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New England Research Institutes (V.K., A.B.A., T.G.T., J.B.M.), Watertown, Massachusetts 02472; and University of Washington (S.T.P., W.J.B.), Seattle, Washington 98195
Address all correspondence and requests for reprints to: Dr. John B. McKinlay, New England Research Institutes, 9 Galen Street, Watertown, Massachusetts 02472. E-mail: jmckinlay{at}neriscience.com.
Background: The metabolic syndrome (MetS), characterized by central obesity, lipid and insulin dysregulation, and hypertension, is a precursor state for cardiovascular disease. The purpose of this analysis was to determine whether low serum sex hormone levels or clinical androgen deficiency (AD) predict the development of MetS.
Methods: Data were obtained from the Massachusetts Male Aging Study, a population-based prospective cohort of 1709 men observed at three time points (T1, 19871989; T2, 19951997; T3, 20022004). MetS was defined using a modification of the ATP III guidelines. Clinical AD was defined using a combination of testosterone levels and clinical signs and symptoms. The association between MetS and sex hormone levels or clinical AD was assessed using relative risks (RR), and 95% confidence intervals (95% CI) were estimated using Poisson regression models.
Results: Analysis was conducted in 950 men without MetS at T1. Lower levels of total testosterone and SHBG were predictive of MetS, particularly among men with a body mass index (BMI) below 25 kg/m2 with adjusted RRs for a decrease in 1 SD of 1.41 (95% CI, 1.061.87) and 1.65 (95% CI, 1.122.42). Results were similar for the AD and MetS association, with RRs of 2.51 (95% CI, 1.125.65) among men with a BMI less than 25 compared with an RR of 1.22 (95% CI, 0.662.24) in men with a BMI of 25 or greater.
Conclusions: Low serum SHBG, low total testosterone, and clinical AD are associated with increased risk of developing MetS over time, particularly in nonoverweight, middle-aged men (BMI, <25). Together, these results suggest that low SHBG and/or AD may provide early warning signs for cardiovascular risk and an opportunity for early intervention in nonobese men.
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