Does testosterone treatment increase AST and ALT levels? This is a common concern for men considering or receiving testosterone replacement therapy (TRT) in the UK. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are liver enzymes that, when elevated, may indicate liver damage. Whilst certain oral testosterone formulations carry significant hepatotoxic risk, standard UK preparations—injectable testosterone undecanoate or enantate, and transdermal gels—pose a low risk of clinically significant liver enzyme elevation. Understanding which formulations are safe, when monitoring is appropriate, and what symptoms warrant medical attention helps patients and clinicians make informed decisions about testosterone therapy.

Understanding AST and ALT: Liver Function Markers

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are enzymes found predominantly in liver cells (hepatocytes). When liver cells are damaged or inflamed, these enzymes leak into the bloodstream, making them valuable markers for assessing liver health. Blood tests measuring these enzymes form part of the liver function test (LFT) panel routinely requested by GPs and specialists.

In UK practice, ALT is the standard transaminase measured in routine LFT panels, alongside alkaline phosphatase (ALP), bilirubin, albumin, and often gamma-glutamyl transferase (GGT). AST is not routinely included in many UK laboratory LFT panels. ALT is considered highly liver-specific, as it is found primarily in the liver. AST is present in multiple tissues including the heart, muscles, kidneys, and red blood cells, making it less specific for liver pathology when measured.

Reference ranges for liver enzymes are laboratory-specific and vary by assay, sex, and age. Your blood test report will show the reference interval used by your laboratory. Clinicians interpret results using these local ranges rather than fixed values. Elevated transaminase levels can indicate various hepatic conditions, including viral hepatitis, non-alcoholic fatty liver disease (NAFLD), alcohol-related liver disease, drug-induced liver injury (DILI), and autoimmune hepatitis. The pattern and degree of elevation help clinicians determine the underlying cause. Mild elevations (less than twice the upper limit of normal) are common and may be transient, whilst significant elevations warrant thorough investigation.

When AST is measured alongside ALT, clinicians may consider the AST:ALT ratio as supportive information. An AST:ALT ratio greater than 2:1 may suggest alcohol-related liver disease, whilst a ratio less than 1 is more typical of viral hepatitis or NAFLD. However, this ratio is not diagnostic in isolation and must be interpreted within the broader clinical context, including medication history, which is particularly relevant for patients receiving testosterone therapy.

Does Testosterone Treatment Increase AST and ALT Levels?

Testosterone replacement therapy (TRT) with standard UK formulations carries a low risk of liver enzyme elevation, though the risk varies significantly by preparation. Understanding which formulations pose hepatotoxic risk helps clinicians and patients make informed treatment decisions.

17-alpha-alkylated oral testosterone preparations (such as methyltestosterone) carry the highest risk of hepatotoxicity and serious liver injury. These modified compounds undergo first-pass metabolism through the liver, placing significant metabolic stress on hepatocytes. These oral androgens are not licensed for use in the United Kingdom and are not prescribed in routine clinical practice. When discussing hepatotoxicity risk with testosterone therapy, it is essential to distinguish between these high-risk oral androgens and the standard UK formulations.

Injectable testosterone preparations (such as testosterone undecanoate [Nebido] and testosterone enantate) and transdermal preparations (gels such as Testogel and Tostran) are the standard formulations used in the UK. These routes bypass first-pass hepatic metabolism, and the Summary of Product Characteristics (SmPC) for these medicines does not signal routine hepatotoxicity as a significant concern. Mild, transient elevations in liver enzymes have been reported in some patients receiving these formulations, but clinically significant liver injury remains uncommon with prescribed therapeutic use.

It is important to distinguish prescribed TRT from anabolic steroid misuse. Illicit use of high-dose anabolic-androgenic steroids, often including 17-alpha-alkylated compounds, carries substantial hepatotoxic risk including cholestasis, peliosis hepatis, and hepatic tumours. This article addresses medically prescribed testosterone therapy for hypogonadism, not anabolic steroid misuse.

Several factors may contribute to enzyme changes during testosterone therapy. Individual patient factors significantly influence risk, including pre-existing liver disease, concurrent hepatotoxic medications (including excessive alcohol consumption), obesity, and metabolic syndrome. Patients with these risk factors may benefit from baseline liver function assessment and consideration of monitoring during therapy, as advised in product SmPCs and local protocols.

The relationship between physiological testosterone replacement and non-alcoholic fatty liver disease (NAFLD) is complex, with mixed evidence; some studies suggest neutral or even beneficial effects on hepatic fat with appropriate dosing. Clinicians should assess and manage metabolic risk factors (obesity, insulin resistance, dyslipidaemia) as part of comprehensive care, regardless of testosterone therapy.

Monitoring Liver Function During Testosterone Therapy

Baseline liver function testing may be considered before commencing testosterone therapy, particularly in patients with known liver disease, risk factors for liver disease, or concurrent use of potentially hepatotoxic medications. This baseline assessment identifies pre-existing hepatic abnormalities that may influence treatment decisions. The decision to perform baseline LFTs should be individualised and guided by clinical assessment, product SmPC advice, and local protocols.

Routine monitoring of liver function tests is not universally required for patients receiving standard UK testosterone formulations (injectable or transdermal preparations) in the absence of risk factors. The British Society for Sexual Medicine (BSSM) guidance on testosterone therapy emphasises monitoring of testosterone levels, full blood count (FBC) including haematocrit, and prostate-specific antigen (PSA). Monitoring schedules typically include assessment at 3 months, 6 months, and 12 months after treatment initiation, then annually if stable.

Liver function monitoring may be appropriate for patients with:

• Pre-existing liver disease or elevated baseline transaminases

• Concurrent use of potentially hepatotoxic medications

• Obesity, metabolic syndrome, or known NAFLD

• Excessive alcohol consumption

• Clinical symptoms suggesting hepatic dysfunction

If liver function tests are performed and show elevated enzymes, interpretation requires clinical judgement and consideration of alternative causes. The British Society of Gastroenterology (BSG) provides guidance on investigating abnormal liver blood tests. Urgent assessment is warranted if the patient is jaundiced, has prolonged INR (coagulopathy), shows signs of hepatic encephalopathy, is systemically unwell, or has markedly elevated transaminases (e.g., ALT >1000 U/L). In such cases, seek urgent medical assessment and consider withholding testosterone therapy pending investigation.

For mild to moderate asymptomatic elevations, repeat LFTs in 4–6 weeks and investigate for alternative causes, including viral hepatitis serology (hepatitis B and C), autoimmune liver screen, and hepatobiliary ultrasound. If drug-induced liver injury (DILI) is suspected, discuss withholding the suspected medication with the prescribing clinician. NICE Clinical Knowledge Summaries (CKS) on abnormal liver function tests provide primary care guidance on investigation pathways.

Haematocrit and haemoglobin monitoring is essential during testosterone therapy, as polycythaemia (elevated red blood cell count) is a recognised adverse effect. Elevated haematocrit increases blood viscosity and thrombotic risk; management includes dose adjustment, temporary cessation, or therapeutic venesection. Lipid profiles help identify metabolic changes and cardiovascular risk. Prostate-specific antigen (PSA) monitoring forms part of comprehensive testosterone therapy surveillance for prostate health.

Patients should be counselled about lifestyle modifications that support overall health during testosterone therapy, including maintaining a healthy weight, limiting alcohol consumption to within UK Chief Medical Officers' guidelines (no more than 14 units per week, spread over 3 or more days), and managing comorbid conditions such as type 2 diabetes and hypertension. These measures reduce cumulative health risks and support safe, effective treatment.

When to Seek Medical Advice About Elevated Liver Enzymes

Patients receiving testosterone therapy should be aware of symptoms that may indicate liver dysfunction, even between scheduled monitoring appointments. Whilst mild, asymptomatic enzyme elevations are often detected incidentally through routine blood tests, certain warning signs warrant prompt medical attention.

Seek urgent medical advice (contact your GP urgently, call NHS 111, or attend A&E) if you experience:

• Jaundice (yellowing of the skin or whites of the eyes)

• Dark urine (tea-coloured or brown)

• Pale or clay-coloured stools

• Persistent abdominal pain, particularly in the right upper quadrant

• Unexplained fatigue or weakness that interferes with daily activities

• Nausea, vomiting, or loss of appetite lasting more than a few days

• Itching (pruritus) without an obvious skin cause

If you develop jaundice with confusion, drowsiness, bleeding, or severe abdominal pain, call 999 or go to A&E immediately, as these may indicate serious liver dysfunction requiring urgent hospital assessment.

Routine monitoring appointments provide opportunities to discuss any concerns about liver health or other aspects of your treatment. If your blood tests reveal elevated ALT or other liver enzyme abnormalities, your doctor will determine whether this represents a clinically significant finding. Many factors beyond testosterone therapy can affect liver enzymes, including recent alcohol consumption, strenuous exercise, viral infections, other medications, and underlying metabolic conditions. Your clinician will consider the degree of elevation, trend over time, and presence of other abnormalities when deciding on further action.

Do not discontinue testosterone therapy without medical guidance, even if you learn your liver enzymes are elevated. Abrupt cessation can cause hormonal fluctuations and symptom recurrence. Your healthcare provider will weigh the benefits of continued therapy against potential risks, possibly adjusting the dose, changing the formulation, implementing more frequent monitoring, or investigating alternative causes of enzyme elevation.

If you experience a suspected side effect from testosterone therapy, you can report it via the MHRA Yellow Card Scheme at yellowcard.mhra.gov.uk or through the Yellow Card app. Reporting suspected side effects helps improve the safety monitoring of medicines.

Patients should inform all healthcare providers about their testosterone therapy, as this information is crucial when interpreting liver function tests or prescribing additional medications. Maintaining open communication with your medical team ensures safe, effective testosterone therapy whilst minimising hepatic and other adverse effects.

Frequently Asked Questions