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Animal Research Suggests Low-Dose Estrogen Therapy May be Effective for Heart Disease Prevention

WINSTON-SALEM, N.C. – Research in monkeys found that low-dose estrogen therapy significantly reduced the progression of fatty buildup in the arteries leading to the heart, according to research at Wake Forest University Baptist Medical Center, reported today at the annual meeting of the North American Menopause Society in Washington, D.C.

"We’ve shown that you can get the same reduction in coronary artery atherosclerosis with standard-dose or low-dose estrogen," said Thomas B. Clarkson, D.V.M., one of the investigators. "It is very significant."

The findings mirror a recent study in women, said Clarkson and Susan E. Appt, D.V.M., principal investigators of the animal study. Pharmaceutical companies are already marketing lower doses of the drug.

The monkey study looked at whether 0.3 milligrams per day of oral conjugated equine estrogen (CEE) would be as effective at reducing progression of atherosclerosis as the traditional oral dose of 0.625 milligrams per day (found in Premarin). Two groups of postmenopausal monkeys were fed a moderately fatty diet for 10 months – similar to the typical human diet – to induce the buildup of fat deposits in the arteries. For two years, the monkeys were then given the human equivalent of low-dose CEE or no estrogen.

Evaluation of the three main arteries leading to the heart showed that monkeys that were treated with estrogen had 55 percent less atherosclerosis than the monkeys that didn’t receive estrogen. This is similar to the results previously obtained in monkeys who received the traditional dose of estrogen.

The monkeys were selected to be equivalent to women during the early postmenopausal years.

"This study suggests that low-dose estrogen may be as effective at inhibiting atherosclerosis as the traditional dose in early postmenopausal subjects," said Clarkson, professor of comparative medicine.

Clarkson said the findings are important because they suggest that women who are taking low-dose estrogen for their menopausal symptoms may also benefit from a heart disease perspective. Several studies are evaluating the low-dose therapy in women.

A recent study by Kwang Kon Koh at Hokkaido University Graduate School of Medicine in Japan, compared women who received low-dose and standard-dose estrogen – in combination with the hormone progestin – for two months. The researchers found that the two doses had comparable favorable effects on several markers of cardiovascular health, including cholesterol concentrations and artery flexibility. In addition, the lower doses were less likely to result in changes that increase the risk of blot clot formation, which can lead to heart attacks and stroke.

The Kronos Longevity Research Institute is funding a five-year study of women ages 45 to 54. The study will recruit 900 women to evaluate an oral tablet containing low-dose estrogen, a skin patch delivering estrogen or a placebo. At the end of the five years, researchers will use ultrasound to evaluate the thickness of artery walls. Thickened artery walls are a sign of early atherosclerosis.

Also involved in the Wake Forest Baptist research was Mary Anthony, Ph.D., who was at Wake Forest Baptist at the time the research took place.

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Media Contacts: Karen Richardson, krchrdsn@wfubmc.edu; Shannon Koontz, shkoontz@wfubmc.edu; at 336-716-4587.

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