Estrogen With Or Without Progestin Reduces Dangerous Form Of Cholesterol, PEPI Investigators Report

March 17, 1998

WINSTON-SALEM, NC -- New findings from a large-scale study of estrogen replacement therapy, coordinated at the Wake Forest University Baptist Medical Center, help show why the treatment may help reduce a woman's risk of a heart attack.

Results from the Postmenopausal Estrogen/Progestin Intervention (PEPI) study show that estrogen replacement therapy, with or without progestin, "produces consistent and sustained reductions in plasma lipoprotein (a) concentrations," said Mark A. Espeland, Ph.D., professor and head of the Section on Biostatistics at Wake Forest University School of Medicine.

High levels of lipoprotein (a) have been linked to increased risk of heart attack and stroke, he said.

Espeland, director of PEPI's national coordinating center, and his colleagues report the PEPI findings in the March 17 issue of Circulation, a journal of the American Heart Association.

PEPI was a three-year study of 875 healthy postmenopausal women at seven medical centers. The women were randomly assigned to oral estrogen or one of three estrogen-progestin combinations, or to an inert placebo. PEPI began in 1987, and was the first large federally sponsored clinical trial devoted entirely to women. Support came from five of the National Institutes of Health, but primarily from the National Heart, Lung and Blood Institute.

All four forms of hormone replacement therapy in the PEPI study produced similar reductions of lipoprotein (a) concentration, Espeland said. Assignment to one or another of the treatments resulted in a 17 to 23 percent average drop when compared with the placebo group, which did not get hormone therapy.

The declines remained across the three years of the study.

Lipoprotein (a) is a biochemical relative of low-density lipoprotein -- LDL, the so-called bad cholesterol. It increases the risk of heart attacks and strokes by transporting cholesterol to the walls of blood vessel, where it collects to begin narrowing the blood vessels. Lipoprotein (a) also helps stimulate development of blood clots, which can block blood vessels that already are narrowed by atherosclerosis.

The three progestin treatment arms were added to minimize the risk of endometrial cancer, one risk of estrogen therapy. One group got a small daily dose of estrogen plus Provera, a second got a larger dose of estrogen plus Provera for 12 days each month, and a third group got estrogen plus a dose of micronized progesterone -- a new form of progestin.

At one year, the group receiving estrogen therapy alone had a 25.8 percent drop in lipoprotein (a) levels compared with placebo; after three years, the drop was 20.4 percent. Women assigned to take a small daily dose of estrogen plus Provera experienced a 27 percent drop in lipoprotein (a) at 12 months, a decline that held steady at 36 months.

Women taking the estrogen plus Provera for 12 days each month had a 23 percent drop in lipoprotein (a) at both 12 months and 36 months. Those who took estrogen plus micronized progestin had a 16 percent drop after 12 months, which increased to 26 percent after three years.

"The study confirms that hormone therapy has a broad-scale and sustained impact on cholesterol metabolism," Espeland said. "And we found that the results were the same regardless of a woman's age, weight or prior hormone use."

Earlier analyses from PEPI showed:

Estrogen replacement therapy improved women's cholesterol profiles, primarily by increasing levels of HDL cholesterol, the so-called good cholesterol. The levels of LDL, the so-called bad cholesterol, dropped sharply in all treatment groups.

Hormone replacement therapy decreased osteoporosis. Bone mineral density in the spine increased from 3.5 to 5 percent in women in one of the treatment arms, while women in the placebo control lost 1.8 percent in bone mineral density. Osteoporosis is the direct effect of the loss of bone density.

Hormone replacement therapy led to a 1.7 percent increase in bone mineral density in the hip, compared to a loss of 1.7 percent in the control group.

And in results reported earlier, PEPI progestins were effective in preventing the precancerous changes in the endometrium of women who still have a uterus -- changes that estrogen taken alone can produce.
Contact: Robert Conn, Jim Steele or Mark Wright at 336-716-4587

Wake Forest Baptist Medical Center

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