What Are the Benefits and Risks of Testosterone Replacement Therapy?

Testosterone replacement therapy (TRT) is a popular medical intervention for men with low testosterone levels but it comes with certain risks. Learn more about TRT benefits & risks.

What Are the Benefits and Risks of Testosterone Replacement Therapy?

The symptoms of hypogonadism can be difficult to assess, as they are not specific and restoring testosterone (T) to physiological levels may not lead to clinical improvement. For this reason, it is important to understand which patients will benefit from Testosterone Optimization Program (TOP) and which risks are associated with it. TOP is a comprehensive program that includes testosterone replacement therapy (TRT) and other treatments to optimize testosterone levels. We hypothesized that men with a higher burden of systemic disease would be less likely to continue with TRT.

Testosterone is a hormone derived from Leydig cells that influences growth, mood, voice, and several other bodily functions. As men age, their testosterone levels decrease, as does their libido and energy levels. HIV infection has also been associated with a decrease in serum testosterone levels. Exogenous testosterone replacement can be achieved through several modalities (oral, topical, injectable), each of which has distinct advantages and disadvantages. Recent reports have made the practice of TRT increasingly controversial due to its potential risks.

Several small, retrospective studies have associated testosterone replacement with an increased risk of cardiovascular complications. Therefore, the substitute should be used sparingly until more conclusive data are available on the efficacy and safety of testosterone. Your chest won't change much in response to testosterone therapy. That said, surgeons usually recommend waiting at least 6 to 12 months after starting testosterone therapy before undergoing masculinizing thoracic surgery, also known as upper surgery, to first allow the contours of the muscles and soft tissues of the chest wall to adapt to their new pattern.

A meta-analysis conducted by Fernández-Balsells et al14 focused on the adverse effects of testosterone replacement therapy (including oral, transdermal, and intramuscular formulations). Testosterone increases levels of the platelet aggravating factor, thromboxane A2, which increases the risk of stroke and other thrombotic events. What complicates treatment planning is the fact that the symptoms of low testosterone are not specific and can be shared with other comorbid disorders. American College of Physicians guidelines indicate that testosterone therapy may improve sexual function a little in some men, but there is little evidence that it improves other functions, such as vitality and energy.

People who start taking testosterone later in life may experience less overall facial hair development than those who start at younger ages. Testosterone will cause thickening of the vocal cords, resulting in a more masculine voice. A systematic review by Ding et al.7 examined the relative risk of developing diabetes in relation to levels of endogenous sex hormones. Many men begin to experience the benefits of TRT within a few weeks of starting treatment, and achieve their wellness goals within four to six months. Some have reported that protease inhibitors can actually increase serum testosterone levels by reducing endogenous metabolism of the hormone. However, the benefits of testosterone replacement therapy should clearly outweigh the risks, especially in men with a history of myocardial infarction or coronary artery disease.

As mentioned above, testosterone levels naturally decline with age, and approximately 20% of men over 60 and approximately 50% of men over 80 have lower than normal testosterone levels compared to younger men.

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