A J-shaped association between plasma testosterone and risk of ischemic arterial event in elderly men: The French 3C cohort study

Objectives

Low plasma testosterone is associated with increased mortality in men. However, the relation between testosterone and cardiovascular disease is uncertain. We assessed the association of plasma sex hormones with the incidence of ischemic arterial disease (IAD) in elderly men.

Methods

We used data from the French Three-City prospective cohort study (3650 men aged >65 years). A case-cohort design was set up including a random sample of 495 men and 146 incident cases of first IAD event (112 coronary heart disease (CHD) and 34 strokes) after a 4-year follow-up. Plasma total and bioavailable testosterone, total estradiol and sex hormone-binding globulin (SHBG) were measured at baseline. Multivariate hazard ratios (HRs) and 95% confidence intervals for IAD were assessed using Cox model.

Results

After adjustment for cardiovascular risk factors, a J-shaped association between plasma total testosterone and IAD risk was found (p < 0.01). The HRs associated with the lowest and the highest total testosterone quintiles relative to the second quintile were 2.23 (95% CI: 1.02; 4.88) and 3.61 (95% CI: 1.55; 8.45) respectively. Additional analysis for CHD showed similar results (HR: 3.11, 95% CI: 1.27; 7.63 and HR: 4.75, 95% CI: 1.75; 12.92, respectively). Similar J-shaped association was observed between bioavailable testosterone and IAD risk (p = 0.01). No significant association of estradiol and SHBG with IAD was found.

Conclusion

High and low plasma testosterone levels are associated with an increased risk of IAD in elderly men. Optimal range of plasma testosterone may confer cardiovascular protection and these results may have clinical implications in the management of testosterone deficiency.