In an adult male receiving testosterone replacement therapy who has a total testosterone level of 1026 ng/dL, how should the treatment regimen be adjusted?

Dose Reduction Required for Supraphysiologic Testosterone Level

Your patient's testosterone level of 1026 ng/dL is more than double the target mid-normal range of 450–600 ng/dL, and you must reduce the dose by approximately 50% immediately to minimize the risk of erythrocytosis and other adverse effects. 1, 2

Immediate Action: Dose Reduction

• Reduce the current testosterone dose by 50% to bring serum levels into the target mid-normal range of 450–600 ng/dL. 1, 2
• The American Urological Association explicitly recommends using the minimal dosing necessary to achieve testosterone levels in the normal physiologic range of 450–600 ng/dL, not supraphysiologic levels. 1, 2
• Supraphysiologic testosterone concentrations (>1000 ng/dL) significantly increase the risk of erythrocytosis, with injectable testosterone causing elevated hematocrit in up to 43.8% of users. 1

Why This Level Is Too High

• The goal of testosterone replacement therapy is to normalize testosterone levels combined with symptom improvement, not to maximize serum concentrations. 2
• Levels above 1000 ng/dL are considered supraphysiologic and carry dose-dependent risks, particularly erythrocytosis (elevated hematocrit/hemoglobin), which can increase blood viscosity and exacerbate cardiovascular, cerebrovascular, and peripheral vascular disease. 1
• The FDA-approved dosing for testosterone cypionate is 50–400 mg every 2–4 weeks, with the goal of achieving mid-normal testosterone levels, not peak levels exceeding 1000 ng/dL. 1, 3

Monitoring After Dose Adjustment

• Recheck testosterone levels 2–3 months after the dose reduction, measuring midway between injections (days 5–7 for weekly dosing or days 7–10 for bi-weekly dosing) to target 450–600 ng/dL. 1, 2
• Monitor hematocrit/hemoglobin at the same visit, as supraphysiologic testosterone levels markedly increase erythrocytosis risk; withhold therapy if hematocrit exceeds 54% and consider phlebotomy in high-risk cases. 1
• Once stable levels in the 450–600 ng/dL range are confirmed, monitor every 6–12 months with testosterone, hematocrit, PSA (if >40 years), and digital rectal examination. 1, 2

Formulation Considerations

• If the patient is on injectable testosterone (cypionate or enanthate), consider switching to transdermal testosterone gel (e.g., 1.62% gel at 40.5 mg daily) to achieve more stable day-to-day levels and reduce erythrocytosis risk (15.4% with transdermal vs. 43.8% with injectable). 1
• Transdermal preparations provide more consistent testosterone exposure without the supraphysiologic peaks seen with injectable formulations. 1, 2

Critical Pitfalls to Avoid

• Do not continue the current dose even if the patient reports feeling well, as supraphysiologic levels increase adverse event risk, particularly erythrocytosis and potential cardiovascular complications. 1
• Do not stop therapy abruptly if the patient was initially hypogonadal; dose reduction—not discontinuation—is the appropriate intervention. 1, 2
• Do not ignore the elevated level because it is "only slightly above 1000 ng/dL"; the target is 450–600 ng/dL, and levels above 1000 ng/dL are associated with significantly higher rates of erythrocytosis. 1, 2
• Do not delay rechecking hematocrit, as erythrocytosis can develop rapidly with supraphysiologic testosterone levels, particularly in older patients or those with pre-existing cardiovascular disease. 1

Expected Outcomes After Dose Reduction

• Testosterone levels should normalize to the mid-normal range (450–600 ng/dL) within 2–3 months of dose reduction. 1, 2
• The patient should continue to experience the small but significant improvements in sexual function and libido (standardized mean difference 0.35) that testosterone therapy provides, without the added risks of supraphysiologic dosing. 1
• Erythrocytosis risk will decrease substantially once testosterone levels are brought into the physiologic range. 1