Testosterone Replacement Therapy (TRT) is a common treatment for men experiencing low testosterone, offering significant benefits like improved energy, mood, and muscle mass. However, TRT carries potential side effects, one of the most common being an elevation in hematocrit (HCT). HCT is the measure of red blood cells to the total blood volume, and its increase, known as erythrocytosis, requires proactive management. Managing this side effect ensures the benefits of TRT can continue safely.
The Mechanism Behind Hematocrit Elevation
Testosterone naturally stimulates the production of red blood cells, a process called erythropoiesis. It does this primarily by influencing the kidneys to release erythropoietin (EPO), a hormone that signals the bone marrow to create more red blood cells. While this effect can be beneficial, excessive stimulation leads to an elevated hematocrit.
The rise in red blood cells is also associated with a suppression of hepcidin, a protein that regulates iron availability, which further supports red blood cell creation. This increase in red blood cell concentration thickens the blood, raising its viscosity. Blood that is too thick does not flow easily through veins and arteries, placing strain on the heart and vascular system.
A high hematocrit level significantly increases the risk of serious health complications, including thrombosis, stroke, and other cardiovascular events. Clinicians generally consider hematocrit levels above 50% or 52% to be problematic in men on TRT, with intervention typically warranted when the level exceeds 54%. Regular monitoring of the complete blood count (CBC) is a necessary part of a TRT protocol to catch these elevations early.
Adjusting TRT Protocols and Lifestyle Factors
Strategies for managing elevated hematocrit involve adjusting the TRT administration method and incorporating specific lifestyle changes. Injectable testosterone formulations, especially those administered less frequently, tend to cause sharp peaks in testosterone levels. These high peaks provide a greater stimulus for EPO release, contributing to the rise in hematocrit.
Switching to a more frequent dosing schedule, such as injecting twice weekly or even daily via subcutaneous injection, can help mitigate this effect. More frequent, lower doses maintain more stable testosterone concentrations, which reduces the peak erythropoietic stimulus. Alternatively, switching from injections to a transdermal gel or patch may also lower the risk of erythrocytosis, as these methods deliver testosterone more gradually.
Simple lifestyle adjustments can significantly impact measured hematocrit, primarily by influencing plasma volume. Maintaining a high level of hydration is an effective strategy, as sufficient water intake dilutes the blood, thereby lowering the hematocrit percentage. Dehydration, which decreases plasma volume, can artificially inflate the hematocrit measurement, sometimes called spurious polycythemia.
Other environmental and personal factors that increase red blood cell production should be addressed. Smoking cessation is strongly advised because the carbon monoxide in smoke causes chronic low-level oxygen deprivation, which independently drives the production of red blood cells. Similarly, individuals living at high altitudes may experience a greater rise in hematocrit while on TRT, necessitating more frequent monitoring and intervention.
Directed Medical Management
When modifications to the TRT protocol and lifestyle factors are not sufficient to keep hematocrit within a safe range, medical intervention is necessary. The most common and effective medical procedure is therapeutic phlebotomy, which is essentially a prescribed blood draw. This procedure removes a unit of blood, immediately reducing the total volume of red blood cells and decreasing the blood’s viscosity.
Therapeutic phlebotomy is typically implemented when hematocrit levels exceed the threshold of 54%. It can lower the measurement by roughly three percentage points per session. The frequency of this procedure is guided by regular blood tests, often required every 8 to 12 weeks to maintain the hematocrit below the target. While similar to a standard blood donation, phlebotomy is a medical procedure requiring a physician’s prescription and is monitored to prevent complications like iron deficiency.
If the hematocrit remains stubbornly high despite phlebotomy and protocol adjustments, the physician may decide to reduce the overall TRT dose by 20–30% or temporarily discontinue treatment altogether. The goal of this temporary cessation is to allow the hematocrit to return to a safe level, usually below 50%, before restarting TRT at a lower dose or with a different formulation.