What is the safest form of oral testosterone (testosterone) replacement therapy?

From the Guidelines

Oral testosterone undecanoate (Jatenzo) is the safest oral testosterone formulation currently available, due to its specialized delivery system that bypasses the liver's first-pass metabolism and lacks the 17-alpha-alkyl group associated with liver toxicity. This medication is designed to be taken twice daily with food, with a typical dosing range of 158 to 396 mg. According to the American College of Physicians, the FDA recently approved this oral formulation of testosterone undecanoate for use in the United States 1. The American Urological Association also recommends against prescribing alkylated oral testosterone due to its association with liver toxicity, making Jatenzo a safer alternative 1.

When considering oral testosterone replacement therapy, it is essential to weigh the potential benefits against the risks, including cardiovascular effects, such as blood pressure increases, and monitoring requirements for hormone levels, hematocrit, lipid profiles, and prostate health. Patients should be aware that oral testosterone generally has lower bioavailability compared to injections or topical applications, which may affect its efficacy for some individuals.

Key considerations for oral testosterone undecanoate include:

• Monitoring for potential cardiovascular effects, including blood pressure increases
• Regular monitoring of hormone levels, hematocrit, lipid profiles, and prostate health
• Awareness of lower bioavailability compared to injections or topical applications
• Individualized treatment under medical supervision to ensure the safest approach.

In the context of real-life clinical medicine, prioritizing the safety and well-being of patients is crucial, and oral testosterone undecanoate (Jatenzo) is the recommended oral formulation due to its safer profile compared to older oral testosterone preparations.

From the FDA Drug Label

Testosterone Undecanoate Capsules can cause blood pressure (BP) increases that can increase the risk of major adverse cardiovascular events (MACE), including non-fatal myocardial infarction, non-fatal stroke and cardiovascular death Due to this risk, use Testosterone Undecanoate Capsules only for the treatment of men with hypogonadal conditions associated with structural or genetic etiologies Monitor hemoglobin or hematocrit approximately every 3 months to detect increased red blood cell mass and polycythemia. Discontinue Testosterone Undecanoate Capsules if necessary Worsening of Benign Prostatic Hyperplasia (BPH) and Potential Risk of Prostate Cancer: Monitor patients for worsening of signs and symptoms of BPH. Evaluate patients for prostate cancer, including monitoring prostate specific antigen (PSA) prior to initiating and during treatment with androgens

The safest form of oral testosterone replacement therapy is not explicitly stated in the provided drug label. However, Testosterone Undecanoate Capsules are indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone.

• The label recommends monitoring for potential risks, including blood pressure increases, polycythemia, and worsening of BPH.
• It is essential to weigh the benefits and risks of Testosterone Undecanoate Capsules in patients who develop cardiovascular risk factors or cardiovascular disease on treatment 2. Key considerations for safe use include:
• Baseline cardiovascular risk assessment
• Blood pressure monitoring
• Hemoglobin or hematocrit monitoring
• Prostate cancer screening

From the Research

Safety of Oral Testosterone Replacement Therapy

• The safety of oral testosterone replacement therapy has been evaluated in several studies, with a focus on the formulation of oral testosterone undecanoate (TU) 3, 4, 5, 6, 7.
• Oral TU has been shown to be a convenient and effective option for many patients, with improved compliance compared to injectable forms of testosterone therapy 3.
• However, concerns have been raised about the potential liver toxicity of oral testosterone therapy, particularly with older formulations such as methyltestosterone 4.
• Newer formulations of oral TU have been developed, which have been shown to have a safer profile with regards to liver function 4, 5.
• Studies have demonstrated that oral TU is not associated with significant liver toxicity, and that increased liver function test values are not generally associated with oral TU formulations 4, 5.

Efficacy of Oral Testosterone Replacement Therapy

• The efficacy of oral TU has been evaluated in several clinical trials, which have shown that it can effectively restore serum testosterone levels to the physiologic range 5, 7.
• Oral TU has been shown to improve symptoms associated with hypogonadism, such as decreased energy and libido, as well as improve body composition and bone density 5.
• The pharmacokinetics of oral TU have been evaluated in several studies, which have shown that it can achieve therapeutic levels of testosterone with twice-daily dosing 7.

Comparison of Oral Testosterone Formulations

• Different formulations of oral testosterone have been developed, including testosterone undecanoate and methyltestosterone 3, 4.
• Testosterone undecanoate has been shown to be a safer and more effective option compared to methyltestosterone, with a lower risk of liver toxicity 4.
• Newer formulations of oral TU have been developed, which have improved storage conditions and pharmacokinetic profiles compared to older formulations 6, 7.