Women who started hormone therapy early after menopause saw a significant slowing of atherosclerotic progression, whereas those who waited more than a decade saw no impact on vascular health, the ELITE trial showed, supporting the "timing hypothesis."
Carotid intima-media thickness (CIMT) was significantly less in women randomized to estradiol within 6 years of menopause in the trial compared with women put on placebo in the same time frame (P=0.008), Howard N. Hodis, MD, of the University of Southern California in Los Angeles, and colleagues found.
CIMT came out no different between estradiol and placebo among the group randomized to treatment 10 or more years after entering menopause (P=0.29; P=0.007 for interaction of treatment by timing), the researchers reported at the American Heart Association meeting in Chicago.Coronary artery calcium scores and total stenosis scores showed no significant differences between groups.
"ELITE supports the concept that hormone therapy reduces early atherosclerosis but has no effect on established lesions," the group concluded."ELITE results are consistent with the majority of the literature that shows that women who are young and/or in close proximity to menopause when starting hormone therapy have reduced coronary heart disease and overall mortality," Hodis said.
The Women's Health Initiative, aiming for cardiovascular prevention with menopausal hormone therapy, had raised major concerns about stroke and myocardial infarction (MI) in its somewhat older, later menopause population.The KEEPS study subsequently showed that for a younger (ages 42 to 58) women within 3 years of onset of menopause at baseline, there was no impact on the surrogate endpoints of CIMT or coronary calcium scores.ELITE was designed to directly test the hypothesis that timing makes all the difference in safety of hormone therapy after menopause.
"I think it's important that clinicians not interpret this as you should start estrogen to try to prevent heart disease, but that the younger, newly menopausal woman who has menopausal symptoms should not be denied hormone therapy because of concerns about heart disease risk, as was seen in older women," JoAnn E. Manson, MD, of Brigham and Women's Hospital in Boston, told MedPage Today."There are other factors to take into consideration [such as risk of thrombosis]," she explained. "But because a newly menopausal woman is generally at low absolute risk of heart attack, stroke, thrombosis, all of those outcomes, it tends to be a favorable balance of benefit-to-risk." While suggestive that early hormone therapy wouldn't have an impact on later heart disease risk, "this trial wasn't large enough to look at clinical events," Manson cautioned.
ELITE included 643 healthy postmenopausal women without pre-existing cardiovascular disease or diabetes. They were randomized to double-blind treatment with placebo or oral micronized 17beta-estradiol (1 mg daily) with vaginal micronized progesterone gel for 12 days every month given to women with a uterus. Randomization was stratified by time since menopause. Medication compliance was 98% across groups. In the early randomization group, the only heart disease event was one myocardial infarction in the placebo group. In those initiating 10 or more years after menopause (an older group), there were two patients with events in the placebo group and three in the hormone group.
The researchers disclosed no relevant relationships with industry.
Primary source: American Heart Association
Source reference: Hodis HN, et al "Testing the menopausal hormone therapy timing hypothesis: The early versus late intervention trial with estradiol" AHA 2014; Abstract 13283.