Testogel is a widely prescribed testosterone replacement therapy (TRT) in the UK for men with confirmed hypogonadism. Whilst it typically improves energy levels, some patients report feeling lethargic during treatment—a seemingly paradoxical effect. Fatigue on Testogel can result from dosing issues, haematological changes such as polycythaemia, exacerbation of sleep apnoea, or underlying comorbidities. Understanding these mechanisms is essential for appropriate management. This article explores why Testogel might cause tiredness, when to seek medical advice, and how to optimise treatment outcomes through dose adjustment, monitoring, and lifestyle modifications in line with UK clinical guidance.

What Is Testogel and How Does It Work?

Testogel is a transdermal testosterone gel licensed in the UK for testosterone replacement therapy (TRT) in men with confirmed hypogonadism—a condition characterised by abnormally low testosterone levels. The gel contains testosterone as the active ingredient and is applied daily to clean, dry skin. Once absorbed, testosterone enters the bloodstream and mimics the body's natural hormone production.

The mechanism of action involves supplementing endogenous testosterone to restore physiological levels. Testosterone is a crucial androgen hormone responsible for maintaining muscle mass, bone density, libido, mood regulation, and energy levels. In men with hypogonadism, insufficient testosterone production can lead to fatigue, reduced sexual function, depression, and decreased physical performance. Testogel aims to alleviate these symptoms by providing a steady, controlled release of testosterone through the skin.

Testogel is available in two formulations in the UK: Testogel 16.2 mg/g pump (applied to shoulders/upper arms) and Testogel 50 mg/5 g (1%) sachets (applied to shoulders, arms or abdomen). Treatment should only be initiated following biochemical confirmation of low testosterone levels on at least two separate morning blood tests, alongside compatible clinical symptoms.

To prevent transfer to others, it's essential to wash hands thoroughly after application, allow the gel to dry completely before dressing, cover the application site with clothing, and wash the site before any skin-to-skin contact with others—particularly women and children. The gel is flammable, so avoid fire, flames or smoking until the gel has dried.

Dosing is individualised based on clinical response and serum testosterone monitoring. Regular follow-up with a GP or endocrinologist is necessary to assess efficacy and monitor for potential adverse effects. It's important to note that TRT can suppress sperm production and is not suitable for men with prostate or breast cancer, or severe cardiac, hepatic or renal insufficiency.

Why Might You Feel Tired While Using Testogel?

While Testogel is prescribed to improve energy levels in men with hypogonadism, some patients report feeling lethargic or fatigued during treatment. This seemingly paradoxical effect can occur for several reasons, and understanding the underlying mechanisms is important for appropriate management.

Dosing issues are a common cause of persistent fatigue. If the dose is too low, testosterone levels may remain suboptimal, failing to adequately address hypogonadism symptoms. Conversely, excessive dosing can lead to supraphysiological testosterone levels, which may cause side effects including mood disturbances and fatigue. In some cases, conversion of testosterone to oestradiol (via aromatisation) may contribute to symptoms such as fluid retention and mood changes. Regular monitoring of serum testosterone and haematocrit is essential to ensure appropriate dosing.

Haematological effects represent another important consideration. Testosterone therapy stimulates erythropoiesis (red blood cell production), which can lead to polycythaemia—an abnormally high red blood cell count. Whilst mild increases in haemoglobin are expected and often beneficial, excessive elevation can cause blood hyperviscosity, resulting in fatigue, headaches, and increased cardiovascular risk. The British Society for Sexual Medicine (BSSM) recommends monitoring full blood count at baseline, 3, 6, and 12 months, then annually thereafter.

Sleep disturbances, including obstructive sleep apnoea (OSA), may be exacerbated by testosterone therapy. OSA causes fragmented sleep and nocturnal hypoxia, leading to daytime somnolence and fatigue. Testosterone can worsen pre-existing OSA or unmask previously undiagnosed cases. Patients experiencing excessive daytime sleepiness, witnessed apnoeas, or loud snoring should be evaluated for sleep-disordered breathing according to NICE guidance.

Additionally, underlying comorbidities such as hypothyroidism, anaemia, depression, or chronic disease may contribute to fatigue independently of testosterone therapy. Medications (including opioids, sedatives, and glucocorticoids) and alcohol can also cause fatigue or suppress testosterone production. A comprehensive clinical assessment is necessary to identify and address these factors.

When to Seek Medical Advice About Testogel Side Effects

Patients using Testogel should be aware of key warning signs that warrant prompt medical review. Whilst mild fatigue may improve with dose adjustment, certain symptoms require urgent evaluation to exclude serious complications.

Contact your GP or specialist if you experience:

• Persistent or worsening fatigue despite several weeks of treatment, particularly if accompanied by other symptoms such as breathlessness, chest pain, or palpitations

• Severe headaches, visual disturbances, or dizziness—these may indicate polycythaemia or hypertension

• Mood changes, including depression, anxiety, irritability, or aggressive behaviour

• Signs of sleep apnoea, such as excessive daytime sleepiness, morning headaches, or witnessed breathing pauses during sleep

• Swelling of the ankles or legs, which may suggest fluid retention or cardiac complications

• Skin reactions at the application site, including severe irritation, rash, or allergic symptoms

• Worsening urinary symptoms such as difficulty passing urine, increased frequency, or blood in urine

• Breast tenderness or swelling

Seek immediate medical attention (call 999 or attend A&E) if you develop:

• Chest pain or pressure, particularly if radiating to the arm, jaw, or back

• Sudden breathlessness or difficulty breathing

• Symptoms of stroke, including facial drooping, arm weakness, or speech difficulties

• Painful, prolonged erection (priapism) lasting more than four hours

• Signs of blood clot, such as sudden leg pain, swelling, warmth, or redness

Regular monitoring is essential for safe testosterone therapy. The BSSM recommends baseline assessments including prostate-specific antigen (PSA), full blood count, lipid profile, and liver function tests, with follow-up testing at 3, 6, and 12 months, then annually thereafter. Patients should attend all scheduled appointments and report any concerning symptoms promptly. Never adjust your Testogel dose or stop treatment without medical guidance, as this can cause recurrence of hypogonadism symptoms.

If you suspect you're experiencing side effects from Testogel, you can report them directly to the MHRA through the Yellow Card Scheme (yellowcard.mhra.gov.uk or the Yellow Card app).

Managing Fatigue During Testosterone Replacement Therapy

Effective management of lethargy during Testogel therapy requires a systematic, individualised approach addressing both medication-related factors and lifestyle considerations.

Optimising testosterone dosing is the cornerstone of management. Your clinician will review serum testosterone levels (measured according to the specific product guidance—typically pre-dose or 2-4 hours after gel application at steady state) to ensure they fall within the physiological range. If levels are suboptimal, dose escalation may be appropriate. Conversely, if testosterone levels are elevated, dose reduction may be considered. Some patients benefit from switching to alternative testosterone formulations available in the UK, such as intramuscular injections (Nebido or Sustanon) or other gel preparations, which provide different pharmacokinetic profiles.

Addressing haematological complications is crucial. If polycythaemia develops (haematocrit >0.54), your doctor may recommend temporarily reducing or stopping testosterone therapy and arranging urgent clinical review. Therapeutic venesection (blood removal) may be necessary to reduce blood viscosity and associated symptoms. Ensuring adequate hydration and addressing risk factors such as smoking or untreated sleep apnoea can help maintain haematocrit within safe limits.

Lifestyle modifications play a significant role in managing fatigue:

• Sleep hygiene: Maintain regular sleep-wake times, create a comfortable sleep environment, and avoid screens before bedtime. If sleep apnoea is diagnosed, continuous positive airway pressure (CPAP) therapy can dramatically improve energy levels

• Physical activity: Regular exercise enhances testosterone's beneficial effects on muscle mass, mood, and energy. Aim for at least 150 minutes of moderate-intensity activity weekly, as recommended by NHS guidelines

• Nutrition: A balanced diet rich in whole foods, adequate protein, and essential micronutrients supports optimal hormone function. Your doctor may consider testing for vitamin D or B12 deficiency if clinically indicated

• Stress management: Chronic stress elevates cortisol, which can counteract testosterone's benefits. Mindfulness, cognitive behavioural therapy, or relaxation techniques may help

Treating comorbidities is equally important. Screen for and manage conditions such as hypothyroidism, diabetes, depression, and cardiovascular disease, all of which can cause or exacerbate fatigue. If you're planning a family, discuss fertility implications with your doctor, as TRT can suppress sperm production.

A holistic approach, combining appropriate testosterone dosing with lifestyle optimisation and comorbidity management, offers the best outcomes for patients experiencing lethargy during TRT.

Frequently Asked Questions