Low testosterone levels may increase mortality in men with CHD

Ma RCW. Heart. 2010;doi:10.1136/hrt.2010.207068.

Malkin CJ. Heart. 2010;doi:10.1136/hrt.2010.195412.

One-quarter of men with coronary heart disease were found to be testosterone-deficient in a new study, leading researchers to conclude that low levels of testosterone are common in this patient population.

“We have demonstrated that testosterone deficiency is associated with premature death in a cohort of patients with vascular disease; many of these patients died and will continue to die from cardiovascular disease,” researchers wrote in the journal Heart.

However, data from the longitudinal follow-up study did not indicate whether low testosterone levels contribute to or serve as a marker for increased mortality risk in men with CHD.

Researchers said the study had two aims: to assess the effect of testosterone levels on all-cause mortality and to identify the prevalence of biochemical testosterone deficiency in men with CHD.

The study included a cohort of 930 men with CHD whom the researchers followed for a mean of 6.9 years. All of the men underwent elective coronary angiography at a tertiary cardiac referral center between 2000 and 2002.

Link between testosterone, mortality found

For the study, hypogonadism was defined as bioavailable testosterone levels less than 2.6 nmol/L or total testosterone levels less than 8.1 nmol/L. When using bioavailable testosterone levels as a benchmark, the prevalence of hypogonadism was 20.9%, whereas total testosterone levels indicated a prevalence of 16.9%. Use of either measure yielded 24% prevalence.

Of 129 deaths in the study cohort, 73 had vascular causes. Only eight of 16 deaths, however, among 148 men with normal coronary arteries who were excluded from the original analysis were vascular. Results suggested that, at 21%, the mortality rate was higher among patients with testosterone deficiency compared with those without the condition (12%; P=.002).

The researchers also noted that factors influencing time to all-cause mortality included left ventricular dysfunction (HR=2.85; 95% CI, 1.72-8.33), aspirin therapy (HR=0.63; 95% CI, 0.38-1), beta-blocker therapy (HR=0.45; 95% CI, 0.31-0.67) and low serum bioavailable testosterone (HR=2.27; 95% CI, 1.45-3.6).

Further analyses linked low serum bioavailable testosterone with age (OR=1.03; 95% CI, 1-1.1), BMI (OR=1.06; 95% CI, 1-1.1) and former smoking (OR=0.59; 95% CI, 0.4-0.9). BMI was the only predictor of low total testosterone (OR=1.14; 95% CI, 1.1-1.2), but age (OR=1.02; 95% CI, 1-1.04), BMI (OR=1.09; 95% CI, 1.04-1.13) and former smoking (OR=0.64; 95% CI, 0.5-0.9) remained significantly associated with biochemical testosterone deficiency when assessed using either reference point.

‘Important pathway warrants attention’

According to the researchers, testosterone replacement therapy may be a viable and effective treatment option for men with CHD.

“If androgen deficiency is part of the underlying pathophysiology of atherosclerotic disease in men, then the serum testosterone level could be viewed as a modifiable risk factor,” they wrote.

In an accompanying editorial, Ronald C.W. Ma, MBChB, and Peter C.Y. Tong, MBBS, of the Chinese University of Hong Kong, said testosterone prescriptions have recently increased.

“While the long-term CV impact of testosterone supplement in those with low levels remains to be demonstrated, accumulating evidence suggests there is a sound basis for examining this,” the editorialists wrote, adding that testosterone therapy is risky and requires careful medical supervision.

Ma and Tong said the gender-specific nature of testosterone is a potential connection to CHD.

“Compared with research on estrogens and CVD, the role of androgens in the pathogenesis of metabolic and CVDs has taken a backseat for many years,” they wrote. “Recent data suggest that this important pathway warrants a lot more attention.” – by Melissa Foster

This is the largest study to date strongly implicating that hypogonadism in men with established coronary artery disease is an independent predictor of all-cause and vascular mortality. The prevalence in this population with established CAD was high, whereby close to one out of four men were diagnosed with hypogonadism and this number increased as the number of affected coronary vessels increased.

Especially today, in light of conflicting signals on this issue, a study looking at the impact of testosterone replacement therapy in hypogonadal men with established CAD is, as the researchers stated, the logical next step — and, in my opinion, is urgently needed.

– Natan Bar-Chama, MD
Director of Male Reproductive Medicine and Surgery,
Associate Professor of the Department of Urology, Mount Sinai School of Medicine

Bararia et al (N Engl J Med. 2010;363:109-122) prematurely stopped a randomized trial of testosterone gel in older men, owing to significantly increased rates of adverse CV events. Thus, the higher baseline rate of coronary heart disease reported in association with low testosterone levels may not be reversed by testosterone replacement therapy. Evidence once again that association does not prove causation. Indiscriminant use of testosterone, particularly in the older population, should be discouraged until evidence of clear benefit without harm can be produced.

– Alan J. Garber, MD

Endocrine Today Chief Medical Editor

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