What is the efficacy of oral testosterone (testosterone undecanoate) for testosterone replacement therapy?

Oral Testosterone Undecanoate Efficacy for Testosterone Replacement Therapy

Oral testosterone undecanoate is an effective testosterone replacement therapy option with minimal hepatotoxicity compared to older oral testosterone formulations, though it has less robust efficacy data compared to injectable and transdermal formulations. 1

Efficacy Profile

• Oral testosterone undecanoate provides the unmodified testosterone molecule while partially avoiding first-pass liver metabolism 2
• Clinical effectiveness:
  • Restores normal hormonal values and corrects signs and symptoms of hypogonadism 2
  • Can improve sexual function and libido, which are the most consistently documented benefits of testosterone replacement therapy 3
  • May enhance quality of life, increase lean body mass, and reduce abdominal subcutaneous adipose tissue 3

Pharmacokinetic Considerations

• Plasma testosterone levels with oral testosterone undecanoate generally undergo larger fluctuations compared to injectable or transdermal formulations 2
• Requires more frequent dosing (typically daily) compared to injectable formulations 2
• Absorption can be variable with oral formulations, affecting bioavailability 2
• Target testosterone levels should be in the middle tertile of the normal reference range (450-600 ng/dL) 4

Safety Profile

• Unlike older methyltestosterone formulations, newer oral testosterone undecanoate formulations have not shown significant hepatotoxicity in clinical trials 1
• Long-term safety studies (10 years) have demonstrated no alterations in biochemical parameters of liver function 5, 6
• The American College of Physicians notes that oral testosterone undecanoate does not appear to have appreciable hepatotoxicity 4
• Despite this improved safety profile, the FDA specifically states that oral formulations are contraindicated in men with "age-related hypogonadism" not associated with structural or genetic etiologies 4

Clinical Considerations

• Oral testosterone undecanoate should not be prescribed to men who are currently trying to conceive, as it can interrupt normal spermatogenesis 4
• Monitoring requirements include:
  • PSA and hematocrit/hemoglobin levels at baseline and periodically during treatment 4, 3
  • Digital rectal examination 4
  • Evaluation for sleep apnea symptoms and cardiovascular parameters 3

Comparative Efficacy

• Injectable and transdermal formulations have more robust efficacy data compared to oral formulations 4
• The American College of Physicians suggests that intramuscular formulations would be preferred over transdermal options due to lower cost, with similar clinical effectiveness 3

Important Caveats

• Alkylated oral testosterone (methyltestosterone) should not be prescribed due to established liver toxicity 4
• Commercially manufactured testosterone products should be prescribed rather than compounded testosterone when possible 4
• Testosterone therapy should not be commenced for a period of three to six months in patients with a history of cardiovascular events 4
• Testosterone replacement therapy has been associated with exacerbation of sleep apnea, particularly in men treated with higher doses 4

Oral testosterone undecanoate represents a viable option for testosterone replacement therapy with improved safety compared to older oral formulations, though its efficacy profile may not match that of injectable formulations, particularly for patients requiring stable serum testosterone levels.