Erythrocytosis and Polycythemia Vera

Any person undergoing testosterone replacement therapy (TRT) may experience an elevated red blood cell count, a condition known as secondary erythrocytosis (SE). This phenomenon is more common in individuals receiving injectable testosterone compared to those using topical testosterone forms, such as creams or gels. 

Many physicians, including endocrinologists, often express unnecessary concern regarding elevated red blood cell counts because they mistakenly associate it with a blood disorder called polycythemia vera (PCV). PCV leads to hyperviscosity (thick blood) and increases the risk of clotting, as well as potential complications like heart attacks, strokes, and pulmonary embolisms. However, it is important to note that TRT does NOT cause polycythemia vera. The two conditions are frequently confused by healthcare providers, despite having entirely different causes, diagnoses, treatments, and outcomes.

TRT can lead to secondary erythrocytosis due to the increased production of a kidney hormone called erythropoietin. This process is similar to what occurs in people living at high altitudes, where the body naturally increases red blood cell production to adapt to lower oxygen levels. This is why many Olympic training centers are located at high altitudes. Training in such conditions enhances athletes' endurance by allowing their bodies to deliver more oxygen to cells when they compete at sea level.

People who live at high altitudes and athletes who train there do not require medical attention for SE because it represents a physiological, natural, and beneficial adaptation that occurs specifically in red blood cells, unlike PCV, which affects other blood cells and clotting factors. Individuals with chronic lung diseases such as 

COPD also develop SE. This response is similarly physiological and beneficial, as it allows the blood to carry more oxygen, thereby improving their quality of life.

Physicians often observe a high red blood cell count, along with increased hematocrit and hemoglobin levels, in clients receiving TRT. However, they frequently misinterpret this condition as PVC. PVC is a harmful myeloproliferative neoplasm, a type of bone marrow cancer that leads to an increase in red blood cells, white blood cells, and platelets. Unlike SE resulting from TRT, PCV is characterized by a quantitative increase in the number of circulating blood cells as well as a qualitative disruption that raises the risk of clot formation.

Additionally, PCV is associated with defects in endothelial cells—the cells lining blood vessels—which can cause inflammation. This inflammation can trigger the clotting cascade, leading to thrombosis and an increase in platelet counts. These abnormal characteristics of PVC raise the risk of blood clots, often necessitating treatment through phlebotomy or blood donation to reduce blood cell counts and help prevent complications associated with the condition.

PVC is defined as an increase in red blood cells, white blood cells, platelets, splenomegaly (enlarged spleen), and clotting disorders. Research clearly shows that testosterone causes SE but not polycythemia. The risks associated with an elevated hematocrit in individuals with polycythemia cannot be applied to the elevated hematocrit seen in patients undergoing TRT. To date, testosterone administration has not been linked to any risks of clotting or thrombotic events in any randomized controlled trials or prospective studies. However, if a patient on TRT experiences SE and they or their physician are concerned about the levels, donating blood may be a suitable option.

Michael Furci is a Certified Nurse Practitioner. Contact Mike to schedule a FREE consultation or an appointment HERE