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Torkel Vikan, Henrik Schirmer, Inger Njølstad and Johan Svartberg

Objective

To study the impact of endogenous testosterone levels in community-dwelling men on later risk for myocardial infarction (MI) and all-cause, cardiovascular disease (CVD), and ischemic heart disease (IHD) mortality.

Design

Population-based prospective cohort study.

Methods

For the analyses, we used a cohort of 1568 randomly selected men, with sex-hormone data participating in the fourth Tromsø Study (1994–1995). Defined end points were first-ever MI (fatal or nonfatal), all-cause, CVD, and IHD mortality. A committee performed thorough ascertainment of end points, following a detailed protocol. Complete ascertainment of end points was until 30 September 2007 for all-cause mortality, until 31 December 2005 for CVD/IHD mortality, and until 31 December 2004 for first-ever MI. The prospective association between total and free testosterone and end points were examined using Cox proportional hazard regression, allowing for multivariate adjustment for age and cardiovascular risk factors.

Results

During follow-up, there were 395 deaths from all causes, 130 deaths from CVD and 80 deaths from IHD, while 144 men experienced a first-ever MI. There was a significant increase in all-cause mortality risk for men with free testosterone in the lowest quartile (<158 pmol/l) compared with the higher quartiles after age adjustment hazard ratios (HR 1.24, 95% confidence interval, CI 1.01–1.53) and after multivariate adjustments (HR 1.24, 95% CI 1.01–1.54). Total testosterone was not associated with mortality risk. Likewise, there were no significant changes in risk for first-ever MI across different total or free testosterone levels.

Conclusion

Men with free testosterone levels in the lowest quartile had a 24% increased risk of all-cause mortality.

Free access

Torkel Vikan, Henrik Schirmer, Inger Njølstad and Johan Svartberg

Objective

To study the impact of endogenous sex hormone levels in community-dwelling men on later risk for type 2 diabetes.

Design

Population-based prospective cohort study.

Methods

For the analyses, 1454 men who participated in the fourth Tromsø study (1994–1995) were used. Cases of diabetes were retrieved and validated until 31.12.05 following a detailed protocol. The prospective association between sex hormones and diabetes was examined using Cox proportional hazard regression analysis, allowing for multivariate adjustments.

Results

There was a significantly lowered multi-adjusted risk for later diabetes with higher normal total testosterone levels, both linearly per s.d. increase (hazard ratio (HR) 0.71, confidence interval (CI) 0.54–0.92) and in the higher quartiles of total testosterone than in the lowest quartiles (HR 0.53, CI 0.33–0.84). A reduced multi-adjusted risk for incident diabetes was also found for men with higher sex hormone-binding globulin (SHBG) levels, both linearly per s.d. increase (HR 0.55, CI 0.39–0.79) and when comparing the third (HR 0.38, CI 0.18–0.81) and the fourth quartile (HR 0.37, CI 0.17–0.82) to the lowest quartile. The associations with total testosterone and SHBG were no longer significant after inclusion of waist circumference to the multivariate models. Estradiol (E2) was positively associated with incident diabetes after multivariate adjustments including waist circumference when comparing the second (HR 0.49, CI 0.26–0.93) and the third (HR 0.51, CI 0.27–0.96) quartile to the highest quartile.

Conclusion

Men with higher E2 levels had an increased risk of later diabetes independent of obesity, while men with lower total testosterone and SHBG had an increased risk of diabetes that appeared to be dependent on obesity.