Many men using Testogel (testosterone gel) for hypogonadism initially experience significant symptom improvement, yet some report diminishing benefits over months or years of treatment. Whilst Testogel does not inherently lose potency, various physiological, lifestyle, and application-related factors can influence absorption and response. Understanding why effectiveness may appear to decline—and distinguishing true treatment failure from other contributing factors—is essential for optimising therapy. Regular monitoring through blood tests, as recommended by NICE and UK endocrine guidance, ensures testosterone levels remain therapeutic. If symptoms return despite continued use, medical review is warranted rather than accepting reduced efficacy as inevitable.

Can the Effects of Testogel Decrease Over Time?

Testogel (testosterone gel) is a widely prescribed hormone replacement therapy for men with confirmed hypogonadism, a condition characterised by low testosterone levels. Many patients initially experience significant improvements in symptoms such as fatigue, reduced libido, and mood disturbances. However, some men report that the beneficial effects appear to diminish after months or years of treatment, raising concerns about whether the medication becomes less effective over time.

The phenomenon of reduced effectiveness is not uncommon and can occur for several reasons. Whilst Testogel itself does not inherently lose potency when used correctly, various physiological, lifestyle, and application-related factors can influence how well the body absorbs and responds to the testosterone. It is important to distinguish between true treatment failure and other contributing factors that may create the impression of reduced efficacy, including non-androgen causes that will be discussed later.

Clinical evidence suggests that testosterone replacement therapy generally maintains its effectiveness when testosterone levels remain within the therapeutic range. UK clinical guidance from NICE Clinical Knowledge Summaries (CKS), the British Society for Sexual Medicine (BSSM), and the Society for Endocrinology emphasises the importance of regular monitoring through blood tests to ensure adequate dosing and response. Target ranges and sampling times vary by formulation according to the manufacturer's recommendations. If symptoms return despite continued use, this warrants medical review rather than simply accepting diminished results as inevitable.

Why Testosterone Gel Effectiveness May Change

Several physiological mechanisms can contribute to changes in how the body responds to Testogel over time. One key factor is the development of changes in sex hormone-binding globulin (SHBG) levels, which can bind to testosterone and reduce the amount of free, biologically active hormone available to tissues. SHBG levels naturally increase with age and oestrogen exposure, while they typically decrease with obesity, insulin resistance, hypothyroidism, and certain medications.

The body's androgen receptor sensitivity may also vary over time, though there is limited clinical evidence for true receptor desensitisation with physiological testosterone replacement. Unlike anabolic steroid abuse, which can lead to receptor downregulation, properly dosed testosterone therapy aims to restore levels to the normal physiological range. However, individual receptor sensitivity can be affected by genetic factors, concurrent medications, and overall health status.

Changes in body composition and metabolism can significantly impact treatment response. Weight gain, particularly increased adipose tissue, can alter testosterone metabolism through increased aromatase activity, which converts testosterone to oestradiol. This enzymatic conversion is more pronounced in adipose tissue, meaning that men who gain weight during treatment may experience relatively lower testosterone effects despite maintaining the same dose. Additionally, age-related changes in skin properties and blood flow may affect how efficiently testosterone is absorbed through the skin.

Concurrent medical conditions and medications may also interfere with testosterone action. Conditions such as diabetes, thyroid disorders, and chronic inflammation can affect hormone metabolism and receptor function, potentially reducing the perceived effectiveness of Testogel even when blood levels appear adequate.

Signs That Testogel May Be Less Effective

Recognising the symptoms of reduced Testogel effectiveness is crucial for timely medical intervention. The most common indicators mirror the original symptoms of hypogonadism returning despite continued treatment. These include persistent or worsening fatigue that is not explained by other factors, reduced libido and sexual function, and mood changes such as low mood, irritability, or reduced motivation.

Physical signs may also become apparent over time. Men may notice a decline in muscle mass or strength, increased difficulty maintaining or building muscle despite regular exercise, and changes in body composition with increased fat accumulation, particularly around the abdomen. Some patients report reduced energy levels for physical activity and longer recovery times after exercise. Changes in sleep patterns, including poor sleep quality or increased sleep disturbances, can also indicate suboptimal testosterone levels.

Cognitive and emotional symptoms should not be overlooked. Difficulty concentrating, reduced mental clarity (often described as "brain fog"), and decreased overall sense of wellbeing are important indicators that treatment may need adjustment. Some men also experience reduced confidence or changes in their sense of vitality and drive.

It is important to note that these symptoms are non-specific and can result from numerous other medical conditions. Depression, thyroid disorders, vitamin D deficiency, sleep apnoea, and cardiovascular disease can all produce similar symptoms. Therefore, if you experience a return of hypogonadal symptoms whilst using Testogel, it is essential to contact your GP or endocrinologist for comprehensive evaluation rather than assuming the medication has simply stopped working. Blood tests measuring total testosterone, SHBG, and other relevant hormones will help determine whether the issue is related to testosterone levels or requires investigation for other causes. In UK practice, calculated free testosterone (derived from total testosterone, SHBG and albumin) is preferred over direct free testosterone assays.

Factors That Reduce Testogel Absorption and Response

Application technique is one of the most significant factors affecting Testogel absorption. The gel must be applied to clean, dry, intact skin according to the specific product instructions. For Testogel 50 mg/5 g (1% gel), application sites include shoulders, upper arms, or abdomen, while Testogel 16.2 mg/g pump formulation should only be applied to shoulders and upper arms. Applying the gel to damp skin can significantly reduce absorption. Similarly, applying moisturisers, sunscreen, or other topical products to the same area may potentially impede testosterone absorption. The product information advises allowing the gel to dry completely before dressing, and waiting before showering or swimming (at least 6 hours for the 1% gel and at least 2 hours for the 16.2 mg/g formulation) to ensure adequate absorption.

Skin-to-skin contact with others, particularly women and children, poses both a safety risk and can result in testosterone transfer, effectively reducing the dose absorbed by the patient. Covering the application site with clothing and washing hands thoroughly after application are essential precautions. If skin-to-skin contact is anticipated, washing the application site beforehand is recommended. The gel should never be applied to the genital area or broken skin.

Environmental and lifestyle factors can substantially impact absorption and metabolism. Excessive alcohol consumption can affect liver function and hormone metabolism, potentially reducing treatment effectiveness. Obesity increases aromatase activity and can lower free testosterone levels. Poor sleep quality and chronic stress elevate cortisol levels, which can antagonise testosterone action and contribute to symptoms that mimic low testosterone.

Medication interactions should be carefully considered. According to the Testogel SmPC, interactions may occur with oral anticoagulants (requiring closer INR monitoring), corticosteroids/ACTH (potentially increasing fluid retention), and antidiabetic medications/insulin (potentially enhancing glucose-lowering effects). Opioid pain medications are particularly notable for suppressing testosterone production and can counteract the effects of replacement therapy.

Changes in the application site can affect absorption over time. Rotating application sites within the approved areas can help maintain consistent absorption. Additionally, skin conditions such as eczema, psoriasis, or dermatitis at the application site can significantly impair testosterone absorption and should be managed appropriately.

What to Do If Testogel Stops Working as Well

The first and most important step is to arrange a medical review with your GP or specialist. Do not adjust your dose independently or discontinue treatment without medical guidance. Your healthcare provider will typically arrange blood tests to measure testosterone levels, with timing dependent on the specific Testogel formulation you use. For the 1% gel, sampling is usually done before the morning dose, while for the 16.2 mg/g formulation, sampling may be done 2-4 hours after application. These tests should include total testosterone, SHBG, and potentially other hormones such as luteinising hormone (LH), follicle-stimulating hormone (FSH), oestradiol, and prolactin to provide a comprehensive picture.

A thorough review of your application technique is essential. Your healthcare provider or practice nurse can verify that you are applying Testogel correctly, to appropriate sites, and at the right time of day. They may recommend adjustments such as changing application sites, ensuring adequate drying time, or modifying the timing relative to showering and exercise. Keeping a symptom diary for 2-4 weeks before your appointment can help identify patterns and provide valuable information for clinical decision-making.

If blood tests confirm suboptimal testosterone levels despite proper application, several options are available. Your doctor may adjust the Testogel dose within the licensed range (25-100 mg daily for the 1% gel or 20.25-81 mg daily for the 16.2 mg/g formulation), switch to a different testosterone formulation (such as injections, patches, or alternative gel preparations), or investigate and address factors that may be reducing absorption or effectiveness. Weight management, treatment of concurrent medical conditions, and medication review may all form part of an optimised treatment strategy.

UK clinical guidance recommends regular monitoring of testosterone replacement therapy, including assessment of symptoms, testosterone levels, full blood count (to monitor for polycythaemia), liver function, and lipid profile. If haematocrit reaches or exceeds 0.54, dose reduction or temporary cessation may be required with appropriate investigation. Prostate-specific antigen (PSA) monitoring and digital rectal examination (DRE) are also recommended for men over 40 or those with risk factors for prostate disease, with referral according to NICE suspected cancer guidelines if PSA is above age-specific ranges or DRE is abnormal.

If symptoms persist despite adequate testosterone levels, further investigation for other causes is warranted. Conditions such as sleep apnoea, depression, thyroid disorders, or vitamin deficiencies may require separate treatment. A multidisciplinary approach, potentially involving endocrinology, urology, or other specialties, may be beneficial for complex cases. Remember that testosterone replacement therapy is most effective as part of a holistic approach that includes healthy lifestyle measures such as regular exercise, balanced nutrition, adequate sleep, stress management, and maintaining a healthy body weight.

If you experience any suspected side effects from Testogel, report them via the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk or the Yellow Card app).

Frequently Asked Questions