The Cardiac Benefit of Testosterone Replacement in Men With Low Testosterone Levels With Coronary Artery Disease After Successful Intervention of the Blockage or Narrowed Heart Artery

• cardiac stress test [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
  objective markers of cardiac disease following successful percutaneous coronary intervention (3 months after the procedure) for coronary artery disease as measured by cardiac stress test
  
  

• Seattle Angina Questionnaire (SAQ) [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
  objective markers of cardiac disease following successful percutaneous coronary intervention (3 months after the procedure) for coronary artery disease as measured by cardiac stress test
  
  
• reactive hyperemia peripheral arterial tonometry (PAT) [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
  Improve Endothelial function as measured PAT. Non-invasive tool to identify subjects with coronary endothelial dysfunction by measuring changes in digital pulse volume during reactive hyperemia.
  
  
• Improve Cardiac inflammatory markers [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
  
• Improve Metabolic syndrome-related parameters e) [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
  
• Improve Quality of life parameters [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
  
• Improve erectile function [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
  

Males with coronary heart disease have lower serum levels of bioavailable testosterone than men of a similar age with normal coronary angiograms (English, European Heart Journal, 2000). Low plasma testosterone has been associated with known risk factors for CHD, including age, obesity, hyperinsulinemia, diabetes, and adverse lipid profile.

Testosterone has also been shown in numerous studies to be a vasodilator. Recently, testosterone replacement compared with placebo, in hypogonadal men was shown to improve time to ischemic threshold, assessed by treadmill exercise testing at 4 and 12 weeks (Malkin, Heart, 2000). Prior studies had also shown a beneficial effect on exercise-induced ischemia in men with CAD, but not exclusively hypogonadal men (Jaffe,Br Heart J 1977; Rosano, Circulation, 1999; English, Circulation, 2000). In addition, this proposed study would be the first study to assess if the anti-anginal effects persists long term.

This is a randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of testosterone supplementation in hypogonadal men with coronary artery disease following successful revascularization with percutaneous coronary intervention (PCI). Only those men who had successful coronary artery revascularization, and on stable cardiac medical regimen for the prior 4 weeks will be included. Eligible patients will then be randomized on a 2:1 basis with 50 subjects receiving 5 grams of AndroGel and 25 subjects receiving placebo gel.

The men in this study who demonstrate hypogonadism represent a novel population to demonstrate the safety and efficacy of testosterone supplementation to improve cardiac function and outcomes. We hypothesize that treatment of hypogonadism in men with CAD, following successful PCI, will significantly improve cardiac ischemic threshold as assessed by cardiac stress testing. Furthermore, additional cardiac endpoints such as angina status, endothelial function and inflammatory serum markers will also demonstrate significant benefit in the testosterone treated group.