This chapter reviews data that examine the relationship between androgens and coronary artery disease (CAD) in men. Androgens can exert both beneficial and deleterious actions on a myriad of factors implicated in the pathogenic mechanisms of atherosclerosis and CAD. Androgen/androgen receptor (AR) can modulate arterial disease and vascular function via genomic (AR) or non-genomic mechanisms in animal models and in vitro experimental studies. The diversity and complexity of the actions of testosterone (and its metabolites E2 and DHT) and DHEA on the vasculature reflect the multiple cellular targets in the vessel wall, differences between species, gender, concomitant disease and, most importantly, level/dosage of testosterone exposure. At present, it is not possible to determine the net effect of androgens on CAD pathogenesis and clinical outcomes. While observational clinical studies showed a consistent association between low testosterone and CAD (risk factors, events and mortality), and some experimental studies may suggest positive effects of androgens on CAD risk factors, body composition and individual vascular mechanisms, it is hazardous to suggest that manipulation of the androgenic milieu will result in clinical benefits in a complex multifactorial condition such as CAD. This ongoing uncertainty also underlines recent concerns regarding the possibility of adverse cardiovascular side effects in androgen treatment of endocrine and non-endocrine conditions, hampering efforts to exploit the potential therapeutic benefits of testosterone for men in the treatment of osteoporosis, sarcopaenia, chronic debilitating disease and obesity-related hypoandrogenism in the ageing male population. Large-scale prospective randomised placebo-controlled trials of sufficient size and duration are urgently needed to assess not only the benefits in terms of meaningful clinical benefits and patient-important outcomes but also to document the risks of serious adverse events in testosterone treatment. In the meantime, for patients with established pathological hypogonadism, there are no substantive data to suggest that physiological testosterone therapy is associated with increased cardiovascular risk and their management should not deviate from current recommended practice. For complete coverage of this and related topics, please visit www.endotext.org
