements showed that animals treated with estrogen had less atherosclerosis overall than the untreated group. But, the most dramatic differences were seen in monkeys that had the healthiest arteries to start with.

In the group of monkeys with the lowest levels of vessel disease at menopause, fatty lesions were 85 percent smaller in the estrogen-treated animals than in those that were untreated. In animals with intermediate levels of atherosclerosis at menopause, the estrogen-treated group had lesions that were about 25 percent smaller than the control group, but the differences were not statistically significant. In animals with the highest levels of atherosclerosis at menopause, there was no difference in lesion size between treated and untreated animals.

“These results imply that starting estrogen therapy at the earliest stages of atherosclerosis provides the greatest chance of slowing the disease’s progress,” said Anthony. “The animals that showed the greatest benefits of estrogen had levels of atherosclerosis typically found in women during the perimenopausal years. This implies that women may need estrogen supplements as their production of the hormone begins to wane.”

The results may bring a new factor into the equation of whether or not women should take estrogen for the prevention of heart disease – the timing of therapy may determine its effectiveness.

For years, doctors routinely prescribed hormone replacement therapy to prevent heart disease in postmenopausal women. These treatment decisions were based on observational studies showing that women who took the therapy had fewer heart attacks.

But, as researchers conducted more thorough research, they found that in women with existing heart disease, the estrogen showed no benefit at slowing the disease or preventing heart attacks.

“Our study suggests one possible explanation for the results found in women – that estrogen might be more effective in women with the healthiest vessels,” said Anthony.

Anthony said she would expect similar results if a combination of estrogen and progestin had been used in the study. At one time, researchers suspected that progestin could negate the effects of estrogen on the blood vessels. But most animal and human studies have shown that estrogen and the estrogen/progestin combination have similar effects on the vessels. In the United States, most women taking hormone replacement therapy take both estrogen and progestin.


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