Testosterone Replacement Therapy: Indications, Application Protocols, and Side Effect Profile

Testosterone Replacement Therapy has evolved from speculative attempts in the 18th and 19th centuries to the isolation and synthesis of the hormone in the 1930s, followed by the development of different and safer methods of administration throughout the 20th century, leading to today's modern treatment protocols. Testosterone is the male sex hormone and is essential for maintaining male secondary sexual characteristics and fertility. Androgen deficiency seen in young men due to problems in brain regions such as the hypothalamus and pituitary gland, genetic problems, testicular disease, or damage caused by chemotherapy can be treated with testosterone replacement. Over the past decade, testosterone replacement therapy has been preferred for middle-aged or elderly men with age-related or obesity related declines in serum testosterone levels. However, these conditions are not approved indications for testosterone therapy. The benefits and safety of these drugs for treating age-related low testosterone levels have not yet been established. Some studies suggesting that testosterone replacement therapy increases the risk of cardiovascular disease led the FDA to issue a warning on January 31, 2014, which included explanations about the potential cardiovascular risks of testosterone replacement therapy. On February 28, 2025, the FDA issued a statement updating the risks of stroke, heart attack, and death after reviewing the results of a clinical study showing that approved testosterone products did not increase the risk of heart attack or stroke compared to a placebo, an inactive treatment. The FDA removed warnings about these risks from FDA-approved drugs. Only a warning regarding potential increases in blood pressure levels was added. The benefits of testosterone replacement therapy in treating the symptoms of hypogonadism have been proven by studies. This article contains a brief summary of studies conducted over the last 10 years regarding assessments of cardiovascular risks that may be associated with testosterone replacement therapy.