How is polycythemia managed in chronic testosterone (exogenous androgen) users?

Management of Polycythemia in Chronic Testosterone Users

The primary management of testosterone-induced polycythemia involves therapeutic phlebotomy when hematocrit exceeds 54%, combined with dose reduction or temporary discontinuation of testosterone therapy. 1, 2

Monitoring Strategy

Establish a rigorous monitoring schedule:

• Measure hematocrit/hemoglobin at baseline before initiating testosterone therapy 1, 2
• Recheck at 1-2 months after starting or dose adjustment 2
• Monitor every 3-6 months during the first year 2
• Continue annual monitoring once stable 1
• Use hemoglobin rather than hematocrit when possible, as it provides more accurate measurements with less variability 2

Critical Intervention Threshold

Hematocrit >54% (hemoglobin ≥180 g/L) mandates immediate intervention due to increased blood viscosity and cardiovascular risk. 1, 2 This threshold is particularly critical in elderly patients or those with pre-existing vascular disease, where elevated hematocrit aggravates coronary, cerebrovascular, and peripheral circulation. 2

If baseline hematocrit exceeds 50%, withhold testosterone therapy until the underlying etiology is formally investigated, as this may represent primary polycythemia vera or secondary erythrocytosis from another cause rather than medication-induced erythrocytosis. 1, 2

Management Algorithm When Hematocrit Exceeds 54%

Three intervention options exist, often used in combination:

1. Therapeutic Phlebotomy

• First-line intervention to remove excess red blood cells 2
• Reduces blood viscosity and cardiovascular risk 2
• Important caveat: Research demonstrates that repeat blood donation alone is often insufficient to maintain hematocrit below 54% in testosterone users, with 44% of repeat donors maintaining persistently elevated hemoglobin levels despite regular donation. 3 This means phlebotomy should not be relied upon as the sole intervention.

2. Dose Reduction

• Decrease testosterone dosage to reduce erythropoiesis stimulation 1, 2
• Higher trough serum testosterone concentrations independently predict polycythemia development (odds ratio 15.0), making dose adjustment particularly effective 4

3. Temporary Discontinuation

• Withhold testosterone therapy temporarily until hematocrit normalizes 1, 2
• Resume at lower dose once hematocrit returns to acceptable range 1

Formulation-Specific Risk Considerations

Injectable testosterone formulations carry substantially higher risk than transdermal preparations:

• Injectable testosterone: 43.8% incidence of erythrocytosis 2
• Transdermal preparations: 15.4% incidence 2
• Testosterone pellets may have even higher rates (30.2% at 24 months) 5
• Transdermal testosterone showed 0% polycythemia in one study of transmasculine individuals 6

Consider switching from injectable to transdermal formulations in patients who develop recurrent polycythemia, as this may eliminate the need for repeated phlebotomy. 2, 6

Additional Risk Factors Requiring Closer Monitoring

Patients with the following conditions need more aggressive surveillance:

• Chronic obstructive pulmonary disease or other conditions that independently raise hematocrit 1, 2
• Advanced age, diabetes, hypertension, or smoking history 2
• Pre-existing cardiovascular or cerebrovascular disease 2

Diagnostic Workup for Elevated Hematocrit

Before attributing polycythemia solely to testosterone, exclude other causes:

• Measure serum erythropoietin (EPO) level—testosterone-induced polycythemia typically shows normal or slightly elevated EPO, whereas polycythemia vera shows low EPO 7
• Check for hypoxia-driven causes (sleep apnea, chronic lung disease) 7
• Rule out androgen-secreting tumors if testosterone levels are disproportionately elevated 1

Critical Pitfalls to Avoid

Do not assume blood donation alone adequately manages testosterone-induced polycythemia. Research shows 25% of clinic visits by testosterone users had hemoglobin ≥180 g/L despite regular donation, and nearly half maintained persistently elevated levels. 3 This creates a false sense of security while cardiovascular risk persists.

Do not continue testosterone at the same dose while relying solely on phlebotomy, as this addresses the symptom rather than the cause and exposes patients to ongoing cardiovascular risk. 2, 3

Duration of testosterone therapy does not predict polycythemia risk—trough testosterone levels do. 4 Focus monitoring on achieving appropriate testosterone levels rather than assuming longer treatment duration increases risk.

Cardiovascular Risk Context

Despite theoretical concerns, direct evidence linking testosterone-associated erythrocytosis to thromboembolic events remains limited, with no testosterone-associated thromboembolic events directly reported in major studies. 2 However, the increased blood viscosity from elevated hematocrit impairs microcirculation and oxygen delivery, particularly in vulnerable populations. 2