How to lower hematocrit on trt safely and effectively

Testosterone therapy can optimize your life, but it often comes with a hidden cost: thicker blood. Here is the science behind high red blood cell counts and the specific steps you can take to manage it without sacrificing your progress.

“We often see men panic when their hematocrit climbs, fearing they must stop therapy immediately. In reality, this is usually a mechanical issue of dosage and delivery method. We don’t just want to bleed you; we want to adjust the protocol so your body stops overproducing red cells in the first place.”

Susan Carter, MD, Endocrinologist & Longevity expert

The relationship

Testosterone replacement therapy (TRT) is a powerful tool for men dealing with hypogonadism, helping to restore muscle mass, libido, and cognitive function. However, the same biological mechanisms that revitalize your energy can also drive your bone marrow into overdrive. This results in secondary erythrocytosis, a condition where the body produces too many red blood cells.

The primary marker for this condition is hematocrit. Hematocrit measures the volume percentage of red blood cells in your blood. When you introduce exogenous testosterone—testosterone that comes from outside your body—you significantly alter the hormonal signals sent to your kidneys and bone marrow. Research indicates that anywhere from 5 percent to 66 percent of men on TRT will experience elevated hematocrit, making it the most common dose-limiting side effect of therapy.

This relationship is dose-dependent and formulation-dependent. Men using injectable testosterone esters, particularly those on less frequent dosing schedules (like once every two weeks), experience higher peaks in serum testosterone. These sharp peaks signal the body to produce red blood cells more aggressively than steady-state methods like transdermal gels or creams. Understanding how to lower hematocrit on TRT often begins with understanding that your current protocol might be too “spiky” for your physiology.

How it works

The EPO pathway

The primary driver of high hematocrit in men on TRT is erythropoietin (EPO). EPO is a hormone produced by the kidneys that signals the bone marrow to produce red blood cells. Testosterone stimulates the kidneys to secrete more EPO, directly increasing red blood cell production.^[1] This is a natural function of male biology; androgens naturally drive higher hemoglobin and hematocrit levels. However, when you inject testosterone, you may elevate levels beyond your physiological baseline, causing an exaggerated EPO response.

Hepcidin suppression

A less discussed but critical mechanism involves hepcidin, a key regulator of iron metabolism. Hepcidin is a peptide hormone produced by the liver that controls how much iron your body absorbs from food and releases from storage.

Testosterone suppresses hepcidin levels.^[2] When hepcidin is low, your body absorbs iron more efficiently from your diet and unlocks stored iron for use. Since iron is a primary building block of red blood cells, this increased availability removes the “brakes” on red blood cell production. The combination of high EPO (stepping on the gas) and low hepcidin (releasing the parking brake) creates the perfect storm for rapid erythrocytosis.

Estradiol conversion

Some testosterone converts to estradiol through a process called aromatization. While the evidence is mixed, some data suggests that estradiol may potentiate the effects of EPO or directly influence stem cells in the bone marrow. Men with higher body fat percentages often convert more testosterone to estradiol, potentially compounding the risk of high hematocrit, although this is secondary to the direct androgen effect.

Meta analyses indicate that symptomatic men with total testosterone below 350 ng/dL (≈12 nmol/L) are most likely to benefit from TRT. If total testosterone is borderline, measure free testosterone; values below 100 pg/mL (≈10 ng/dL) support hypogonadism. In practice, use 350 ng/dL for total or 100 pg/mL for free as decision thresholds when symptoms persist. When treating to these levels, managing the delicate balance of red blood cell production becomes critical.

Conditions linked to it

The primary clinical concern with high hematocrit is hyperviscosity—essentially, the thickening of the blood. As blood becomes more viscous, blood flow resistance increases, forcing the heart to pump harder and potentially slowing the transit of oxygen through the smallest blood vessels (capillaries).

If left unmanaged, TRT-induced polycythemia is associated with an increased risk of venous thromboembolism (VTE). VTE includes deep vein thrombosis (DVT), a clot in the deep veins of the leg, and pulmonary embolism (PE), where a clot breaks loose and travels to the lungs.^[3] The risk is particularly relevant during the first year of treatment when hematocrit levels tend to rise most sharply.

There is also a link to hypertension (high blood pressure) and potential cardiovascular events like myocardial infarction (heart attack) and stroke. However, it is important to note a limitation in the data: secondary erythrocytosis (caused by TRT) may not carry the exact same immediate risk profile as primary polycythemia vera (a bone marrow cancer), but clinical guidelines from the American Urological Association advise treating it as a significant risk factor regardless of the origin.^[4]

Symptoms and signals

Many men with elevated hematocrit are asymptomatic, meaning they feel fine even as their numbers climb into the danger zone. This is why routine blood work is non-negotiable. However, when symptoms do appear, they are often distinct.

Facial flushing: A persistent redness in the face, neck, or ears, often looking like a mild sunburn that won’t go away.
High blood pressure: Unexplained increases in systolic or diastolic pressure despite no changes in diet or stress.
Headaches: A dull, throbbing sensation or a feeling of “fullness” in the head.
Blurry vision: Transient visual disturbances caused by sluggish blood flow in the retinal vessels.
Fatigue: Paradoxically, while red blood cells carry oxygen, blood that is too thick moves so slowly that oxygen delivery becomes inefficient, leading to tiredness.
Itching (Pruritus): Specifically after a warm shower or bath, known as aquagenic pruritus.
Night sweats: Excessive sweating during sleep that is not related to room temperature.

What to do about it

If your lab work shows a hematocrit level above 52% or 54% (depending on your urologist’s threshold), you need an actionable plan. Do not ignore it, but do not panic. Here is the evidence-based approach to lowering hematocrit while maintaining the benefits of therapy.

1. Switch to subcutaneous or transdermal administration

The pharmacokinetics—how the drug moves through your body—matter immensely. Intramuscular injections (IM) creates high “supraphysiological” peaks of testosterone shortly after the shot. These peaks trigger EPO release aggressively. Shifting to subcutaneous injections (small needles into belly fat) leads to slower absorption and lower peaks, often mitigating the hematocrit rise.

Alternatively, switching to transdermal gels or creams mimics the body’s natural diurnal rhythm and avoids the massive spikes associated with injections. Studies consistently show that transdermal testosterone is associated with a significantly lower risk of erythrocytosis compared to injectable formulations.^[5]

2. Therapeutic phlebotomy (Blood donation)

This is the most immediate way to lower hematocrit. Phlebotomy involves removing approximately one pint of blood, which instantly reduces blood volume and red cell count. For many men, donating blood every 8 to 12 weeks keeps levels in check.

However, this is a double-edged sword. Frequent blood donation depletes ferritin (stored iron). If your ferritin crashes too low, you will experience fatigue, restless legs, and brain fog—symptoms that mimic low testosterone. You must monitor ferritin levels alongside hematocrit. If ferritin is low (under 30-50 ng/mL) but hematocrit is high, you cannot simply donate blood without crashing your iron. In this scenario, dosage adjustment is the only viable path.

3. Address sleep apnea

This is the most overlooked factor. Obstructive Sleep Apnea (OSA) causes your oxygen levels to drop at night. In response to this hypoxia (low oxygen), your kidneys churn out EPO to make more red blood cells to capture whatever oxygen is available. TRT can worsen untreated sleep apnea. If you snore or wake up unrefreshed, get a sleep study. Treating apnea with a CPAP machine often resolves high hematocrit without needing to change your TRT dose.^[6]

Myth vs Fact: Managing Thick Blood

Myth: Drinking more water will permanently fix high hematocrit.

Fact: Hydration only helps temporarily. Dehydration concentrates your blood, giving a falsely high reading on a lab test. Rehydrating fixes the test result, but it does not stop your bone marrow from overproducing cells.
Myth: Taking aspirin lowers hematocrit.

Fact: Aspirin does not lower red blood cell count. It is an anti-platelet agent that stops blood cells from sticking together. It may reduce clot risk, but it does not change the volume of cells.
Myth: You should stop TRT immediately if you hit 54%.

Fact: You should not stop cold turkey unless directed by a doctor for an emergency. Stopping abruptly causes a hormonal crash. The standard of care is to hold the dose, phlebotomize if safe, and restart at a lower dose or different frequency.
Myth: Eating grapefruit helps lower hematocrit.

Fact: There is some limited evidence that naringin (in grapefruit) may increase red blood cell destruction, but the effect is minimal and unpredictable. Grapefruit also interferes with many medications. Do not rely on produce to manage clinical side effects.

Bottom line

High hematocrit is a manageable side effect of testosterone replacement therapy, not a reason to abandon treatment entirely. It is a signal that your protocol needs tuning. By monitoring your blood work, ensuring you are hydrated before tests, screening for sleep apnea, and potentially switching to more frequent micro-dosing or transdermal applications, you can maintain healthy blood viscosity. Work with a urologist who treats the patient, not just the number, and prioritize keeping your ferritin levels healthy if you choose to donate blood.

References

Bachman E, Travison TG, Basaria S, et al. Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point. The journals of gerontology. Series A, Biological sciences and medical sciences. 2014;69:725-35. PMID: 24158761
Guo W, Bachman E, Li M, et al. Testosterone administration inhibits hepcidin transcription and is associated with increased iron incorporation into red blood cells. Aging cell. 2013;12:280-91. PMID: 23399021
Martinez C, Suissa S, Rietbrock S, et al. Testosterone treatment and risk of venous thromboembolism: population based case-control study. BMJ (Clinical research ed.). 2016;355:i5968. PMID: 27903495
Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and Management of Testosterone Deficiency: AUA Guideline. The Journal of urology. 2018;200:423-432. PMID: 29601923
Ohlander SJ, Varghese B, Pastuszak AW. Erythrocytosis Following Testosterone Therapy. Sexual medicine reviews. 2018;6:77-85. PMID: 28526632
Killick R, Wang D, Hoyos CM, et al. The effects of testosterone on ventilatory responses in men with obstructive sleep apnea: a randomised, placebo-controlled trial. Journal of sleep research. 2013;22:331-6. PMID: 23331844