CHICAGO– The “timing hypothesis” of estrogen’s ability to slow progression of atherosclerotic disease in relatively young postmenopausal women received a boost in results from a randomized trial with 643 participants.
The trial, designed about a decade ago to test the timing hypothesis, produced results showing that systemic treatment with 17beta-estradiol alone (plus topical progesterone) slowed progression of carotid intima-media thickness compared with placebo in women fewer than 6 years out from menopause, while the same treatment had no effect compared with placebo in women 10 or more years removed from menopause, Dr. Howard N. Hodis said at the American Heart Association Scientific Sessions.
Dr. Howard Hodis
The new results “support the timing hypothesis, whereby women who start hormone therapy within 6 years of menopause show a significant slowing of subclinical carotid-artery atherosclerosis, whereas women who are more than 10 years postmenopausal when starting hormone therapy show no difference from placebo,” said Dr. Hodis, professor of medicine and director of the atherosclerosis research unit at the University of Southern California, Los Angeles. The findings “are consistent with the majority of the literature” that previously reported evidence supporting a net benefit from hormone therapy when started in women who are young, and not long after they entered menopause, he added.
The ELITE (Early Versus Late Intervention Trial With Estradiol) investigators enrolled 643 postmenopausal women at the University of Southern California and stratified them into two subgroups: women fewer than 6 years removed from the onset of menopause, and women 10 or more years out from menopause. The average age of women in the younger group was about 55 years, and they averaged just under 4 years since menopause onset. Women in the older group averaged about 64 years and were an average of about 14 years removed from menopause onset.
Dr. Hodis and his associates randomized women within each of the two subgroups to daily treatment with 1 mg oral, micronized 17beta-estradiol or placebo. Women treated with estradiol who had an intact uterus also applied a micronized progesterone gel on 12 days out of every cycle, while those who received a daily placebo also applied a placebo gel. The study’s primary endpoint was the rate of change in the intima-media thickness (IMT) of the common carotid artery, measured once every 6 months. Compliance with the assigned regimens reached or exceeded 98% among all women in the study.
During 6 years of follow-up, the rate of increase in carotid IMT among the women who entered the study at least 10 years after the start of menopause tracked nearly identically between those on hormone therapy and those on placebo, with a difference between the two arms that was not statistically significant. In contrast, the women who began hormone therapy fewer than 6 years after menopause onset showed a statically significant difference in the rate of change in their carotid IMT, depending on their treatment assignment. After 6 years, the average increase in carotid IMT was roughly 40% less in women who received hormone therapy, compared with those randomized to placebo. The difference in IMT change between the older women and the younger women was also statistically significant, Dr. Hodis reported.
Dr. Hodis had no disclosures.
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