Low Testosterone in Men with Cardiovascular Disease or Risk Factors: To Treat or Not To Treat?

OPINION STATEMENT: Current evidence supports the use of testosterone replacement in men with the clinical-biochemical syndrome of hypogonadism, defined as low testosterone serum levels and symptoms such as fatigue, exercise intolerance, erectile dysfunction, low libido, or depression. Although the evidence consistently shows that hypogonadism is associated with elevated cardiovascular risk, evidence is mixed regarding whether testosterone (T) replacement provides cardiovascular (CV) benefit or harm. For a man with symptomatic hypogonadism in the setting of CV disease, clinical heart failure, and/or traditional CV risk factors (hypertension, diabetes, and hyperlipidemia), a balanced approach would be to counsel him that overall, the evidence should not dissuade him from utilizing T replacement for non-cardiac symptom relief but that more data are needed before a definitive recommendation can be made about T replacement for CV benefit. The preponderance of available evidence, reviewed in this article, suggests that T replacement, at appropriate doses and with monitored response, is likely to be safe for men with CV disease or CV risk factors and may even reduce major adverse cardiovascular events (MACE). The 2015 American Association of Clinical Endocrinologists and American College of Endocrinology position statement supports this stance and calls for improved prospective data. There is a clear need for a large, prospective randomized trial evaluating the impact of T replacement on MACE, for men both with and without CV disease or CV risk factors. Clinicians should be aware that all men who elect to take T replacement therapy require regular follow-up with the prescribing physician to include both clinical assessment and surveillance laboratory assessment of total T level, complete blood count, and prostate specific antigen.