Testosterone replacement therapy (TRT) is prescribed for men with clinically confirmed hypogonadism to restore physiological testosterone levels and alleviate symptoms such as reduced libido, fatigue, and decreased muscle mass. Whilst testosterone is known to stimulate red blood cell production—sometimes leading to polycythaemia—questions occasionally arise about whether testosterone treatment can cause low white blood count (leucopenia). Understanding the haematological effects of testosterone therapy is essential for both patients and healthcare professionals. This article examines the evidence regarding testosterone treatment and white blood cell counts, reviews recognised side effects on blood parameters, and outlines appropriate monitoring and safety considerations in line with UK guidance from NICE, the MHRA, and the BNF.

Understanding Testosterone Treatment and Blood Cell Production

Testosterone replacement therapy (TRT) is prescribed to men with clinically confirmed hypogonadism—a condition characterised by abnormally low testosterone levels accompanied by relevant symptoms such as reduced libido, fatigue, and decreased muscle mass. The diagnosis requires two early-morning testosterone measurements (8–11 am) showing levels below 12 nmol/L, alongside assessment for reversible causes such as obesity, sleep apnoea, opioid use, or alcohol excess. Treatment aims to restore physiological testosterone concentrations, thereby alleviating symptoms and improving quality of life. In the UK, testosterone therapy is regulated by the Medicines and Healthcare products Regulatory Agency (MHRA) and prescribed according to guidance from the National Institute for Health and Care Excellence (NICE CKS: Testosterone deficiency in adult men).

Testosterone exerts various physiological effects throughout the body, including on the bone marrow where blood cells are produced. The bone marrow is responsible for haematopoiesis—the formation of red blood cells (erythrocytes), white blood cells (leucocytes), and platelets (thrombocytes). Testosterone is known to stimulate erythropoiesis, the production of red blood cells, which is why one of the recognised side effects of testosterone therapy is polycythaemia (elevated red blood cell count). This effect occurs through increased erythropoietin production, direct stimulation of erythroid progenitor cells, and suppression of hepcidin (which increases iron availability).

White blood cells form a crucial component of the immune system, defending the body against infections and foreign pathogens. They include several subtypes: neutrophils, lymphocytes, monocytes, eosinophils, and basophils, each with distinct functions. Leucopenia refers to a total white blood cell count below 4.0 x10^9/L, while neutropenia specifically indicates reduced neutrophil counts (mild: <1.5 x10^9/L; moderate: <1.0 x10^9/L; severe: <0.5 x10^9/L). Understanding how testosterone therapy might influence white blood cell production requires examination of both the pharmacological mechanisms of testosterone and clinical evidence from patients receiving treatment. Whilst testosterone's effects on red blood cells are well-established, its relationship with white blood cell counts is less clearly defined and warrants careful consideration.

Can Testosterone Therapy Cause Low White Blood Count?

There is no established causal link between testosterone replacement therapy and low white blood cell count (leucopenia). Current medical literature and UK product information (as detailed in electronic Medicines Compendium SmPCs for products such as Nebido, Testogel and Tostran) do not list leucopenia as a recognised adverse effect of testosterone treatment. The primary haematological concern associated with testosterone therapy relates to elevated red blood cell production rather than suppression of white blood cells.

Clinical studies examining the safety profile of testosterone preparations have not demonstrated a consistent pattern of reduced white blood cell counts in treated patients. Large-scale trials and post-marketing surveillance data have focused predominantly on cardiovascular risks, prostate safety, and polycythaemia, with leucopenia not emerging as a significant safety signal. When white blood cell abnormalities do occur in patients receiving testosterone therapy, they are typically coincidental rather than causally related to the treatment itself.

However, it is important to recognise that any medication can potentially cause idiosyncratic reactions in susceptible individuals, and rare haematological effects cannot be entirely excluded. If a patient develops leucopenia whilst on testosterone therapy, a thorough investigation is warranted to identify alternative causes. These might include:

• Concurrent medications that are known to suppress bone marrow function (such as certain antibiotics, anticonvulsants, or immunosuppressants)

• Underlying infections, particularly viral illnesses that can temporarily reduce white blood cell production

• Autoimmune conditions affecting the bone marrow or causing peripheral destruction of white blood cells

• Nutritional deficiencies (vitamin B12, folate, copper)

• Bone marrow disorders or haematological malignancies

Healthcare professionals should maintain a broad differential diagnosis when leucopenia is identified, rather than automatically attributing it to testosterone therapy. A comprehensive medication review and appropriate investigations are essential to determine the underlying cause. Urgent medical assessment is required for fever with suspected neutropenia, and patients with neutrophil counts below 1.0 x10^9/L should seek prompt medical advice.

Recognised Side Effects of Testosterone Treatment on Blood

Whilst low white blood cell count is not a recognised adverse effect in UK product information, testosterone therapy does have several well-recognised haematological effects that require monitoring. The most clinically significant is polycythaemia—an elevation in red blood cell count, haemoglobin concentration, and haematocrit. This occurs because testosterone stimulates erythropoietin production in the kidneys and directly promotes red blood cell formation in the bone marrow. Polycythaemia increases blood viscosity, potentially raising the risk of thromboembolic events such as deep vein thrombosis, pulmonary embolism, or stroke.

Product information for testosterone preparations (as detailed in the electronic Medicines Compendium SmPCs) includes polycythaemia as an adverse reaction requiring monitoring. The condition typically develops gradually over months of treatment and is dose-dependent. Patients using higher doses or certain formulations (particularly intramuscular injections that produce supraphysiological peaks) may be at increased risk. Older men and those with pre-existing cardiovascular risk factors require particularly careful monitoring.

Other haematological considerations during testosterone therapy include:

• Increased haemoglobin and haematocrit: Regular monitoring is essential, with treatment adjustment or temporary cessation if levels exceed safe thresholds (typically haematocrit >0.54 or 54%)

• Evaluation of contributory factors: When polycythaemia occurs, assessment for obstructive sleep apnoea, smoking, and dehydration is recommended

• Management options: Dose reduction, temporary cessation, and occasionally specialist referral for therapeutic venesection if persistent despite other measures

NICE guidance emphasises the importance of baseline and ongoing haematological monitoring for all patients receiving testosterone therapy. The benefits of treatment must be carefully balanced against potential risks, with individualised assessment of each patient's cardiovascular and haematological profile. Patients should be informed about these recognised effects and the rationale for regular blood test monitoring throughout their treatment journey. Any suspected adverse reactions should be reported via the MHRA Yellow Card Scheme (yellowcard.mhra.gov.uk).

When to Seek Medical Advice During Testosterone Therapy

Patients receiving testosterone replacement therapy should be aware of specific symptoms that warrant prompt medical attention. Whilst routine monitoring is scheduled at regular intervals, certain warning signs require earlier assessment by a healthcare professional. Understanding these red flags empowers patients to seek timely intervention when necessary.

Symptoms potentially indicating blood count abnormalities include:

• Unusual or persistent fatigue that differs from pre-treatment symptoms and progressively worsens

• Frequent or severe infections, particularly if they occur more often than usual or fail to resolve with standard treatment

• Unexplained fever, especially if recurrent or accompanied by other systemic symptoms

• Easy bruising or bleeding, including nosebleeds, bleeding gums, or prolonged bleeding from minor cuts

• Petechiae (small red or purple spots on the skin) or unexplained rashes

• Severe headaches, visual disturbances, or neurological symptoms that could indicate hyperviscosity from polycythaemia

Emergency situations requiring immediate action:

• Call 999 for chest pain, shortness of breath, or symptoms of stroke (sudden weakness, speech difficulties, or facial drooping)

• Seek same-day urgent assessment for fever or rapidly worsening infection if you have known or suspected low neutrophils

• Contact NHS 111 for urgent advice when symptoms are concerning but not immediately life-threatening

Patients should contact their GP or specialist if they experience any of these symptoms, rather than waiting for their next scheduled appointment. It is particularly important not to dismiss new symptoms as simply related to the underlying condition being treated, as they may indicate complications requiring investigation.

Additionally, patients should seek medical advice if they develop:

• Leg swelling or pain (potential signs of deep vein thrombosis)

• Severe mood changes or psychological symptoms

• Urinary symptoms that are new or worsening

Healthcare professionals can arrange urgent blood tests and clinical assessment to determine whether symptoms relate to testosterone therapy or indicate an unrelated condition requiring treatment. Early identification of complications allows for timely intervention, which may include dose adjustment, temporary treatment cessation, or additional investigations. Patients should not discontinue testosterone therapy without medical guidance, unless specifically instructed to do so for safety concerns.

Monitoring Blood Tests While on Testosterone Treatment

Comprehensive blood test monitoring forms an essential component of safe testosterone replacement therapy. NICE CKS and specialist endocrinology guidance recommend a structured approach to haematological surveillance, ensuring early detection of potential complications whilst confirming therapeutic efficacy. The monitoring schedule typically varies according to treatment phase, with more frequent testing during initiation and dose adjustment periods.

Baseline blood tests before commencing testosterone therapy should include:

• Full blood count (FBC): Establishes baseline haemoglobin, haematocrit, red blood cell count, white blood cell count, and platelet count

• Testosterone levels: Confirms hypogonadism diagnosis (typically two morning samples showing levels <12 nmol/L)

• LH, FSH, prolactin, and SHBG: To characterise the type of hypogonadism and interpret total vs free testosterone

• Liver function tests: Assesses hepatic health before treatment

• Lipid profile: Evaluates cardiovascular risk factors

• Prostate-specific antigen (PSA): In men over 40 or those with prostate symptoms

• HbA1c or glucose: Screens for diabetes, which commonly coexists with hypogonadism

During treatment, monitoring protocols typically recommend:

• FBC at 3 months, 6 months, then annually: Primarily to detect polycythaemia, though also identifying any unexpected changes in white blood cells or platelets

• Testosterone levels at 3–6 months: Ensures achievement of mid-normal range per local laboratory reference range, with correct timing (e.g., pre-dose/trough levels for injectable formulations)

• Annual review of liver function, lipids, PSA, and metabolic parameters

If haematocrit rises above 0.54 (54%), clinical guidelines recommend dose reduction or temporary treatment cessation until levels normalise, followed by reinitiation at a lower dose. Some patients may require evaluation for contributory factors (sleep apnoea, smoking, dehydration) and occasionally referral to haematology for therapeutic venesection if polycythaemia persists despite dose adjustment.

Should a low white blood cell count be incidentally discovered during routine monitoring, the healthcare professional will typically:

• Repeat the test to confirm the finding and exclude laboratory error

• Review the full blood count in detail, examining white blood cell differential and other parameters

• Assess for symptoms of infection or immune dysfunction

• Consider alternative causes including medications, infections, or haematological conditions

• Refer to haematology if leucopenia is persistent (WBC <3.0 x10^9/L) or neutropenia is significant (ANC <1.5 x10^9/L)

• Arrange urgent same-day assessment for neutrophil count <1.0 x10^9/L or fever with neutropenia

Patients should attend all scheduled monitoring appointments and ensure results are reviewed by their prescribing clinician. This collaborative approach to monitoring optimises treatment safety whilst maintaining therapeutic benefits. Any concerns about blood test results should be discussed openly with healthcare professionals, who can provide context-specific interpretation and appropriate management recommendations.

Frequently Asked Questions