Association of hormonal dysregulation with metabolic syndrome in older women: data from the InCHIANTI study

1 Clinical Research Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland; 2 Tuscany Regional Health Agency, Florence; 3 Department of Internal Medicine and Biomedical Sciences, Section of Geriatrics, School of Endocrinology, University of Parma; 4 Geriatric Rehabilitation Unit, Azienda Sanitaria di Firenze, Florence, Italy; 5 Department of Medicine, Division of Endocrinology, Johns Hopkins University School of Medicine, Bayview Medical Center, Baltimore, Maryland; 6 Department of Geriatric Medicine and Metabolic Diseases II, University of Naples, Naples; 7 Department of Clinical and Experimental Medicine, Section of Internal Medicine, Gerontology and Geriatrics, University of Ferrara, Ferrara, Italy; and 8 Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland Submitted 12 July 2006 ; accepted in final form 30 August 2006 Metabolic syndrome (MetS) is a strong risk factor for type 2 diabetes and cardiovascular disease. Conditions associated with hyperandrogenism are often associated with glucose intolerance and other features of MetS in young women. As the prevalence of MetS increases with age and is probably multifactorial, it is reasonable to hypothesize that age-related changes in androgens and other hormones might contribute to the development of MetS in older persons. However, this hypothesis has never been tested in older women. We hypothesized that high levels of testosterone, dehydroepiandrosterone sulfate (DHEA-S), and cortisol and low levels of sex hormone-binding globulin (SHBG) and IGF-I would be associated with MetS in a representative cohort of older Italian women independently of confounders (including inflammatory markers). After exclusion of participants on hormone replacement therapy and those with a history of bilateral oophorectomy, 512 women ( 65 yr) had complete data on testosterone, cortisol, DHEA-S, SHBG, fasting insulin, total and free IGF-I, IL-6, and C-reactive protein (CRP). MetS was defined according to ATP-III criteria. Insulin resistance was calculated according to HOMA. MetS was found in 145 women (28.3%). Participants with vs. those without MetS had higher age-adjusted levels of bioavailable testosterone ( P < 0.001), IL-6 ( P < 0.001), CRP ( P < 0.001), and HOMA ( P < 0.001) and lower levels of SHBG ( P < 0.001). After adjustment for potential confounders, participants with decreased SHBG had an increased risk of