Many men considering testosterone replacement therapy (TRT) wonder whether the treatment uses real testosterone or a synthetic substitute. The answer is reassuring: all licensed testosterone preparations in the UK contain testosterone that is molecularly identical to the hormone naturally produced by the body. Whether administered as gels or injections, pharmaceutical testosterone is bioidentical—meaning it has the same chemical structure (C₁₉H₂₈O₂) and interacts with the body in exactly the same way as endogenous testosterone. Understanding the nature of testosterone medications, their regulation, and how they differ from unregulated products is essential for men seeking safe, effective treatment for clinically confirmed testosterone deficiency.

What Is Testosterone Replacement Therapy?

Testosterone replacement therapy (TRT) is a medical treatment prescribed to men with clinically confirmed testosterone deficiency, also known as hypogonadism. This condition occurs when the testes produce insufficient testosterone, leading to symptoms such as reduced libido, erectile dysfunction, fatigue, decreased muscle mass, and mood disturbances. TRT aims to restore testosterone levels to within the normal physiological range, thereby alleviating these symptoms and improving quality of life.

Before initiating TRT, patients must undergo thorough assessment including at least two early-morning blood tests (taken before 11:00) to confirm low testosterone levels. According to NICE and the British Society for Sexual Medicine (BSSM), testosterone deficiency is typically diagnosed when total testosterone is below 8 nmol/L. Levels between 8 and 12 nmol/L are considered borderline and require assessment of sex hormone-binding globulin (SHBG) and calculated free testosterone, alongside clinical context. Additional blood tests should include luteinising hormone (LH), follicle-stimulating hormone (FSH), and prolactin to distinguish between primary testicular failure and secondary (central) hypogonadism, which may require specialist referral.

Clinicians must identify the underlying cause of testosterone deficiency and assess for conditions requiring caution. Absolute contraindications include prostate cancer and male breast cancer. Conditions such as untreated obstructive sleep apnoea, severe heart failure, and significant liver or kidney disease require careful monitoring and are not absolute contraindications but warrant specialist input. Baseline prostate assessment (PSA and, where appropriate, digital rectal examination) should be performed according to age and individual risk factors. The decision to commence TRT should be made collaboratively between patient and clinician, considering both potential benefits and risks.

TRT is available in various formulations including gels and injections. The choice of formulation depends on patient preference, lifestyle factors, cost considerations, and individual response to treatment. Regular monitoring is essential throughout treatment, with follow-up blood tests typically conducted at 3 months, 6 months, and then annually. Monitoring includes testosterone levels, full blood count (to detect polycythaemia), liver function, and prostate-specific antigen (PSA) according to age and risk. Patients should be referred to endocrinology or urology if they have low or inappropriately normal LH/FSH (suggesting pituitary or hypothalamic causes), markedly low testosterone, raised prolactin, visual disturbances, persistent headaches, or if fertility is desired.

It is important to distinguish TRT from the misuse of testosterone for performance enhancement or bodybuilding purposes, which involves supraphysiological doses and carries significant health risks. Legitimate TRT is a regulated medical intervention prescribed only for diagnosed testosterone deficiency under specialist or experienced GP supervision.

Types of Testosterone Used in Medical Treatment

All testosterone preparations used in licensed medical treatment in the UK contain testosterone itself or testosterone esters—these are not fundamentally different substances but rather the same hormone in different pharmaceutical formulations. Testosterone esters such as those found in Sustanon and testosterone undecanoate are modified forms where an ester group is attached to the testosterone molecule. This modification affects how quickly the testosterone is absorbed and how long it remains active in the body, but once in the bloodstream, the ester is cleaved off, releasing natural testosterone.

Injectable testosterone preparations are among the most commonly prescribed forms in the UK. Sustanon is a blend of four testosterone esters (propionate, phenylpropionate, isocaproate, and decanoate) administered via intramuscular injection, typically every 2 to 3 weeks, with dosing intervals individualised according to response. Testosterone undecanoate (Nebido) is a long-acting injection given every 10 to 14 weeks after an initial loading phase. Nebido must be administered by a healthcare professional due to the injection volume and the rare risk of pulmonary oil microembolism (POME). Short-acting injections such as Sustanon may be suitable for self-administration after appropriate training.

Transdermal testosterone gels (such as Testogel and Tostran) are applied daily to the skin, usually on the shoulders, upper arms, or abdomen. The testosterone is absorbed through the skin into the bloodstream, providing steady hormone levels throughout the day. Gels offer convenience and avoid the peaks and troughs sometimes associated with injections, though users must take precautions to prevent transfer to others through skin contact, particularly to women and children.

All licensed testosterone medications in the UK are regulated by the Medicines and Healthcare products Regulatory Agency (MHRA) and must meet stringent quality and safety standards. Formulations such as testosterone patches, buccal tablets, and oral testosterone undecanoate capsules are not currently marketed or licensed in the UK. The choice of formulation depends on individual patient factors including convenience, tolerability, and achievement of target testosterone levels as confirmed by monitoring.

Bioidentical vs Synthetic Testosterone: Understanding the Difference

The term "bioidentical" has gained popularity in recent years, particularly in private healthcare settings, but it is important to understand what this actually means in the context of testosterone therapy. Bioidentical testosterone refers to testosterone that is molecularly identical to the hormone naturally produced by the human body. In reality, virtually all testosterone used in licensed medical preparations in the UK—whether gels or injections—is bioidentical in this sense. The testosterone molecule itself (C₁₉H₂₈O₂) is the same whether produced by the testes or manufactured pharmaceutically.

Pharmaceutical testosterone is typically synthesised from plant sources such as soya or wild yam through chemical processes that create a molecule identical to endogenous testosterone. Once administered and absorbed, the body cannot distinguish between testosterone produced by the testes and that provided through TRT—they are biochemically identical and interact with androgen receptors in exactly the same way. The term "synthetic" in this context does not mean the testosterone is chemically different; rather, it refers to the manufacturing process.

Some private clinics market "bioidentical hormone replacement therapy" (BHRT) as superior to conventional TRT, but there is no evidence that such preparations offer advantages over licensed products. In fact, regulatory bodies including the MHRA and professional societies such as the British Menopause Society have raised concerns about unregulated compounded bioidentical hormone preparations, which may lack the quality assurance and standardisation of licensed medications. Compounded preparations are unlicensed, are not subject to the same rigorous testing, and may have inconsistent dosing, posing safety risks.

Patients should be aware that all licensed testosterone preparations available through the NHS or regulated private prescriptions contain body-identical testosterone and are quality-assured by the MHRA. The key differences between products lie in their delivery method, absorption rate, and duration of action—not in the fundamental nature of the testosterone molecule itself. When considering TRT, patients should focus on choosing a licensed, regulated product under appropriate medical supervision rather than being swayed by marketing terminology. Compounded or unlicensed "bioidentical" preparations are not recommended.

Safety and Regulation of Testosterone Medications

Testosterone medications available in the UK are strictly regulated by the Medicines and Healthcare products Regulatory Agency (MHRA), which ensures that all licensed products meet rigorous standards for quality, safety, and efficacy. These medications are classified as prescription-only medicines (POM) and as controlled drugs under the Misuse of Drugs Act 1971 (Class C) and the Misuse of Drugs Regulations 2001 (Schedule 4, Part II). This means testosterone can only be legally prescribed by registered medical practitioners for legitimate medical purposes. Schedule 4 controlled drugs do not require the additional prescription writing requirements that apply to Schedule 2 or 3 controlled drugs.

Licensed testosterone preparations undergo extensive clinical trials before approval, and post-marketing surveillance continues to monitor for adverse effects. The MHRA has reviewed cardiovascular safety data and concluded that there is no consistent evidence of increased cardiovascular risk with appropriate use of testosterone therapy, but emphasised the importance of prescribing only for confirmed hypogonadism and maintaining regular monitoring. This regulatory framework provides assurance that patients receiving TRT through legitimate medical channels are using products of verified quality and consistency.

Common adverse effects of TRT include acne, oily skin, increased red blood cell production (polycythaemia), fluid retention, and breast tenderness. More serious potential risks include cardiovascular events and worsening of pre-existing prostate conditions. Regular monitoring is essential to detect and manage these effects early. Blood tests should include haemoglobin and haematocrit levels (to identify polycythaemia); if haematocrit exceeds 54%, TRT should be withheld or the dose adjusted, and investigation for secondary causes of polycythaemia should be undertaken. Monitoring should also include liver function tests, lipid profiles, and PSA levels according to age and individual risk, following the guidance in the product Summary of Product Characteristics (SmPC).

Patients should contact their GP if they experience symptoms such as persistent headaches, visual disturbances, chest pain, shortness of breath, leg swelling, or urinary symptoms whilst on TRT. These may indicate complications requiring urgent assessment. Additionally, men on TRT should be counselled about fertility implications, as exogenous testosterone suppresses natural sperm production and can cause temporary or, rarely, permanent infertility. Men who are actively trying to conceive should not use TRT; alternative treatments such as human chorionic gonadotrophin (hCG) or selective oestrogen receptor modulators (SERMs) may be considered under specialist supervision.

Patients are encouraged to report any suspected side effects via the MHRA Yellow Card Scheme, which can be accessed at www.mhra.gov.uk/yellowcard or via the Yellow Card app. Purchasing testosterone from unregulated online sources or using products not prescribed by a qualified clinician carries significant risks, including exposure to counterfeit medications, incorrect dosing, contaminated products, and absence of medical monitoring. The NHS and NICE emphasise that TRT should only be initiated and monitored by healthcare professionals with appropriate expertise, ensuring both safety and therapeutic benefit.

Frequently Asked Questions