Does testosterone (testosterone) cause polycythemia (increased red blood cell count)?

From the Guidelines

Yes, testosterone can cause polycythemia, which is an abnormal increase in red blood cell count, as evidenced by a direct relation between testosterone dosage and the incidence of erythrocytosis 1. This is a well-documented side effect of testosterone replacement therapy (TRT), particularly when testosterone levels exceed the normal physiological range. The risk increases with higher doses and longer duration of treatment.

Key Points to Consider

• Testosterone stimulates erythropoiesis (red blood cell production) in the bone marrow by increasing erythrocytoietin production in the kidneys, with this effect being dose-dependent, as seen in a study where erythrocytosis occurred in 2.8 percent of men receiving 5 mg per day by nonscrotal patches and in 11.3 percent and 17.9 percent of men treated with gel preparations of 50 mg per day and 100 mg per day, respectively 1.
• Men on TRT should have their complete blood count monitored regularly, typically every 3-6 months during the first year of treatment and then annually thereafter.
• If hematocrit rises above 54%, testosterone therapy may need to be adjusted or temporarily discontinued, and therapeutic phlebotomy (blood removal) might be necessary to reduce blood viscosity and associated cardiovascular risks, as recommended for monitoring and management 1.
• Patients with risk factors for cardiovascular disease should be monitored more closely, and staying well-hydrated and avoiding smoking can help minimize the risk of complications from testosterone-induced polycythemia.

Monitoring and Management

• Regular monitoring of hematocrit or hemoglobin levels is crucial for early detection of erythrocytosis, allowing for timely interventions such as dosage reduction, withholding of testosterone, or therapeutic phlebotomy 1.
• The choice of intervention depends on the severity of erythrocytosis and the individual patient's risk factors, emphasizing the need for personalized care in managing TRT-related polycythemia.

From the FDA Drug Label

Laboratory tests: Hemoglobin and hematocrit levels (to detect polycythemia) should be checked periodically in patients receiving long-term androgen administration. The FDA drug label suggests that polycythemia (increased red blood cell count) is a potential concern in patients receiving long-term testosterone administration, as it recommends periodic checks of hemoglobin and hematocrit levels to detect it.

• This implies that testosterone may cause polycythemia in some patients, and therefore, monitoring is necessary.
• The label does not provide a clear causal relationship but indicates a need for monitoring, which suggests a potential association between testosterone and polycythemia 2.

From the Research

Testosterone and Polycythemia

• Testosterone therapy has been associated with an increased risk of polycythemia, a condition characterized by an elevated red blood cell count 3, 4, 5, 6, 7.
• Studies have shown that different formulations of testosterone therapy may have varying effects on the development of polycythemia, with intramuscular testosterone enantate and testosterone cypionate being associated with a higher risk of polycythemia compared to transdermal testosterone and nasal testosterone gel 3, 5.
• The prevalence of polycythemia in men treated with testosterone therapy has been reported to range from 10% to 40%, with some studies suggesting that the risk of polycythemia may be higher with certain formulations of testosterone therapy 3, 4, 5, 7.
• Regular monitoring of hematocrit levels is recommended for men undergoing testosterone therapy to detect and manage polycythemia, and to reduce the risk of adverse vascular events 3, 4, 6.

Risk Factors and Formulations

• Intramuscular testosterone enantate and testosterone cypionate have been associated with a higher risk of polycythemia compared to transdermal testosterone and nasal testosterone gel 3, 5.
• Subcutaneous testosterone pellet therapy has also been linked to an increased risk of polycythemia, with an estimated rate of 10.4% at 6 months, 17.3% at 12 months, and 30.2% at 24 months 7.
• Smoking and higher body mass index (BMI) may also be risk factors for the development of polycythemia in men undergoing testosterone therapy 5.

Management and Monitoring

• Regular laboratory monitoring and discontinuing testosterone therapy or reducing the dose if the hematocrit exceeds 54% are recommended to manage polycythemia 4, 6.
• Phlebotomy or blood donation may be considered in some cases, but the evidence for its effectiveness in reducing the risk of polycythemia is limited 4, 6.
• Clinicians should be aware of the potential risks of polycythemia associated with testosterone therapy and take steps to monitor and manage this condition to reduce the risk of adverse vascular events 3, 4, 6.