Testogel is a widely prescribed testosterone replacement therapy in the UK for men with hypogonadism, a condition where the testes produce insufficient testosterone. Whilst Testogel effectively restores testosterone levels and alleviates symptoms such as fatigue and reduced libido, many men wonder whether it affects their body's natural hormone production. Understanding how Testogel interacts with the hypothalamic-pituitary-gonadal axis is essential for informed treatment decisions, particularly for men concerned about fertility or long-term testicular function. This article explains the mechanisms behind Testogel's effects on natural testosterone production and what this means for your health.

How Testogel Works in the Body

Testogel is a transdermal testosterone replacement therapy (TRT) licensed in the UK for treating male hypogonadism—a condition where the testes produce insufficient testosterone. The gel contains testosterone in an alcohol-based formulation that, when applied to clean, dry skin, allows the hormone to be absorbed directly into the bloodstream through the skin.

Application sites vary by formulation: Testogel 16.2 mg/g (1.62%) is typically applied to shoulders and upper arms only, while the 1% formulation (50 mg/5 g) may also be applied to the abdomen. Never apply to the genital area or to broken or irritated skin. The gel is flammable until dry.

Once absorbed, exogenous testosterone from Testogel circulates throughout the body, binding to androgen receptors in various tissues including muscle, bone, and the brain. This supplementation aims to restore testosterone levels to the normal physiological range (which is laboratory-specific, typically aiming for mid-normal values), thereby alleviating symptoms of hypogonadism such as fatigue, reduced libido, erectile dysfunction, loss of muscle mass, and mood disturbances.

The mechanism of action bypasses the natural testosterone production pathway. In healthy males, the hypothalamus releases gonadotrophin-releasing hormone (GnRH), which stimulates the pituitary gland to secrete luteinising hormone (LH) and follicle-stimulating hormone (FSH). LH then signals the Leydig cells in the testes to produce testosterone. When Testogel provides testosterone externally, the body's feedback mechanisms detect adequate circulating levels and respond accordingly.

Testogel is typically applied once daily, with dosing adjusted based on blood testosterone measurements taken at intervals specified in the product information (for Testogel 16.2 mg/g, typically 2-4 hours after application at steady state). To prevent unintended testosterone transfer, it's essential to: wash hands thoroughly after application, allow the gel to dry completely before dressing, cover the application site with clothing, and avoid skin-to-skin contact with others (particularly women and children) for several hours after application. Avoid bathing or showering for at least 2 hours after applying Testogel 16.2 mg/g (longer for other formulations).

Effects of Testosterone Replacement on Natural Production

Yes, Testogel does suppress the testicles' natural testosterone production—this is a well-established physiological response to exogenous testosterone therapy. When the body detects adequate testosterone levels from an external source, the hypothalamic-pituitary-gonadal (HPG) axis responds through negative feedback inhibition.

This feedback mechanism works as follows: elevated testosterone levels signal the hypothalamus to reduce GnRH secretion, which in turn decreases pituitary production of LH and FSH. With reduced LH stimulation, the Leydig cells in the testes significantly decrease or cease their testosterone production. Similarly, reduced FSH affects Sertoli cell function, which can impact spermatogenesis (sperm production). This suppression typically occurs within weeks of starting TRT and can be substantial—intratesticular testosterone levels may decrease significantly, potentially by 90% or more according to clinical studies.

For most men using Testogel for confirmed hypogonadism, this suppression is not problematic because their testes were already underproducing testosterone. However, the degree of testicular suppression varies between individuals and depends on factors including dosage, duration of treatment, baseline testicular function, and individual sensitivity to feedback mechanisms.

An important consequence of this suppression is potential testicular atrophy (shrinkage), which some men notice during long-term TRT. This occurs because the reduced hormonal stimulation leads to decreased activity in testicular tissue. Additionally, fertility may be significantly impaired or temporarily lost, as spermatogenesis requires both adequate intratesticular testosterone (much higher than serum levels) and FSH stimulation.

Importantly, TRT is not a reliable contraceptive and should generally be avoided by men actively trying to conceive. The NICE Clinical Knowledge Summary on male hypogonadism emphasises discussing fertility implications before initiating TRT, particularly in younger men who may wish to father children.

Managing Testicular Function During TRT

For men concerned about maintaining testicular function whilst on Testogel, several management strategies exist, though their appropriateness depends on individual circumstances and treatment goals. It's important to understand that complete preservation of natural testosterone production whilst on TRT is generally not achievable due to the feedback mechanisms described above.

If fertility preservation is a priority, men should discuss this with their endocrinologist or urologist before starting Testogel. Options may include:

• Sperm banking (cryopreservation) before commencing TRT, particularly recommended for younger men

• Co-treatment with human chorionic gonadotrophin (hCG), which mimics LH and can help maintain intratesticular testosterone and spermatogenesis during TRT—this is an off-label, specialist-initiated treatment in the UK requiring informed consent

• Alternative treatments such as selective oestrogen receptor modulators (SERMs) like clomifene, which may stimulate natural testosterone production rather than replacing it—though these are off-label in the UK for this indication, less effective for severe hypogonadism, and should only be initiated by specialists

• Intermittent TRT protocols are not standard practice in the UK and lack robust evidence—these should only be considered under specialist guidance

Regular monitoring is essential for all men on Testogel. UK guidelines recommend checking testosterone levels, full blood count (particularly haematocrit, as testosterone can increase red blood cell production), and symptoms at baseline, after 3-6 months, then annually once stable. Prostate-specific antigen (PSA) testing and digital rectal examination are recommended for men aged 40 or over and those with prostate cancer risk factors. Liver function tests are not routinely required for transdermal TRT unless clinically indicated.

For men who discontinue Testogel, natural testosterone production may gradually resume, though recovery is not guaranteed and can take months to years. The likelihood and speed of recovery depend on treatment duration, age, and baseline testicular function. Some men may require specialist supervision during treatment cessation or remain hypogonadal, necessitating long-term TRT. There is no guarantee of full recovery of testicular function after stopping treatment, particularly after prolonged use.

When to Speak to Your Doctor About Testogel

You should contact your GP or prescribing specialist if you experience any concerning symptoms whilst using Testogel or have questions about its effects on testicular function. Testosterone replacement therapy requires ongoing medical supervision to ensure safety and effectiveness.

Seek medical advice promptly if you notice:

• Significant testicular shrinkage or pain—whilst some reduction in size may occur, marked changes or discomfort warrant assessment

• Symptoms suggesting excessive testosterone levels, including aggressive behaviour, severe acne, significant mood changes, or sleep disturbances

• Signs of polycythaemia (excessive red blood cells), such as headaches, dizziness, visual disturbances, or ruddy complexion—this is a known risk with TRT and may require dose adjustment if your haematocrit exceeds 0.54

• Urinary symptoms including difficulty urinating, weak stream, or increased frequency, which may indicate prostate issues

• Cardiovascular symptoms such as chest pain, shortness of breath, or leg swelling—seek urgent medical attention (call 999 or attend A&E) for severe chest pain or acute shortness of breath

• Skin reactions at application sites, including severe irritation, rash, or persistent redness

You should also arrange a consultation if:

• You're planning to start a family or have concerns about fertility—this discussion should ideally occur before starting Testogel

• You're considering stopping treatment and want to understand the implications for natural testosterone recovery

• Your symptoms of hypogonadism haven't improved after 3–6 months of treatment at an adequate dose

• You've missed multiple doses or are having difficulty adhering to the daily application regimen

• You're concerned about accidental transfer to others—if this occurs, the affected person should wash the area thoroughly with soap and water

Never stop Testogel abruptly without medical guidance, as this can lead to a temporary period of very low testosterone whilst your natural production recovers (if it does). Your doctor can advise on appropriate monitoring and, if necessary, strategies to support HPG axis recovery.

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

Frequently Asked Questions