Estrogen therapy within 6 years after menopause curbs atherosclerosis

Oral estradiol therapy was linked with less progression of subclinical atherosclerosis, compared with a placebo, when treatment began within 6 years after the start of menopause, but not when initiated after 10 years or more, according to data published in the New England Journal of Medicine.

“After dozens of observational studies consistently showed inverse association between postmenopausal hormone therapy and the risk of coronary heart disease and death from any cause, it was difficult to understand the null or adverse effects of the therapy on coronary heart disease that were reported from randomized, controlled trials,” Howard N. Hodis, MD, of the atherosclerosis research unit at the Keck School of Medicine, University of Southern California, in Los Angeles, and colleagues wrote. “One explanation is that in observational studies, women were younger (approximately 50 years of age) and closer to menopause (typically within 2 years) when they initiated hormone therapy than were the women included in randomized trials (mean age in the 60s, typically >10 years past menopause).”

To test their hypothesis that hormone therapy would reduce subclinical atherosclerosis progression when started within 6 years after menopause, but not when initiated after a decade, the researchers recruited 643 postmenopausal women. The participants were stratified by time since menopause, with 271 assigned to the early-postmenopause stratum, defined as less than 6 years, and 371 in the late-postmenopause stratum, defined as 10 years or more. Members of each stratum were then randomly assigned to either receive 1 mg per day of 17β-estradiol, plus 45 mg progesterone vaginal gel for women with a uterus, for 10 days of each 30-day cycle, or a placebo along with a corresponding placebo vaginal gel for women with a uterus.

The primary outcome was the rate of change in carotid-artery intima-media thickness (CIMT), measured every 6 months. Secondary outcomes were an assessment of coronary atherosclerosis by cardiac computed tomography (CT), performed once participants completed their treatment regimen.

According to the researchers, after 5 years, the estradiol treatment, with or without the progesterone, produced different outcomes regarding CIMT progression, based on early- or late-postmenopause strata (P = .007 for the interaction). In the early stratum, the mean CIMT increased by 0.0078 mm per year in the placebo group, compared with 0.0044 mm per year in the estradiol group (P = .008). In the late group, the rate of CIMT progression was 0.0088 mm in the placebo group, and 0.01 mm among those who received estradiol (P = .29).

“In conclusion, we found that the effects of estradiol (with or without progesterone) on the progression of atherosclerosis, assessed as CIMT, differed according to the time of initiation of therapy, with benefit noted when it was initiated in women who were less than 6 years past menopause but not when it was initiated in women who were 10 or more years past menopause,” Hodis and colleagues wrote. “However, we did not find an effect of timing of estradiol treatment relative to menopause with regard to CT measures of coronary atherosclerosis.” – by Jason Laday

Disclosure: See the full study for researchers’ relevant financial disclosures.