When to re-check testosterone levels in patients on testosterone replacement therapy (TRT)?

When to Re-Check Testosterone Levels on TRT

Measure testosterone levels at 1-2 months after initiating therapy or any dose change to assess efficacy, then monitor every 3-6 months during the first year, and annually thereafter. 1, 2

Initial Monitoring Timeline

• First follow-up should occur at 1-2 months after starting testosterone replacement therapy to evaluate treatment response and determine if dose adjustments are needed 1, 2
• Formal testosterone testing should be performed at 2-3 months after treatment initiation or after any dose modification 1, 2
• Subsequent monitoring visits occur at 3-6 month intervals for the first year of treatment 3, 1
• After the first year, annual monitoring is sufficient for stable patients 3, 1

Critical Timing Considerations for Blood Draws

The timing of blood collection relative to testosterone administration is crucial and varies by formulation:

For Injectable Testosterone (Cypionate/Enanthate)

• Measure testosterone levels midway between injections (typically day 5-7 for weekly injections) to accurately assess treatment efficacy 1, 2
• Peak serum testosterone occurs 2-5 days post-injection, with return to baseline by 10-14 days 1, 4
• Injectable formulations create fluctuating levels with peaks and valleys that must be considered when interpreting results 1
• Avoid measuring at peak (days 1-2) or trough (days 10-14) as these will not reflect average therapeutic levels 4

For Transdermal Gel

• Measure at both peak (+2 hours post-application) and trough (+23 hours) to ensure adequate levels throughout the day 5
• Serum testosterone levels are significantly lower at +23 hours compared to +2 hours after gel application 5
• Only 36.7% of patients with adequate levels at peak maintain therapeutic levels at trough 5

Target Testosterone Levels

• Aim for total testosterone in the mid-to-upper normal range (450-600 ng/dL, or middle tertile of normal) 1, 2
• If testosterone levels are in the low-normal range with suboptimal clinical response, increase the dose 1
• Discontinue therapy if target levels are achieved without symptom improvement after 3-6 months 2

Comprehensive Monitoring Beyond Testosterone

At each follow-up visit, the following parameters must be assessed:

Hematologic Monitoring

• Check hematocrit prior to initiating treatment 6, 7
• Re-evaluate hematocrit at 3-6 months after starting treatment, then annually 3, 6, 7
• If hematocrit becomes elevated above the reference range, temporarily withhold testosterone, reduce dosage, or perform phlebotomy 1, 6, 7

Prostate Monitoring

• Perform digital rectal examination at baseline and each follow-up visit 3, 1
• Measure PSA at baseline and each monitoring visit 3, 1, 2
• Perform prostate biopsy or refer to urology if PSA rises above 4.0 ng/mL 3, 1, 2
• Consider biopsy if PSA increases by ≥1.0 ng/mL within any 12-month period 3, 1, 2
• If PSA rises by 0.7-0.9 ng/mL in one year, repeat PSA in 3-6 months and perform biopsy if further elevation occurs 3, 1, 2

Clinical Assessment

• Assess symptomatic response to treatment, including libido, erectile function, energy, and mood 1
• Evaluate voiding symptoms for worsening benign prostatic hyperplasia 3, 1
• Screen for sleep apnea or its exacerbation 3, 1
• Check for gynecomastia 3

Common Pitfalls to Avoid

• Don't measure testosterone at random times: Injectable testosterone requires midway measurement between doses; morning measurement is essential for all formulations 2
• Don't rely solely on peak or trough levels: For transdermal preparations, both measurements provide important information about adequacy of dosing 5
• Don't ignore hematocrit monitoring: Polycythemia is a common adverse effect that increases thromboembolic risk and requires dose adjustment or discontinuation 6, 7
• Don't use different PSA assays: All PSA values should be obtained using the same assay, preferably at the same laboratory, for accurate trend monitoring 1
• Don't measure testosterone during recovery from GnRH agonists: After discontinuation of GnRH agonists, testosterone may not return to normal for a median of 16.6 weeks 1

Dose Adjustment Protocol

• If testosterone levels are subtherapeutic at 2-3 months, increase the dose and recheck in another 2-3 months 1, 2
• If testosterone levels are supraphysiologic, reduce the dose to minimize cardiovascular and hematologic risks 2, 6, 7
• Monitor every 6-12 months during maintenance therapy to ensure therapeutic levels and early detection of supraphysiologic levels 2