Andropause: Clinical implications of the decline in serum testosterone levels with aging in men

In men, there is a gradual and progressive decline in serum T levels with aging that is accentuated by age-associated comorbid illnesses, medications, and malnutrition. Age-related alterations in body composition, sexual function, mood, cognitive function, sleep, and erythropoiesis occur in conjunction with the declining serum T levels. Similar alterations occur in young androgen-deficient hypogonadal men and are improved with T replacement therapy. Therefore, it is reasonable to posit that age-related androgen deficiency may contribute, at least in part, to the changes in physiological function that occur with aging. Initial short-term controlled studies of T therapy in small numbers of healthy older men suggest beneficial effects on body composition, BMD, LDL cholesterol, angina, and exercise-induced cardiac ischemia, and possibly muscle strength, libido, general well-being, and certain aspects of cognitive function. In these studies, there have been no significant adverse effects except for erythrocytosis requiring a reduction in dose in some men. Given these findings, it is reasonable to consider T replacement therapy in older men with a clinical syndrome consistent with androgen deficiency and repeatedly low serum-free and bioavailable T levels, in whom the potential benefits of therapy outweigh the potential risks. Because age-related alterations in physiological function are usually a result of multiple etiologies, it is important to evaluate and treat other factors (e.g., inadequate nutritional intake, confounding illness and medication, inactivity or poor conditioning, excessive alcohol, and smoking) in addition to low T levels that may contribute to the clinical syndrome. A major caveat in treating older men with T is that long-term benefits on fracture incidence, onset of dementia, major cardiovascular outcomes, physical function, frailty and quality of life, and risks of clinical prostate disease (BPH and prostate cancer) and cardiovascular disease are not known. Therefore, routine T treatment of older men cannot be recommended. The balance of benefits and risks of T therapy in older men with low T levels needs to be determined in carefully designed, large, long-term, randomized, placebo-controlled studies. Until the results of these studies are available, practitioners must rely on sound clinical judgment in managing older men with symptoms and signs of andropause. At present, the most prudent course of action is to treat only older men with repeatedly low serum T levels and symptoms and signs consistent with androgen deficiency in whom the potential benefits of therapy clearly outweigh the potential risks, and to carefully monitor treated men for adverse effects. Attention to appropriate exercise and nutrition, and evaluation and treatment of other etiological factors that may contribute to clinical manifestations are essential for optimal management of age-related functional decline in older men.