Testogel is a widely prescribed testosterone replacement therapy in the UK, but many patients wonder whether it contains a natural or synthetic hormone. The answer lies in understanding the distinction between molecular structure and manufacturing process. Testogel contains bioidentical testosterone—chemically identical to the hormone naturally produced by the human body—yet it is synthesised in pharmaceutical laboratories under strict regulatory standards. This article explores what Testogel is, how it is made, the difference between bioidentical and synthetic hormones, and when testosterone replacement therapy is clinically appropriate for men with confirmed hypogonadism.

What Is Testogel and How Is It Made?

Testogel is a transdermal testosterone replacement therapy (TRT) formulated as a clear, colourless gel containing testosterone as the active pharmaceutical ingredient. It is manufactured through a controlled pharmaceutical process that involves synthesising testosterone in laboratory conditions, then combining it with a gel base containing excipients such as ethanol, carbomer, isopropyl myristate, and purified water. The gel is designed to deliver testosterone through the skin, where it is absorbed into the bloodstream to restore physiological testosterone levels in men with confirmed hypogonadism.

The manufacturing process adheres to stringent Good Manufacturing Practice (GMP) standards regulated by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. Testosterone used in Testogel is chemically identical to the hormone naturally produced by the human testes, with the molecular formula C₁₉H₂₈O₂. This structural identity is crucial for its therapeutic efficacy and safety profile.

Testogel is available in two main formulations in the UK:

• Testogel 16.2 mg/g transdermal gel (metered-dose pump): Each pump actuation delivers 1.25 g of gel containing 20.25 mg of testosterone. The usual starting dose is 40.5 mg (two pump actuations) once daily, which may be adjusted between 20.25 mg and 81 mg depending on clinical response and testosterone levels. This formulation should be applied to the shoulders and/or upper arms only.

• Testogel 50 mg/5 g gel in sachets (1% gel): Each sachet contains 5 g of gel delivering 50 mg of testosterone. The usual starting dose is 50 mg once daily, adjusted according to clinical and biochemical response. This formulation may be applied to the shoulders, upper arms, or abdomen.

The gel is applied once daily to clean, dry, intact skin. It should never be applied to the genitals or broken skin. After application, the alcohol carrier evaporates, leaving testosterone on the skin surface, from which it is gradually absorbed over several hours. This delivery method provides relatively stable serum testosterone concentrations.

The pharmaceutical synthesis of testosterone involves starting materials derived from plant sterols, particularly diosgenin extracted from wild yam or stigmasterol from soya, which undergo multiple chemical transformations to produce the final testosterone molecule. This process, whilst laboratory-based, creates a hormone that is molecularly indistinguishable from endogenous testosterone. For full details of excipients in each formulation, refer to the relevant Summary of Product Characteristics (SmPC) on the electronic Medicines Compendium (EMC).

Understanding Bioidentical vs Synthetic Testosterone

The term 'bioidentical' refers to hormones that have the exact same chemical and molecular structure as those produced naturally by the human body. Testosterone in Testogel is bioidentical—it is chemically and structurally identical to the testosterone synthesised by Leydig cells in the testes. This is an important distinction from synthetic hormones, which may have altered molecular structures that differentiate them from their naturally occurring counterparts.

Some confusion arises because the term 'synthetic' can refer to the method of production (laboratory synthesis) rather than the molecular structure. In pharmaceutical terminology, testosterone in licensed medicines like Testogel is often described as 'synthetic' because it is manufactured in a laboratory rather than extracted from animal or human sources. However, this does not mean the molecule itself differs from natural testosterone—the end product is bioidentical.

Examples of truly synthetic androgens include modified testosterone derivatives such as methyltestosterone or nandrolone, which have altered chemical structures that change their pharmacological properties, including oral bioavailability, receptor binding affinity, and metabolic pathways. These modifications can result in different side effect profiles and therapeutic applications. In contrast, bioidentical testosterone in Testogel is metabolised by the same enzymatic pathways as endogenous testosterone, converting to dihydrotestosterone (DHT) via 5α-reductase and to oestradiol via aromatase.

The clinical significance of using bioidentical testosterone lies in its physiological action. Because the molecule is identical to endogenous testosterone, it binds to androgen receptors in the same manner, producing the expected androgenic and anabolic effects without the unpredictable responses that can occur with structurally modified synthetic androgens.

It is important to note that NICE Clinical Knowledge Summaries (CKS) and the British Society for Sexual Medicine (BSSM) support the use of licensed testosterone preparations for confirmed hypogonadism. Testogel is a licensed medicine that contains testosterone identical to the endogenous hormone. Compounded or unregulated 'bioidentical' products marketed outside the licensed medicines framework are not recommended by UK regulators and should be avoided due to safety, quality, and efficacy concerns.

Who Should Use Testogel and When Is It Prescribed?

Testogel is indicated for testosterone replacement therapy in adult males with hypogonadism, a condition characterised by insufficient testosterone production. According to NICE CKS guidance, diagnosis requires both biochemical evidence and clinical symptoms of testosterone deficiency. Biochemical confirmation involves measuring serum total testosterone on at least two separate occasions, preferably in the morning (typically before 11 am) when levels are highest. If sex hormone-binding globulin (SHBG) is abnormal, calculated free testosterone should be considered.

Common symptoms of hypogonadism include:

• Reduced libido and erectile dysfunction

• Decreased energy levels and persistent fatigue

• Loss of muscle mass and increased body fat

• Reduced bone mineral density (osteoporosis risk)

• Mood disturbances, including depression and irritability

• Cognitive difficulties and reduced concentration

• Decreased facial and body hair growth

Hypogonadism may be primary (testicular failure due to genetic conditions, chemotherapy, radiation, trauma, or infection) or secondary (hypothalamic-pituitary dysfunction due to tumours, medications, obesity, or chronic illness). Testogel is appropriate for both types, though the underlying cause should be investigated and addressed where possible.

Before prescribing Testogel, clinicians should conduct a thorough assessment including medical history, physical examination, and baseline investigations. Blood tests should measure total testosterone (ideally between 8–11 am on two separate occasions), luteinising hormone (LH), follicle-stimulating hormone (FSH), and SHBG. If LH and FSH are low or normal in the presence of low testosterone, measure prolactin to exclude hyperprolactinaemia. Additional baseline tests include full blood count (FBC) and haematocrit, liver function, lipid profile, prostate-specific antigen (PSA), and digital rectal examination (DRE) as appropriate. Bone density scanning may be considered in older men or those with risk factors for osteoporosis.

Contraindications to Testogel (per the SmPC) include:

• Known or suspected prostate carcinoma or male breast cancer

• Hypersensitivity to testosterone or any excipients

Warnings and precautions require careful monitoring and may necessitate dose reduction, temporary discontinuation, or specialist referral. These include:

• Severe heart failure

• Untreated severe obstructive sleep apnoea

• Polycythaemia or elevated haematocrit (>0.54)

• Abnormal PSA or DRE findings (refer per NICE NG12 if suspected prostate cancer)

• Epilepsy, migraine, hypertension, or renal/hepatic impairment

Fertility considerations: Exogenous testosterone suppresses spermatogenesis and should not be used in men actively trying to conceive. Men seeking fertility should be referred to an endocrinologist or reproductive specialist to consider alternative treatments such as gonadotrophin therapy.

Monitoring during treatment is essential and should follow NICE CKS and SmPC guidance:

• Measure serum testosterone at baseline, 3 months, 6 months, 12 months, and then annually. Adjust dose to achieve testosterone levels in the mid-normal physiological range.

• Check FBC and haematocrit at baseline, 3 months, 6 months, 12 months, and then annually. If haematocrit exceeds 0.54, reduce the dose or stop treatment temporarily and investigate.

• Monitor PSA and perform DRE as clinically appropriate, particularly in men over 50 or those with risk factors. Refer urgently per NICE NG12 if PSA or DRE findings suggest prostate cancer.

• Assess clinical response, including symptom improvement, bone density (if indicated), and cardiovascular risk factors.

Application and transfer precautions are critical to prevent unintended exposure to others, particularly women and children:

• Apply the gel to clean, dry, intact skin on the shoulders and upper arms (16.2 mg/g pump) or shoulders, upper arms, or abdomen (50 mg/5 g sachet). Never apply to the genitals or broken skin.

• Wash hands thoroughly with soap and water immediately after application.

• Allow the gel to dry completely before dressing. Cover the application site with clothing.

• Wash the application site with soap and water before any close skin-to-skin contact with others.

• Avoid swimming or bathing for at least 6 hours after application to ensure adequate absorption.

Testogel should be prescribed only after careful consideration of risks and benefits, with regular monitoring of testosterone levels, haematocrit, PSA, and clinical response. The goal is to restore testosterone to the mid-normal physiological range, alleviating symptoms whilst minimising adverse effects.

Is Testogel a Natural or Synthetic Hormone?

The question of whether Testogel is 'natural' depends on how one defines the term. From a molecular perspective, Testogel contains bioidentical testosterone—the hormone is chemically and structurally identical to the testosterone naturally produced by the human body. In this sense, the active ingredient itself can be considered natural in its molecular identity, even though it is produced through pharmaceutical synthesis rather than extracted from biological sources.

However, from a production standpoint, Testogel is synthetically manufactured in pharmaceutical laboratories. The testosterone is not harvested from animal or human tissues but is created through chemical synthesis starting from plant-derived steroid precursors. This manufacturing process, whilst producing a bioidentical molecule, is an industrial pharmaceutical procedure subject to regulatory oversight and quality control standards by the MHRA.

It is important to distinguish Testogel from unregulated 'natural' testosterone products sometimes marketed through non-medical channels. These products may claim to contain plant-based or 'natural' testosterone but are not licensed medicines in the UK and should be avoided. Such products pose significant safety risks, including contamination, inconsistent potency, absence of clinical evidence, and lack of regulatory approval. In contrast, Testogel is a licensed medicine that has undergone rigorous clinical trials demonstrating efficacy and safety.

The bioidentical nature of testosterone in Testogel means it functions physiologically in the same manner as endogenous testosterone. It undergoes identical metabolic pathways, binds to the same receptors, and produces the expected androgenic effects. This is fundamentally different from modified synthetic androgens with altered structures.

For patients considering testosterone therapy, the key consideration should not be whether the hormone is 'natural' in origin but whether it is:

• Prescribed appropriately for confirmed hypogonadism

• Administered at physiological replacement doses

• Monitored regularly for efficacy and safety

• Obtained through legitimate medical channels as a licensed medicine

Patients should discuss any concerns about testosterone therapy with their GP or endocrinologist. If symptoms of low testosterone persist despite treatment, or if side effects develop (such as skin reactions at the application site, mood changes, signs of polycythaemia such as headache or visual disturbances, or cardiovascular symptoms), medical review is essential.

If you experience any side effects, including those not listed in the patient information leaflet, you should report them via the MHRA Yellow Card Scheme at yellowcard.mhra.gov.uk or search for 'MHRA Yellow Card' in the Google Play or Apple App Store. Reporting side effects helps improve the safety information available about medicines.

Testogel should never be shared with others, and care must be taken to avoid skin-to-skin transfer to partners or children after application by following the precautions outlined above. For further information on hypogonadism and testosterone replacement, consult the NHS website or speak to your healthcare professional.

Frequently Asked Questions