What is the treatment (Trt)?

From the Guidelines

Testosterone Replacement Therapy (TRT) is a treatment used for men with low testosterone levels, and it typically involves administering testosterone through injections, patches, gels, or pellets.

Treatment Options

The most recent and highest quality study, published in 2020 in the Annals of Internal Medicine 1, provides guidance on the treatment of adult men with age-related low testosterone.

• Common injectable formulations include testosterone cypionate or enanthate at doses of 50-100mg weekly or 100-200mg every two weeks.
• Topical options include gels like AndroGel or Testim applied daily to the shoulders, upper arms, or abdomen.

Monitoring and Risks

Before starting TRT, patients should undergo comprehensive blood testing to confirm low testosterone levels and rule out contraindications.

• Regular monitoring of testosterone levels, hematocrit, PSA, and liver function is necessary during treatment.
• TRT can improve energy, libido, muscle mass, and mood in men with true deficiency, but carries risks including polycythemia, sleep apnea exacerbation, and potential cardiovascular effects.

Patient Preferences

According to a study published in 2020 in the Annals of Internal Medicine 1, 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.

Clinical Considerations

The American College of Physicians clinical guideline published in 2020 in the Annals of Internal Medicine 1 provides guidance on the treatment of adult men with age-related low testosterone.

• The guideline recommends that treatment decisions be made on a case-by-case basis, taking into account the individual patient's preferences, values, and medical history.
• The annual cost of TRT can vary significantly, with the transdermal formulation costing $2135.32 per beneficiary and the intramuscular formulation costing $156.24 per beneficiary, according to 2016 Medicare Part D Drug Claims data.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Testosterone Replacement Therapy (TRT)

• TRT aims to improve symptoms and signs of testosterone deficiency, including decreased libido, erectile dysfunction, and loss of muscle and bone mass, by increasing serum testosterone levels to a physiologic range 2.
• The routes of delivery approved for use in the Western world include buccal, nasal, subdermal, transdermal, and intramuscular (IM) 2.
• Testosterone gel formulations have become a popular TRT option since their advent in the year 2000, restoring testosterone levels to mid-normal physiological levels as early as within 24 hours 3.

Benefits and Risks of TRT

• Studies suggest that TRT may improve sexual function, depressive symptoms, bone density, and lean body mass 4.
• Evidence is conflicting regarding the effect of TRT on cardiovascular events and mortality, although a large, randomized trial showed that it does not increase the risk of myocardial infarction or stroke, even in patients at high risk 4.
• Clinicians must consider the unique characteristics of each patient and make necessary adjustments in the management of late-onset hypogonadism (LOH) to provide the safest and most beneficial results 2.

Treatment Options and Monitoring

• Treatment method should take into consideration patient preference, pharmacokinetics, potential for medication interactions, formulation-specific adverse effects, treatment burden, and cost 4.
• Clinicians should monitor men receiving TRT for symptom improvement, potential adverse effects, and adherence, and measure serum testosterone, hematocrit, and prostate-specific antigen levels at baseline and at least annually in men 40 years or older receiving TRT 4.
• Testosterone replacement gel has been shown to be efficacious with an acceptable safety profile, although further optimization of titration schema to reduce maximum testosterone concentration (Cmax) is warranted while maintaining the average steady-state total testosterone concentration 5.