NIH testosterone trial in older men halted due to increased cardiovascular events

Fran Lowry

July 01, 2010

Boston, MA- Testosterone treatment in men aged 65 years and older who have limitations in mobility is associated with an increased risk for cardiovascular events, including MI and hypertension, according to a study published online June 30, 2010 in the New England Journal of Medicine[1].

Because of these events, the treatment phase of the trial, which was supported by the National Institute on Aging of the National Institutes of Health, has been stopped.

"In men, an age-related decline in the serum testosterone concentration is associated with reduced muscle mass and lower extremity strength, limitations in physical function, and poor mobility," write Dr Sh ehzad Basaria (Boston University School of Medicine, MA) and colleagues. "Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men. The safety and efficacy of testosterone treatment in older men who have limitations in mobility have not been studied."

The Testosterone in Older Men with Mobility Limitations trial was undertaken to address this question.

In the trial, 209 men were randomly assigned to receive 10 g of a transdermal gel, containing either placebo or 100 mg of testosterone, to be applied to the skin once daily for six months. Efficacy outcomes were changes in chest- and leg-press strength and the ability to walk and climb stairs.

The men in the trial were an average of 74 years old and had high rates of chronic diseases such as diabetes and cardiovascular disease.

The treatment phase of the trial was stopped on December 31, 2009, after a review by the study's data and safety monitoring board, which found that 23 of the 106 men who had received testosterone experienced adverse cardiovascular-related events during the study, compared with five of the 103 men who received placebo. In addition, seven men in the testosterone group and one in the placebo group had atherosclerosis-related events.

The cardiovascular-related events included MI, arrhythmias, hypertension, and one death from a suspected MI.

At the time the trial was stopped, the testosterone group had significantly greater improvements in leg-press and chest-press strength and in stair climbing while carrying a load.

Clarification needed

The study authors write that the generalizability of their data about the safety of testosterone is limited by several factors, including the study's small size and the fact that the study population was older and had higher rates of chronic diseases and mobility limitation than individuals in most other studies.

They note that physicians and patients, especially older men, should consider the study findings on adverse effects along with other information on the risks and benefits of testosterone therapy and that further research is needed to clarify the safety issues raised by this trial.

The authors also state that chance may have played a role in the outcomes observed and that the diversity of the adverse cardiac events that were seen in the prematurely terminated trial makes them less easily explained by a single mechanistic explanation.

Finally, the study authors caution against extrapolating their study findings to other doses and formulations of testosterone or to other populations, "particularly young men who have hypogonadism without cardiovascular disease or limitations in mobility."

Basaria reports financial relationships with Novartis, GlaxoSmithKline, Solvay Pharmaceuticals, Merck, and Ligand Pharmaceuticals.

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