From the Guidelines
Testosterone replacement therapy (TRT) should be approached with caution in patients with polycythemia, as testosterone can worsen this condition by stimulating red blood cell production. For patients who require TRT but have polycythemia, the recommended approach is to first address the elevated hematocrit through therapeutic phlebotomy to bring levels below 54% before initiating testosterone, as suggested by the general principles of managing polycythemia 1. Once TRT is started, use the lowest effective dose that maintains testosterone levels in the mid-normal range (400-600 ng/dL). Topical formulations like gels (AndroGel 1% 5-10g daily or Testim 1% 5-10g daily) or transdermal patches (Androderm 2-4mg daily) may cause less erythrocytosis than injectable forms. If injectable testosterone is necessary, consider reduced dosing such as testosterone cypionate 50-100mg every 7-10 days rather than standard 200mg every 2 weeks. Regular monitoring is essential, with complete blood counts every 3-6 months, and testosterone levels 4-6 weeks after dose adjustments. If hematocrit rises above 54% during treatment, temporarily discontinue testosterone and perform therapeutic phlebotomy. The relationship between testosterone and polycythemia occurs because testosterone stimulates erythropoietin production and directly affects bone marrow stem cells, increasing red blood cell production, as noted in a study on the risks of testosterone-replacement therapy 1. Key considerations in managing polycythemia include the use of hydroxyurea as a first-line therapy for patients who require cytoreduction, as recommended by the European LeukemiaNet 1. However, the primary concern in the context of TRT is the potential for exacerbating polycythemia, thus the approach should prioritize minimizing this risk while effectively managing the patient's testosterone levels. Given the potential for testosterone to stimulate erythropoiesis, careful monitoring and adjustment of therapy are crucial to prevent complications associated with increased red blood cell production. In the management of polycythemia vera, guidelines suggest maintaining the hematocrit at less than 45% through phlebotomy and considering cytoreductive therapy in high-risk patients 1, but these principles must be balanced with the need to manage testosterone levels appropriately in patients undergoing TRT. Ultimately, the goal is to minimize the risk of morbidity and mortality associated with both polycythemia and testosterone replacement therapy, while optimizing the patient's quality of life.
From the FDA Drug Label
Hemoglobin and hematocrit should be checked periodically for polycythemia in patients who are receiving high doses of androgens. The treatment for polycythemia with testosterone replacement is to monitor hemoglobin and hematocrit levels periodically.
- Key points:
- Monitoring is necessary for patients receiving high doses of androgens.
- Polycythemia is a potential risk with androgen therapy.
- No specific treatment for polycythemia is mentioned in the label, only monitoring. 2
From the Research
Treatment for Polycythemia with Testosterone Replacement
- Polycythemia is a common adverse effect of testosterone replacement therapy (TRT) and may predispose patients to adverse vascular events 3.
- Current guidelines recommend regular laboratory monitoring and discontinuing TRT or reducing the dose if the hematocrit exceeds 54% (hemoglobin ≥180 g/L) 3.
- Studies have shown that men with polycythemia secondary to TRT have a higher risk of major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE) 4.
- The development of polycythemia while on TRT is an independent risk factor for MACE and VTE in the first year of therapy 4.
- Erythrocytosis and polycythemia secondary to TRT are associated with an increased risk of venothromboembolism (VTE) 5.
- The evidence regarding the risk for VTE with increased hematocrit is inconclusive, and further trials are needed to fully evaluate the hematological side effects associated with TRT 5, 6.
Management of Polycythemia with Testosterone Replacement
- Clinicians may adjust TRT dosing, stop therapy, order a phlebotomy, or recommend a combination of these upon encountering secondary erythrocytosis 6.
- Routine hematologic monitoring is recommended for patients taking testosterone, with adjustment of therapy when appropriate 7.
- The hematocrit-based cutoffs present in multiple guidelines appear to be arbitrarily chosen, and the evidence for secondary polycythemia causing harm during TT is scarce 6.
- Different formulations of TRT may have varying effects on blood parameters, and injectables tend to produce the greatest effect on hematocrit 5.