Non-alcoholic fatty liver disease (NAFLD) and low testosterone are increasingly recognised as interconnected conditions affecting men's health. Research demonstrates that men with fatty liver frequently have lower testosterone levels, whilst testosterone deficiency may contribute to hepatic fat accumulation. Both conditions share common risk factors including obesity, insulin resistance, and metabolic syndrome. Understanding this bidirectional relationship is clinically important, as addressing one condition may positively influence the other. This article examines the evidence linking fatty liver and testosterone deficiency, explores underlying mechanisms, and outlines integrated management approaches aligned with UK clinical guidance.

Understanding the Link Between Fatty Liver and Low Testosterone

The relationship between non-alcoholic fatty liver disease (NAFLD) and testosterone levels has become an important area of clinical research in recent years. NAFLD, characterised by excessive fat accumulation in the liver (hepatic steatosis), affects approximately 25–30% of adults in the UK and is closely associated with metabolic syndrome, obesity, and type 2 diabetes. Emerging evidence suggests an association between fatty liver disease and low testosterone (hypogonadism) in men, though the exact mechanisms and direction of causation remain under investigation.

Key points about this relationship include:

• Men with NAFLD frequently present with lower testosterone levels compared to those without liver disease

• Low testosterone may contribute to the development of fatty liver through effects on body composition and metabolism

• Both conditions share common risk factors, including obesity, insulin resistance, and sedentary lifestyle

• The relationship appears bidirectional, with each condition potentially influencing the other

Research published in endocrinology and hepatology journals has demonstrated that men with NAFLD have lower total and free testosterone levels than age-matched controls. This association persists even after adjusting for body mass index (BMI) and other metabolic factors. However, current UK clinical guidance does not recognise NAFLD as a direct cause of hypogonadism; instead, both conditions are understood as interconnected components of metabolic dysfunction.

It is important to note that normal liver function tests (LFTs) do not exclude NAFLD, as many people with significant hepatic steatosis have normal blood results. Understanding this connection is clinically relevant because both NAFLD and low testosterone are associated with increased cardiovascular risk, reduced quality of life, and progression to more serious conditions such as cirrhosis or metabolic complications. Addressing one condition may positively influence the other, making integrated assessment and management essential for optimal patient outcomes.

How Non-Alcoholic Fatty Liver Disease Affects Hormone Levels

The mechanisms by which NAFLD may influence testosterone production are multifactorial and involve complex interactions between liver function, inflammation, and endocrine regulation. The liver plays a crucial role in hormone metabolism, including the production of sex hormone-binding globulin (SHBG), which binds to testosterone and regulates its bioavailability in the bloodstream.

When the liver becomes infiltrated with fat, several physiological changes occur that may impact testosterone levels. Hepatic steatosis is associated with:

• Reduced SHBG production: The fatty liver produces less SHBG, which lowers total testosterone levels. Low SHBG complicates interpretation of testosterone results, as total testosterone may appear low whilst free (bioavailable) testosterone remains normal. Measurement of SHBG and calculation of free testosterone is therefore essential in men with obesity, insulin resistance, or NAFLD

• Increased aromatase activity: Fat tissue, particularly visceral adipose tissue often present alongside NAFLD, contains aromatase enzymes that convert testosterone to oestradiol, effectively reducing circulating testosterone

• Chronic low-grade inflammation: NAFLD triggers inflammatory cytokines (such as TNF-alpha and IL-6) that may suppress the hypothalamic-pituitary-gonadal (HPG) axis, reducing luteinising hormone (LH) secretion and subsequent testosterone production

• Insulin resistance: This metabolic disturbance, common in NAFLD, may impair Leydig cell function in the testes, reducing testosterone synthesis

The inflammatory state associated with non-alcoholic steatohepatitis (NASH), the more severe form of NAFLD, may further exacerbate hormonal disruption. Oxidative stress and hepatocellular injury can impair the liver's metabolic functions, creating a cycle where worsening liver disease further compromises hormone regulation. Additionally, the accumulation of visceral fat—often accompanying NAFLD—creates an environment that promotes testosterone deficiency through multiple pathways, making it difficult to isolate the liver's specific contribution to hormonal changes.

Clinicians should measure SHBG alongside total testosterone and calculate or measure free testosterone when assessing men with suspected hypogonadism in the context of obesity, metabolic syndrome, or NAFLD, to avoid misdiagnosis based on low total testosterone alone.

Symptoms of Low Testosterone in Men with Fatty Liver

Men with both NAFLD and low testosterone may experience a range of symptoms that significantly impact quality of life, though these symptoms can be non-specific and overlap with other conditions. Recognising these signs is important for prompting appropriate medical evaluation and investigation.

Common symptoms of testosterone deficiency include:

• Sexual dysfunction: Reduced libido, erectile dysfunction, and decreased spontaneous erections are frequently reported

• Physical changes: Loss of muscle mass, increased body fat (particularly abdominal), and persistent fatigue

• Mood alterations: Depression, irritability, difficulty concentrating, and reduced motivation

• Sleep disturbances: Poor sleep quality and increased daytime tiredness

• Reduced physical performance: Decreased strength, endurance, and exercise tolerance

Complications of long-standing testosterone deficiency include:

• Reduced bone mineral density (osteoporosis), increasing fracture risk

• Progressive loss of muscle mass (sarcopenia)

It is important to note that NAFLD itself is often asymptomatic in early stages, with many patients unaware they have liver disease until detected through routine blood tests showing elevated liver enzymes (ALT, AST) or imaging studies. Some individuals with more advanced disease may experience right upper quadrant discomfort, fatigue, or general malaise, but these symptoms are non-specific.

The challenge in clinical practice is that symptoms of low testosterone overlap considerably with those of metabolic syndrome and obesity—conditions frequently coexisting with NAFLD. Fatigue, for instance, could result from poor sleep associated with obesity, insulin resistance, or genuinely low testosterone levels. Similarly, mood changes and reduced physical performance may reflect the psychological burden of chronic disease rather than hormonal deficiency alone.

When low testosterone is confirmed, clinicians should assess luteinising hormone (LH), follicle-stimulating hormone (FSH), and prolactin to distinguish primary testicular failure from secondary (central) hypogonadism. Red-flag symptoms suggesting pituitary pathology include:

• Persistent headaches

• Visual field defects or double vision

• Other pituitary hormone deficiencies (e.g., fatigue with low cortisol, cold intolerance with low thyroid)

These require urgent specialist assessment. Patients experiencing symptoms of testosterone deficiency, particularly in the context of known metabolic risk factors or abnormal liver function tests, should discuss them with their GP. A comprehensive assessment can help determine whether symptoms relate to testosterone deficiency, liver disease, or other underlying conditions requiring attention.

Medical Evidence: Does Fatty Liver Cause Low Testosterone?

The medical literature demonstrates a strong association between NAFLD and low testosterone, but establishing direct causation remains complex. Multiple observational studies and systematic reviews have documented that men with NAFLD have lower testosterone levels than those without liver disease, with some studies reporting testosterone reductions of 20–30% in affected individuals.

Meta-analyses examining data from thousands of men have confirmed that low testosterone is independently associated with NAFLD, even after controlling for age, BMI, and metabolic factors. However, the relationship appears bidirectional rather than unidirectional:

• Men with pre-existing low testosterone have increased risk of developing NAFLD

• Men with established NAFLD frequently develop testosterone deficiency

• Both conditions share common pathophysiological mechanisms involving insulin resistance and inflammation

Prospective studies have shown that testosterone deficiency predicts future development of NAFLD, suggesting that low testosterone may contribute to hepatic fat accumulation through effects on body composition, insulin sensitivity, and lipid metabolism. Conversely, worsening liver disease severity (progression from simple steatosis to NASH and fibrosis) correlates with progressively lower testosterone levels.

Despite these associations, there is no definitive evidence that fatty liver directly causes low testosterone in a simple cause-and-effect manner. Instead, current understanding suggests these conditions are interconnected components of metabolic dysfunction, with shared risk factors and mutually reinforcing pathophysiology. Current UK clinical guidance does not list NAFLD as a recognised aetiology of primary or secondary hypogonadism, though the metabolic connections are acknowledged.

NICE guidance (NG49) on NAFLD recommends assessing for metabolic complications in patients with fatty liver disease, though routine testosterone screening is not specifically mandated. However, given the high prevalence of testosterone deficiency in this population and its clinical implications, assessment of testosterone levels should be considered in symptomatic men with confirmed fatty liver disease, in line with general guidance on investigating male hypogonadism.

Treatment Options for Fatty Liver and Testosterone Deficiency

Management of coexisting NAFLD and low testosterone requires an integrated approach addressing both conditions, with lifestyle modification forming the cornerstone of treatment. NICE guidelines (NG49) emphasise that no pharmacological treatments are currently licensed specifically for NAFLD in the UK, making lifestyle interventions the primary therapeutic strategy.

Lifestyle modifications beneficial for both conditions include:

• Weight loss: Even modest weight reduction (5–10% of body weight) can significantly improve liver histology and increase testosterone levels. This represents the most effective intervention for both conditions

• Dietary changes: A Mediterranean-style diet rich in vegetables, fruits, whole grains, and healthy fats, whilst limiting refined carbohydrates and saturated fats, benefits both liver health and metabolic function

• Regular physical activity: UK Chief Medical Officers recommend at least 150 minutes of moderate-intensity aerobic exercise weekly, plus muscle-strengthening activities on two or more days per week. Resistance training may be particularly beneficial for increasing muscle mass and testosterone production

• Alcohol reduction: Limiting alcohol intake protects liver health and may improve hormonal balance

• Management of comorbidities: Optimising control of diabetes, hypertension, and dyslipidaemia improves both hepatic and endocrine outcomes

Testosterone replacement therapy (TRT) may be considered for men with confirmed hypogonadism after careful assessment. Diagnosis requires symptoms of testosterone deficiency plus consistently low testosterone levels on at least two morning blood samples (taken between 8–10 am). Typical thresholds are total testosterone below 8 nmol/L with symptoms, or below 12 nmol/L in some guidelines. When SHBG is low (as in obesity, insulin resistance, or NAFLD), free or calculated bioavailable testosterone should be assessed, as total testosterone alone may be misleading.

TRT options available in the UK include:

• Transdermal gels (e.g., Testogel, Tostran): applied daily to the skin

• Intramuscular injections: testosterone undecanoate (Nebido) given every 10–14 weeks, or shorter-acting testosterone esters given more frequently

Important considerations for TRT:

• Contraindications and precautions: TRT should not be used in men with prostate or breast cancer, severe heart failure, uncontrolled polycythaemia (haematocrit >0.54), high PSA or suspicious prostate examination, or severe lower urinary tract symptoms. Men wishing to father children should avoid TRT, as it suppresses sperm production; specialist alternatives may be considered

• Monitoring: Before starting TRT, baseline haematocrit, PSA (age- and risk-appropriate), and prostate examination should be performed. During treatment, monitor testosterone levels, haematocrit (target <0.54), PSA, symptoms, and adverse effects at 3–6 months, then annually. Liver function tests are not routinely required for non-oral testosterone preparations

• Potential benefits for NAFLD: Some studies suggest TRT may improve liver fat content and insulin sensitivity in hypogonadal men, potentially benefiting NAFLD, though this remains an area of ongoing research

The decision to initiate TRT should be made by specialists (endocrinologists or urologists) after comprehensive evaluation, including measurement of LH, FSH, and prolactin to identify the cause of hypogonadism.

For NAFLD management, specialist-initiated pharmacological options may be considered in selected patients with biopsy-proven NASH under NICE NG49 guidance, including pioglitazone (in patients with or without type 2 diabetes) and vitamin E (in non-diabetic patients), though these are off-label uses requiring careful risk-benefit assessment.

Reporting adverse reactions: If you experience any suspected side effects from testosterone therapy or other medicines, report them via the MHRA Yellow Card scheme at https://yellowcard.mhra.gov.uk or by searching for 'Yellow Card' in the Google Play or Apple App Store.

When to See Your GP About Liver Health and Hormone Concerns

Knowing when to seek medical advice is crucial for early detection and management of both NAFLD and testosterone deficiency. Many men delay consultation because symptoms develop gradually or are attributed to normal ageing, but timely assessment can prevent progression and improve outcomes.

You should arrange to see your GP if you experience:

• Persistent fatigue, reduced energy levels, or unexplained weight changes

• Sexual dysfunction, including reduced libido or erectile difficulties

• Mood changes, depression, or reduced motivation affecting daily life

• Known risk factors for liver disease (obesity, type 2 diabetes, metabolic syndrome) without recent liver function assessment

• Abnormal liver function tests detected during routine blood work

• Right upper abdominal discomfort or unexplained symptoms

Seek urgent same-day medical assessment if you develop:

• Yellowing of the skin or eyes (jaundice)

• Swelling of the abdomen (ascites)

• Confusion or altered mental state

• Vomiting blood or passing black, tarry stools

• Severe abdominal pain with fever

• Persistent headaches with visual disturbances (may indicate pituitary problems)

Your GP will typically conduct an initial assessment including:

• Detailed medical history and symptom review

• Physical examination, including measurement of BMI and waist circumference

• Blood tests: liver function tests (LFTs), fasting glucose and lipids, and potentially testosterone levels (measured on at least two occasions between 8–10 am when levels peak), along with SHBG, LH, FSH, and prolactin if testosterone is low

• Assessment of cardiovascular risk factors

• Exclusion of other causes of liver disease, including alcohol history, viral hepatitis screening (hepatitis B and C), autoimmune liver disease, and medication review

If NAFLD is suspected, your GP will calculate a fibrosis risk score using the FIB-4 or NAFLD fibrosis score, applying age-specific thresholds as per NICE NG49 guidance. If the score is indeterminate or high, an enhanced liver fibrosis (ELF) blood test may be arranged, or you may be referred to hepatology. Liver ultrasound scanning may also be performed to confirm hepatic steatosis.

For testosterone deficiency, at least two morning testosterone measurements are required before diagnosis, as levels fluctuate. SHBG should be measured, and free or bioavailable testosterone calculated or measured, particularly in men with obesity or metabolic syndrome where SHBG is typically low.

Referral to specialists may be appropriate if:

• Liver fibrosis is suspected or confirmed on risk scoring or ELF testing (referral to hepatology per NICE NG49 thresholds)

• Testosterone deficiency is confirmed and TRT is being considered, or if secondary hypogonadism or pituitary pathology is suspected (referral to endocrinology)

• There are complex metabolic issues requiring specialist input

• Symptoms persist despite initial management

Early intervention with lifestyle modifications can significantly improve both conditions, making prompt medical consultation worthwhile. Do not dismiss symptoms as simply part of ageing—many men experience substantial improvements in quality of life following appropriate diagnosis and treatment. Your GP can coordinate investigations, initiate management, and arrange specialist referral when necessary, ensuring comprehensive care for both liver health and hormonal balance.

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