Testosterone normalization associated with lower risk of heart attack, stroke and mortality from all causes over follow-up

Tuesday, August 11, 2015. On August 5, 2015, an article published in European Heart Journal reported that normalization of low testosterone levels through the use of testosterone replacement therapy (TRT) was associated with a significant decrease in the risk of myocardial infarction (MI, or heart attack), stroke and premature mortality from all causes in a large group of male veterans.

The study included older men who received their medical care at the Veterans Health Administration from December 1999 to May 2014. Subjects were limited to men without a history of heart attack or ischemic stroke whose initial total testosterone levels were below normal laboratory reference ranges. These included 43,931 patients who had normal total testosterone levels after receiving testosterone replacement therapy, 25,701 men who continued to have subnormal testosterone after therapy, and 13,378 patients with low testosterone who were untreated.

Over follow-up, the group with normalized testosterone levels had 47% fewer deaths than men whose hormone levels failed to normalize after testosterone replacement and 56% fewer deaths than those who did not receive TRT. When myocardial infarction was evaluated, men whose testosterone levels were normalized had an 18% lower risk than those whose levels failed to normalize and a 24% lower risk than untreated men. Ischemic stroke risk in normalized men was 30% lower than those who failed to attain normal testosterone levels and 36% lower than those who did not receive the hormone. As potential protective mechanisms, the authors cite testosterone's beneficial effects on adipose tissue, insulin sensitivity and lipids, as well as its anti-inflammatory and anticoagulant effects.

"In this study of men, without previous history MI or stroke, with low testosterone levels, normalization of testosterone levels using TRT is associated with lower mortality, fewer MIs, and strokes," corresponding author Rajat S. Barua, MD, concluded. "This is the first study to demonstrate that significant benefit is observed only if the dose is adequate to normalize the testosterone levels."

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Testosterone replacement enhances aerobic capacity

The joint meeting of the International Society of Endocrinology and the Endocrine Society was the site of a presentation on June 22 concerning findings obtained from a clinical trial of men with limited mobility which revealed improved aerobic capacity among those treated with testosterone.

The current study evaluated data from 64 men with low testosterone enrolled in the Testosterone in Older Men with Mobility Limitation Trial. Participants in the trial received 10 milligrams testosterone in gel form or a placebo gel daily for six months. Cycle exercise tests conducted at the beginning and end of the treatment period provided measures of aerobic function, including peak oxygen uptake and gas exchange lactate threshold.

At the trial's conclusion, men who received a placebo saw a reduction in peak oxygen uptake, while those treated with testosterone experienced improvement.

"We believe this is the first report of enhanced endurance performance as a result of testosterone therapy in men who have difficulty performing some physical tasks but are otherwise healthy," announced lead author Thomas W. Storer, PhD, who is the Director of the Exercise Physiology Laboratory at Brigham and Women's Hospital in Boston. "At least in the short term, testosterone therapy may lessen the rate of decline of an important marker of physical fitness in older men with low testosterone."

"These findings are potentially relevant to older men who have experienced the age-related decline in endurance capacity that may be due in part to low testosterone," he added. "If proven safe over the long-term, restoring testosterone to normal levels may improve an important measure of physical performance and enhance their quality of life."

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Health Concern

Male hormone restoration

The significance of testosterone for male sexual function is apparent to most Life Extension members. New insights, however, underscore the critical role testosterone plays in maintaining youthful neurological structure, alleviating depression, as well as inducing fat loss in those who are unable to reduce body weight regardless of diet and exercise.

Recent studies have demonstrated that low testosterone in men is strongly associated with metabolic syndrome, type 2 diabetes, cardiovascular disease (Miner and Seftel 2007), and an almost 50% increase in mortality over a seven year period (Malkin et al 2010).

Restoring testosterone to youthful ranges in middle-aged, obese men resulted in an increase in insulin sensitivity as well as a reduction in total cholesterol, fat mass, waist circumference and pro-inflammatory cytokines associated with atherosclerosis, diabetes, and the metabolic syndrome (Kapoor et al 2006, Malkin et al 2004, Heufelder et al 2009). Testosterone therapy also significantly improved erectile function (Fukui 2007) and improved functional capacity

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