This was originally posted by Dr. Scally.

Low Endogenous Testosterone Levels Are Associated With Increased Risk Of All-Cause And Cardiovascular Disease Death

Serum testosterone levels exhibit a gradual decline as men age, with longitudinal studies showing declines between 0.4 and 2.6% per year. At the same time, SHBG rises, resulting in a greater decline (>/=2% per year) in free testosterone. The prevalence of late-onset hypogonadism (defined according to recent clinical guidelines as presence of clinical symptoms and low testosterone levels) is less than 10%.

In observational studies, low serum testosterone and late-onset hypogonadism have been associated with abdominal obesity, cardiovascular risk factors and the metabolic syndrome, type 2 diabetes mellitus, increased inflammatory biomarkers, and dyslipidemia among other outcomes that may increase risk of premature death. In recent years, several observational studies have examined the association between endogenous testosterone levels and mortality. Many, but not all, of these studies have shown that low testosterone levels are associated with increased overall and cardiovascular disease (CVD) mortality. Pooling of data from these studies in a systematic review and meta-analysis may provide clarity to the conflicting data or identify study or subject characteristics associated with variation in results among studies.

The primary objective of this research is to assess the association between endogenous testosterone levels and all-cause and CVD mortality from observational studies conducted in men. Secondarily, it will assess whether important clinical [e.g. baseline testosterone level, smoking status, and body mass index (BMI)], demographic (e.g. age), or study-related (e.g. length of follow-up and type of testosterone assay) factors influence or modify study results.

In this systematic review and meta-analysis, researchers identified 21 studies that met protocol-defined inclusion criteria, 12 of which were eligible for meta-analysis. Although meta-analysis of these community-based studies showed that a decrease of 2.18 SD in total testosterone was associated with a 35 and 25% increased risk of all-cause and CVD mortality, respectively, the observation of considerable between-study heterogeneity (significant for all-cause mortality and borderline significant for CVD mortality) limits the validity of these summary estimates. Factors implicated in study heterogeneity were age, baseline total testosterone, length of the follow-up period, and whether blood samples were collected in the morning.


jcem.endojournals.org/content/early/2011/07/28/jc.2011-1137.abstract