Testosterone replacement therapy (TRT) is a medical treatment administered to men with low testosterone to restore hormone levels to a normal range. TRT has a well-established connection to an increase in the body’s red blood cell (RBC) count, a condition known as erythrocytosis or polycythemia. While increased RBCs improve oxygen-carrying capacity, excessive elevation leads to health concerns. This side effect is common in men undergoing TRT, making regular monitoring and management necessary.
How Testosterone Affects Red Blood Cell Production
Testosterone’s influence on red blood cell production is primarily due to its ability to stimulate erythropoietin (EPO), a hormone mainly produced by the kidneys. When testosterone levels rise following TRT, it signals the kidneys to release more EPO into the bloodstream. EPO then travels to the bone marrow, which functions as the body’s primary blood-cell factory. The bone marrow responds to the increased EPO signal by accelerating erythropoiesis, the creation of new red blood cells. This mechanism leads directly to a higher number of circulating red blood cells.
The specific method of TRT administration influences the degree of stimulation and the resulting RBC increase. Injectable forms, which cause higher peak testosterone concentrations, are associated with a greater risk of developing erythrocytosis compared to transdermal preparations. Short-acting injectable formulations show the highest incidence of elevated hematocrit. Conversely, formulations that maintain a stable, steady-state level of testosterone are less likely to cause a dramatic spike in EPO production and the subsequent rise in RBCs.
Risks Associated With Elevated Red Blood Cells
An abnormally high red blood cell count is termed erythrocytosis, monitored by measuring the hematocrit (HCT). HCT is the percentage of blood volume occupied by red blood cells. A high HCT level, typically defined as above 52% to 54% in men, indicates that the blood is becoming too concentrated.
This excessive concentration leads to hyperviscosity, meaning the blood becomes thicker. Thicker blood is more difficult for the heart to pump, forcing the cardiovascular system to work harder and potentially raising blood pressure. The most serious danger is a significantly increased risk of thromboembolic events, which are blood clots forming inside vessels. These dangerous clots can manifest as deep vein thrombosis (DVT), pulmonary embolism (PE), heart attack, or ischemic stroke. Therefore, erythrocytosis is a serious side effect requiring careful management during TRT.
Monitoring and Management of Red Blood Cell Levels
Monitoring red blood cell parameters is an integral part of safe TRT due to the risk of blood clots. Before starting therapy, baseline HCT and HGB levels should be established via a complete blood count (CBC) test. Following TRT initiation, patients require regular blood testing, typically every three to six months during the first year, and then at least annually thereafter.
The clinical threshold for intervention is generally an HCT level exceeding 54%. If the HCT level becomes too high, the first line of management is adjusting the TRT protocol. This often involves lowering the testosterone dose to reduce the stimulation of EPO production.
Another effective strategy is changing the method of administration, such as switching from high-peak injectable testosterone to a transdermal gel or patch. Using a delivery method that provides more stable hormone concentrations minimizes the spikes in testosterone that drive excessive RBC generation. If HCT levels remain elevated despite dose adjustments, therapeutic phlebotomy is often prescribed.
Therapeutic phlebotomy is a procedure similar to blood donation where a controlled amount of blood, typically 500 milliliters, is removed to reduce circulating red blood cells. This removal usually lowers the HCT by about three percentage points. The goal is to reduce blood viscosity and bring the HCT down to a safer target, usually below 50%. The frequency of phlebotomy is determined by the patient’s response, but it may be required every eight to twelve weeks to maintain safe levels.