Exogenous testosterone treatment in men with cardiovascular disease

The longterm effects of exogenous testosterone on coronary event rates has not been investigated. However, in several small studies therapeutic doses of testosterone reduced the severity and frequency of angina pectoris events and improved electrocardiographic signs of myocardial ischemia. Webb and colleagues (Webb etal. 1999) showed that a single i.v. bolus of 2.3 mg of testosterone increased time to 1-mm ST segment depression by 66 sec in 14 men with coronary artery disease and low plasma testosterone. The plasma testosterone increased from 5.2 to 117 nmol/L. Infusion of testosterone over three minutes into the coronary arteries of 13 men with established coronary artery disease during coronary angiog-raphy at supraphyisological doses of 8 |xmol/L but not the physiological dose of 8 nmol/L led to significant increases in coronary vessel diameter and blood flow at all four doses of testosterone. These results have been confirmed by a similar study

(Rosano et al. 1999) in 14 men with established coronary artery disease and have been interpreted as beneficial effects of testosterone on coronary artery vasore-activity. However, it is important to note that these direct acute pharmacological effects of testosterone on the coronary vasculature have been only found upon acute injection of supraphysiological concentrations and may not be relevant to the physiological situation. Thus, in contrast to these acute experiments, flow-mediated and hence endothelium-dependent dilation of the brachial artery, which is strongly correlated with coronary endothelium-dependent vasoreactivity, was found worsened after three months testosterone substitution in hypogonadal men (Zitzmann etal. 2002).

Even less information is available on the effects of testosterone on other outcomes of cardiovascular disease. In a small placebo-controlled pilot study, treatment of 20 chronic heart failure patients with weekly injections of 100 mg testosterone enan-thate led to improvements of left ventricular ejection fraction and exercise capacity (Unpublished, quoted after Liu et al. 2003). In agreement with this, treatment of 12 stable heart failure patients with 60 mg testosterone or placebo via the buccal route resulted in significant increases in serum levels of bioavailable testosterone and cardiac output and in a significant decrease of peripheral artery resistance with a maximal effect seen after three hours (Pugh et al. 2003). No study has been performed on the effects of testosterone on stroke and no study showed any positive effect of testosterone on subjective measures such as pain or walking distance or time and objective measures such as muscle blood flow, plethysmographic parameters or foot pulses (Liu etal. 2003). However, there is evidence that testosterone can induce nitric oxide production in penile vasculature in animals and humans and testosterone supplements can improve erectile response to sildenafil in men with low testosterone and erectile dysfunction (Aversa etal. 2000; 2003; Guay etal. 2001).

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