Endocrine Abstracts

Low endogenous testosterone levels in men have been associated with a more adverse cardiovascular disease risk factor profile including lower HDL-cholesterol and higher blood glucose levels, and increased risk of cardiovascular disease. However, it is uncertain whether low testosterone levels may precede disease onset, or are a result of preexisting disease. Prospective studies may help clarify this relationship.

The EPIC Norfolk study reported that in 11 606 men aged 40–79 years first seen in 1993–1997 and followed up to 2003, endogenous testosterone levels at baseline were inversely related to mortality due to all causes (825 events) cardiovascular disease and cancer. Odds ratios (95% CI) for mortality for increasing quartiles of endogenous testosterone compared with the lowest quartile were 0.75 (0.55–1.00), 0.62 (0.45–0.84); and 0.59 (0.49–0.85) respectively (P<0.001) independent of age, blood pressure, lipids, smoking, diabetes and other hormone levels. An increase of 6 nmol/l serum testosterone (1 S.D.) was ssociated with a 0.81 (0.71–0.92, P<0.01) odds ratio for mortality. Inverse relationships were also observed for cardiovascular disease and cancer deaths.

The Rancho Bernardo study reported that in 794 men aged 50–91 followed up from baseline in 1984–1987 to 2004, in whom 538 deaths occurred, Men with total testosterone in the lowest quartile were 40% (HR 1.40, 95% CI 1.14–1.71) more likely to die than those with higher levels, independent of age, adiposity and lifestyle as well as lipids, blood pressure and other metabolic covariates. In this study low testosterone also predicted increased risk of cardiovascular and respiratory disease mortality.

These two prospective population studies in UK and US indicate that low testosterone levels are predictive of subsequent mortality over a long time period in apparently healthy men and independently of known risk factors. Whether testosterone supplementation may improve health outcomes in men remains to be tested in clinical trials.