From the Guidelines
Traditional oral testosterone is not an effective treatment option for testosterone replacement therapy due to first-pass metabolism, but specially formulated oral testosterone undecanoate capsules can be effective. Standard testosterone pills are rapidly broken down by the liver before reaching the bloodstream, making them ineffective and potentially causing liver damage with long-term use 1. Instead, effective testosterone replacement options include testosterone undecanoate capsules (Jatenzo, Kyzatrex) which are specially formulated to be absorbed through the lymphatic system, bypassing first-pass metabolism; these are taken twice daily with food 1. Other effective options include:
- Testosterone injections (typically 50-200mg every 1-2 weeks)
- Transdermal gels (applied daily to shoulders, upper arms, or abdomen)
- Patches
- Buccal tablets (applied to the gums)
- Pellets implanted under the skin These alternative delivery methods allow testosterone to enter the bloodstream directly, maintaining proper hormone levels while avoiding liver toxicity 1. The choice between these options depends on patient preference, cost considerations, and individual response to treatment. It's essential to note that the FDA has approved an oral formulation of testosterone undecanoate for use in the United States, but it is contraindicated in men with hypogonadal conditions not associated with structural or genetic etiologies, citing demonstrated increases in blood pressure and lack of established efficacy 1.
From the FDA Drug Label
Testosterone Undecanoate Capsules is expected to produce testosterone concentrations that approximate normal concentrations seen in healthy men. The average daily NaF/EDTA plasma testosterone concentration was 393.3 (±113. 6) ng/dL after 90 days of treatment (normal eugonadal range in NaF/EDTA plasma: 222-800 ng/dL. The primary efficacy endpoint of achieving testosterone C avg in normal testosterone range was met
Oral testosterone, specifically testosterone undecanoate, is an effective treatment option as it produces testosterone concentrations that approximate normal concentrations seen in healthy men, with the primary efficacy endpoint of achieving testosterone C avg in the normal range being met 2.
- The average daily plasma testosterone concentration was within the normal range after 90 days of treatment.
- The treatment is expected to produce testosterone concentrations that approximate normal concentrations seen in healthy men.
From the Research
Effectiveness of Oral Testosterone
- Oral testosterone undecanoate (TU) is a formulation of testosterone that can be taken by mouth, providing a convenient option for patients with testosterone deficiency 3, 4.
- Studies have shown that oral TU can effectively increase testosterone levels in hypogonadal men, with significant improvements in symptoms such as decreased energy and libido 5, 6.
- The efficacy of oral TU has been demonstrated in various clinical trials, with results showing that it can improve testosterone levels, sexual function, and overall quality of life in men with testosterone deficiency 7, 6.
Safety of Oral Testosterone
- Concerns have been raised about the potential liver toxicity of oral testosterone formulations, particularly older formulations such as methyltestosterone 3.
- However, newer formulations of oral TU have been shown to have a safer profile, with no significant increase in liver function test values or clinically significant liver toxicities noted in clinical trials 3, 7.
- Oral TU has also been found to be well-tolerated in hypogonadal patients, with no significant risk of adverse effects or serious adverse effects compared to placebo 6.
Comparison to Other Testosterone Therapies
- Oral TU is one of several testosterone therapy options available, including injectable, transdermal, and nasal formulations 4, 5.
- Each formulation has its own benefits and drawbacks, and the choice of therapy should be individualized based on patient needs and preferences 4, 7.
- Oral TU may be a convenient option for patients who prefer a oral formulation, but it may not be suitable for all patients, particularly those with certain medical conditions or taking certain medications 7, 6.