Monitoring Testosterone Levels in Patients on Testosterone Replacement Therapy
You should check total testosterone levels yearly (or every 6-12 months once stable) in patients on testosterone supplementation, and free testosterone is only necessary if total testosterone results are borderline or the patient has conditions affecting sex hormone-binding globulin (SHBG) such as obesity or diabetes. 1, 2
Initial Monitoring Phase (First 3-6 Months)
The most intensive monitoring occurs early in treatment when dose adjustments are most likely needed:
- Measure total testosterone at 2-3 months after treatment initiation or any dose change to ensure therapeutic levels are achieved 2, 3
- Target mid-normal testosterone levels of 500-600 ng/dL during treatment 2
- For injectable testosterone (cypionate/enanthate), draw levels midway between injections (days 5-7 after injection), not at peak (days 2-5) or trough (days 13-14) 2, 3
- For transdermal gel, levels can be measured at any consistent time, though some data suggest checking both at +2 hours and +23 hours after application provides the most complete picture 4
Long-Term Monitoring (After Stabilization)
Once therapeutic testosterone levels are confirmed and the patient is clinically stable:
- Monitor total testosterone every 6-12 months 2, 3
- Continue checking hematocrit at each visit - withhold treatment if >54% and consider phlebotomy 2, 3
- Monitor PSA levels in men over 40 years - refer for urologic evaluation if PSA increases >1.0 ng/mL in first 6 months or >0.4 ng/mL per year thereafter 2, 3
When to Check Free Testosterone
Free testosterone measurement is not routinely necessary for monitoring but should be obtained in specific situations 2, 3:
- Borderline total testosterone levels (near 300 ng/dL threshold) where clinical decision-making is unclear 5, 6
- Obesity - where low SHBG may artificially lower total testosterone while free testosterone remains normal 2, 6
- Diabetes or metabolic syndrome - conditions that alter SHBG levels 6
- When total testosterone is in the low-normal range but symptoms persist 5
Use equilibrium dialysis method for free testosterone measurement, as it is the most accurate technique 2, 6
Critical Monitoring Beyond Testosterone Levels
The AUA guidelines emphasize that nearly half of men on testosterone therapy never have their levels checked - a dangerous practice pattern 1. Beyond testosterone measurement, you must monitor:
- Hematocrit/hemoglobin - Injectable testosterone carries a 43.8% risk of erythrocytosis (hematocrit >52%) compared to 2.8-17.9% with gels 3
- Clinical symptom response - particularly sexual function and libido, which show the most reliable improvement (standardized mean difference 0.35) 2
- Reassess at 12 months - discontinue testosterone if no improvement in sexual function, as continued therapy without benefit exposes patients to unnecessary risks 2
Common Pitfalls to Avoid
- Never draw testosterone at peak levels (days 2-5 post-injection) as supraphysiologic values may lead to inappropriate dose reduction 2
- Never draw at trough (days 13-14 post-injection) as low values may trigger unnecessary dose escalation 2
- Don't measure testosterone at random times - always use morning samples (8-10 AM) due to diurnal variation 1, 3
- Don't rely on free testosterone alone for routine monitoring - total testosterone is the primary screening and monitoring test 7, 5
- Don't continue therapy indefinitely without reassessing benefit - if symptoms haven't improved by 12 months, particularly sexual symptoms, discontinuation should be strongly considered 2