Target Testosterone Levels During Testosterone Replacement Therapy
The target testosterone level during testosterone replacement therapy should be in the mid-normal range of 450-600 ng/dL, measured at the appropriate time point for the formulation used, while levels above 750 ng/dL are considered elevated and require dose reduction. 1, 2
Normal Therapeutic Range
The American Urological Association defines the therapeutic target as 450-600 ng/dL (middle tertile of normal range), using the minimal dosing necessary to achieve this level. 1, 2
The broader acceptable range is 300-1,000 ng/dL, but targeting mid-normal values (450-600 ng/dL) optimizes clinical response while minimizing adverse effects. 1
Treatment programs should aim for normalization of testosterone levels combined with improvement in symptoms or signs. 2
Elevated Levels Requiring Intervention
Testosterone levels greater than 750 ng/dL are considered elevated and require dose reduction by approximately 20.25 mg (one pump actuation or equivalent). 3
Supraphysiological testosterone levels (>1,000 ng/dL) significantly increase the risk of adverse effects, particularly erythrocytosis. 1
Levels above 1,500 ng/dL represent dangerously elevated concentrations that substantially increase cardiovascular and hematologic risks. 4
Timing of Measurement by Formulation
For injectable testosterone (enanthate/cypionate):
- Measure levels midway between injections, targeting 500-600 ng/dL at this timepoint. 1, 5
- Peak levels occur 2-5 days after injection, while trough levels return toward baseline by 10-14 days post-injection. 1
- Weekly dosing (50-100 mg) provides more stable levels compared to biweekly administration (100-200 mg every 2 weeks). 1, 5
For transdermal preparations (gels/patches):
- Levels can be measured at any time, with peak values occurring 6-8 hours after gel application. 2
- More consistent day-to-day levels are achieved compared to injectable formulations. 2
For testosterone undecanoate:
- Mean average levels of 494.9 ng/dL during the 10-week dosing interval are typical, with 94% of patients maintaining levels within 300-1,000 ng/dL. 4
Monitoring Schedule
Measure testosterone levels at 2-3 months after treatment initiation or any dose change. 1, 2, 5
Once stable therapeutic levels are confirmed on a given dose, monitoring every 6-12 months is sufficient. 1, 2, 5
Each monitoring visit should include assessment of hematocrit/hemoglobin, as erythrocytosis risk is dose-dependent (43.8% with IM injections vs 15.4% with transdermal patches). 1
Dose Adjustment Algorithm
When levels are >750 ng/dL:
- Reduce dose by approximately 50% initially if levels are more than double the upper target range. 1
- For gel formulations, decrease by 20.25 mg (one pump actuation). 3
- Recheck levels in 2-3 months after adjustment. 1
When levels are 350-750 ng/dL:
- Continue current dose if patient is symptomatic improvement. 3
- Consider slight increase if levels are in low-normal range (350-450 ng/dL) with suboptimal clinical response. 1
When levels are <350 ng/dL:
- Increase dose by 20.25 mg (one pump actuation or equivalent). 3
- If maximal transdermal dose fails to achieve adequate levels, consider switching to intramuscular injection therapy. 1
Common Pitfalls to Avoid
Do not continue supraphysiological doses even if the patient reports feeling well, as elevated levels increase adverse event risk regardless of symptoms. 1
Do not measure testosterone levels at random times for injectable formulations—timing matters significantly for accurate interpretation. 1, 2
Avoid stopping therapy abruptly in patients who were initially hypogonadal with elevated levels; dose reduction is the appropriate intervention. 1
Do not ignore hematocrit monitoring, as erythrocytosis is the most common dose-dependent adverse effect requiring intervention. 1
Injectable testosterone may carry greater cardiovascular risk compared to transdermal preparations, possibly due to fluctuating testosterone levels with supraphysiological peaks. 1, 5