Menopause and the metabolic syndrome: the Study of Women's Health Across the Nation

Abstract

Background: Cross-sectional studies suggest that prevalence of the metabolic syndrome (MetS) increases from premenopause to postmenopause in women, independent of age. Little is known about why. We hypothesized that the incidence of the MetS increases with progression through menopause and that this increase is explained by the progressive androgenicity of the hormonal milieu.

Methods: This longitudinal, 9-year study of 949 participants in the Study of Women's Health Across the Nation investigates the natural history of the menopausal transition. Participants of 5 ethnicities at 7 geographic sites were recruited when they were premenopausal or early perimenopausal and were eligible for this study if they (1) reached menopause during the study; (2) had never taken hormone therapy, and (3) did not have diabetes mellitus or the MetS at baseline. The primary outcome was the presence of MetS using National Cholesterol Education Program Adult Treatment Panel III criteria. Secondary outcomes were the components of the MetS.

Results: By the final menstrual period, 13.7% of the women had new-onset MetS. Longitudinal analyses, centered at the final menstrual period, were adjusted for age at menopause, ethnicity, study site, marital status, education, body mass index, smoking, and aging. Odds of developing the MetS per year in perimenopause were 1.45 (95% confidence interval, 1.35-1.56); after menopause, 1.24 (95% confidence interval, 1.18-1.30). These odds were significantly different (P < .001). An increase in bioavailable testosterone or a decrease in sex hormone-binding globulin levels increased the odds.

Conclusions: As testosterone progressively dominates the hormonal milieu during the menopausal transition, the prevalence of MetS increases, independent of aging and other important covariates. This may be a pathway by which cardiovascular disease increases during menopause.

Figure 1

Odds of developing the metabolic syndrome (MetS) by aging after adjustment for standard risk factors, including age at final menstrual period (FMP), ethnicity, study site, education, marital status, smoking, baseline body mass index (BMI), and change in BMI from baseline.

Figure 2

Changes in components of the metabolic syndrome by aging after adjustment for standard risk factors, including baseline outcome, age at final menstrual period (FMP), ethnicity, study site, education, marital status, smoking, baseline body mass index (BMI), and change (Δ) in BMI from baseline. Components include waist circumference (A), high-density lipoprotein cholesterol (HDL-C) levels (B), glucose levels (C), triglyceride levels (D), and systolic blood pressure (E). To convert glucose to millimoles per liter, multiply by 0.0555; HDL-C to millimoles per liter, multiply by 0.0259; and triglyceride to millimoles per liter, multiply by 0.0113.