Adding Progestins May Negate Heart Protection From Estrogen Replacement Therapy

April 06, 1998

DALLAS, April 7 -- Adding progestins to estrogen replacement therapy may weaken some of its beneficial effects in helping women prevent heart attacks, according to a study reported in today's Circulation: Journal of the American Heart Association.

Estrogen replacement therapy (ERT) is used to relieve symptoms of menopause and may help protect against heart disease. Progestins are combined with estrogen because replacement therapy using estrogen alone is associated with increased risk of uterine cancer. But progestins may subtract some of the heart protection from ERT, according to a study by Keld Sorensen, M.D., associate professor in cardiology and Inge Dorup, M.D., D.M.Sc., associate professor in cardiology from the cardiology department at Skejby University Hospital, Aarhus, Denmark. The research team also included a group of investigators from the department of endocrinology and metabolism at Aarhus County Hospital.

In an accompanying editorial appearing in Circulation: Journal of the American Heart Association, Robert Vogel, M.D., says the study "raises a flag that progestins may undo some of the cardiovascular benefits of ERT."

"The study is important because it indicates that there is a difference between estrogen and estrogen plus progestin," says Vogel, Herbert Berger professor of medicine and head of the division of cardiology at the University of Maryland School of Medicine, Baltimore.

Estrogen acts like a "fountain of youth," helping the blood vessels' inner layer -- the endothelium -- remain flexible and be able to "relax and expand" in response to the body's need for blood. This property, called vascular reactivity, often declines after age 50, making blood vessels stiff and less effective in delivering blood to the body's tissues. Excess cholesterol in the blood and high blood pressure can damage the endothelium, resulting in a decrease in vascular reactivity.

To determine the effect of ERT plus progestins on the blood vessels, researchers performed a study that divided 100 postmenopausal women into two groups; one received ERT plus progestins and the other received no therapy.

After the women had been taking the ERT plus progestins for about three years, researchers tested blood vessel reactivity. The test involves inflating a blood pressure cuff on the forearm to block the blood vessel. After about four minutes, the cuff is deflated and images of the blood vessels are recorded by ultrasound as the blood rushes into the vessel. A similar degree of vessel dilation was seen in both groups, indicating that ERT plus progestins did not improve vascular reactivity, Dorup reports.

"In earlier studies, estrogen alone would beneficially alter vascular reactivity, and this was thought to be one way it lowered risk of heart disease. But we found that there is no difference between those receiving HRT plus progestins and no treatment. Progestin may impair the positive effects normally seen by estrogen alone," adds Dorup.

According to Vogel, larger studies, such as the Women's Health Initiative, may help determine whether ERT with progestins can reduce the death rate of cardiovascular disease. "These studies are important because the current study just looked at the endothelium and not death rates," says Vogel.

"However, we still don't know if the endothelium function is an accurate predictor for increased risk of death from cardiovascular disease, although other research has documented that it signals the first stages of atherosclerosis," he says.

In atherosclerosis, blood vessels narrow due to blockages from cholesterol or blood clots, setting the stage for a heart attack or stroke.

Previous studies have found that women taking estrogen lowered their risk of heart disease by 30 percent. However, in most cases, the women were taking estrogen alone.

The effect of ERT plus progestins has not been well researched, notes Vogel.

Estrogen protects against heart disease because of its "anti-aging" effects. However, the study results indicate that ERT plus progestins may still be protective against heart disease, but not because of ERT's anti-aging affects on the endothelium, say the authors.

The benefit of ERT plus progestins may come from its effects on cholesterol levels in the blood. Women taking ERT plus progestins did have lower total cholesterol levels and higher levels of the high-density lipoprotein, the "good" cholesterol, which helps blood vessels stay free of cholesterol buildup.

The scientists recommend that women should still consider ERT plus progestins as a treatment that confers protection against heart disease after menopause, a time when their risk of heart disease is as high as men. Attention should also be paid to lowering cholesterol, smoking cessation, diet and exercise.
NR 98-4883 (Circ/Sorensen)

Media advisory: Dr. Dorup and Dr. Sorensen can be reached by phone at 45-8949-6109. Dr. Vogel can be reached at (410) 328-8795. (Please do not publish telephone numbers.)

American Heart Association

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