What Should My Hematocrit Levels be on TRT?

Normal hematocrit levels will vary based on both age and race for men and women. In adult men, the normal ranges are around 40-50% where in women it tends to be lower around 35-44%. Its important to keep levels in a normal range to prevent an increased risk of medical issues like stroke and blood clots. Cycling superstar Lance Armstrong had used a medication called EPO to increase endurance and red blood cell production to increase performance. As the most successful cyclist in history, he had his blood levels under huge scrutiny, due to suspicion of illegal performance, enhancing drug use. It has been rumored that he had hematocrit levels in the 60% range when competing which increases the risks of blood clots. But what is a safe range for men on testosterone therapy?

The American Endocrine Society as well as the Canadian Men’s Health Foundation Multidisciplinary Guidelines Task Force on Testosterone Deficiency recommend testosterone replacement therapy for men with symptomatic androgen deficiency and low serum testosterone levels. Some of the possible side effects though can be erythrocytosis and/or polycythemia. Polycythemia and erythrocytosis are related terms, but they refer to slightly different aspects of red blood cell abnormalities.

What Causes Hematocrit Levels to Rise When on TRT?

1. Polycythemia:
Polycythemia is a medical condition characterized by an abnormally high number of red blood cells in the bloodstream. This can lead to an increase in hemoglobin concentration and hematocrit levels. The primary feature of polycythemia is an elevated red blood cell count, which can result in thicker blood.

There are different types of polycythemia, with the two main categories being primary and secondary.

A. Primary Polycythemia (Polycythemia Vera): This is a rare disorder where the bone marrow produces too many blood cells, including red blood cells, white blood cells, and platelets. The cause of polycythemia vera is often a genetic mutation in the bone marrow cells.

B. Secondary Polycythemia: This form is a response to external factors that stimulate the increased production of red blood cells. Common causes include chronic hypoxia (reduced oxygen levels), which can occur in conditions like chronic lung disease or living at high altitudes. Additionally, certain tumors or conditions that increase the production of erythropoietin (a hormone that stimulates red blood cell production) can lead to secondary polycythemia.

In the context of testosterone therapy, polycythemia can be a side effect. Elevated levels of red blood cells can contribute to increased blood viscosity, potentially leading to complications such as high blood pressure and an increased risk of cardiovascular events like stroke or heart attack. Regular testing and monitoring of blood levels is essential for individuals undergoing testosterone therapy to detect and manage polycythemia promptly.

2. Erythrocytosis:
Erythrocytosis specifically refers to an increase in the number of red blood cells (erythrocytes) in the bloodstream. It is a predictable yet underrecognized effect of testosterone therapy, defined by hemoglobin and hematocrit levels which can be measured in a simple blood test, or CBC. Distinguishing primary bone marrow disorders from secondary causes is crucial in managing erythrocytosis, with primary erythrocytosis characterized by low serum erythropoietin.

It is characterized by elevated levels of hemoglobin and hematocrit, which are components of red blood cells.  In men, erythrocytosis is often defined by a hemoglobin level above 185 g/L and a hematocrit percentage over 49%. In women, the thresholds are lower, typically set at 165 g/L for hemoglobin and 48% for hematocrit.

Primary and Secondary Forms: Similar to polycythemia, erythrocytosis can also be categorized as primary (related to bone marrow disorders) or secondary (resulting from external factors).

While polycythemia encompasses an overall increase in various types of blood cells, erythrocytosis focuses specifically on the increase in red blood cells. Both terms are interconnected, and elevated red blood cell counts can be a component of polycythemia, whether it is the primary form (Polycythemia Vera) or secondary to other factors like chronic hypoxia or testosterone replacement therapy.

Notably in a study titled Comparison of hematocrit change in testosterone-deficient men treated with intranasal testosterone gel vs intramuscular testosterone cypionate: A randomized clinical trial,  by Rivero MJ, Ory J, Diaz P, et al. published in the Journal of Urology in May of 2023, it was reported that a rise in hematocrit levels had been reported after 4 months of intramuscular testosterone therapy, but not with intranasal testosterone gel. Previous research links polycythemia during testosterone therapy to a higher risk of cardiovascular events.

A recent randomized trial showed increased serum testosterone in both groups, more significantly in the intramuscular group, with a corresponding rise in hematocrit and changes in estradiol and 17-hydroxyprogesterone levels. This is why frequent blood tests and monitoring by a licensed and experienced physician is so important when undergoing testosterone therapy.

How Can I Lower My Hematocrit Levels?

For men looking to lower their hematocrit levels, it typically would require addressing the underlying cause of the elevated numbers. As elevated hematocrit is often a symptom of TRT rather than a standalone condition, there are steps that can be taken to help lower the levels. Here are some general tips/approaches to manage or reduce high hematocrit, however it should be noted that its important to speak with your physician directly to address these conditions:

1. Hydration: (Drink lots of water!)

Staying well-hydrated has been shown to help reduce blood thickness (viscosity), making it less likely for the blood hematocrit levels to rise and to become too thick. This can have a positive impact on hematocrit levels and is good for overall health.

2. Donate Blood (Phlebotomy)  

In cases of significant polycythemia, therapeutic phlebotomy could be recommended. This typically involves the removal of a certain amount of blood to help decrease the number of red blood cells and may help to improve blood flow.

3. Addressing Underlying Causes and medical conditions
If underlying medical conditions or taking certain medications are contributing to elevated hematocrit levels, addressing or managing those conditions may help normalize hematocrit levels and bring them back to normal ranges.

4. Adjusting Testosterone Therapy Dose/Protocol
For individuals on prescription testosterone replacement therapy (TRT), adjusting the dose or switching to a different form of testosterone delivery (e.g., from intramuscular injections to intranasal gel) may be considered to help manage erythrocytosis. Splitting a dose from 150mg a week to 75mg bi-weekly is a possible option as well. Speaking to your physician prior to making any change in protocol is important.

5. Medication Adjustments:
In some cases, medications that can contribute to increased red blood cell production may need to be adjusted. This like switching your TRT dose, be done under the guidance of your doctor or a licensed and experienced healthcare professional.

6. Dietary Changes.

For some patients, reducing food with high iron or even consuming grapefruit may help to lower hematocrit levels. In one study titled Ingestion of grapefruit lowers elevated hematocrits in human subjects by Robbins and Martin, the effect on hematocrits of adding grapefruit to the daily diet was determined using 36 human subjects (12 F, 24 M) over a 42-day study. The hematocrits ranged from 36.5 to 55.8% at the start and 38.8% to 49.2% at the end of the study.

It's important to note that the approach when it comes to lowering hematocrit levels needs to be personalized and guided by a healthcare professional. They will make a determination based on the specific circumstances, underlying medical conditions, and potential risks and benefits before offering any guidance in the form of any interventions or recommendations. If you get tested and your labs find you to be experiencing elevated hematocrit levels, it’s important to speak with your doctor for a thorough medical evaluation and appropriately manage your symptoms.

Testosterone Replacement Therapy (TRT) may be able to offer symptom relief for most men, but there is always a chance that it could cause some side effects as mentioned above like polycythemia. Through the regular monitoring of hemoglobin and hematocrit levels a qualified provider can detect signs of polycythemia early. While it may not affect every patient on TRT, both awareness and preventive care are essential to manage any potential complications, like high blood pressure and/or an increased risk of stroke and heart attack. A good doctor can manage these symptoms which makes TRT a safe and valuable option for men with low testosterone, starting with the right blood tests, followed by lab review a consultation and deamination of the appropriateness of starting hormone therapy.