Atherosclerosis Progression Differs According to Timing of Estradiol Therapy After Menopause

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With higher plasma estradiol levels, atherosclerosis progression is decreased among early postmenopausal women and is increased among late postmenopausal women.
With higher plasma estradiol levels, atherosclerosis progression is decreased among early postmenopausal women and is increased among late postmenopausal women.

Higher levels of plasma estradiol were associated with reduced progression of atherosclerosis in early postmenopausal women, according to findings published in Journal of Clinical Endocrinology & Metabolism. Conversely, high estradiol levels were associated with increased atherosclerosis progression among late postmenopausal women.

Results from the Early versus Late Intervention Trial with Estradiol study have shown that hormone therapy initiated within 6 years of menopause can significantly reduce the progression of subclinical atherosclerosis. When initiated 10 or more years after menopause, therapy with estradiol had no effect on the progression of atherosclerosis. In a secondary analysis of data from the Early versus Late Intervention Trial with Estradiol study, investigators evaluated differential associations between plasma estradiol levels and the progression of subclinical atherosclerosis based on the timing of hormone therapy initiation.

The double-blinded, placebo-controlled trial included 596 postmenopausal women who were randomly assigned to hormone therapy (n = 297) or placebo. Women were also stratified within 6 years of menopause (early postmenopause) and ≥10 years after menopause (late postmenopause). Higher levels of estradiol were inversely associated with carotid artery intima-media thickness progression in the early postmenopausal cohort (P =.041) but positively associated with carotid artery intima-media thickness progression in the late postmenopausal group (P =.006). In the lowest vs highest quartiles of estradiol levels in early postmenopausal women, carotid artery intima-media thickness progression rates were 8.5 µm/year and 7.2 µm/year. For the late postmenopausal cohort, progression rates were 9.8 µm/year and 11.7 µm/year for the lowest and highest estradiol quartiles, respectively.

“Our findings demonstrated that the effect of [hormone therapy]-induced estradiol level on atherosclerosis progression differs according to the timing of [hormone therapy] initiation relative to time since menopause,” concluded the authors. “One possible mechanism may be related to the expression and/or signaling of estrogen receptors in healthy versus atherosclerosis-related tissues as a function of aging and/or time since menopause.”

Reference

Sriprasert I, Hodis HN, Karim R, et al. Differential effect of plasma estradiol on subclinical atherosclerosis progression in early versus late postmenopause [published online September 28, 2018]. J Clin Endocrinol Metab. doi:10.1210/jc.2018-01600

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