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The Study of Women's Health Across the Nation

Imke Janssen, PhD; Lynda H. Powell, PhD; Sybil Crawford, PhD; Bill Lasley, PhD; Kim Sutton-Tyrrell, DrPH

Arch Intern Med. 2008;168(14):1568-1575.

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.

Author Affiliations: Departments of Preventive Medicine (Drs Janssen and Powell) and Medicine, Behavioral Sciences, and Pharmacology (Dr Powell), Rush University Medical Center, Chicago, Illinois; Biostatistics Research Group, Division of Preventive Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester (Dr Crawford); Department of Population Health and Reproduction, University of California at Davis (Dr Lasley); and Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania (Dr Sutton-Tyrrell).

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