CHICAGO- A new study, the largest of its kind ever conducted, confirms the cardiovascular benefits of hormone replacement therapy in post-menopausal women.

The three year Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial compared the cardiovascular effects of four different hormonal regimens in a group of 875 healthy women aged between 45 and 64 years. The women were divided into four groups and placed on regimens of estrogen alone, one of three combinations of estrogen and progestin, or placebo.

All of the women taking any one of four hormone replacement therapies showed significant increases in their levels of high density lipoprotein (HDL) or good cholesterol, considered to be the best predictor of coronary heart disease risk in women. Women receiving the hormone replacement regimens also showed significant decreases in low density lipoprotein (LDL) or bad cholesterol and fibrinogen (a blood clotting factor predictive of stroke and heart attack). Both of these factors are also known to affect a woman's risk of heart disease.

One of the purposes of the trial was to compare the effects of the various hormone replacement regimens now in wide use. While all four hormonal regimens produced significantly greater increases in HDL-cholesterol levels than a placebo, estrogen taken alone and estrogen combined with micronized (natural) progesterone produced the most favorable results. Smaller but still significant improvements in HDL were also seen in women taking estrogen with a cyclic dose of synthetic progestin and in women taking estrogen with continuous synthetic progestin.

Another purpose of the study was to examine the potential link between hormone replacement and endometrial hyperplasia, a condition which can develop into uterine cancer. None of the three estrogen/progestin combinations tested in the PEPI trial caused hyperplasia. However, one-third of the women with an intact uterus who were taking estrogen alone did develop severe endometrial changes.

The PEPI study may also put to rest some of the lingering concerns about hormone replacement. Hormone treatment did not increase blood pressure or insulin levels, two other risk factors associated with heart disease. Also contrary to expectations, hormonal therapy did not cause weight gain.

The observation of lower levels of the clotting factor fibrinogen seen in association with hormone replacement is provides further support for the cardioprotective effects of these treatments. In the large scale Framingham Heart Study, women with high fibrinogen levels, had twice the risk of heart disease as women with low fibrinogen.

"This important study has implications for all post-menopausal women. These women should talk to their doctors about the PEPI results and the effects of different hormonal combinations on heart disease risk," said Dr. Claude Lenfant, director of the National Heart Lung and Blood Institute.

"Even small increases in HDL have a potentially large impact on the risk of heart disease," Dr. Lenfant noted. "The Framingham Heart study found that increases in HDL levels similar to those found in PEPI may decrease the risk of coronary heart disease in women by as much as 20 to 25 percent."

Postmenopausal women who are considering hormone replacement therapy to prevent heart disease should find out their total and HDL cholesterol numbers before beginning therapy, advised Dr. Elizabeth Barrett-Connor, professor and chair, Department of Family and Preventive Medicine, University of California, San Diego, and PEPI Steering Committee chair.

"These results provide the strongest evidence to date that estrogen given alone produces the best effect on HDL-cholesterol.

However, the high rate of potentially harmful endometrial changes makes combination hormone therapy advisable for most women with a uterus," said Dr. Barrett-Connor.

"Because endometrial hyperplasia is reversible with early diagnosis and treatment, the PEPI study shows the value of regular endometrial biopsy for its detection, particularly for women with a uterus taking unopposed estrogen," she said.

Coronary heart disease is the number one killer of American women. Each year, about 250,000 women die of this disease.

The PEPI study was conducted under the auspices of the National Heart, Lung, and Blood Institute (NHLBI). The results appeared in the January 18, 1995 issue of The Journal of the American Medical Association.

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