Testosterone Replacement Therapy (TRT) has become a common treatment for men experiencing symptoms of low testosterone, a condition known as hypogonadism. While TRT can offer significant benefits, such as improved energy, mood, and muscle mass, it is also associated with certain side effects that require careful monitoring. The potential for TRT to cause an increase in red blood cell counts, often referred to as erythrocytosis or secondary polycythemia, is a primary concern. This increase must be managed to ensure the therapy remains safe and effective over the long term.
Testosterone’s Effect on Red Blood Cell Count
Testosterone directly stimulates the body’s production of red blood cells, which is the mechanism that leads to high hemoglobin and hematocrit levels. This process begins with the hormone stimulating the kidneys to produce more erythropoietin (EPO), a growth factor that signals the bone marrow to accelerate red blood cell formation. Testosterone also appears to act on the bone marrow itself and may influence iron metabolism by suppressing a regulatory peptide called hepcidin, further contributing to increased red blood cell production.
The degree to which red blood cell count increases can be influenced by the way the testosterone is administered. Injectable forms of testosterone, particularly those given less frequently, often lead to higher peak testosterone levels shortly after the injection. These higher peaks are associated with a greater risk of stimulating red blood cell production compared to transdermal gels or patches, which provide more stable hormone levels throughout the day. Studies have shown that injectable testosterone can cause high hematocrit in a significantly higher percentage of patients compared to transdermal formulations.
Understanding Monitoring and Thresholds
The clinical definition of “high” red blood cell count in the context of TRT is based on measurements of hemoglobin (Hgb) and hematocrit (Hct). Hematocrit represents the percentage of blood volume made up by red blood cells, and it is the primary value clinicians track. While normal Hct ranges vary, a level consistently above 50% or 52% is considered the threshold for defining testosterone-induced erythrocytosis.
Most clinical guidelines suggest that if the hematocrit level exceeds 54%, intervention is necessary. This often means the testosterone therapy must be stopped or adjusted until the level normalizes. Regular blood work is necessary to track these levels, tested at baseline, then again at three to six months after starting TRT, and then annually or semi-annually thereafter.
Unchecked, a high hematocrit level increases the blood’s viscosity, making it thicker and causing the heart to work harder. This increased viscosity raises the risk of serious clotting events, such as deep vein thrombosis (DVT) and stroke.
Strategies for Managing Elevated Levels
When a patient’s hematocrit level rises above the acceptable threshold, physicians employ several strategies to manage the elevation while continuing the benefits of TRT. The most common initial step is reducing the overall testosterone dose or frequency of administration. Lowering the dose can decrease the stimulation of red blood cell production, often bringing the levels back into a safer range.
If dose adjustment is insufficient, changing the route of administration is another option. Switching a patient from an injectable formulation to a transdermal gel or patch leads to more stable testosterone levels. This stability tends to reduce the magnitude of red blood cell stimulation and helps avoid the high peak levels associated with injections.
For a rapid reduction in the red blood cell count, therapeutic phlebotomy is used. This involves drawing a unit of blood, similar to a blood donation, to physically reduce the volume of circulating red blood cells and decrease blood viscosity. Therapeutic phlebotomy is employed when the hematocrit exceeds the 54% safety threshold and is performed under strict medical supervision.