The Health in Men Study is a population-based cohort study of men aged 65 years and older in Australia. The authors of this study hypothesized that men with low serum free testosterone (T) or elevated luteinizing hormone (LH) are at increased risk of all-cause mortality attributable to cardiovascular disease (CVD) and not other potential causes, over a 5-year period.
In this trial, sex hormones exhibited direct relationships with all-cause mortality, as the relationship between low free T, elevated sex hormone binding globulin (SHBG), and elevated LH were statistically significant in association with cardiovascular mortality. While there was a noticeable relationship between total T and increased mortality, this relationship did not reach statistical significance. Overall, men with both low free T and high LH were at greatest risk of cardiovascular mortality. Higher T levels were associated with lung cancer, and elevated SHBG levels were associated with non-CVD mortality.
The study concluded that low serum free T may predict mortality from CVD, yet a true cause-and-effect relationship cannot be exclusively determined. The authors postulate that prevention and early treatment of androgen deficiency syndrome may improve CV outcomes, but not necessarily mortality from other outcomes.
This study can be contrasted with a previous trial published in 2010 with men who received T supplementation (Basaria S, et al. NEJM 2010). This trial examined 209 men at mean 74 years of age, all of whom had a high prevalence of hypertension, diabetes mellitus, hyperlipidemia, and obesity. The conclusions stated that use of T gel in these men was associated with increased risk of adverse CV events, questioning the safety of T supplementation. Additional and more rigorous trials are needed to better elucidate more clear relationships between T and cardiovascular mortality risks.
Hyde Z, Norman PE, Flicker L, et al. Low free testosterone predicts mortality from cardiovascular disease but not other causes: The Health in Men Study. J Clin Endocrinol Metab published ahead of print as doi:10.1210/jc.2011-1617.