Abstract

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• Testosterone deficiency (TD) afflicts approximately 30% of men ages 40-79 years, with an increase in prevalence strongly associated with aging and common medical conditions including obesity, diabetes, and hypertension. There appears to be a strong relationship between TD and metabolic syndrome, though the relationship is not certain to be causal. Several studies have suggested that repletion of testosterone in deficient men with these comorbidities may indeed reverse or delay their progression. While testosterone repletion has been largely thought of in a sexual realm, we discuss its potential role in general men's health concerns: metabolic, body composition, and its association with decreased all-cause mortality. Recent guidelines and studies have suggested variable prevalence statistics and expanded uses of testosterone repletion in certain populations with both biochemical and clinical signs of testosterone deficiency. Yet, this is not done without risk. A recent randomized placebo-controlled trial of testosterone repletion in elderly frail men with limited mobility has suggested potential negative cardiovascular risks in this older, sicker group of men. Two more recent retrospective studies of variable clinical design and interpretation suggest testosterone poses an increased cardiovascular risk in older men than 65 years and younger men with heart disease. This review examines these and other studies, with practical recommendations for the diagnosis of testosterone deficiency and repletion in middle aged and older men, including an analysis of treatment modalities and areas of concern and uncertainty.