Does testosterone treatment cause muscle pain? Testosterone replacement therapy (TRT) is prescribed for men with clinically confirmed hypogonadism—low testosterone levels with associated symptoms. Whilst muscle pain is occasionally reported during treatment, it is not among the most common adverse effects. Discomfort may arise from injection site reactions, rapid muscle adaptation, or increased physical activity rather than direct pharmacological harm. Understanding the distinction between normal physiological changes and genuine adverse reactions is essential for safe, effective therapy. This article examines the evidence, mechanisms, and management of muscle pain during testosterone treatment.

Does Testosterone Treatment Cause Muscle Pain?

Testosterone replacement therapy (TRT) is prescribed for men with clinically confirmed hypogonadism—a condition characterised by low testosterone levels and associated symptoms. Whilst testosterone is well known for its anabolic effects on muscle tissue, patients occasionally report muscle pain or discomfort during treatment. Understanding whether this is a direct consequence of the therapy requires careful consideration of the evidence.

The relationship between testosterone treatment and muscle pain varies by formulation and individual. Clinical trials and post-marketing surveillance data show that myalgia (muscle pain) is reported as an uncommon adverse effect for some testosterone preparations, while injection-site pain is common with intramuscular formulations. According to the Medicines and Healthcare products Regulatory Agency (MHRA) product information, muscle pain is not among the most frequent adverse reactions for most testosterone products, though it does occur in some patients.

It is important to distinguish between muscle pain as a direct pharmacological effect and discomfort arising from the physiological changes that testosterone induces. Testosterone promotes protein synthesis and increases muscle mass, which can lead to sensations of tightness, soreness, or fatigue—particularly in individuals who were previously hypogonadal and sedentary. These sensations may be misinterpreted as adverse effects when they are actually signs of muscle adaptation and growth.

When muscle discomfort occurs during testosterone therapy, it is often multifactorial, involving changes in physical activity, injection site reactions, or coincidental musculoskeletal conditions. A thorough clinical assessment is essential to determine the underlying cause and ensure patient safety. If you experience persistent or severe muscle pain during testosterone treatment, consult your healthcare provider for evaluation.

Why Muscle Pain May Occur During Testosterone Therapy

Several mechanisms may explain why some men experience muscle pain during testosterone treatment. Understanding these potential causes helps clinicians and patients differentiate between expected physiological responses and genuine adverse reactions.

Rapid muscle growth and adaptation can produce discomfort, especially in men who have been hypogonadal for extended periods. Testosterone stimulates androgen receptors in skeletal muscle, enhancing protein synthesis and nitrogen retention. This anabolic effect leads to increased muscle mass and strength. When previously deconditioned individuals become more active due to improved energy levels, they may experience delayed-onset muscle soreness (DOMS), a benign condition characterised by stiffness and tenderness that typically resolves within a few days.

Injection site reactions are a common source of localised muscle pain with intramuscular testosterone preparations such as testosterone enantate or testosterone undecanoate. According to the Summary of Product Characteristics (SmPC) for products like Nebido and Sustanon, pain, swelling, or induration at the injection site are common adverse reactions. Rotating injection sites and ensuring proper technique as described in the product information can minimise this discomfort.

Increased physical activity often accompanies testosterone therapy. As energy levels and motivation improve, patients may engage in more strenuous exercise than their musculoskeletal system is accustomed to, leading to overuse injuries or muscle strain. This is particularly relevant in men who rapidly increase their training intensity without adequate progression or recovery.

Fluid retention is a recognised side effect of testosterone therapy and can occasionally cause a sensation of muscle tightness or heaviness. Testosterone can promote sodium and water retention, leading to mild oedema, which may be perceived as discomfort in the limbs. Product information for testosterone preparations advises monitoring for signs of oedema, particularly in patients with cardiac, renal or hepatic impairment.

Other medical conditions such as hypothyroidism or vitamin D deficiency may coexist with hypogonadism and can independently cause muscle pain, complicating the clinical picture.

Distinguishing Normal Muscle Changes from Adverse Effects

Differentiating between expected physiological changes and clinically significant adverse effects is crucial for safe testosterone therapy. Not all muscle discomfort warrants discontinuation of treatment, but certain features should prompt further investigation.

Normal muscle adaptation during testosterone therapy typically presents as:

• Mild, generalised muscle soreness or stiffness, particularly after physical activity

• Gradual onset over days to weeks as muscle mass increases

• Improvement with rest, hydration, and gentle stretching

• Absence of systemic symptoms such as fever, weakness, or dark urine

These sensations are generally self-limiting and reflect the body's positive response to restored testosterone levels. Patients should be counselled that some degree of muscle fatigue or soreness can be a normal part of the adaptation process, especially if they are resuming or increasing physical activity.

Adverse effects requiring clinical attention include:

• Severe or persistent muscle pain that does not improve with conservative measures

• Muscle weakness or difficulty performing routine activities

• Dark or cola-coloured urine, which may indicate rhabdomyolysis—a rare but serious condition involving muscle breakdown

• Swelling, redness, or warmth at injection sites, suggesting infection or abscess formation

• Systemic symptoms such as fever, malaise, or unexplained weight loss

Rhabdomyolysis is a medical emergency characterised by the breakdown of muscle tissue and release of myoglobin into the bloodstream, potentially causing acute kidney injury. While there is no established causal link between therapeutic testosterone replacement and rhabdomyolysis, risk factors include concomitant use of statins, excessive physical exertion, and dehydration. Any suspicion of rhabdomyolysis requires urgent assessment, including measurement of creatine kinase (CK) levels and renal function.

Coincidental musculoskeletal conditions must also be considered. Conditions such as polymyalgia rheumatica, fibromyalgia, or inflammatory myopathies can present with muscle pain and may coincidentally emerge during testosterone therapy. A thorough history, physical examination, and appropriate investigations are essential to exclude alternative diagnoses.

When to Seek Medical Advice About Muscle Pain

Patients receiving testosterone therapy should be informed about when muscle pain warrants medical review. Clear safety-netting advice empowers patients to seek timely help whilst avoiding unnecessary anxiety about minor, self-limiting symptoms.

Contact your GP or prescribing clinician if you experience:

• Severe muscle pain that interferes with daily activities or sleep

• Muscle pain accompanied by weakness, particularly if it affects your ability to climb stairs, rise from a chair, or lift objects

• Dark urine or a significant reduction in urine output

• Persistent pain at an injection site lasting more than a few days, especially if accompanied by redness, swelling, or discharge

• Systemic symptoms such as fever, chills, or unexplained fatigue

• Chest pain or shortness of breath

Seek urgent medical attention (A&E, NHS 111, or call 999) if you develop:

• Sudden, severe muscle pain with profound weakness

• Dark brown or red urine suggestive of myoglobin release

• Signs of severe allergic reaction (anaphylaxis), such as difficulty breathing, facial swelling, or widespread rash

• Chest pain, particularly if radiating to the arm or jaw, or associated with breathlessness

Routine monitoring during testosterone therapy, as outlined in NICE Clinical Knowledge Summaries, includes regular review of symptoms, physical examination, and blood tests to assess testosterone levels, haemoglobin/haematocrit, and prostate-specific antigen (PSA) where appropriate. Blood pressure and lipid monitoring may be indicated based on individual cardiovascular risk. Patients should attend all scheduled follow-up appointments, where concerns about muscle pain can be discussed and investigated appropriately.

The evidence regarding testosterone therapy and cardiovascular risk is inconclusive. Your doctor will assess your individual risk factors and monitor you accordingly.

If you suspect an adverse reaction to testosterone therapy, you can report it through the MHRA Yellow Card scheme at yellowcard.mhra.gov.uk.

Managing Muscle Discomfort During Testosterone Treatment

For most men experiencing mild muscle discomfort during testosterone therapy, conservative management strategies are effective and allow continuation of treatment. A structured approach addresses both the symptoms and any modifiable contributing factors.

Conservative measures include:

• Gradual increase in physical activity: Patients should be advised to progress exercise intensity slowly, allowing muscles time to adapt. A structured programme incorporating both resistance training and cardiovascular exercise, ideally supervised by a qualified fitness professional, can optimise the benefits of testosterone therapy whilst minimising injury risk.

• Adequate hydration: Maintaining good fluid intake supports muscle function and reduces the risk of cramps and stiffness.

• Rest and recovery: Ensuring sufficient sleep and incorporating rest days into exercise routines allows muscle repair and reduces overuse injuries.

• Stretching and mobility work: Gentle stretching before and after exercise can alleviate muscle tightness and improve flexibility.

Optimising injection technique is important for patients using intramuscular testosterone. Administration should always follow the specific product's SmPC and healthcare professional training. General principles include:

• Rotating injection sites (typically alternating between the gluteal muscles or vastus lateralis)

• Ensuring the muscle is relaxed during injection

• Using appropriate needle length and gauge as specified in the product information

Note that some formulations, such as Nebido (testosterone undecanoate), are typically administered by healthcare professionals rather than self-administered.

Pharmacological interventions are rarely necessary for mild muscle discomfort, but simple analgesia such as paracetamol may be used if required. Non-steroidal anti-inflammatory drugs (NSAIDs) should be used at the lowest effective dose for the shortest duration if needed, with consideration of gastrointestinal, renal and cardiovascular risks.

Review of concomitant medications is essential, particularly if the patient is taking statins, which are independently associated with myalgia and, rarely, rhabdomyolysis.

Dose adjustment or formulation change may be considered if muscle pain persists despite conservative measures. Switching from intramuscular to transdermal testosterone gels (such as Testogel or Tostran) eliminates injection site reactions, though this should be discussed with the prescribing clinician. Any adjustment to testosterone therapy should be made in consultation with a specialist in endocrinology or andrology, ensuring that treatment remains effective for the underlying hypogonadism whilst minimising adverse effects.

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