From the Guidelines
The primary treatment for polycythemia associated with Testosterone Replacement Therapy (TRT) is therapeutic phlebotomy, which involves removing blood to reduce red blood cell concentration, as recommended by the most recent guidelines 1. This procedure typically removes 450-500 mL of blood per session, with frequency determined by hematocrit levels and patient response. Phlebotomy should be performed when hematocrit exceeds 54%, though some clinicians initiate treatment at lower thresholds (>52%) 1. Additionally, TRT dose reduction or adjustment of administration frequency may be necessary to prevent recurrence. Changing from intramuscular to transdermal testosterone formulations can help as they typically cause less dramatic fluctuations in testosterone levels, as observed in studies comparing different formulations 1. Adequate hydration is important as dehydration can artificially elevate hematocrit readings. Patients should be monitored with regular complete blood counts every 3-6 months after starting TRT. The underlying mechanism of TRT-induced polycythemia involves testosterone's stimulation of erythropoietin production and direct effects on bone marrow, increasing red blood cell production, as explained in the literature 1. Some key points to consider in the management of polycythemia associated with TRT include:
- Monitoring hematocrit levels regularly to detect early signs of polycythemia
- Adjusting TRT dosage or formulation as needed to minimize the risk of polycythemia
- Considering therapeutic phlebotomy when hematocrit levels exceed 54%
- Maintaining adequate hydration to prevent dehydration-related elevations in hematocrit
- Consulting a hematologist if polycythemia persists despite these interventions, to rule out other underlying conditions. It is also important to note that the incidence of polycythemia may vary depending on the specific modality of testosterone used, with injectable testosterone associated with the greatest treatment-induced increases in hemoglobin/hematocrit 1.
From the FDA Drug Label
- 3 Polycythemia
Increases in hematocrit, reflective of increases in red blood cell mass, may require lowering or discontinuation of testosterone. Check hematocrit prior to initiating treatment. It would also be appropriate to re-evaluate the hematocrit 3 to 6 months after starting treatment, and then annually If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable concentration.
The treatment for polycythemia associated with testosterone replacement therapy is to:
- Lower or discontinue testosterone therapy
- Stop therapy until hematocrit decreases to an acceptable concentration if it becomes elevated 2
From the Research
Treatment Options for Polycythemia Associated with Testosterone Replacement Therapy
- Discontinuing TRT or reducing the dose if the hematocrit exceeds 54% (hemoglobin ≥180 g/L) is recommended by current guidelines 3
- Phlebotomy or blood donation may be considered, but repeat blood donation may be insufficient to maintain a hematocrit below 54% 3
- Adjusting TRT dosing, stopping therapy, or ordering a phlebotomy are common interventions upon diagnosis of secondary erythrocytosis 4
- Dose de-escalation of TRT and phlebotomy are management options for hypogonadal men on TRT with polycythemia and obstructive sleep apnea (OSA) 5
- Choosing the right testosterone preparation and route of administration can minimize the extent of hematocrit increases and potential cardiovascular incidents 6, 7
Considerations for Management
- The association between TRT-induced erythrocytosis and subsequent risk for veno-thrombotic events remains inconclusive 6
- Patients with risk factors for veno-thrombotic events may benefit from formulations that provide the smallest effect on blood parameters 6
- Novel methods to treat hypogonadism while minimizing side effects related to hematocrit levels are being explored, including new testosterone preparations 7
- Obstructive sleep apnea (OSA) should be considered in hypogonadal men on TRT who develop secondary polycythemia, particularly those with elevated BMI 5