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This version published online on January 4, 2006
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-1326
A more recent version of this article appeared on March 1, 2006
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Submitted on June 15, 2005
Accepted on December 27, 2005

Low SHBG, Total Testosterone, and Symptomatic Androgen Deficiency are Associated with Development of the Metabolic Syndrome in Non-Obese Men

Varant Kupelian PhD*, Stephanie T. Page MD, Andre B. Araujo PhD, Thomas G. Travison PhD, William J. Bremner MD, and John B. McKinlay PhD

New England Research Institutes, Watertown, MA; University of Washington, Seattle, WA

* To whom correspondence should be addressed. E-mail: vkupelian{at}neriscience.com.

Background: 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 hormones or clinical androgen deficiency (AD) predict the development of MetS.

Methods: Data were obtained from the Massachusetts Male Aging Study (MMAS), a population-based prospective cohort of 1709 men observed at 3 timepoints (T1: 1987-89; T2: 1995-97; T3: 2002-04). MetS was defined by 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 hormones or clinical AD was assessed using relative risks (RR) and 95% confidence intervals (95% CI) estimated using Poisson regression models.

Results: Analysis was conducted among 950 men without MetS at T1. Lower levels of total testosterone and SHBG were predictive of MetS, particularly among men with BMI<25 with adjusted RRs for a decrease in one SD of 1.41 (95CI:1.06-1.87) and 1.65 (95%CI:1.12-2.42). Results were similar for the AD and MetS association with RRs of 2.51 (95%CI:1.12-5.65) among men with BMI<25 compared with a RR=1.22 (95%CI:0.66-2.24) in men with BMI≥25.

Conclusions: Low serum SHBG, low total testosterone, and clinical AD are associated with increased risk of developing MetS over time, particularly in non-overweight middle-aged men (BMI<25). Together, these results suggest that low SHBG and/or AD may provide an early warning sign for cardiovascular risk and an opportunity for early intervention in non-obese men.
Key words: metabolic syndrome • testosterone • sex-hormone binding globulin • androgen deficiency • epidemiology




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