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Submitted on June 17, 2004
Accepted on January 26, 2005
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands;; International Health Foundation, Utrecht, The Netherlands; Department of Internal Medicine, Erasmus University Medical Center Rotterdam, The Netherlands
* To whom correspondence should be addressed. E-mail: y.t.vanderschouw{at}jc.azu.nl.
Background: Sex hormone levels in men change during aging. These changes may be associated with insulin sensitivity and the metabolic syndrome.
Methods: We studied the association between endogenous sex hormones and characteristics of the metabolic syndrome in 400 independently living men between 40 and 80 yr of age in a cross-sectional study. Serum concentrations of lipids, glucose, insulin, total testosterone (TT), sex hormone-binding globulin (SHBG), estradiol (E2), and dehydroepiandrosterone-sulfate (DHEA-S) were measured. Bioavailable testosterone (BT) was calculated using TT and SHBG. Body height, weight, waist-hip circumference, blood pressure, and physical activity were assessed. Smoking and alcohol consumption was estimated from self-report. The metabolic syndrome was defined according to the National Cholesterol Education Program (NCEP) definition and insulin sensitivity was calculated by use of the quantitative insulin sensitivity check index (QUICKI).
Results: Multiple logistic regression analyses showed an inverse relationship according to 1 SD increase for circulating TT (OR=0.43, 95%CI 0.32-0.59), BT (OR=0.62, 95%CI 0.46-0.83), SHBG (OR=0.46, 95%CI 0.33-0.64), and DHEA-S (OR=0.76, 95%CI 0.56-1.02) with the metabolic syndrome. Each SD increase in E2 levels was not significantly associated with the metabolic syndrome (OR=1.16; 95% CI, 0.92-1.45). Linear regression analyses showed that higher TT, BT and SHBG levels were related to higher insulin sensitivity; 
(95%CI) were 0.011 (0.008-0.015), 0.005 (0.001-0.009), and 0.013 (0.010-0.017), respectively, whereas no effects were found for DHEA-S and E2. Estimates were adjusted for age, smoking, alcohol consumption and physical activity score. Further adjustment for insulin-levels and body composition measurements attenuated the estimates and the associations were similar in the group free of cardiovascular disease (CVD) and diabetes.
Conclusions: Higher testosterone and SHBG levels in aging males are independently associated with a higher insulin sensitivity and a reduced risk of the metabolic syndrome, independent of insulin-levels and body composition measurements, suggesting that these hormones may protect against the development of metabolic syndrome.
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