Self-reported menopausal symptoms, coronary artery calcification, and carotid intima-media thickness in recently menopausal women screened for the Kronos early estrogen prevention study (KEEPS)

In recently menopausal women, self-reported climacteric symptoms do not correlate with subclinical atherosclerosis.


Erin Foran Wolff, M.D., Yunxiao He, Ph.D., Dennis M. Black, Ph.D., Eliot A. Brinton, M.D., F.A.H.A., F.N.L.A., Mathew J. Budoff, M.D., Marcelle I. Cedars, M.D., Howard N. Hodis, M.D., Rogerio A. Lobo, JoAnn E. Manson, M.D., Dr.Ph., George R. Merriam, M.D., Virginia M. Miller, Ph.D., Fredrick Naftolin, M.D., Ph.D., Lubna Pal, M.B., B.S., M.S., Nanette Santoro, M.D., Heping Zhang, Ph.D., S. Mitchell Harman, M.D., Ph.D., Hugh S. Taylor, M.D.

Volume 99, Issue 5, Pages 1385-1391, April 2013



To determine whether self-reported menopausal symptoms are associated with measures of subclinical atherosclerosis.


Multicenter, randomized controlled trial.


Recently menopausal women (n=868) screened for the Kronos Early Estrogen Prevention Study (KEEPS).


Cross-sectional analysis.



Main Outcome Measures:

Baseline menopausal symptoms (hot flashes, dyspareunia, vaginal dryness, night sweats, palpitations, mood swings, depression, insomnia, irritability), serum estradiol (E2) levels and measures of atherosclerosis were assessed. Atherosclerosis was quantified using Coronary Artery Calcium (CAC) Agatston scores (n=771) and Carotid Intima-Media Thickness (CIMT). Logistic regression model of menopausal symptoms and E2 was used to predict CAC. Linear regression model of menopausal symptoms and E2 was used to predict CIMT. Correlation between length of time in menopause with menopausal symptoms, estradiol (E2), CAC, and CIMT were assessed.


In early menopausal women screened for KEEPS, neither E2 nor climacteric symptoms predicted the extent of subclinical atherosclerosis. Palpitations (p=0.09) and depression (p=0.07) approached significance as predictors of CAC. Other symptoms of insomnia, irritability, dyspareunia, hot flashes, mood swings, night sweats, and vaginal dryness were not associated with CAC. Women with significantly elevated CAC scores were excluded from further participation in KEEPS; in women meeting inclusion criteria, neither baseline menopausal symptoms nor E2 predicted CIMT. Years since menopause onset correlated with CIMT, dyspareunia, vaginal dryness and E2.


Self-reported symptoms in recently menopausal women are not strong predictors of subclinical atherosclerosis. Continued follow-up of this population will be performed to determine if baseline or persistent symptoms in the early menopause are associated with progression of cardiovascular disease.

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