Can testosterone replacement therapy cause thrombocytosis (elevated platelet count)?

From the Guidelines

Testosterone therapy can cause elevated platelet counts in some individuals, and regular monitoring of complete blood counts is essential to mitigate the risk of thromboembolic events. Testosterone replacement therapy (TRT) has been associated with increases in platelet count and hematocrit levels, a condition known as secondary polycythemia or erythrocytosis, as reported in studies such as 1. This effect is more common with injectable forms of testosterone like testosterone cypionate or enanthate, particularly at higher doses, though it can occur with any form of TRT including gels, patches, or pellets. The mechanism involves testosterone's stimulation of bone marrow to produce more red blood cells and platelets.

Key Considerations

• Patients on TRT should have regular blood tests to monitor complete blood counts, typically every 3-6 months initially and then annually once stable, as recommended by guidelines such as 1.
• If platelet counts become significantly elevated, physicians may recommend temporarily reducing the testosterone dose, switching to a different formulation, or implementing therapeutic phlebotomy to reduce blood viscosity.
• This side effect is more common in older men and those with pre-existing cardiovascular risk factors, and elevated platelets can potentially increase the risk of blood clots, so monitoring is an important part of testosterone therapy management, as noted in studies like 1 and 1.
• Prior to commencing testosterone therapy, all patients should undergo a baseline measurement of hemoglobin/hematocrit, and if the Hct exceeds 50%, clinicians should consider withholding testosterone therapy until the etiology is formally investigated, as suggested by 1.

Monitoring and Management

• Regular monitoring of hematocrit levels is crucial, and a Hct >54% warrants intervention, such as dose reduction or temporary discontinuation, as recommended by 1.
• The incidence of polycythemia for one particular modality of testosterone compared to another cannot be determined, but trials have indicated that injectable testosterone is associated with the greatest treatment-induced increases in hemoglobin/Hct, as reported in 1.

From the Research

Testosterone Therapy and Platelet Count

• The effect of testosterone therapy on platelet count is a topic of interest, with some studies suggesting a potential increase in platelet count.
• A study published in 2020 2 found that testosterone administration was associated with increases in total leukocyte, neutrophil, monocyte, and platelet counts in healthy men.
• The study reported a significant increase in platelet count, with an estimated change from baseline of -7.3,8.4,8.7, and 8.9 × 10^3 cells/µL (P = 0.033).
• However, another study published in 2014 3 did not specifically investigate the effect of testosterone therapy on platelet count, but rather focused on the association between testosterone therapy and thrombosis.

Mechanisms and Risks

• The mechanisms underlying the potential increase in platelet count with testosterone therapy are not fully understood, but may involve the differentiation of hematopoietic progenitors into the myeloid lineage 2.
• The increase in platelet count may also be related to the erythropoietic effects of testosterone, which can lead to an increase in hematocrit and potentially alter blood viscosity and flow characteristics 4, 5.
• However, a systematic review and meta-analysis published in 2018 6 found no evidence of a statistically significant association between testosterone therapy and venous thromboembolism, suggesting that the risk of thrombotic events may be low.

Clinical Implications

• The clinical implications of the potential increase in platelet count with testosterone therapy are not fully understood and require further investigation.
• Monitoring of platelet count and other hematological parameters may be necessary in patients receiving testosterone therapy, particularly those with a history of thrombotic events or other cardiovascular risk factors.
• Further studies are needed to fully understand the effects of testosterone therapy on platelet count and the potential risks and benefits of this treatment.