How often should testosterone levels be rechecked in a patient on testosterone replacement therapy?

Testosterone Level Monitoring During Replacement Therapy

Testosterone levels should be checked at 2-3 months after initiating therapy or any dose change, then every 3-6 months during the first year, and annually thereafter. 1

Initial Monitoring Phase

First follow-up should occur at 1-2 months to assess treatment efficacy and consider dose adjustments if needed. 1 However, formal testosterone level testing should wait until 2-3 months after treatment initiation or dose change to allow steady-state levels to be achieved. 1

The FDA-approved testosterone gel labeling specifies that dose titration should be based on pre-dose morning serum testosterone concentration at approximately 14 days and 28 days after starting treatment or following dose adjustment. 2 This more frequent early monitoring allows for rapid optimization of dosing.

Ongoing Monitoring Schedule

• Monitor every 3-6 months for the first year of therapy. 3, 1
• After the first year, monitor annually if levels are stable and the patient is responding well. 3, 1

Timing of Blood Draw: Critical Considerations

For injectable testosterone (cypionate or enanthate), measure levels midway between injections (typically day 5-7 for weekly injections) to accurately assess treatment efficacy. 1 Peak serum testosterone occurs 2-5 days post-injection, with return to baseline by 10-14 days. 1 Drawing levels at the wrong time will give misleading results—either falsely elevated at peak or falsely low at trough.

For transdermal gels, the timing is more nuanced. While steady-state levels are relatively stable, one study demonstrated that serum testosterone at +2 hours post-application was significantly higher than at +23 hours (just before the next dose). 4 Only 36.7% of patients who had adequate levels at +2 hours maintained adequate levels at +23 hours. 4 This suggests that checking both peak (+2 hours) and trough (+23 hours) levels may provide more complete information about adequacy of dosing throughout the day. 4

Target Levels and Dose Adjustment

Target testosterone levels should be in the middle tertile of the normal reference range (450-600 ng/dL). 3 The AUA guideline emphasizes using minimal dosing necessary to achieve this physiologic range. 3

• If testosterone is below 350 ng/dL: Increase dose by one increment. 3
• If testosterone is 350-750 ng/dL: Continue current dose. 3
• If testosterone exceeds 750 ng/dL: Decrease dose by one increment. 3

Comprehensive Monitoring Beyond Testosterone

At each monitoring visit, the following should be assessed:

• PSA levels at every visit during the first year (every 3-6 months), then annually. 3, 1
• Hematocrit or hemoglobin at each visit, as testosterone can cause erythrocytosis. 3, 1
• Digital rectal examination should be performed at each monitoring visit. 3, 1
• Symptomatic response, voiding symptoms, and sleep apnea assessment. 1

PSA Monitoring Thresholds

Consider prostate biopsy or urology referral if:

• PSA rises above 4.0 ng/mL. 1
• PSA increases by ≥1.0 ng/mL within any 12-month period. 3, 1
• PSA increases 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

Common Pitfalls to Avoid

Drawing testosterone levels at the wrong time is the most common error. For injectable testosterone, levels drawn at peak (2-5 days post-injection) will be falsely elevated, while levels at trough (just before next injection) will be falsely low. 1 Always draw midway between injections for injectable formulations.

Inadequate follow-up monitoring is widespread. A population-based study found that only 36% of men on testosterone therapy had any follow-up testosterone level drawn, and 49% of those with initially low testosterone remained biochemically hypogonadal after starting therapy, suggesting non-compliance or inadequate dosing. 5 This underscores the critical importance of systematic monitoring.

Failing to check both efficacy and safety parameters. Monitoring testosterone levels alone is insufficient—PSA and hematocrit must be checked concurrently to detect prostate-related issues and erythrocytosis. 3, 1