Although there is evidence of testosterone deficiency being associated with increased mortality in multiple cohort studies, it remains unclear whether this is a causal relationship or due to low testosterone level being a biomarker of poor overall health. Considering that CVD occurs most commonly in elderly men and that elderly men typically have lower levels of serum testosterone and increased chronic disease burden, there are multiple confounding variables regarding any potential cause and effect of endogenous testosterone levels on CV health. The evidence overall suggests that normal physiologic levels of testosterone are beneficial to the male CV system and that testosterone deficiency is associated with an unfavorable metabolic profile and increased CVD events, such as MI and mortality. Increased IMT, which has been studied as an indicator of atherosclerotic progression, is found to be associated with testosterone deficiency across multiple phenotypically distinct patient populations, including elderly men and obese adolescent females.
The FDA, the AACE/ACE, and the international consensus panel all state that testosterone therapy is safe and reasonable in patients with symptomatic testosterone deficiency (the FDA definition of testosterone deficiency is the only definition that does not include symptoms). Regarding CAD, multiple studies have found that testosterone therapy is associated with increased time to ischemia. Whereas Malkin et al concluded that low serum testosterone level was an independent parameter that influenced time to mortality, suggesting a possible mortality benefit of testosterone therapy in hypogonadal patients with CAD, Budoff et al found that testosterone therapy was associated with increased total coronary plaque burden in a similar cohort. The ongoing Cardiovascular Trial of The Testosterone Trials will test the hypothesis that testosterone therapy inhibits coronary plaque progression as assessed by serial CCTA.
