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Endogenous Sex Hormones and Metabolic Syndrome in Aging Men

Julius Center for Health Sciences and Primary Care (M.M., D.E.G., Y.T.v.d.S.), University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands; International Health Foundation (I.T.), Utrecht, The Netherlands; and Department of Internal Medicine (S.W.J.L.), Erasmus University Medical Center Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: Yvonne T. van der Schouw, Ph.D., Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, PO Box 85500, Room D 01.335, 3508 GA Utrecht, The Netherlands. E-mail: y.t.vanderschouw{at}jc.azu.nl, Internet: www.juliuscenter.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), 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 definition, and insulin sensitivity was calculated by use of the quantitative insulin sensitivity check index.

Results: Multiple logistic regression analyses showed an inverse relationship according to 1 SD increase for circulating TT [odds ratio (OR) = 0.43; 95% confidence interval (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; ß-coefficients (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 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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