When should testosterone levels be checked in patients on intramuscular (IM) testosterone replacement therapy?

Timing of Testosterone Level Monitoring for IM Testosterone Replacement Therapy

For patients on intramuscular testosterone replacement therapy, testosterone levels should be checked at midpoint of the injection interval (typically 5-7 days after injection for short-acting formulations) to accurately assess therapeutic levels. 1

Initial Monitoring Schedule

• First follow-up: 1-2 months after initiating therapy to assess efficacy and consider dose adjustments 2
• Early monitoring: Every 3-6 months during the first year 2, 1
• Maintenance monitoring: Yearly after the first year once stable 2, 1

Optimal Timing Based on Formulation

Short-Acting Testosterone Cypionate/Enanthate

• Peak levels: Occur 2-5 days post-injection 2
• Trough levels: Return to baseline by 10-14 days post-injection 2
• Recommended timing:
  • Mid-cycle (day 5-7 for weekly injections, day 7-10 for biweekly injections)
  • Consistent timing between injections for accurate comparison

Long-Acting Testosterone Undecanoate (AVEED)

• Dosing schedule: Initial dose, 4 weeks later, then every 10 weeks 3
• Monitoring: After the third injection (at 14 weeks) when steady state is achieved 3
• Target range: Average concentration (Cavg) of 495 ng/dL (142) over the 10-week interval 3

Interpretation of Results

• Target range: Mid to upper-normal range (500-600 ng/dL) 1
• Pharmacokinetic considerations:
  • Weekly 100mg injections: More stable levels, lower risk of erythrocytosis (1% vs 8%) 4
  • Biweekly 200mg injections: Higher peak levels, greater fluctuations 4
  • Body weight impact: Inversely correlated with testosterone levels achieved 3
    • BMI >30 kg/m²: Lower average concentrations (445 ± 116 ng/dL)
    • BMI <26 kg/m²: Higher average concentrations (579 ± 101 ng/dL)

Additional Parameters to Monitor

• Every visit:
  • Hematocrit/hemoglobin (risk of erythrocytosis)
  • PSA (prostate cancer risk)
  • Symptom response
  • Digital rectal examination
  • Voiding symptoms
  • Sleep apnea symptoms 2, 1

Clinical Pitfalls to Avoid

• Timing errors: Checking levels at peak or trough can lead to inappropriate dose adjustments
• Misinterpretation: Not accounting for injection timing when interpreting results
• Overreaction to single values: Clinical response should guide therapy alongside lab values
• Ignoring symptoms: If clinical response is adequate, no dose adjustment needed even with low-normal levels 2
• Missing erythrocytosis: If hematocrit rises above reference range, consider temporarily withholding therapy, reducing dose, or performing phlebotomy 2

Special Considerations

• PSA monitoring: Consider urologic referral if PSA increases >1.0 ng/mL in first 6 months or >0.4 ng/mL per year thereafter 2
• Fertility concerns: Testosterone therapy suppresses spermatogenesis and should be avoided in men desiring fertility 1
• Cardiovascular risk: Carefully monitor men with pre-existing cardiovascular disease 1

By following this structured monitoring approach, clinicians can optimize testosterone replacement therapy while minimizing potential adverse effects and ensuring appropriate therapeutic levels are maintained.