Testosterone Replacement Preparations for hypogonadism

A patient friendly UK guide to gels, injections, oral testosterone and the advantages and disadvantages of each. Clinical review, September 2026.

Choosing the right testosterone preparation for hypogonadism

A UK guide to the available options, their advantages, their drawbacks—and why the “best” testosterone is usually the one that best fits the person using it.

You have been told that your testosterone is genuinely low. The symptoms fit. The blood tests agree. Then comes the apparently simple question:

“Which testosterone should I take?”

This is where testosterone replacement begins to resemble travel planning. Would you prefer a small daily journey, a larger trip every few weeks, or one long-haul departure every three months? Each route can reach the same destination—a physiological testosterone level—but the ride can feel very different.

In the UK, the practical choice is usually between a daily gel and an intramuscular injection. Tablets, patches, nasal gels, gum tablets and pellets exist—or have existed—but most are not routinely available here. The differences are not merely cosmetic. They affect how steady the testosterone level is, how quickly treatment can be adjusted or stopped, the risk of transfer to somebody else, the chance of a raised red-cell count and, rather importantly, whether treatment fits into real life.

There is no universally superior preparation. The aim is not to find the most dramatic product, the highest blood result or the formulation with the most impressive name. It is to replace what the body is missing, as safely and consistently as possible.

The short UK answer: daily testosterone gels and licensed intramuscular testosterone esters are the main options. All injectable testosterone products currently licensed for male hypogonadism in the UK are labelled for intramuscular use. Weekly subcutaneous testosterone is a credible option in selected patients, but in the UK it is off-label and should be prescribed and taught by a clinician familiar with it.

First, what is testosterone replacement actually replacing

Healthy testes do not release testosterone as a monthly tidal wave. Production changes over the day and is controlled by signals from the hypothalamus and pituitary gland. Testosterone then travels in the blood—mostly bound to proteins—and acts on sexual function, muscle, bone, red-cell production, mood and many other tissues.

When the testes cannot produce enough testosterone, or when the pituitary or hypothalamus cannot provide the correct signal, replacement treatment tries to restore testosterone exposure to a normal physiological range. Different preparations solve the delivery problem in different ways:

• A gel creates a small reservoir in the skin and supplies testosterone each day.

• A shorter-acting ester injection creates an oily depot in muscle, releasing testosterone over the following days or weeks.

• Long-acting testosterone undecanoate creates a much larger depot designed to last roughly three months.

• Oral testosterone undecanoate is absorbed with dietary fat into the intestinal lymphatic system, allowing much of it to bypass immediate breakdown by the liver.

The ester is essentially a chemical “tail” attached to testosterone. The body removes that tail after absorption. A longer tail generally delays release; it does not make the resulting testosterone more masculine, more potent or somehow “better”. The pharmacology is sophisticated. The final hormone is pleasingly unexciting: testosterone.

A pause before choosing a preparation

Testosterone replacement should follow a proper diagnosis—not simply tiredness plus one borderline afternoon blood result. UK guidance recommends compatible symptoms or signs, reliable morning fasting testosterone measurements on separate days, and investigation of why the level is low. Obesity, acute illness, sleep disturbance, certain medicines and systemic disease can all complicate interpretation.

And one question must be asked before the first prescription:

Could you want biological children in the near future?

Testosterone from outside the body suppresses the pituitary hormones LH and FSH. Blood testosterone may rise while testosterone inside the testes falls, and sperm production can fall markedly or stop. Testosterone is therefore not a fertility treatment. Men seeking fertility may need semen assessment and, depending on the cause of hypogonadism, specialist treatment with gonadotrophins or other approaches instead. Testosterone is not reliable contraception either—a particularly unhelpful combination of facts, but an important one.

The UK options at a glance

Preparation	Typical Rhythm	UK position in 2026	Strengths	Limitations
Transdermal gel (Testogel®, Tostran®, Testavan®)	Daily	Licensed and widely used	Steady levels, painless, finely adjustable, rapidly reversible	Daily application, variable absorption, skin irritation, transfer to others
Mixed short-acting esters (Sustanon® 250)	Usually every 3 weeks; individualised	Licensed for deep intramuscular injection	Inexpensive, familiar, no daily dosing	Peaks and troughs, injections, raised haematocrit; contains arachis oil
Testosterone enantate	Usually every 2–3 weeks when used according to the UK licence	Licensed for intramuscular injection	Flexible and relatively quick to adjust	Peaks and troughs, injections, raised haematocrit
Long-acting testosterone undecanoate (Nebido® and generics)	Loading dose, then commonly every 10–14 weeks	Licensed for slow, deep intramuscular injection	Smooth profile, infrequent dosing	Large 4 ml injection, clinic attendance, slow to reverse, rare pulmonary oil microembolism
Weekly subcutaneous enantate/cypionate	Commonly every 7 days	Off-label in the UK; cypionate itself is not routinely UK-licensed	Small needle, self-administration, smoother weekly profile	Requires training and careful prescribing; local reactions; evidence base smaller than for licensed routes
Older oral testosterone undecanoate (Andriol®/Restandol® type)	Usually twice or three times daily with meals	Restandol discontinued in the UK; possible only through specialist/unlicensed supply	No gel and no needle; quickly reversible	Food-dependent and variable absorption; frequent dosing; short-lived peaks
Newer oral undecanoate (Jatenzo®, Tlando®, Kyzatrex®)	Usually twice daily with food	Authorised in the US, not routinely licensed or marketed in the UK	Convenient oral route; improved formulation	Food still matters, dose monitoring, blood-pressure/haematocrit effects, cost and no routine UK access

Doses and blood-test timing are product-specific. Testosterone gels are not automatically interchangeable pump-for-pump, and injection intervals must be individualised.

Testosterone gel and the adjustable dimmer switch

For many people beginning testosterone replacement, gel is the most forgiving place to start. It is applied once daily to clean, dry, intact skin. Testosterone enters through the skin over the day, usually producing a smoother profile than a short-acting injection.

Why gel can work well

• It is easy to adjust. The dose can be changed in small steps.

• It is easy to stop. If troublesome side effects occur, exposure falls relatively quickly after discontinuation.

• There is no injection. This matters to anyone with needle anxiety, little muscle bulk, anticoagulation concerns or difficult access to an injection clinic.

• Levels are usually steadier. There is less of the post-injection high followed by an end-of-interval low.

• It may be useful when haematocrit is a concern. Every form can raise red-cell production, but short-acting injections are often more troublesome in practice.

Where gel becomes less charming

It has to be applied every day. That is wonderfully convenient for some people and an administrative burden before breakfast for others. Absorption varies between individuals, and occasionally a perfectly conscientious patient simply does not absorb a particular gel well.

Alcohol-based gels can sting damaged skin or cause dryness. Showering or swimming too soon can reduce absorption, but the required waiting time differs by product. Application sites also differ: Testogel and Testavan are generally applied to the shoulders or upper arms, whereas Tostran is applied to the abdomen or inner thighs. Follow the leaflet for the specific brand rather than relying on instructions remembered from another gel.

The most important drawback is transfer. Testosterone remaining on the skin can pass to a partner, child or even a pet. The MHRA has described premature puberty and genital enlargement in children after repeated accidental exposure. The precautions are simple but non-negotiable:

1. Wash hands with soap and water after application.

2. Let the gel dry and cover the site with clean clothing.

3. After the product-specific waiting period, wash the application site before close skin-to-skin contact.

A useful laboratory trap is worth knowing: gel near the blood-sampling site can contaminate the sample and produce an impressively high—but entirely misleading—testosterone result. Apply it exactly as instructed and tell the clinician or phlebotomist which gel you use and when you applied it.

Gel may particularly suit: someone starting treatment, someone who values smooth daily replacement, someone who needs small dose changes, or someone in whom rapid reversibility is reassuring.

Gel may be a poor fit: someone unlikely to manage daily application, someone with significant skin reactions, or a household in which reliable transfer precautions would be difficult.

Sustanon and four esters sharing one ampoule

Sustanon 250 contains four testosterone esters with different release rates: propionate, phenylpropionate, isocaproate and decanoate. The intention is an early effect from the shorter esters and a longer tail from the slower ones. The UK product information usually describes 1 ml by deep intramuscular injection every three weeks, although clinicians individualise the interval.

The advantages

• It is established, widely recognised and relatively inexpensive.

• There is no daily treatment and no risk of skin-to-skin transfer.

• The 1 ml volume is much smaller than a long-acting undecanoate injection.

• If necessary, the regimen can be adjusted or stopped more quickly than a three-month depot.

The disadvantages

The mixture does not abolish peaks and troughs. Some patients notice a few energetic or restless days after an injection, followed by a gradual return of fatigue, low mood or reduced libido before the next. A symptom diary can reveal a pattern that one isolated blood result misses.

High post-injection concentrations can stimulate red-cell production, so haemoglobin and haematocrit need monitoring. Acne, oily skin and changes in mood or sexual drive may also track the peak. There is the usual discomfort and inconvenience of repeated injections.

One very UK-practical detail: Sustanon is made with refined arachis (peanut) oil and is contraindicated in people allergic to peanut; the UK product information also advises avoidance in soya allergy.

Sustanon may particularly suit: someone wanting a familiar, economical treatment without daily dosing, especially if injections and the peak–trough pattern are well tolerated.

It may be a poor fit: someone troubled by end-of-dose symptoms, recurrent high haematocrit, needle aversion, or peanut/soya allergy.

Testosterone enantate and simpler chemistry, similar practical trade-offs

Testosterone enantate contains a single intermediate-acting ester. The UK licence describes 250 mg intramuscularly every two to three weeks for initial treatment, with subsequent dosing individualised.

Its virtues are flexibility, modest injection volume and a long history of use. Its weakness is familiar: a full dose every few weeks can generate a relatively high peak and a low trough. Dividing treatment into smaller, more frequent doses can flatten this curve, but any departure from the licensed regimen or route should be a deliberate specialist plan—not home pharmacological improvisation.

Testosterone cypionate behaves similarly and is widely used in North America, but it is not a routinely licensed UK product. It may occasionally be supplied as an unlicensed import.

Long-acting testosterone undecanoate and the slow-release depot

Long-acting testosterone undecanoate—best known by the brand Nebido, with generic alternatives now available—is a 1,000 mg ester dose in 4 ml of oil. After a loading injection, a second dose may be given at about six weeks; maintenance injections are then commonly spaced 10–14 weeks apart, guided by symptoms and the testosterone level just before the next injection.

This is the closest the UK testosterone menu comes to “set it and forget it”, although the blood tests and appointments prevent complete amnesia.

The advantages

• Testosterone exposure is generally smoother than with short-acting injections.

• Only around four or five injections may be needed each year once stable.

• There is no daily application and no transfer risk.

• Adherence is visible: the clinic knows when the injection was given.

The disadvantages

Four millilitres of oil is a substantial injection. It must be given very slowly—over about two minutes—and deeply into the gluteal muscle by a trained professional. The long duration is also its central compromise: if acne, mood disturbance, high haematocrit or another problem develops, the depot cannot be removed. The dose has already left the station and is travelling slowly.

Rarely, an oily injection can cause pulmonary oil microembolism (POME), producing sudden cough, breathlessness, chest discomfort, dizziness or faintness during or just after administration. This is why the correct technique and observation around the injection matter.

Long-acting undecanoate may particularly suit: someone stable on testosterone who values infrequent treatment and dislikes hormonal peaks and troughs.

It may be a poor first choice: when the diagnosis, response or tolerance is still being established; when clinic visits are difficult; or when rapid withdrawal might be important.

Subcutaneous injections and good evidence, but an off-label UK route

Here the language matters.

All currently licensed injectable testosterone preparations for male hypogonadism in the UK specify intramuscular administration. That does not mean testosterone esters can only ever work under that licence or by that route. In the US, a pre-filled testosterone enantate autoinjector (Xyosted®) is licensed for weekly subcutaneous use. It is not routinely available in the UK.

UK specialists sometimes prescribe small weekly doses of testosterone enantate—or, less commonly, imported cypionate—subcutaneously using an intramuscular product off-label. A 52-week study in 150 hypogonadal men using a purpose-built subcutaneous enantate autoinjector found that 92.7% achieved the study’s target average testosterone range at week 12. Small crossover and pharmacokinetic studies also suggest that subcutaneous enantate or cypionate can give exposure comparable with intramuscular use and may be preferred because of less anxiety and pain.

Why patients may prefer it

• A shorter, finer needle can be easier to self-administer.

• Small weekly doses may produce a smoother profile than a larger injection every two or three weeks.

• It can reduce dependence on practice-nurse appointments.

• Dose adjustment is relatively straightforward.

Why “off-label” still matters

Off-label does not mean forbidden or automatically unsafe. It means the exact product-and-route combination has not been authorised by the UK regulator on the basis of a manufacturer’s application. The prescriber therefore takes additional responsibility for explaining the evidence, uncertainty, technique and monitoring.

There can be stinging, nodules, bruising or leakage at the injection site. The evidence base is encouraging but smaller than that for established licensed routes. Crucially, the evidence is strongest for small-volume enantate or cypionate regimens; it should not be casually extrapolated to every oily testosterone product.

In particular, a 4 ml long-acting undecanoate injection is not simply a weekly subcutaneous injection writ large. It is strictly intramuscular, and its volume and depot characteristics make it a different proposition.

Never change the route, needle, dose or interval without a prescribing clinician and appropriate injection training.

Oral testosterone undecanoate and the fat question, properly digested

Ordinary testosterone is rapidly broken down during its first pass through the gut wall and liver. Testosterone undecanoate is highly fat-soluble, so it can enter the intestinal lymphatic system with dietary fat and reach the circulation before much of that first-pass metabolism occurs.

That clever detour explains both the attraction of oral therapy and its weakness: absorption depends on what is happening in the intestine at the time.

Is an oral testosterone capsule currently available in the UK

Not as a routinely marketed licensed product. Restandol Testocaps 40 mg was discontinued from the UK market in 2020. An older Andriol/Restandol-type capsule may occasionally be obtained through specialist “specials” or import arrangements, but that is not the same as ordinary licensed NHS availability.

The newer oral testosterone undecanoate products Jatenzo, Tlando and Kyzatrex are authorised in the United States but are not routinely licensed or marketed in the UK at the time of writing.

Does the older capsule require a high-fat diet

It requires food containing a meaningful amount of fat, but “take it with a meal” is more accurate than “follow a high-fat diet”. In a pharmacokinetic study of the older castor-oil formulation, exposure after a meal containing 19 g of fat was far higher than after very-low-fat meals; increasing the fat to 44 g produced no further meaningful gain. Fruit and juice alone would be a poor companion. A deliberately high-fat diet is unnecessary.

The newer formulations use self-emulsifying or lipid-based delivery systems to make absorption more reliable. They still carry instructions to take them with food. They are therefore less fussy about the exact fat content, not magically food-independent.

The advantages of oral undecanoate

• No needle, no gel and no transfer to another person.

• Treatment can be adjusted or withdrawn quickly.

• It avoids the particular liver toxicity associated with older 17-alpha-alkylated oral androgens.

The disadvantages

• Usually twice-daily dosing, sometimes with titration based on carefully timed blood tests.

• Food-dependent absorption and day-to-day variability.

• Shorter peaks and relatively higher dihydrotestosterone exposure than some other routes.

• Raised blood pressure and haematocrit remain relevant concerns with the newer products.

• No routine UK access and limited long-term comparative outcome data.

So the oral route is genuinely interesting, but for a UK patient it is presently more “view from abroad” than standard prescribing choice.

What about patches, nasal gel, gum tablets and pellets

They are worth knowing about, if only to explain why an internet search produces a much larger menu than a UK clinic does.

Route	Advantage	Drawback	UK Reality
Transdermal patch	Daily, steady delivery; no gel transfer	Skin irritation is common and patches may detach	Andropatch® was discontinued; no routine UK product
Nasal testosterone gel	Rapid absorption, no skin-transfer site, short acting	Usually three doses daily; nasal irritation; long-term/fertility evidence limited	Not routinely UK-licensed or marketed
Buccal tablet attached to the gum	Avoids injections and first-pass liver metabolism	Gum irritation, taste/comfort issues, may detach; twice-daily use	Striant® was discontinued in the UK
Subcutaneous pellets/implants	Several months of treatment from one insertion	Minor surgical procedure, scarring, infection or pellet extrusion; difficult to adjust once inserted	No routinely marketed licensed UK implant
Compounded testosterone cream	May be convenient and avoids injections	Absorption and product consistency can vary; transfer remains possible	No standard licensed male hypogonadism cream; compounded supply is unlicensed

These routes are not necessarily bad ideas. They are simply not equal UK options at present. Availability also changes, so the current British National Formulary, local formulary and product information should be checked when treatment is prescribed.

Is one preparation more effective than another

When a preparation reliably produces physiological testosterone exposure, all established routes can improve the consequences of genuine hypogonadism. Sexual interest and well-being may begin to change within weeks; body composition, red-cell production and bone health change over months. No preparation can guarantee that every non-specific symptom will improve.

Direct head-to-head evidence is limited, and much of it concerns hormone levels rather than the outcomes patients care about most. Formulations differ more clearly in convenience, fluctuations, adverse-effect pattern and reversibility than in some unique ability to “work”.

A useful principle is:

Choose the delivery system around the patient; do not force the patient’s life around the delivery system.

How might the choice be made in practice

A gel often makes sense when…

• treatment is new and easy reversibility is valuable;

• dose requirements are uncertain or small adjustments are likely;

• avoiding peaks and troughs is important;

• injections are undesirable;

• haematocrit has tended to rise on an injectable preparation.

A short-acting injection often makes sense when…

• cost and familiarity matter;

• daily adherence would be difficult;

• the patient accepts injections and can recognise peak–trough symptoms;

• flexibility is preferred over a very long-acting depot.

A long-acting injection often makes sense when…

• treatment is already proven to be effective and well tolerated;

• infrequent dosing is a priority;

• a smooth profile matters more than rapid reversibility;

• reliable clinic attendance is possible.

A supervised off-label subcutaneous regimen may make sense when…

• a patient needs smaller, more frequent injections;

• intramuscular injections are painful, impractical or strongly disliked;

• self-administration would materially improve adherence;

• an experienced prescriber can provide training and appropriate follow-up.

And if fertility is the immediate goal, the correct box may be “none of the above” until a reproductive-endocrine plan is made.

Monitoring is part of the treatment not optional packaging

Whichever preparation is chosen, follow-up should assess symptoms, adverse effects, adherence and whether the measured testosterone result makes sense for the timing of that formulation.

Monitoring commonly includes:

• Testosterone, sampled at the correct time: after application for a gel, or near the end of an injection interval for depot treatment, according to the product and specialist protocol.

• Full blood count/haematocrit, because testosterone stimulates red-cell production. A markedly raised haematocrit—major guidelines commonly use 54% as an upper safety threshold—requires prompt review, dose or interval adjustment, investigation of other causes and sometimes interruption of treatment.

• Blood pressure and cardiovascular risk, especially with pre-existing hypertension or cardiovascular disease.

• Prostate and urinary assessment, individualised to age, symptoms, family history, ethnicity and local guidance rather than reduced to one automatic test for everyone.

• Sleep-apnoea symptoms, oedema, acne, breast symptoms, mood and sexual function.

• Bone health where hypogonadism has been prolonged or osteoporosis risk is present.

The large TRAVERSE trial is reassuring: among more than 5,000 middle-aged and older men with confirmed hypogonadism and existing or high cardiovascular risk, testosterone gel was not inferior to placebo for major cardiovascular events over a mean treatment period of about 22 months. There were, however, more cases of atrial fibrillation, acute kidney injury and pulmonary embolism in the testosterone group. The result supports careful replacement in appropriately diagnosed men; it does not prove that every dose, formulation or unregulated “optimisation” regimen is harmless for a lifetime.

The real answer to “Which testosterone is best”

The best preparation is the one that achieves a physiological level, improves the problems genuinely caused by hypogonadism, produces tolerable side effects and can be used consistently.

For one person, that will be a morning gel: quiet, adjustable and pleasantly undramatic. For another, it will be a long-acting injection four times a year. For somebody troubled by intramuscular injections, a carefully supervised off-label subcutaneous regimen may be reasonable. Oral testosterone is an appealing development, but it is not yet a standard UK option—and the older imported capsule needs a normal meal containing fat, not a medical instruction to befriend the full English breakfast.

The decision should be shared. A useful consultation does not end with “Here is testosterone.” It ends with: “Here is why this preparation fits you, here is how we will know it is working, and here is what we will do if it does not.”

Important safety note

This article is for general education and is not a substitute for individual medical advice. Testosterone is a prescription-only controlled drug in the UK. Do not start it on the basis of symptoms alone, use non-prescribed products, or alter the dose, interval or injection route without the clinician responsible for treatment. Seek urgent medical help for chest pain, sudden breathlessness, collapse, a painful swollen leg, or a prolonged painful erection.

Further reading

1. Jayasena CN, Anderson RA, Llahana S, et al. Society for Endocrinology guidelines for testosterone replacement therapy in male hypogonadism. Clinical Endocrinology. 2022;96:200–219.

2. Jayasena CN, et al. Standardising the biochemical confirmation of adult male hypogonadism: a joint UK position statement. Clinical Endocrinology. 2024.

3. European Association of Urology. Male hypogonadism guideline.

4. Electronic Medicines Compendium. Current UK product information for Testogel 16.2 mg/g, Testogel 40.5 mg sachets, Tostran, Testavan, Sustanon 250, testosterone enantate and testosterone undecanoate injection.

5. MHRA. Topical testosterone: risk of harm to children following accidental exposure. Drug Safety Update. 2023.

6. Al-Futaisi AM, et al. The effect of food composition on serum testosterone after oral Andriol Testocaps. Clinical Endocrinology. 2007;66:579–585.

7. Kaminetsky J, et al. A 52-week study of dose-adjusted subcutaneous testosterone enanthate. Journal of Urology. 2019;201:587–594.

8. Spratt DI, et al. Subcutaneous testosterone as an alternative to intramuscular injection. Journal of Clinical Endocrinology & Metabolism. 2017;102:2349–2355.

9. Nackeeran S, et al. Effect of testosterone route on haematocrit: systematic review and network meta-analysis. Journal of Urology. 2022;207:44–51.

10. Lincoff AM, et al. Cardiovascular safety of testosterone-replacement therapy (TRAVERSE). New England Journal of Medicine. 2023;389:107–117.

11. US prescribing information for Jatenzo, Tlando and Kyzatrex, used here only to describe formulations not routinely available in the UK.