Lipids, Menopause, and Early Atherosclerosis in Study of Women’s Health across the Nation Heart Women

Medscape Today

Genevieve A. Woodard, PhD; Maria M. Brooks, PhD; Emma Barinas-Mitchell, PhD; Rachel H. Mackey, PhD; Karen A. Matthews, PhD; Kim Sutton-Tyrrell, DrPH

Posted: 04/22/2011; Menopause. 2010;18(4):376-384. © 2010 The North American Menopause Society

Abstract and Introduction


Objective: The risk of cardiovascular disease increases after menopause. Recent evidence suggests that it is possible for high-density lipoprotein (HDL) to become proatherogenic or dysfunctional in certain situations. Our objective was to evaluate whether the relationship of HDL cholesterol (HDL-C) to subclinical cardiovascular disease differed across the menopausal transition, which would provide insight for this increased risk.

Methods: Aortic calcification (AC), coronary artery calcification (CAC), carotid plaque, and intima media thickness (IMT) were measured in an ancillary study of the Study of Women’s Health Across the Nation. Women not using hormone therapy were stratified into premenopausal or early perimenopausal (Pre/EP, n = 316) and late perimenopausal or postmenopausal (LP/Post, n = 224).

Results: The inverse relationship of HDL-C to subclinical atherosclerosis measures among Pre/EP women was weaker or reversed among LP/Post women, adjusted for age, site, race, systolic blood pressure, glucose, body mass index, smoking, menopause status, and low-density lipoprotein cholesterol. Specifically, multivariable modeling demonstrated an inverse association between HDL-C level and AC and IMT among Pre/EP women; however, the protective effect of HDL-C for AC, left main CAC, carotid plaque, and IMT was not seen in LP/Post women. In a small subset (n = 53), LP/Post women had more total and small HDL particles, higher triglyceride levels, and more total low-density lipoprotein particles compared with Pre/EP women (P < 0.05).

Conclusions: These results suggest that the protective effect of HDL may be diminished as women transition in menopause. Future studies should examine whether this may be due to changes in HDL size, functionality, or related changes in other lipids or lipoproteins.


Cardiovascular disease (CVD) is the leading cause of mortality for women. As women age, they are increasingly exposed to high levels of major CVD risk factors, including a poor lipid profile and weight gain. In addition to adverse changes associated with chronological aging, women experience the biological changes of the menopausal transition. Decreasing estrogen levels during the transition have been linked to endothelial dysfunction and larger vessel diameters, markers of early adverse vascular changes.[1–5] Therefore, the decreased estrogen level after the menopausal transition leaves the vasculature vulnerable to CVD risk factors, such as lipids.

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Author: Leslie Carol Botha

Author, publisher, radio talk show host and internationally recognized expert on women's hormone cycles. Social/political activist on Gardasil the HPV vaccine for adolescent girls. Co-author of "Understanding Your Mood, Mind and Hormone Cycle." Honorary advisory board member for the Foundation for the Study of Cycles and member of the Society for Menstrual Cycle Research.

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