Postmenopausal women can significantly lower their risk of heart disease by taking hormone therapy, according to a highly anticipated study released by the American Heart Association.


The Postmenopausal Estrogen/Progestin Interventions, or PEPI, study is the first to monitor how various hormone regimens affect key cardiovascular risk factors. The results should help women and their doctors better determine the risks versus benefits of hormone replacement therapy, which has long been a complicated and widely debated issue.


The study, which followed 875 healthy women for three years, showed that those taking any one of four hormone regimens experienced an increase in high-density lipoprotein, or the so-called good cholesterol -- which reduced their risk of heart disease by 12 percent to 25 percent, depending on which regimen they followed.


All four treatments also caused a drop in low-density lipoproteins, the so-called bad cholesterol, compared to a placebo group. The hormone therapies also triggered a decrease in fibrinogen, a blood clotting factor that usually increases with age and is strongly associated with increassed incidence of stroke and heart attack. The hormone therapies had no effect on blood pressure.


The hormone regimes also did not appear to increase the risk of breast cancer, as some had suggested it might. However experts pointed out that the study did not last long enough to draw any definitive conclusions about this risk.


"The results of this landmark study provide the best available guide for postmenopausal women and their physicians as they seek safe hormonal regimens that will improve their heart disease risk factors," said Dr. Claude Lenfant, director of the National Heart, Lung and Blood Institute, which sponsored the study at seven research centers around the country.


Natural sex hormones apparently help protect women against heart disease before age 50. But after menopause, when the woman's body stops producing those sex hormones, the rate of heart disease in women climbs quickly -- and eventually equals the rate among men. As it is for men, heart disease is today the leading cause of death among American women.


Earlier studies of women who had experienced heart attacks and those who had not found that those taking hormones had as much as 50 percent lower risk.


The PEPI study was the first to measure the risk factors for heart disease in a large group of women from the time they started on hormone therapy.


"The PEPI results are a significant step forward in our understanding of hormonal therapy and its effects on HDL cholesterol, fibrinogen, and other factors which affect a woman's risk of heart disease," Lenfant said.


The women, ages 45 to 64, were randomly assigned to one of five groups using, aside from a placebo (the so-called "control" group) various combinations of three female sex hormones: daily estrogen alone; daily estrogen plus a daily synthetic progestin; daily estrogen plus a synthetic progestin taken 12 days a month; or daily estrogen combined with natural progesterone taken 12 days a month.


The results indicated that hormone therapy, when tailored to the individual, can indeed protect against heart disease without boosting the risk of cancer or other problems.


Previous studies had shown that estrogen, when taken alone, as was done in one of the PEPI groups, promotes the growth of a uterine tissue called the endometrium, and that that can lead to cancer. But when progestin is added to the regimen, the risk of endometrial cancer vanishes, so physicians typically prescribe progestin for part of the month.


But other studies had indicated that adding the progestin might eliminate part or all of the cardiovascular benefits of the estrogen, and might also increase the risk of breast cancer.


"No one knew how much progestin would diminish the protective effect," said Suzanne Oparil, president of the American Heart Association. "Some studies showed it would completely diminish the positive effect; others, not at all. [PEPI] shows the truth is somewhere in-between.


These results provide the strongest evidence to date that estrogen 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. Elizabeth Barrett-Connor, a University of California, San Diego, researcher who helped direct the PEPI trial.