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Exercise performance in men with stable angina improved by testosterone over 12 month period

Long term benefits of testosterone replacement therapy on angina threshold and atheroma in men. Mathur A, Malkin C, Saeed B et al. European Journal of Endocrinology. 2009;161;443 –449.

Key Points

  • This is the longest term study investigating testosterone in patients with stable chronic angina.1
    (Angina is severe chest pain due to ischemia of the heart muscle, generally due to obstruction or spasm of the coronary arteries. Coronary artery disease, the main cause of angina, is due to atherosclerosis of the cardiac arteries)
  • In the testosterone group, 'time to ST depression' is significantly prolonged,1 ie the time during exercise when severe chest pain occurs as a result of ischemia (which also becomes visible on the electrocardiogram). This reflects an increase in exercise capacity
  • Peak metabolic equivalents (METS) also increased significantly1 in the testosterone treated patients indicating an improved exercise capability
  • BMI and triglycerides were numerically, though significantly reduced in the treatment group1
  • There was a non-significant reduction in waist-to-hip ratio (a measure of visceral obesity) in the Nebido® group
  • Carotid intima-media thickness (CIMT), a measure of atherosclerosis, improved in the Nebido group and did not change in the placebo group. However, the comparison between groups did not reach statistical significance.1

This was a double-blind, randomised, parallel group placebo-controlled trial involving a single centre study that investigated 13 (originally 15) hypogonadal men (mean T was 9.9nmol/l1) with stable angina on optimal anginal treatment randomised to Nebido 1000mg/3 months or placebo. Exercise (treadmill) testing was conducted at 3, 6, and 12 months after baseline tests along with metabolic parameters.

This was the first 12 months outcome study showing a sustained effect on time to ST depression.1

There were no adverse effects.1

What is known

Recent in vitro studies have demonstrated that testosterone inhibits L-type calcium channels and the authors of this study postulate that this may be the mechanism improving exercise time to ischaemia in anginal patients.1

Coronary Heart Disease (CHD) is strongly associated with Erectile Dysfunction (ED)2 and Testosterone Deficiency Syndrome.3 Testosterone therapy may be an option to salvage patients who fail with PDE5Is.4 The same authors have shown decreased survival in CHD patients with low testosterone (see Figure 1 below) but long-term studies have yet to show that mortality is reduced by treating low testosterone in CHD patients.1

What this study adds

This is the first study to show improvement in exercise time to ischaemia with T supplementation improving up to 12 months. This was an additive benefit in patients optimally treated with anti-anginal therapy and the magnitude of effect was similar to nifedipine.1 There was no evidence of tachphyaxis.1

This is the first study to show effect of T on CIMT although the results were not clinically significant;1 more patients and longer studies are required. The metabolic benefits on BMI and waist circumference have been seen in many other studies.5 The important finding is that the significantly prolonged time to ischaemia was achieved1 in a stable group on optimal therapy. The effect was comparable to that seen with nifedipine.1

Figure 1

Figure 1: Survival by Testosterone Status. Bio-T / all cause mortality. (adjusted)

References

1. "Long term benefits of testosterone replacement therapy on angina threshold and atheroma in men." Mathur A, Malkin C, Saeed B et al. European Journal of Endocrinology. 2009;161;443–449.
2. "CHD Risk Factors Predict ED." Fung et al. JACC. April 21 2004;43(8);1405–11.
3. "The effects of testosterone on risk factors for, and the mediators of, the atherosclerotic process." Hugh Jones T, Saad F. Atherosclerosis. Dec 2009;207(2);318-327.
4. "How to optimise treatment of erectile dysfunction above and beyond the beneficial effects of a phosphodiesterase type 5 inhibitor." Gooren L. Journal of Men's Health June 2008;5(2);163-170.
5. "Waist Circumference, Body Mass Index, and their Association with Cardiometabolic and Global Risk." Christian AH, et al. J Cardiometab Syndr. 2009 Winter;4(1):12–19.

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