Everything you need to know about testosterone replacement therapy (TRT)

Is testosterone replacement therapy (TRT) right for you? We describe how TRT works, as well as its potential risks and benefits of TRT.

Author: Dr Sam Rodgers - Chief Medical Officer, MBBS, MRCGP

Published on: 26 April 2022

Testosterone replacement therapy (TRT) is a form of controlled hormone replacement therapy that can help reverse the effects of low testosterone in men. When administered by a medical professional, it can significantly improve symptoms and quality of life.

There’s a lot of conflicting information about TRT. This guide aims to give you a balanced view based on current evidence and guidelines.

What is testosterone replacement therapy (TRT)?

TRT is the administration of testosterone to improve symptoms in men with hypogonadism/testosterone deficiency syndrome. It is proven to improve libido, erectile function, and sexual satisfaction [1].

TRT is not suitable for everyone, and often, even if testosterone levels are low and you are experiencing symptoms, your doctor will usually first try to address the reasons for your low testosterone levels.

You should be fully informed about both the possible benefits and side effects of therapy so a joint decision can be made between you and your doctor. Testosterone replacement therapy is not a quick fix, and it is an ongoing process that will usually continue long term.

If testosterone replacement therapy is suitable for you, it must be prescribed by a medical professional to ensure the right amounts are delivered in the right way for your situation. It should also be given alongside weight loss and lifestyle advice.

How is TRT administered?

TRT can be administered in different ways, each with its advantages and drawbacks.

Many men opt for injections due to the reduced frequency of administration, (usually every 12 weeks). However, it can cause pain and bruising at the injection site and there may be some fluctuation in symptoms towards the end of the cycle (just before the next dose). Other options include topical gels and capsules.

Testosterone therapy options include:

Route of administration	Advantages	Disadvantages
Testosterone gel - applied to skin daily	Fast onset Provides steady testosterone levels for 24 hours	Skin irritation Daily commitment
Oral capsules - taken once or twice daily	Decreased liver involvement	Levels can fluctuate Daily commitment Must be taken with food
Intramuscular injection - every 10 – 14 weeks	Steady levels Lower frequency of administration	Pain and bruising at the injection site Longer-acting — prevents the drug from being stopped quickly in the event of side effects
Intramuscular injection - every 2 – 3 weeks	Shorter acting — if unwanted side effects occur and they are not tolerated, they can be stopped quickly	Levels can fluctuate

Table adapted from Hackett et al. (2017)

What are the benefits of TRT?

When used correctly for people with a diagnosed testosterone deficiency, TRT can be very effective at reducing symptoms and improving the overall quality of life.

TRT can improve many symptoms, including:

Sexual desire
Erectile function
Sexual satisfaction

It can also help to reduce body mass index and waist size in men who are obese and hypogonadal.

Beyond six months, there is also evidence that TRT can benefit body composition and bone mineralisation, as well as improve blood sugar control and lipid (fat) levels. For people with prediabetes or cardiovascular disease, this means they are less likely to develop type 2 diabetes and have a reduced risk of cardiovascular events and mortality [1].

How to get TRT in the UK

TRT is prescribed by a doctor. If you have symptoms of hypogonadism, your GP may investigate these with a blood test to check your testosterone levels and other hormones.

You can check your hormone levels at home with our Male Hormone Blood Test, but bear in mind that even if your testosterone levels are low, it does not necessarily mean you will be considered for TRT — this decision is based on several factors. And not every man with low testosterone levels is started on TRT.

If your testosterone levels are found to be low, it is best to discuss this with your GP. They can then advise on how to manage this and whether TRT is an option for you.

How long does TRT take to work?

TRT should be administered and monitored for at least six months to see an improvement in symptoms. Although, it might take longer than twelve months before the maximum benefit can be seen [1].

Everyone is unique in how they respond to TRT, but one study looked at the improvement of symptoms and the subsequent typical timeframes [2]:

Libido	Effects appear after three weeks, but plateau at six weeks with no change expected beyond this.
Erectile dysfunction	Changes in erections/ejaculations may require up to six months of testosterone replacement before any effects are seen.
Quality of life	Quality of life improvements can be seen within three to four weeks, but maximum benefits can take longer.
Depressive mood	Improvements in depressive mood can be seen after three to six weeks, and these stabilise after 18-30 weeks.
Erythropoiesis (red blood cell production)	Effects on erythropoiesis can be seen at three months, peaking at nine to 12 months.
Prostate-specific antigen (PSA)	Prostate-specific antigen and volume rise marginally over time, plateauing at 12 months; any further increase should be attributed to ageing rather than therapy.
Lipids	Effects on lipids appear after four weeks and reach their maximum after six to 12 months.
Insulin	Insulin sensitivity may improve within a few days, but effects on glycaemic control only become evident after three to 12 months.
Body mass	Changes in fat mass, lean body mass, and muscle strength occur within 12-16 weeks, stabilise at six to 12 months, but can marginally continue over the years.
Inflammation	Effects on inflammation occur within three to 12 weeks.
Bone weakness	Effects on bone are detectable after six months and continue for at least three years.

What are the potential risks of TRT?

Serious adverse effects of testosterone therapy are rare. When starting TRT, your doctor will monitor you for risks and side effects of treatment. You can also monitor yourself at home for side effects of treatment with our TRT (Testosterone Replacement Therapy) Blood Test.

Risks of TRT include:

Too much testosterone being administered — This can be easily managed by adjusting the dosage, stopping treatment, or switching to a different formulation.
Pain and bruising at the injection site (if injecting into a muscle).
Skin irritation or variable levels of absorption with transdermal gels.
Polycythaemia - An increase in both the number of red blood cells and the haemoglobin content of the blood. This occurs because testosterone stimulates the body to make red blood cells, so the blood is thicker than usual. Polycythaemia increases your risk of stroke and heart attacks. For this reason, your blood count will be monitored before and during treatment. If your haematocrit (concentration of red blood cells) rises too high, your treatment will be stopped.
Gynecomastia – Excess testosterone can be converted to oestrogen and cause swelling or tenderness of the breast tissue. Breast swelling or pain may be seen in up to 10-25% of men taking TRT [3].
Skin conditions – A rise in testosterone causes an increase in sebum production, which can lead to acne, though this effect is typically minimal [3].
Sleep apnoea — TRT may have a transient harmful effect on sleep apnoea. It’s therefore generally not recommended for people with severe, untreated sleep apnoea [1].

Does TRT cause blood clots?

Even if haematocrit (concentration of red blood cells) remains stable during treatment, it’s been previously thought that TRT could increase the risk of heart attacks and strokes, but the data in this area is conflicting. Recent research shows no correlation. However, the strength of this evidence was classed as low [4].

Your doctor will assess your cardiovascular risk before and during therapy — this means discussing your medical and family history of heart problems and looking at any relevant test results.

Does TRT cause prostate cancer?

There is no compelling evidence that TRT increases the risk of developing prostate cancer [1]. That said, prostate health should be carefully monitored before and during TRT with a physical examination and Prostate-Specific Antigen (PSA) Blood Test. PSA levels are likely to increase when starting testosterone.

The use of TRT in men with a history of prostate cancer is controversial. Previously, there were fears it may cause cancer to return. However, more recent evidence has shown this not to be true. TRT can be a safe and effective treatment for men who have been fully treated for low-risk prostate cancer [1].

TRT isn't appropriate for men with active prostate cancer as it may cause it to progress.

Who shouldn’t take TRT?

Some people should not use TRT due to potential health risks.

TRT should not be started in people with [1]:

Active prostate cancer
Male breast cancer
An active desire to have children
High levels of red blood cells (haematocrit >54%)
Severe chronic heart failure

Is TRT the right treatment for you?

If you have no symptoms or only very mild symptoms of low testosterone, TRT is unlikely to be the best treatment option for you, particularly if your testosterone levels are only slightly reduced. In these cases, lifestyle changes can be very effective.

However, for men with significant symptoms of low testosterone that affect their quality of life, TRT can have a positive impact.

If you’re affected, we encourage you to discuss your symptoms openly with your GP who can help guide you to the best solution.

References

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