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(Circulation. 2007;116:2694-2701.)
© 2007 American Heart Association, Inc.

Epidemiology

Endogenous Testosterone and Mortality Due to All Causes, Cardiovascular Disease, and Cancer in Men

European Prospective Investigation Into Cancer in Norfolk (EPIC-Norfolk) Prospective Population Study

Kay-Tee Khaw, MBBChir, FRCP; Mitch Dowsett, PhD; Elizabeth Folkerd, PhD; Sheila Bingham, PhD; Nicholas Wareham, MBBS, PhD; Robert Luben, BSc; Ailsa Welch, PhD; Nicholas Day, PhD

From the Department of Public Health and Primary Care (K.-T.K., R.L., A.W., N.D.), Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, UK; Academic Department of Biochemistry (M.D., E.F.), Royal Marsden Hospital, London, UK; and MRC Dunn Human Nutrition Unit (S.B.) and MRC Epidemiology Unit (N.W.), Cambridge, UK.

Correspondence to Kay-Tee Khaw, Clinical Gerontology Unit Box 251, Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK. E-mail kk101{at}medschl.cam.ac.uk

Received June 1, 2007; accepted September 11, 2007.

Background— The relation between endogenous testosterone concentrations and health in men is controversial.

Methods and Results— We examined the prospective relationship between endogenous testosterone concentrations and mortality due to all causes, cardiovascular disease, and cancer in a nested case-control study based on 11 606 men aged 40 to 79 years surveyed in 1993 to 1997 and followed up to 2003. Among those without prevalent cancer or cardiovascular disease, 825 men who subsequently died were compared with a control group of 1489 men still alive, matched for age and date of baseline visit. Endogenous testosterone concentrations at baseline were inversely related to mortality due to all causes (825 deaths), cardiovascular disease (369 deaths), and cancer (304 deaths). Odds ratios (95% confidence intervals) for mortality for increasing quartiles of endogenous testosterone compared with the lowest quartile were 0.75 (0.55 to 1.00), 0.62 (0.45 to 0.84), and 0.59 (0.42 to 0.85), respectively (P<0.001 for trend after adjustment for age, date of visit, body mass index, systolic blood pressure, blood cholesterol, cigarette smoking, diabetes mellitus, alcohol intake, physical activity, social class, education, dehydroepiandrosterone sulfate, androstanediol glucuronide, and sex hormone binding globulin). An increase of 6 nmol/L serum testosterone (1 SD) was associated with a 0.81 (95% confidence interval 0.71 to 0.92, P<0.01) multivariable-adjusted odds ratio for mortality. Inverse relationships were also observed for deaths due to cardiovascular causes and cancer and after the exclusion of deaths that occurred in the first 2 years.

Conclusions— In men, endogenous testosterone concentrations are inversely related to mortality due to cardiovascular disease and all causes. Low testosterone may be a predictive marker for those at high risk of cardiovascular disease.

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