What is the recommended approach for testosterone management in patients with hypogonadism?

Testosterone Management in Hypogonadism

The recommended approach for testosterone management in hypogonadism is to confirm the diagnosis with morning total testosterone levels <300 ng/dL on at least two separate occasions, followed by initiating testosterone replacement therapy (TRT) with intramuscular formulations as first-line treatment due to similar clinical effectiveness to other formulations and lower cost. 1, 2

Diagnosis and Evaluation

• Confirm hypogonadism with:

  • Morning total testosterone levels <300 ng/dL on at least two separate occasions
  • Comprehensive hormonal evaluation including LH and FSH measurements
  • Assessment of symptoms: sexual (reduced libido, erectile dysfunction), physical (decreased energy, strength), and psychological (low mood, decreased motivation) 1

• Baseline measurements before starting therapy:

  • Testosterone, LH, and FSH levels
  • Hemoglobin and hematocrit levels
  • Cardiovascular risk factors assessment 1

Treatment Options

First-Line Therapy

1. Intramuscular testosterone formulations

   • 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
   • Note: Injectable testosterone can cause fluctuating levels and should be measured midway between injections 1

2. Transdermal preparations (gels and patches)

   • Alternative first-line treatment
   • Provide more stable day-to-day testosterone levels
   • Apply to clean, dry, intact skin of upper arms and shoulders only 1, 2
   • Avoid application to abdomen, genitals, chest, armpits, or knees 2
   • Cover application site with clothing once dry 2
   • Wait minimum 2 hours after application before swimming or showering 2

Alternative Options for Men Desiring Fertility Preservation

• Clomiphene citrate (CC)

  • Commonly prescribed off-label
  • Preserves or may improve fertility 1

• Gonadotropin therapy

  • Start with human chorionic gonadotropin (hCG) alone
  • Add follicle-stimulating hormone (FSH) if needed 1

Dose Adjustment and Monitoring

• Dose adjustment based on pre-dose morning testosterone levels:

  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%

• Monitoring schedule:

  • Measure testosterone levels after starting treatment
  • Continue monitoring every 6-12 months while on therapy
  • Target level: mid-normal range (450-600 ng/dL)
  • Monitor hemoglobin/hematocrit (discontinue if Hct >54%)
  • Monitor PSA according to guidelines 1
  • Consider discontinuation after 3-6 months if symptoms don't improve 1

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

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

Special Considerations

• Secondary exposure risk:

  • Virilization has been reported in children secondarily exposed to testosterone gel
  • Children should avoid contact with unwashed or unclothed application sites
  • Patients should strictly adhere to recommended instructions for use 2

• Limitations of use:

  • Safety and efficacy not established in "age-related hypogonadism" or "late-onset hypogonadism"
  • Not established in males under 18 years old 2

• Application site considerations:

  • Absorption varies by application site, with arms/shoulders providing best absorption compared to chest/abdomen or legs 3
  • The application site and dose of testosterone gel 1.62% are not interchangeable with other topical testosterone products 2

By following this structured approach to testosterone management in hypogonadism, clinicians can optimize treatment outcomes while minimizing potential risks and adverse effects.