Testosterone replacement therapy (TRT) is increasingly prescribed for men with confirmed hypogonadism, yet concerns about liver health often arise. Fatty liver disease, or hepatic steatosis, occurs when excess fat accumulates in liver cells and is commonly associated with metabolic conditions such as obesity and type 2 diabetes. Understanding whether testosterone causes fatty liver is essential for patients considering or currently receiving TRT. Current evidence indicates that appropriately prescribed testosterone replacement does not cause fatty liver disease. However, the relationship between testosterone, metabolic health, and liver function is complex and requires careful clinical consideration, particularly in patients with pre-existing risk factors.

Understanding Fatty Liver Disease and Hormonal Influences

Fatty liver disease, medically termed hepatic steatosis, occurs when excess fat accumulates in liver cells. In clinical practice, steatosis is diagnosed when more than 5% of hepatocytes contain fat on liver biopsy, or when validated imaging techniques (such as MRI-PDFF) demonstrate hepatic fat content above 5%. This condition exists in two primary forms: non-alcoholic fatty liver disease (NAFLD), which develops independently of alcohol consumption, and alcoholic fatty liver disease, directly related to excessive alcohol intake.

NAFLD encompasses a spectrum of liver conditions, ranging from simple steatosis (fat accumulation without significant inflammation) to non-alcoholic steatohepatitis (NASH), which involves inflammation and hepatocyte injury. Over time, NASH may progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD has become increasingly prevalent in the UK, affecting a substantial proportion of adults, particularly those with metabolic syndrome, obesity, type 2 diabetes, and dyslipidaemia. Risk factors also include obstructive sleep apnoea and hypothyroidism.

The liver plays a crucial role in metabolising hormones, including testosterone and oestrogen. Hormonal balance significantly influences hepatic fat metabolism, insulin sensitivity, and inflammatory processes within the liver. Testosterone, the primary male sex hormone (androgen), affects body composition, fat distribution, and metabolic function. In physiological concentrations, testosterone generally promotes lean muscle mass and may influence insulin sensitivity, though evidence from randomised controlled trials remains mixed.

Low testosterone levels (hypogonadism) in men have been associated with increased visceral adiposity and metabolic syndrome components, which are themselves risk factors for NAFLD. However, the relationship between exogenous testosterone therapy and liver health remains complex and context-dependent. Sex hormones influence hepatic lipid metabolism through multiple pathways, including effects on adipose tissue distribution, insulin signalling, and inflammatory mediators.

Understanding these hormonal influences is essential when considering testosterone replacement therapy (TRT) or when investigating the causes of fatty liver disease. The interplay between endogenous hormone levels, exogenous hormone administration, underlying metabolic health, and liver function requires careful clinical consideration and individualised patient assessment.

Does Testosterone Cause Fatty Liver?

Current evidence does not demonstrate that appropriately prescribed testosterone replacement therapy causes fatty liver disease. The relationship between testosterone and hepatic steatosis is nuanced and depends on multiple factors, including dosage, route of administration, baseline liver health, and individual metabolic status. UK-licensed testosterone products, when used at recommended therapeutic doses, do not list hepatic steatosis as a recognised adverse effect in their Summaries of Product Characteristics (SmPCs).

Physiological testosterone replacement in hypogonadal men—when administered at doses that restore normal testosterone levels—does not typically cause hepatic steatosis. Observational studies suggest that men with low testosterone levels have higher rates of NAFLD, and some research indicates that testosterone replacement may potentially improve metabolic parameters associated with NAFLD, including insulin resistance and visceral adiposity. However, evidence from robust randomised controlled trials remains limited and mixed, and any metabolic benefits should be interpreted cautiously.

In contrast, supraphysiological doses of testosterone, particularly oral 17-alpha-alkylated compounds or anabolic-androgenic steroids (AAS) used for performance enhancement, present different risks. Oral testosterone preparations, especially alkylated formulations, can cause hepatotoxicity, cholestasis, and in rare cases, serious liver complications including peliosis hepatis and hepatic tumours. These formulations are rarely used in legitimate medical practice in the UK.

Modern testosterone preparations approved by the MHRA for therapeutic use—primarily transdermal gels (such as Testogel and Tostran) and intramuscular injections (such as Nebido and Sustanon)—have favourable hepatic safety profiles when used appropriately. Subcutaneous implants are not routinely available or commonly used in current UK practice. These licensed preparations bypass first-pass hepatic metabolism (transdermal and injectable routes), reducing potential liver stress compared with oral formulations.

Important safety information: SmPCs for UK-licensed testosterone products advise caution in patients with severe hepatic impairment and recommend monitoring for fluid retention in patients with severe hepatic, cardiac, or renal disease. Patients should be reassured that medically supervised testosterone therapy, when indicated for confirmed hypogonadism, does not inherently cause fatty liver disease. Any concerns about liver health should be discussed with their prescribing clinician.

Risk Factors for Fatty Liver in Testosterone Users

Whilst therapeutic testosterone replacement does not directly cause fatty liver disease, certain risk factors warrant consideration in patients receiving testosterone therapy. Understanding these factors enables appropriate patient selection, monitoring, and risk mitigation.

Pre-existing metabolic conditions represent the most significant risk factors. Patients with obesity (BMI >30 kg/m²), type 2 diabetes, metabolic syndrome, dyslipidaemia, obstructive sleep apnoea, or hypothyroidism have substantially elevated baseline risk for NAFLD, independent of testosterone use. These conditions often coexist with hypogonadism, creating a complex clinical picture. Testosterone therapy in these patients requires careful metabolic monitoring, as any improvements in body composition and insulin sensitivity may take months to manifest and evidence remains mixed.

Concomitant hepatotoxic medications or substances increase liver-related risks. Excessive alcohol consumption remains the most important modifiable risk factor for liver disease. Patients should be advised that UK Chief Medical Officers' low-risk drinking guidelines (not exceeding 14 units weekly, spread over three or more days) apply regardless of testosterone therapy. Other potentially hepatotoxic medications, including certain antibiotics or over-the-counter preparations, require consideration. Note: Statins are generally safe in NAFLD and should not be stopped without medical advice; patients taking lipid-lowering therapy should consult their clinician before making any changes.

Supraphysiological dosing or non-prescribed use dramatically increases risks. Anabolic steroid misuse, often involving multiple compounds at high doses ('stacking'), significantly elevates hepatotoxicity risk. Such use falls outside legitimate medical practice and is associated with numerous adverse effects beyond liver damage.

Route of administration influences hepatic exposure. Oral testosterone formulations undergo first-pass hepatic metabolism, potentially increasing liver stress. Injectable and transdermal preparations bypass initial hepatic metabolism, offering improved safety profiles. This partly explains why oral 17-alpha-alkylated preparations are rarely prescribed in contemporary UK practice.

Additional risk factors include:

• Weight gain (increases NAFLD risk irrespective of testosterone therapy; weight management is essential)

• Polypharmacy, particularly with metabolically active drugs

• Genetic predisposition to liver disease

• Viral hepatitis (hepatitis B or C)

• Haemochromatosis or other metabolic liver conditions

Baseline assessment before initiating testosterone therapy should include:

• Full blood count (FBC) including haematocrit and haemoglobin

• Liver function tests (LFTs): alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), bilirubin, and albumin

• Metabolic profile: fasting glucose, HbA1c, lipid profile

• Prostate-specific antigen (PSA) with age-appropriate prostate assessment

• Body mass index and waist circumference

• Comprehensive medication history, including over-the-counter preparations and supplements

• Alcohol consumption assessment

Clinicians should conduct comprehensive baseline assessments and consider individual risk profiles before initiating testosterone therapy.

Monitoring During Testosterone Treatment

UK guidance and endocrine society recommendations emphasise the importance of regular monitoring for patients receiving testosterone replacement therapy. Whilst liver toxicity is uncommon with modern non-oral preparations, systematic surveillance ensures early detection of any abnormalities.

Ongoing monitoring protocols for testosterone therapy typically involve:

• Haematocrit and haemoglobin: Check at baseline, at 3–6 months, then annually (polycythaemia is a recognised risk with testosterone therapy)

• Prostate-specific antigen (PSA): Check at baseline (with age-appropriate prostate assessment), at 3–12 months, then according to clinical guidance and patient risk factors

• Serum testosterone levels: Check at 3–6 months to ensure appropriate dosing and guide dose titration

• Symptom review: Assess treatment response, adverse effects, and general wellbeing at each review

• Liver function tests (LFTs): Check at baseline; subsequently, perform LFTs only if baseline results are abnormal, if clinical concerns arise, or if the patient has risk factors for liver disease. Routine LFTs are not mandated for non-oral testosterone preparations in UK practice.

• Metabolic parameters: Monitor glucose control, HbA1c, and lipid profiles as clinically indicated, particularly in patients with diabetes or metabolic syndrome

Interpretation of liver function tests requires clinical context. Mild elevations in transaminases (ALT/AST up to twice the upper limit of normal) are relatively common and may reflect underlying NAFLD rather than testosterone-related toxicity. Significant elevations (more than three times the upper limit of normal) warrant investigation according to British Society of Gastroenterology guidance on abnormal liver blood tests. Consider stopping or suspending potentially causative drugs if drug-induced liver injury (DILI) is suspected, and refer for specialist assessment if abnormalities persist.

NAFLD risk stratification: For patients with suspected or confirmed NAFLD, calculate the FIB-4 score to assess fibrosis risk. If the FIB-4 score is indeterminate or high, arrange an Enhanced Liver Fibrosis (ELF) test. Refer to hepatology if advanced fibrosis is likely, in line with NICE guideline NG49 on non-alcoholic fatty liver disease assessment and management.

Patient safety advice includes:

• Attend scheduled monitoring appointments

• Maintain healthy lifestyle measures: balanced diet, regular physical activity, weight management, and alcohol moderation (not exceeding 14 units weekly, spread over three or more days)

• Inform all healthcare providers about testosterone therapy

• Avoid hepatotoxic substances, including excessive alcohol and non-prescribed anabolic steroids

• Do not stop prescribed medicines (such as statins) without consulting your clinician

• Report new symptoms: jaundice (yellowing of skin or eyes), dark urine, pale stools, persistent nausea, or right upper quadrant abdominal pain

When to seek same-day medical advice (contact your GP or NHS 111):

• Jaundice or significant yellowing of the eyes

• Severe or persistent right upper quadrant abdominal pain, especially with fever

When to go to A&E or call 999:

• Confusion, drowsiness, or altered mental state with jaundice

• Vomiting blood or passing black, tarry stools

• Signs of acute liver failure (severe jaundice, confusion, bleeding)

Reporting suspected side effects: Patients and healthcare professionals are encouraged to report suspected adverse drug reactions via the MHRA Yellow Card scheme at yellowcard.mhra.gov.uk or by searching for MHRA Yellow Card in the Google Play or Apple App Store.

Patients should be reassured that with appropriate monitoring and adherence to prescribed regimens, testosterone replacement therapy has an excellent safety profile. Regular communication with healthcare providers ensures any concerns are addressed promptly, optimising both treatment efficacy and safety.

Frequently Asked Questions