When should testosterone levels be rechecked after initiating testosterone replacement therapy (TRT)?

When to Recheck Testosterone Levels After Initiating TRT

Testosterone levels should be measured at 2-3 months after initiating testosterone replacement therapy or after any dose change, with subsequent monitoring at 3-6 month intervals during the first year, then annually thereafter. 1

Initial Monitoring Timeline

The first testosterone level check occurs at 2-3 months (approximately 14 and 28 days for dose titration purposes) after treatment initiation. 1, 2

• For testosterone gel formulations specifically, the FDA label recommends measuring pre-dose morning serum testosterone at approximately 14 days and 28 days after starting treatment to guide dose adjustments 2
• The first follow-up visit should occur at 1-2 months to assess treatment efficacy and consider dose adjustments if needed 1
• After the initial titration period, monitoring visits should be performed at 3-6 month intervals for the first year 1
• Following the first year of stable therapy, annual monitoring is sufficient 1

Timing Considerations Based on Formulation

For injectable testosterone (cypionate or enanthate), blood should be drawn midway between injections—typically day 5-7 for weekly injections—to accurately assess treatment efficacy. 1

• Peak serum testosterone levels occur 2-5 days post-injection, with return to baseline by 10-14 days 1
• Injectable formulations create fluctuating levels with peaks and valleys that must be considered when interpreting results 1
• Clinicians must interpret blood test results based on the interval since the most recent injection 1

For transdermal gel formulations, measuring both peak (+2 hours post-application) and trough (+23 hours) levels can provide a more complete picture of testosterone exposure throughout the day. 3

• Research demonstrates that 70% of patients achieve adequate testosterone levels at +2 hours, but only 36.7% maintain adequate levels at +23 hours 3
• This dual measurement approach helps prevent both supra-physiological peaks and inadequate trough concentrations 3

Target Levels and Dose Adjustment Criteria

Target testosterone levels should be in the mid-to-upper normal range (350-750 ng/dL), with dose adjustments made based on pre-dose morning measurements. 1, 2

Dose Adjustment Algorithm (per FDA labeling):

• If pre-dose testosterone >750 ng/dL: Decrease daily dose by 20.25 mg 2

• If pre-dose testosterone 350-750 ng/dL: Continue current dose 2

• If pre-dose testosterone <350 ng/dL: Increase daily dose by 20.25 mg 2

• If clinical response is suboptimal and testosterone levels are in the low-normal range, increase the dosage while carefully monitoring for side effects 1

Comprehensive Monitoring Beyond Testosterone Levels

At each follow-up visit, measure serum testosterone, PSA, and hematocrit/hemoglobin, while assessing symptomatic response and performing digital rectal examination. 1

PSA Monitoring Schedule and Action Thresholds:

• PSA >4.0 ng/mL: Perform prostate biopsy or refer to urology 1
• PSA increase ≥1.0 ng/mL within any 12-month period: Consider biopsy 4, 1
• PSA increase of 0.7-0.9 ng/mL in one year: Repeat PSA in 3-6 months and perform biopsy if further elevation occurs 4, 1
• PSA increase >1.0 ng/mL during first 6 months of treatment: Urologic referral for possible biopsy 4
• PSA increase >0.4 ng/mL per year after first 6 months: Urologic referral for possible biopsy 4

Hematocrit Monitoring:

• If hematocrit rises above the reference range, consider temporarily withholding testosterone therapy, reducing the dosage, or performing phlebotomy 1

Critical Pitfalls to Avoid

Do not measure testosterone levels when serum testosterone is unstable or rebounding post-androgen deprivation therapy. 4

• Serum testosterone concentration should be relatively stable over the measurement period (ideally ≤10% variation) 4
• After discontinuation of GnRH agonists, testosterone may not return to normal for a median of 16.6 weeks 4

Ensure all PSA values used for monitoring are obtained using the same assay, preferably at the same laboratory. 4

• PSA values should be recorded with a maximum of 2 significant digits after the decimal point 4
• Treatment that may affect PSA (e.g., saw palmetto, 5-alpha reductase inhibitors) must be constant during monitoring 4