Testosterone Replacement Therapy

The aim of testosterone replacement therapy (TRT) is to improve symptoms and signs of testosterone deficiency, including decreased libido, erectile dysfunction, depressed mood, anaemia, and loss of muscle and bone mass, by increasing serum testosterone levels to the physiologic range. ^[1] TRT has been used for the last 70 years, and numerous preparations with routes of delivery including buccal, nasal, subdermal, transdermal and intramuscular have been developed. ^[1] The Endocrine Society recommends diagnosing hypogonadism only in men with symptoms and signs consistent with testosterone deficiency and unequivocally and consistently low serum testosterone concentrations, and recommends testosterone therapy for such men to induce and maintain secondary sex characteristics and correct symptoms. ^[2]

Approved testosterone replacement methods, when used according to recommendations, can restore normal serum testosterone concentrations and relieve symptoms in most hypogonadal men. ^[3] Testosterone is a hormone that plays a key role in carbohydrate, fat and protein metabolism and has a major influence on body fat composition and muscle mass in the male. ^[4] Testosterone treatment induces reversible suppression of spermatogenesis, so when fertility is desired agents that stimulate endogenous testosterone production may be used instead. ^[3]

Studies suggest that testosterone replacement therapy may improve sexual function, depressive symptoms, bone density, and lean body mass. ^[5] Although prior studies suggested that testosterone replacement therapy increased the risk of cardiovascular disease, a large randomized trial showed that it does not increase the risk of myocardial infarction or stroke, even in patients at high risk. ^[5] In the last decade large clinical trials and an individual patient data meta-analysis confirmed that testosterone therapy induces modest but statistically significant improvements in sexual function without increasing short-term to medium-term cardiovascular or prostate cancer risks in men with functional hypogonadism. ^[6] Testosterone improves bone mineral density and insulin sensitivity in these men, but trials suggest insufficient evidence to determine its safety and effectiveness for the prevention of fractures or

Contraindications to testosterone replacement therapy include prostate and breast cancers, uncontrolled congestive heart failure, severe lower-urinary-tract symptoms, and erythrocytosis. ^[7] The Endocrine Society recommends against starting testosterone therapy in men with breast or prostate cancer, a prostate nodule, elevated prostate-specific antigen, elevated hematocrit, untreated severe obstructive sleep apnea, uncontrolled heart failure, or a myocardial infarction or stroke within the last 6 months. ^[2] Clinicians should measure serum testosterone, hematocrit, and prostate-specific antigen levels at baseline and at least annually in men 40 years or older receiving testosterone replacement therapy. ^[5] European Academy of Andrology guidelines note that high-dose testosterone therapy can induce obstructive sleep apnea and that a haematocrit above 48% to 50% represents a relative contraindication for TRT. ^[8]