Nature Reviews Urology

Update on testosterone deficiency and therapeutic options for testosterone replacement therapy

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Abstract

Testosterone deficiency, or male hypogonadism, is a clinical syndrome characterized by the presence of clinical features with persistently low serum testosterone levels. Testosterone deficiency is an important health concern owing to its wide-ranging effects on sexual function, metabolic health, bone integrity, mood and overall quality of life. Testosterone deficiency can be classified as primary (testicular), secondary (hypothalamic-pituitary) or functional hypogonadism - the latter is commonly associated with ageing, obesity and chronic systemic disease. Diagnosis requires both clinical symptoms and biochemical confirmation of low testosterone levels, typically assessed using morning serum testosterone measurements. In instances of borderline values or discordance between symptoms and total testosterone levels, free testosterone and sex hormone-binding globulin measurements can provide additional diagnostic clarity. Evidence demonstrates that testosterone replacement therapy can provide clinically meaningful benefits in appropriately selected men with confirmed testosterone deficiency. Improvements have been reported in sexual function, mood, anaemia, body composition, bone mineral density and metabolic parameters, and contemporary data do not support an increased risk of prostate cancer or major adverse cardiovascular events when therapy is appropriately monitored. Multiple therapeutic formulations are available, including transdermal, oral, intramuscular, subdermal and intranasal preparations, each with distinct pharmacokinetic profiles and practical considerations. Individualized treatment selection, careful patient counselling and ongoing monitoring are essential to optimize clinical outcomes and minimize potential risks in men undergoing testosterone therapy.