~ 120407 Low Testosterone Levels In Men Associated With Greater Mortality From All Causes Over Seven Year Follow-Up Period

A report published online on November 26, 2007 in the American Heart Association journal Circulation concluded that men with low testosterone levels had a greater risk of dying from any cause during up to a decade of follow-up. Lower testosterone levels were also specifically associated with a greater risk of dying from cardiovascular disease as well as cancer.

Researchers at the University of Cambridge and Royal Marsden Hospital in London studied 11,606 men aged 40 to 79 who participated in the European Prospective Investigation into Cancer in Norfolk study. Blood serum samples drawn during the subjects' initial visit between 1993 and 1997 were analyzed for total testosterone and other factors. Deaths were tracked until 2003, and causes of death recorded.

Among men without pre-existing cancer or cardiovascular disease, there were 825 deaths over the follow-up period, including 369 deaths from cardiovascular disease and 304 cancer deaths. These participants were matched for age and initial clinic visit date with 1,489 living study participants. A downward trend in deaths from any cause was associated with increasing serum testosterone levels. After adjustment for age, body mass index, and several other factors, men whose testosterone levels were in the top 25 percent of participants experienced a risk of dying over follow-up that was 41 percent lower than men whose levels were in the lowest fourth.

After excluding deaths that occurred during the first two years of the study, the researchers also found an inverse relationship between testosterone and deaths from cancer and cardiovascular causes. Although inflammatory markers, insulin, and hemostatic factors were not measured in the study, the authors note that higher testosterone levels have been associated with lower concentrations of these factors. It is possible that testosterone's apparent cardioprotective effect could operate through these mechanisms, or via improved endothelial function and coronary vasodilation.

'The present study suggests that high endogenous testosterone concentrations appear to be beneficially associated with mortality due to all causes, cardiovascular disease, and cancer,' the authors conclude. 'Data from the present study may encourage consideration of further research into the role of testosterone in health in men.'

Health Concern: Male hormone restoration

The exact causes of the age-related reduction in testosterone levels is not known; it is probably the result of a combination of factors, including increased body fat (and therefore increased aromatase activity), oxidative damage to tissues responsible for the production of testosterone, and declining levels of precursor molecules such as DHEA. The results of the decline, however, are strikingly apparent.

There is a clear relationship between low levels of testosterone and increased incidence of cardiovascular disease, particularly as testosterone level relates to metabolic syndrome (Dobrzycki S et al 2003; Hak AE et al 2002; Zhao SP et al 1998; Jeppesen LL et al 1996). Metabolic syndrome is the combination of abdominal obesity, high blood pressure, insulin resistance, and lipid disorders in the same person. This condition is associated with a high risk of cardiovascular disease. Studies have shown that testosterone administration (500 milligrams of intramuscular injections) in middle-aged, obese men was able to increase insulin sensitivity (Marin P et al 1992a). These results were confirmed in another study in which testosterone treatment led to reduced insulin resistance (Marin P et al 1992b). Later studies also showed that testosterone administration is helpful in the context of metabolic syndrome (Bhasin S 2003; Boyanov MA et al 2003).

Nutrients function by increasing testosterone availability, often by affecting testosterone's interaction with SHBG or by decreasing its aromatization (conversion) into estrogen. Natural supplements can complement hormone replacement therapy. For people who choose not to (or should not) use hormone replacement therapy, nutrients can be a vital part of a comprehensive program to reduce the impact of aging on the systems of sex hormone production, regulation, and metabolism.

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