What are the benefits of testosterone replacement therapy (TRT) for men over 50 with hypogonadism?

From the Guidelines

Testosterone replacement therapy (TRT) may provide small improvements in sexual functioning and quality of life for men over 50 with hypogonadism, but its benefits for other common symptoms of aging are limited. According to a recent study published in the Annals of Internal Medicine 1, TRT can improve energy levels and mood, but its effects on cognitive function and other symptoms are less clear. The study found that TRT may provide small improvements in sexual functioning, with enhanced libido and better erectile function, but its benefits for other common symptoms of aging, such as decreased energy and mobility, are limited.

Benefits of TRT

• Improved sexual functioning, with enhanced libido and better erectile function
• Small improvements in quality of life
• Potential improvements in energy levels and mood
• Increased muscle mass and bone density, which can help prevent osteoporosis

Common TRT Options

• Injections (testosterone cypionate or enanthate, typically 100-200mg every 1-2 weeks)
• Daily transdermal gels (AndroGel, Testim, 50-100mg)
• Patches (Androderm, 2-6mg daily)
• Pellets implanted subcutaneously every 3-6 months

Important Considerations

• Regular monitoring is essential, including testosterone levels, complete blood count, PSA testing, and digital rectal exams, as TRT may increase red blood cell production (potentially causing polycythemia) and could affect prostate health
• Men with prostate cancer, severe heart disease, sleep apnea, or high red blood cell counts should approach TRT cautiously
• TRT works by directly supplementing the body's declining testosterone levels, allowing the hormone to bind to androgen receptors throughout the body and restore normal physiological functions that depend on adequate testosterone levels. A study published in the Annals of Internal Medicine 1 found that evidence from 20 observational studies with a mean follow-up ranging from 0.73 to 10.3 years showed no increased risk for mortality, cardiovascular events, prostate cancer, or pulmonary embolism or deep venous thrombosis. However, evidence for long-term safety is lacking.

Patient Preferences

• A study published in the Annals of Internal Medicine 1 found that 53% of patients receiving testosterone treatment chose injectable testosterone over gel-based pellet regimens, mostly because of lower cost
• Another study found that most patients (71%) preferred a topical gel over an injection or patch for reasons attributed to convenience, ease of use, and nonstaining of clothes, among others.

From the FDA Drug Label

Limitations of use: Safety and efficacy of testosterone gel 1.62% in men with “age-related hypogonadism” have not been established. Safety and efficacy of testosterone gel 1.62% in males less than 18 years old have not been established. Safety and efficacy of Testosterone Enanthate Injection, USP in men with age-related hypogonadism have not been established.

The FDA drug label does not answer the question.

From the Research

Benefits of Testosterone Replacement Therapy for Men over 50 with Hypogonadism

The benefits of testosterone replacement therapy (TRT) for men over 50 with hypogonadism include:

• Improvement in sexual function, depressive symptoms, bone density, and lean body mass 2
• Relief of symptoms in most hypogonadal men, with all approved testosterone replacement methods able to restore normal serum testosterone concentrations 3
• Increase in skeletal muscle mass and bone mineral density (BMD) 4
• Improvement in physical function, anaemia, visceral adiposity, and reduction in the risk of diabetes mellitus, coronary artery disease, falls, and fractures 4

Considerations for Testosterone Replacement Therapy

When considering TRT for men over 50 with hypogonadism, the following points should be taken into account:

• The treatment should be individualized, with the selection of the method depending on the patient's preference and advice from the physician 3
• The use of hepatotoxic androgens should be avoided 3
• Testosterone treatment induces reversible suppression of spermatogenesis, and alternative treatments may be necessary if fertility is desired in the near future 3
• Clinicians should monitor men receiving TRT for symptom improvement, potential adverse effects, and adherence, with regular measurements of serum testosterone, hematocrit, and prostate-specific antigen levels 2

Safety and Efficacy of Testosterone Replacement Therapy

The safety and efficacy of TRT for men over 50 with hypogonadism have been studied in several clinical trials, with the following findings:

• TRT may improve sexual function, depressive symptoms, bone density, and lean body mass, but the evidence is conflicting regarding its effect on cardiovascular events and mortality 2
• A large, randomized trial showed that TRT does not increase the risk of myocardial infarction or stroke, even in patients at high risk 2
• The recommendations for TRT are based on data from a limited number of randomized controlled trials, as well as non-randomized clinical studies and observational studies 5