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The Emergence of the Metabolic Syndrome with Menopause

Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, Washington 98195-6426

Address all correspondence and requests for reprints to: Molly C. Carr, M.D., Division of Metabolism, Endocrinology, and Nutrition, Box 356426, University of Washington, Seattle, Washington 98195-6426. E-mail: carr{at}u.washington.edu.

Women with the metabolic syndrome (central obesity, insulin resistance, and dyslipidemia) are known to be at especially high risk for cardiovascular disease (CVD). The prevalence of the metabolic syndrome increases with menopause and may partially explain the apparent acceleration in CVD after menopause. The transition from pre- to postmenopause is associated with the emergence of many features of the metabolic syndrome, including 1) increased central (intraabdominal) body fat; 2) a shift toward a more atherogenic lipid profile, with increased low density lipoprotein and triglycerides levels, reduced high density lipoprotein, and small, dense low density lipoprotein particles; 3) and increased glucose and insulin levels. The emergence of these risk factors may be a direct result of ovarian failure or, alternatively, an indirect result of the metabolic consequences of central fat redistribution with estrogen deficiency. It is unclear whether the transition to menopause increases CVD risk in all women or only those who develop features of the metabolic syndrome. This article will review the features of the metabolic syndrome that emerge with estrogen deficiency. A better understanding of these metabolic changes with menopause will aid in the recognition and treatment of women at risk for future CVD, leading to appropriate interventions.

This work was supported in part by a grant from the Bristol-Myers Squibb Foundation and NIH Grant K23 (to M.C.C.).

Abbreviations: apo B, Apolipoprotein B; BMI, body mass index; CETP, cholesteryl ester transfer protein; CRP, C-reactive protein; CT, computed tomography; CVD, cardiovascular disease; E₂, estradiol; FFA, free fatty acid; HDL, high density lipoprotein; HL, hepatic lipase; HRT, hormone replacement therapy; LDL, low density lipoprotein; Lp(a), lipoprotein(a); PAI-1, plasminogen activator inhibitor-1; TG, triglycerides; tPA, tissue plasminogen activator; VLDL, very low density lipoprotein.

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