What should be done if testosterone levels drop while on testosterone replacement therapy (TRT)?

Management of Dropping Testosterone Levels During Testosterone Replacement Therapy

When testosterone levels drop during testosterone replacement therapy (TRT), the dosage should be adjusted or the formulation changed, with careful monitoring for adverse effects such as erythrocytosis.

Causes of Dropping Testosterone Levels During TRT

• Inadequate dosing relative to patient metabolism or absorption 1
• Inappropriate formulation selection for the individual patient 2
• Timing of blood tests relative to administration (especially with injectable formulations) 3
• Development of tolerance or changes in sex hormone binding globulin levels 4

Assessment Steps When Testosterone Levels Drop

1. Confirm the drop with repeat testing

   • Obtain morning testosterone levels on two separate occasions 3
   • Ensure proper timing of blood draws relative to administration (for injectable TRT, measure at trough levels before next injection) 3

2. Evaluate adherence to therapy

   • Verify patient is using medication as prescribed 4
   • Check for proper application technique with topical formulations 2

3. Consider formulation-specific issues

   • Transdermal preparations may have variable absorption 4
   • Injectable formulations have peaks and troughs that affect measured levels 2

Management Options

Dosage Adjustment

• Increase dosage if levels remain below target range (mid to upper-normal range) and patient is symptomatic 3
• For injectable testosterone:
  • Consider more frequent but smaller doses to maintain more stable levels 2
  • Adjust timing of injections based on symptom recurrence 4

Change Formulation

• Consider switching formulations if adequate levels cannot be achieved with current method 2
• Injectable testosterone may provide more reliable absorption than topical preparations for some patients 5
• 53% of patients prefer injectable testosterone over gel-based regimens, primarily due to lower cost 5
• However, 71% of patients who tried multiple formulations preferred topical gel for convenience and ease of use 5

Monitor for Adverse Effects

• Watch for erythrocytosis, especially with dosage increases or injectable formulations 5

  • Erythrocytosis occurs in 2.8% of patients using patches, 11.3-17.9% with gels, and up to 43.8% with injections 5
  • If erythrocytosis develops, consider dosage reduction, temporary discontinuation, or therapeutic phlebotomy 5

• Monitor prostate health

  • Prostate volume typically increases during the first six months of TRT 5
  • Regular PSA monitoring and digital rectal examination are recommended 3

Special Considerations

• For men desiring fertility

  • Consider alternative treatments that preserve hypothalamic-pituitary-gonadal axis function 6
  • Options include clomiphene citrate, tamoxifen, or gonadotropins, though these are often off-label uses 6

• For men with cardiovascular concerns

  • Use testosterone cautiously in men with congestive heart failure due to potential fluid retention 3
  • Evidence on long-term cardiovascular effects remains inconclusive 5

Follow-up Protocol

• Schedule first follow-up visit 1-2 months after dosage adjustment to assess efficacy 3
• Monitor at 3-6 month intervals for the first year, then yearly thereafter 3
• At each visit, assess:
  • Symptomatic response to treatment
  • Serum testosterone levels
  • Hematocrit or hemoglobin
  • PSA levels and perform digital rectal examination 3

Common Pitfalls to Avoid

• Treating based on symptoms alone without laboratory confirmation 3
• Targeting supraphysiologic testosterone levels, which increases risk of adverse effects 3
• Failing to consider timing of blood draws relative to testosterone administration 4
• Not addressing adherence issues before changing therapy 2