What are the guidelines for testosterone replacement therapy via injections in patients with confirmed hypogonadism?

Guidelines for Testosterone Injection Therapy in Confirmed Hypogonadism

Testosterone replacement therapy via injections is recommended for men with confirmed hypogonadism, with a standard dosage of 50-400 mg administered every 2-4 weeks intramuscularly, with 200 mg every 2 weeks or 300 mg every 3 weeks being the most effective regimens for normalizing hormone levels while minimizing injection frequency. 1, 2

Diagnosis Criteria for Hypogonadism

• Diagnosis requires:
  • Consistent symptoms of hypogonadism
  • Confirmed low testosterone levels (<300 ng/dL) on at least two separate morning measurements 1
  • Comprehensive hormonal evaluation including morning total testosterone, LH, and FSH 1

Injection Protocol

Dosing Guidelines

• FDA-approved dosage: 50-400 mg every 2-4 weeks via deep intramuscular injection in the gluteal muscle 2
• Most effective regimens based on evidence:
  • 200 mg every 2 weeks
  • 300 mg every 3 weeks 3
  • These regimens provide optimal suppression of elevated LH/FSH while maintaining testosterone levels within normal range 3

Administration

• Injections must be administered intramuscularly only (never intravenously) 2
• Deep gluteal muscle is the recommended injection site 2
• Inspect solution for particulate matter before administration 2
• If crystals form during storage, warming and shaking the vial should redissolve them 2

Monitoring Protocol

• Testosterone levels:

  • Measure after starting treatment and every 6-12 months while on therapy
  • Target level: mid-normal range (450-600 ng/dL)
  • For injectable testosterone, measure levels midway between injections 1

• Dose adjustment based on pre-dose morning testosterone:

  Pre-Dose Morning Testosterone	Dose Adjustment
  >750 ng/dL	Decrease daily dose by 20-25%
  350-750 ng/dL	No change
  <350 ng/dL	Increase daily dose by 20-25%

• Safety monitoring:

  • Hemoglobin/hematocrit: Discontinue if Hct >54%
  • PSA: Monitor according to AUA guidelines
  • Evaluate symptoms after 3 months, reassess at 12 months and periodically thereafter 1

Considerations for Injection vs. Other Formulations

• Intramuscular testosterone is recommended as initial treatment due to:

  • Similar clinical effectiveness to other formulations
  • Considerably lower cost compared to transdermal options
  • Established efficacy for improving sexual function 1

• However, injectable testosterone may cause:

  • Fluctuating testosterone levels (peaks and troughs)
  • Higher risk of elevated estradiol and hematocrit compared to subcutaneous formulations 4
  • Subcutaneous testosterone enanthate autoinjector (100 mg weekly) may provide a more favorable safety profile with lower post-therapy estradiol and hematocrit levels 4

Contraindications and Precautions

Absolute Contraindications

• Prostate cancer
• Breast cancer
• Desire for near-term fertility
• Severe sleep apnea
• Uncontrolled heart failure
• Recent cardiovascular events 1

Relative Contraindications

• History of hepatocellular carcinoma
• Thrombosis
• Other cardiovascular risk factors 1

Special Considerations for Fertility

• Exogenous testosterone should not be prescribed to men interested in current or future fertility, as it suppresses spermatogenesis 1
• For men wishing to preserve fertility, consider alternative treatments:
  • Human chorionic gonadotropin (hCG)
  • Selective estrogen receptor modulators (SERMs)
  • Aromatase inhibitors 1, 5

Common Adverse Effects

• Erythrocytosis (dose-dependent: 2.8-17.9%)
• Suppression of spermatogenesis
• Peripheral edema
• Emotional lability
• Potential cardiovascular effects (long-term safety uncertain) 1

Cardiovascular Safety

• Recent evidence from the TRAVERSE study indicates that testosterone replacement therapy is reasonable and does not increase the risk of stroke in men 45-80 years of age with confirmed hypogonadism 6