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October 26, 2010

Reduced testosterone levels in men linked to increased mortality over 7 year period

Reduced testosterone levels in men linked to increased mortality over 7 year period

A report published in November 2010 in the British journal Heart reveals an increased risk of premature death from all causes and cardiovascular disease among men whose testosterone levels were deficient.

Researchers at Royal Hallamshire Hospital in Sheffield, England analyzed data from 930 men with cardiovascular disease who underwent elective coronary angiography in a cardiac referral center between June 2000 and June 2002. Serum total testosterone and bioavailable testosterone were measured on the day of the procedure.

The subjects were followed for an average of 6.9 years, during which 129 deaths occurred. Seventy-three of the deaths were due to cardiovascular causes. Twenty-four percent of the participants had either low total or bioavailable testosterone.

While the use of aspirin or beta-blockers was associated with a decrease in the adjusted risk of mortality, increased risk was associated with heart failure and reduced bioavailable testosterone. Twenty-one percent of those with deficient bioavailable testosterone levels died from all causes over follow-up, compared to 12 percent of those with normal levels. Low bioavailable testosterone levels were also associated with an increased risk of dying of cardiovascular causes. Additionally, borderline low levels of total testosterone were associated with an increased risk of dying over follow-up.

The current study's finding calls into question the belief of some physicians that testosterone replacement therapy contributes to an increased risk of heart disease. "In patients with coronary disease testosterone deficiency is common and impacts significantly negatively on survival," the authors conclude. "Prospective trials of testosterone replacement are needed to assess the effect of treatment on survival."

In an accompanying editorial, Dr Ronald C. W. Ma and Peter C. Y. Tong of Chinese University of Hong Kong and Prince of Wales Hospital note that "Clinical studies of testosterone supplementation in men with low testosterone are associated with reduced visceral adiposity, improved insulin sensitivity and an improved metabolic profile. Studies in subjects with cardiovascular diseases also suggested beneficial effects, with improved functional capacity in heart failure and improved symptoms in subjects with coronary artery disease."

"Compared with research on estrogens and cardiovascular disease, the role of androgens in the pathogenesis of metabolic and cardiovascular diseases has taken a backseat for many years," they note. "Recent data suggest that this important pathway warrants a lot more attention."

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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 [mg] 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).

When testosterone levels are measured, it is critical to determine the levels of both free and total testosterone to understand the cause of any observed symptoms of deficiency or excess (Pardridge WM 1986).

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