Is there such a thing as ‘The Best TRT Protocol?’

Finding the best TRT protocol for you can be a tricky task with lots of stepping stones. If you don’t take your time, and make incremental progress, then you can be left suffering with new symptoms and extra issues. Some clinics and doctors will try to sell their clinic on the premise that they have the ‘best’ protocol, or that only they know how to treat a condition properly.

However, in most cases, treatment needs to be personalised and patient-centred.

So, is there one specific protocol which is better than anything else or does it depend on the individual concerned?

Read on to find out more about what, if anything, makes the best TRT protocol.

Individual differences and TRT Approach

Individuals are different. This is true in all domains but it is more important in medicine than most people imagine.

Patients respond differently to medications, and have different specific lifestyle and genetic factors which affect how their condition should be treated.

Men also have different naturally occurring levels of sex hormones and other molecules (such as SHBG) which govern how they act in the body. This means that some men will require a higher level of testosterone to feel the benefits of treatment, or may produce more oestrogen and DHT from the testosterone they receive.

The Best TRT Protocol – Follows a system!

As with many things in life, having a system leads to exceptional results.

If you want to get stronger in the gym, you can’t rely on goals alone – it is the system of consistent, measured and sustainable action which results in real improvements. Having a goal is part of the solution but won’t get you very far.

The same is true of a good TRT protocol. Many men start TRT expecting amazing results after a couple of months. They may feel good initially, but then the symptoms return or they don’t feel quite right. At this point many men stop, exclaiming that it ‘hasn’t worked’. In reality, they haven’t followed the system. 

To get fantastic results with TRT you need to have your blood results analysed regularly. This is followed by incremental adjustments in your protocol. Effective monitoring and changes lead to ‘dialling in’ of your TRT. Dialling in changes can take a few months up to a year in some cases.

Some things work and others don’t – but you need to trust the process and follow the system to achieve the best results.

Testosterone differences in men

Men have different levels of testosterone production.

This should be fairly obvious to most people but natural levels vary from very small amounts (which are naturally low and often need treatment) to higher natural levels up to around 30nmol/l.

Some men will feel better with higher levels than other men. This may be what they are used to, or due to the factors including Androgen receptor sensitivity and oestrogen conversion rates. Natural SHBG levels and DHT conversion rates will also play a part.

These factors will influence how men respond to


Best TRT protocol

doses compared to other individuals and should influence how doctors adjust their dosing strategies.

Men on HCG (which is an important component of effective TRT) will also produce varying amounts of their own testosterone. This impacts how much exogenous testosterone is needed to ‘top up’ levels and improve symptoms.

SHBG (Sex Hormone Binding Globulin) differences

SHBG levels also vary between men. SHBG increases as men age, which can lead to worsening low testosterone symptoms.

SHBG binds to testosterone and reduces the amount available in the blood. It also has a role in carrying and transporting sex hormones including testosterone, so if levels are low in the blood then this can affect how quickly testosterone ‘clears’ in the body.

Insulin sensitivity is one factor that can lead to a lower SHBG level.

Alcohol abuse has been shown to raise SHBG levels but these do reduce as less alcohol is consumed.

Lifestyle changes can, therefore, be very important in improving issues around SHBG.

Using different dosing strategies can be important for treating men with high or low SHBG levels. High androgen levels reduce SHBG in the blood. This is largely related to the binding of DHT with the molecule which then reduces the amount of SHBG circulating and can increase free testosterone levels as a result. This is why certain medications are used alongside TRT to reduce SHBG in some men.

Unfortunately these medications (such as Mesterolone or Danazol) often suppress testosterone themselves so TRT may need to be used with them in some cases.

Oestrogen (Oestradiol) differences in men

As with Testosterone and SHBG, there are differences in how men produce oestrogen (oestradiol) and how this impacts the best TRT protocol for that individual.

Oestrogen is primarily converted in men from the testosterone they produce. It is converted by the enzyme aromatase which shears off part of the testosterone molecule and makes it into oestrogen.


Best TRT protocol

Men have differing levels of aromatase in their bodies. There are a few reasons for this. Some are things we can change whereas others we are stuck with.

1. Body fat levels – adipose tissue, known as fat, contains aromatase. The more aromatase we have, the more oestrogen is produced via conversion from testosterone. This also means that the more testosterone is added (via TRT for example) the more oestrogen is produced until the aromatase enzyme is saturated and can’t convert any more.

2. Lifestyle factors including diet – alcohol has a major effect on how much testosterone is converted into oestrogen. High alcohol consumption, in particular, causes increased aromatisation of testosterone into oestrogen. There is also some evidence that certain foods contain plant oestrogens which have a mild effect on levels.

3. Genetics – I recently completed a genetic analysis through MyFitnessGenes. Interestingly this analysis showed that I had higher than normal production of aromatase and therefore oestrogen levels. This fits with my personal requirement for an aromatase inhibitor despite not carrying huge amounts of body fat.

4. Other factors – there are other factors which may affect how much oestradiol levels affect different men. In particular, as with androgen receptors, oestrogen receptors have different levels of effect in different men and in different target tissues. Some men will develop gynaecomastia with small increases in oestrogen levels whereas others will not notice any symptoms despite having very raised oestrogen.

Aromatase Inhibitor Use and Response

Aromatase inhibitors are often used in TRT to reduce the conversion of testosterone into oestrogen.

They work by binding to the aromatase enzyme and stopping it from binding to testosterone. As a result less oestrogen is produced and men may benefit from this change.

Generally, aromatase inhibitors should be avoided if possible. Aromatase inhibitors (AIs) have side effects as with all medications. Lowering oestrogen too much has a negative effect on bone density, joint health, epithelial health and lipid profile. All of which can make other diseases more likely.

However, in men who have excess adipose tissue, or who are genetically more susceptible to raised oestrogen levels (as seen on blood test or genetic testing) an AI may be necessary. In other men, a lower dose or splitting the dose is a good alternative to reduce oestrogen to manageable levels.

Androgen Receptors in men

The CAG length part of the DNA sequence for the androgen receptor affects how much androgens (such as testosterone) can act on certain body tissues. This means that two men with the same testosterone levels can see different levels of effects such as muscle mass or bone density.

Androgen receptor type is probably more important than androgen concentration in men.

CAG length can be from 8 -35, with a lower number meaning a higher sensitivity to testosterone effects in target tissues.

Unfortunately, we can’t change our androgen receptors, but it goes some way to explain differences in individuals and how they respond to testosterone levels. Clearly this impacts how effective dosages are for individuals on TRT and therefore the best TRT protocol for them.

Lifestyle differences and how these affect what makes the Best TRT Protocol

Not all men have time for daily injections of testosterone and HCG. Others may be happy to spend extra time and effort to get the best possible results.

Most men want a balance between the most convenient treatment protocol with the best results possible. Whilst daily injections of HCG and testosterone might give the most steady levels, this is usually too much for most men to adhere to. The best protocol is one that men can stick to consistently.

Whilst men, in general, do best with an injection protocol, there are some who do not like injections or have a phobia of needles. In these men, and those who travel regularly to certain countries, a gel, patch or pellet may be a better option out of convenience.

HCG dosing and response

HCG is an LH (luteinising hormone) analogue. This means that it does the same role as LH in the body by being the same chemical structure.

LH is important for the downregulation of hormones from the production of pregnenolone, as well as the production of testosterone in the testicles.

When provided to men on TRT, it prevents testicular shrinkage and maintains testosterone production.

Some men with low testosterone have issues with the testicles’ ability to produce testosterone (primary hypogonadism). Others have issues with the production of LH and FSH in the pituitary gland resulting in reduced stimulation of testosterone production in the testicles (secondary hypogonadism).

Men with primary hypogonadism will produce less testosterone from HCG use than men with secondary hypogonadism.

It is, however, difficult to predict the effect that HCG will have on a man’s production. Doses of HCG and testosterone should therefore be adjusted accordingly based on follow up blood test results.


Testosterone medication options

Knowing how many factors can affect the levels of testosterone, its metabolites and other hormones such as oestrogen in the body, plus their effects, you can start to see how a TRT protocol has to be individual and can take time to perfect.

Whilst starting protocols may look similar to each other, these are then adapted to the patient, their blood work and their lifestyle.

The following medication options all have positives and negatives, but there are some clear all-rounders which clinics the world-over have found to produce the best results.

Testosterone cypionate – Cypionate has a half-life of around 8 days due to the carbon length of its ester which is one carbon longer than enanthate. This means slightly longer release times in the body. Learn more about cypionate here.

Testosterone enanthate – Enanthate has a half-life of around 7 days which also gives it a medium release time. Slower than propionate but longer than an ester such as undecanoate. You can read more about testosterone enanthate here.

Sustanon – Sustanon has 4 different esters with varying ester lengths and release rates. It has propionate which releases quickly into the blood over a few days. It has medium esters such as isocaproate and phenylpropionate which are released over several days. It also has longer esters such as decanoate which have a half-life of around 14 days. Whilst these different esters lengths are meant to lead to steady levels over 3-4 weeks, in reality, they cause various peaks and troughs which negatively affect oestradiol, DHT and blood lipids in some men. You can learn more about Sustanon here.

Nebido – Nebido is a large 4ml injection of testosterone undecanoate. Undecanoate is a long ester with a very long half-life. This medication is usually provided in NHS clinics as it is injected by a nurse on average every 12 weeks. Many men find that this leads to a peak and trough with predictably poor results. For others, it is a convenient and effective medication option. You can learn more about this treatment option here.

Gel formulations – these are applied daily and have a short half-life. Whilst they work well for some men, they have absorption issues in others which can affect results. There is also a risk of transfer to women, children and other men which makes them inappropriate for many. There is more information on testogel use here.

HCG – HCG is recommended for all men on TRT, regardless of fertility requirements it is an integral part of an effective treatment protocol. In most men it is used alongside TRT for the best possible results, as well as maintaining testicular size, fertility and testosterone production, it also maintains other hormones which are lost when using TRT alone due to the suppression of the HPT Axis. You can learn more about HCG here.

Can I inject testosterone subcutaneously?

Traditionally testosterone was injected into the muscle and left to release in a large depot over a long period of time. More recently new research has indicated that testosterone has a smoother release profile if injected subcutaneously.

Subcutaneous testosterone injection

Subcutaneous injections are done under the skin between the muscle and subdermal layer. It has a slower more stable release which means less oestrogen and less DHT. This can mean less side effects and better results. It is also safer and easier to inject in this manner for most men as it is easily visible and there are no large blood vessels or nerves near the surface.

At Optimale we now prefer to encourage men to inject subcutaneously due to its various benefits over intramuscular injections.

Optimale preferred protocol

There is no one ‘best TRT protocol’ or ‘Gold standard’ of TRT. All protocols should be individual to the patient and their needs with a patient-centred approach.

However, the medications which are generally the most effective for achieving this balance are either Testosterone Cypionate or Enanthate combined with HCG on either a biweekly or every other day protocol.

Injections are usually the best way of administering testosterone. These medications maintain even, steady levels, reduces oestrogen and testosterone peaks and troughs whilst maintaining a level of convenience which is acceptable for most of the busy men who are our patients.


As you can see, there are many factors which need to be considered to achieve the best protocol.

There needs to be a balance between genetic, lifestyle, convenience and medication characteristics to ensure the best protocol for each individual.

If you’d like more information on the best TRT protocol for you, then please get in touch below to find out more.

Dr Chris Airey

Dr Chris Airey

Medical Director

This article has been medically reviewed for accuracy by Dr Airey on 12th September 2020.

Dr Chris Airey is a fully registered UK doctor with the GMC (General Medical Council) Reference No: 7490533.
He trained at the University Hospital Southampton and graduated as a Doctor with a joint Bachelor of Medicine and a Bachelor of Surgery, plus a Masters in Medical Science, completing his research project in the Medical Neurosciences Department.
He is undertaking a Master of Science course in Endocrinology and is a member of the European Society for Sexual Medicine, and the Androgen Society.
He has personal experience with taking Testosterone Replacement Therapy and is a pioneer in UK treatment protocols for Testosterone Deficiency Syndrome.

Please contact us below for more information!


Beilin J., Ball, E.M., Favaloro, J.M., Zajac, J.D. (2000) Effect of the androgen receptor CAG repeat polymorphism on transcriptional activity: specificity in prostate and non-prostate cell lines. J Mol Endocrinol. 

Butler, M. G., & Manzardo, A. M. (2015). Androgen receptor (AR) gene CAG trinucleotide repeat length associated with body composition measures in non-syndromic obese, non-obese and Prader-Willi syndrome individuals. Journal of assisted reproduction and genetics32(6), 909–915.

N. Yazdani & S. Branch (2018) Daily subcutaneous testosterone for management of testosterone deficiency. Frontiers In Bioscience, Elite. 10, 334-343