ORIGINAL RESEARCH—ENDOCRINOLOGY Metabolic Syndrome, Testosterone, and Cardiovascular Mortality in Men Jou-Wei Lin, MD, MPH, PhD,* † Jen-Kuang Lee, MD, †‡§ Cho-Kai Wu, MD,* † James L. Caffrey, PhD, ¶ Man-Huei Chang, MPH,** Juey-Jen Hwang, MD, PhD, † Nicole Dowling, PhD,** and Yu-Sheng Lin, ScD †† *Cardiovascular Center and Health Management Center, National Taiwan University Hospital Yun-Lin Branch, Dou-Liou, Taiwan; † Department of Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan; ‡ Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan; § Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan; ¶ Department of Integrative Physiology and Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, TX, USA; **Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, GA, USA; †† Department of Environmental and Occupational Health, University of North Texas Health Science Center, Fort Worth, TX, USA DOI: 10.1111/j.1743-6109.2011.02343.x ABSTRACT Introduction. Interactions among testosterone, metabolic syndrome (MetS), and mortality risk in men remain to be elucidated. Aim. To examine relationships among testosterone, MetS, and cardiovascular mortality risk in U.S. men, middle- aged and older. Methods. The analysis included the men aged 40 years and above in Phase 1 (1988–1991) of the Third National Health and Nutrition Examination Survey (NHANES III). Serum testosterone and sex hormone binding globulin were measured, and free testosterone and bioavailable testosterone were calculated. MetS was determined according to the Adult Treatment Panel III (ATP-III) criteria. Main Outcome Measures. Cardiovascular and other causes of mortality were obtained from the NHANES III- linked follow-up file through December 31, 2006. Multivariate Cox regression models were applied to assess associations of interest. Results. Of 596 men included in the analysis, 187 men were found to have MetS. During a median follow-up of 15.6 years, 97 men died of cardiovascular causes (cardiovascular mortality rate: 9.84 and 5.77 per 1,000 person-years for those with and without MetS, respectively). Higher calculated bioavailable testosterone (CBT) was associated with a lower odds of MetS (odds ratio: 0.80 for each ng/mL, 95% confidence interval [CI]: 0.76–0.84, P < 0.001) and lower risk of cardiovascular mortality (hazard ratios [HRs]: 0.72 for each log ng/mL, 95% CI: 0.54–0.96, P = 0.03) in subjects with MetS. The influence of CBT was not observed in those without MetS (HR: 0.84 for each log ng/mL, 95% CI: 0.68–1.04, P = 0.10). Conclusions. The combination of lower bioavailable testosterone and ATP-III-defined MetS is associated with an increased cardiovascular mortality in the men aged 40 years and above. Lin J-W, Lee J-K, Wu C-K, Caffrey JL, Chang MH, Hwang J-J, Dowling N, and Lin Y-S. Metabolic syndrome, testosterone, and cardiovascular mortality in men. J Sex Med 2011;8:2350–2360. Key Words. Testosterone Deficiency and Cardiovascular Mortality; Metabolic Cardiovascular Syndrome; Mortality; Nutrition Surveys 2350 J Sex Med 2011;8:2350–2360 © 2011 International Society for Sexual Medicine