Drugs Aging 2004; 21 (6): 361-376

Age-related decline in testosterone levels is associated with a number of mild, Abstract nonspecific symptoms, including depressive symptoms. The relationship between depressive symptoms and testosterone levels is confounded by numerous factors, including medical illness, obesity, smoking, alcohol use, diet and stress, and is thus complex. Studies have not consistently supported an integral role of reduced testosterone levels in major depressive disorder, although levels may often be reduced in men with treatment-refractory depression and older men with dysthymia. Low testosterone levels may also increase the risk of incident depression in older males, although this may depend upon androgen receptor genetic polymorphisms. Testosterone replacement has demonstrated short-term tolerability and efficacy in augmenting antidepressants to alleviate treatment-refractory depression in adult males. Case studies support the potential need for maintenance therapy to maintain response. In a placebo-controlled trial, testosterone monotherapy was not effective in treating major depressive disorder in men with hypogonadism. However, in an open-label, noncomparative study, testosterone monotherapy appeared effective in treating late-onset but not early-onset major depressive disorder in older males. Testosterone therapy is not without potential for adverse effects, the most worrisome of which is the worsening of pre-existing prostate carcinoma. Oral, shortand long-acting parenteral, and transdermal patch and gel formulations are available. Testosterone has demonstrated usefulness in the treatment of a number of depressed populations, but further studies are needed to fully elucidate its role in the treatment of depressive syndromes in the aging male.