Is oral testosterone a recommended treatment option?

Oral Testosterone Should Not Be Used Due to Liver Toxicity Risks

Clinicians should not prescribe alkylated oral testosterone due to significant liver toxicity risks, including abnormal liver function tests, cholestasis, and jaundice. 1

Types of Oral Testosterone and Safety Concerns

Oral testosterone formulations fall into two main categories:

1. 17-alpha-alkylated androgens (e.g., methyltestosterone)

   • FDA-approved but not recommended due to:
     • Significant liver toxicity 1
     • Risk of abnormal liver function tests
     • Potential for cholestasis and jaundice
   • The American Urological Association (AUA) explicitly recommends against their use

2. Newer testosterone undecanoate oral formulations

   • Recently FDA-approved (2022) 2
   • Better safety profile than alkylated forms 3
   • Requires administration with food 2
   • Still carries risks including:
     • Increased blood pressure
     • Potential cardiovascular events
     • Polycythemia
     • Worsening of BPH symptoms

Preferred Alternative Testosterone Delivery Methods

Given the risks associated with oral testosterone, alternative delivery methods are preferred:

• Transdermal testosterone gels

  • Favorable pharmacokinetic profile with steady-state levels within 24 hours 4
  • Lower risk of polycythemia compared to injectable forms
  • Fewer application site reactions compared to patches
  • Caution needed to prevent interpersonal transfer

• Injectable testosterone

  • Traditional options (testosterone enanthate) require frequent injections
  • Newer formulations like intramuscular testosterone undecanoate offer more stable levels with injections every 3 months 5

Special Considerations

For Men Desiring Fertility

If testosterone therapy is needed in men who wish to preserve fertility:

• Avoid all exogenous testosterone (oral, injectable, or topical) 1
• Consider alternative therapies:
  • Selective estrogen receptor modulators (SERMs)
  • Human chorionic gonadotropin (hCG)
  • Aromatase inhibitors 1, 6

For Patients with Cardiovascular Risk

• Testosterone therapy should not be initiated for 3-6 months after cardiovascular events 1
• Oral testosterone undecanoate can increase blood pressure, potentially increasing risk of major adverse cardiovascular events 2
• Regular blood pressure monitoring is essential if any form of testosterone is used 2

Monitoring Requirements

For patients on any testosterone therapy:

• Initial follow-up testosterone level to ensure target levels are achieved
• Testosterone levels every 6-12 months during therapy 1
• Monitor for polycythemia (hematocrit/hemoglobin)
• Monitor prostate-specific antigen levels
• Target testosterone level: 450-600 ng/dL 1, 6

Common Pitfalls to Avoid

• Using oral testosterone despite availability of safer alternatives
• Failing to monitor for liver toxicity if oral testosterone is used
• Not considering fertility preservation in younger men
• Overlooking cardiovascular risk factors
• Using testosterone for "age-related hypogonadism" without proper diagnosis

In conclusion, while newer oral testosterone undecanoate formulations show improved safety profiles compared to older alkylated forms, the AUA guidelines clearly recommend against oral testosterone due to liver toxicity concerns. Transdermal gels and injectable formulations remain the preferred options for testosterone replacement therapy.