Testosterone levels decline gradually with advancing age; the trajectory of age-related decline in testosterone levels is influenced by adiposity, co-morbid conditions, and genetic factors. Low testosterone levels in men are associated with low sexual desire and erectile dysfunction; reduced muscle mass and strength, and impaired physical function; decreased bone mineral density (BMD) and increased risk of osteoporotic fractures. Low testosterone as well as SHBG levels are each independently associated with increased risk of type 2 diabetes mellitus (T2DM) and all-cause mortality. it is possible that low testosterone level is a marker of poor health.
Testosterone treatment of older men with low libido and low testosterone levels improves sexual activity, sexual desire, and erectile function. Testosterone treatment increases muscle mass, muscle strength and leg power, and modestly improves stair climbing power, aerobic capacity, and self-reported mobility. Testosterone modestly improves depressive symptoms and corrects unexplained anemia of aging. Testosterone treatment of older hypogonadal men increases areal and volumetric BMD and estimated bone strength in the hip and spine. Testosterone administration reduces whole body and visceral fat mass. In the T4DM Trial, testosterone treatment administered in conjunction with a lifestyle program for 2 years was more efficacious than placebo in reducing the proportion of men with diabetes.
The adverse effects of testosterone treatment include erythrocytosis, growth of metastatic prostate cancer, reduced sperm production, and increased risk of detection of subclinical prostate cancer. Testosterone treatment does not worsen lower urinary tract symptoms. However, no adequately-powered trial of sufficiently long duration has been conducted to determine the effects of testosterone on the risk of prostate cancer or major adverse cardiovascular events (MACE). An ongoing randomized trial (TRAVERSE Trial) in hypogonadal men, 45-80 years, at increased cardiovascular risk, will provide definitive information on the effects of long-term testosterone treatment on MACE and other efficacy and safety outcomes.
Because of the lack of evidence of long-term safety and limited evidence of long-term efficacy, testosterone treatment of all older men with low testosterone levels is not justified. Instead, an expert panel of the US Endocrine Society suggested that testosterone therapy should be offered on an individualized basis...in men >65 years who have symptoms or conditions suggestive of testosterone deficiency (e.g., low libido or unexplained anemia) and consistently low testosterone”. The decision to offer testosterone treatment to older men with testosterone deficiency should be guided by an individualized assessment of potential benefits and risks, the burden of symptoms, and patient preferences. A shared decision to initiate testosterone treatment should be accompanied by a standardized monitoring plan.