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Early menopause predicts future coronary heart disease and stroke: the Multi-Ethnic Study of Atherosclerosis

Wellons, Melissa MD, NCMP1; Ouyang, Pamela MBBS2; Schreiner, Pamela J. PhD3; Herrington, David M. MD4; Vaidya, Dhananjay PhD2

Menopause: The Journal of The North American Menopause Society: October 2012 - Volume 19 - Issue 10 - p 1081–1087
doi: 10.1097/gme.0b013e3182517bd0
Original Articles

Objective Cardiovascular disease is the number one killer of women. Identifying women at risk of cardiovascular disease has tremendous public health importance. Early menopause is associated with increased cardiovascular disease events in some predominantly white populations, but not consistently. Our objective was to determine if self-reported early menopause (menopause at an age <46 y) identifies women as at risk for future coronary heart disease or stroke.

Methods The study population came from the Multi-Ethnic Study of Atherosclerosis, a longitudinal, ethnically diverse cohort study of US men and women aged 45 to 84 years enrolled in 2000-2002 and followed up until 2008. The association between a personal history of early menopause (either natural menopause or surgical removal of ovaries at an age <46 y) and future coronary heart disease and stroke was assessed in 2,509 women (ages 45-84 y; 987 white, 331 Chinese, 641 black, and 550 Hispanic) from the Multi-ethnic Study Atherosclerosis who were free of cardiovascular disease at baseline.

Results Of 2,509 women, 693 (28%) reported either surgical or natural early menopause. In survival curves, women with early menopause had worse coronary heart disease and stroke-free survival (log rank P = 0.008 and P = 0.0158). In models adjusted for age, race/ethnicity, Multi-ethnic Study Atherosclerosis site, and traditional cardiovascular disease risk factors, this risk for coronary heart disease and stroke remained (hazard ratio, 2.08; 95% CI, 1.17-3.70; and hazard ratio, 2.19; 95% CI, 1.11-4.32, respectively).

Conclusions Early menopause is positively associated with coronary heart disease and stroke in a multiethnic cohort, independent of traditional cardiovascular disease risk factors.

Supplemental digital content is available in the text.

From the 1Departments of Medicine & Obstetrics and Gynecology, University of Alabama, Birmingham, AL; 2Department of Medicine, Johns Hopkins Medical Institute, Baltimore, MD; 3Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN; and 4Department of Internal Medicine, Wake Forest University, Winston-Salem, NC.

Received December 23, 2011; revised and accepted February 22, 2012.

Funding/support: This research was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI). Drs. Ouyang, Schreiner, Herrington, and Vaidya receive grant support from the NIH. Dr. Wellons is supported by a career development award (K23-HL-87114) from the NIH/NHLBI. Dr. Wellons and Ouyang receive consulting fees from the Society for Women’s Health Research and the Women’s Health Initiative (NIH), respectively.

Financial disclosures/conflicts of interest: None reported.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (

Address correspondence to: Melissa Wellons,MD,MHS, NCMP, Division of Reproductive Endocrinology and Infertility, University of Alabama at Birmingham, 1700 6th Avenue South, WIC Room 10390, Birmingham, AL 35249-7333. E-mail:

©2012The North American Menopause Society