HRT fails again in two secondary prevention studies: findings show worsening of preexisting heart disease or no cardiac benefit. (Older Postmenopausal Women).

CHICAGO -- The results of two more studies of estrogen therapy in postmenopausal women with coronary artery disease continued the losing streak of this once promising approach.

Both studies involved relatively small numbers of women, and both tested whether estrogen replacement could slow the progression of preexisting coronaryartery stenotic lesions as measured by quantitative, digital angiography The results failed to show any benefit of estrogen over placebo, and in the larger of the two studies there actually was more disease progression and worse clinical outcome among the women treated with estrogen, researchers reported at the annual scientific sessions of the American Heart Association.

The findings from the smaller trial also stood in sharp contrast with the results from a parallel study published in 2001. In the earlier report, estrogen treatment led to significant slowing of atherosclerotic progression, compared with placebo in postmenopausal women without coronary artery disease. Because the current study was limited to women with documented coronary disease, they tended to be older, on average about 18 years beyond menopause, said Dr. Howard N. Hodis, director of the athero-sclerosis research unit at the University of Southern California in Los Angeles.

"Perhaps estrogen is more effective when it is used earlier, when a woman's vascular walls are still responsive to estrogen," he said.

His study involved 226 women who had at least one coronary artery lesion that was at least 30% stenotic; the average age of the women was 63.4 years. They were randomized to treatment with 1 mg/day of micronized, 17-[beta] estradiol or placebo. Women with an intact uterus who received estrogen also received 5 mg/day of medroxyprogesterone acetate for 12 days each month.

After an average follow-up of 3 years, angiography showed that the extent of atherosclerotic progression was roughly comparable for all three treatment groups.

The second, larger study involved 423 ...