From the Guidelines
Testosterone Replacement Therapy (TRT) for men is most safely and effectively administered orally through testosterone undecanoate capsules (brand name Jatenzo or Andriol), typically dosed at 120-240 mg daily divided into two doses with meals, as it bypasses first-pass liver metabolism and has been recently approved by the FDA 1.
Key Considerations
- The oral formulation of testosterone undecanoate is contraindicated in men with hypogonadal conditions not associated with structural or genetic etiologies, such as age-related hypogonadism, due to demonstrated increases in blood pressure and lack of established efficacy 1.
- A complete regimen includes regular monitoring of testosterone levels (aiming for 350-900 ng/dL), hematocrit, liver function, and PSA levels every 3-6 months 1.
- Patients should be aware that oral TRT may take 2-3 weeks to reach steady-state levels in the bloodstream.
- Alternative oral options include testosterone buccal adhesive (Striant), which adheres to the gum above the incisor and delivers 30 mg of testosterone directly into the bloodstream twice daily, avoiding liver metabolism.
Important Precautions
- Men with liver disease, uncontrolled heart failure, untreated sleep apnea, or prostate cancer should avoid TRT or use it with extreme caution under close medical supervision 1.
- The evidence for long-term safety of TRT is lacking, and most studies excluded men with recent cardiovascular disease 1.
Patient Preferences and Costs
- Patient preferences for TRT options vary, with some studies showing a preference for injectable testosterone over gel-based pellet regimens due to lower cost, while others prefer topical gels for convenience and ease of use 1.
- The annual cost of TRT can vary significantly, with transdermal formulations being more expensive than intramuscular formulations 1.
From the FDA Drug Label
The safety of Testosterone Undecanoate Capsules was evaluated in Study MRS-TU-2019EXT in 155 hypogonadal males [see Clinical Studies (14)]. All patients initially received Testosterone Undecanoate Capsules 200 mg orally twice daily If needed, the dosage was titrated to 100 mg once daily in the morning or 100 mg, 300 mg, or 400 mg twice daily to achieve testosterone concentrations in the normal range.
The safest and most effective oral Testosterone Replacement Therapy (TRT) option for men with hypogonadism, based on the provided drug label, is Testosterone Undecanoate Capsules. The dosage can be titrated to achieve normal testosterone concentrations, with initial dosing at 200 mg orally twice daily, and adjusted as needed to 100 mg once daily or 100 mg, 300 mg, or 400 mg twice daily 2.
- Key considerations for the use of Testosterone Undecanoate Capsules include:
- Monitoring for adverse reactions such as hypertension, polycythemia, and cardiovascular risk
- Adjusting the dosage to minimize the risk of adverse reactions
- Regular monitoring of lipid profiles and thyroid function
- Caution in patients with pre-existing cardiac, renal, or hepatic disease, as well as those at risk of hypercalcemia or sleep apnea.
From the Research
Safest and Most Effective Oral TRT Options
The safest and most effective oral Testosterone Replacement Therapy (TRT) options for men with hypogonadism include:
- Testosterone undecanoate (TU), which has been shown to be a safe and effective treatment option with a convenient dosing schedule and favorable pharmacokinetic and safety profiles 3
- Oral testosterone undecanoate (TLANDO), a novel oral testosterone undecanoate therapy that does not require dose titration and has been shown to be well tolerated with no deaths, no drug-related serious adverse events, and no hepatic adverse events 4
Characteristics of Oral TRT Options
The characteristics of oral TRT options include:
- Testosterone undecanoate (TU): long-acting, convenient dosing schedule, favorable pharmacokinetic and safety profiles, stable levels of testosterone, and few side effects 3
- Oral testosterone undecanoate (TLANDO): no dose titration requirement, well tolerated, and able to restore testosterone levels to the normal range in the majority of hypogonadal males 4
- Testosterone undecanoate (Andriol): safe oral androgen, no alteration in biochemical parameters of liver function, and no increased hepatic enzymatic breakdown of the androgen over time 5
Comparison with Other TRT Options
Oral TRT options have been compared with other TRT options, including:
- Intramuscular injections of esters, such as testosterone enanthate, which have been shown to have large fluctuations in serum testosterone levels and unsatisfactory shifts in mood and sexual function in some men 6
- Transdermal testosterone patches, which have been shown to have moderate to severe skin reactions in many users 6
- Hydroalcoholic gel containing 1% testosterone, which has been shown to be as efficient as a testosterone patch, but with fewer side-effects and a higher grade of patient satisfaction 6
Safety and Efficacy
The safety and efficacy of oral TRT options have been evaluated in several studies, including:
- A 10-year safety study of testosterone undecanoate (Andriol), which found no alteration in biochemical parameters of liver function and no increased hepatic enzymatic breakdown of the androgen over time 5
- A study of oral testosterone undecanoate (TLANDO), which found that 80% of subjects achieved a testosterone Cavg in the normal range and restored testosterone levels to mean testosterone Cavg of 476 ± 184 ng/dl at steady state 4