Common side effects of testosterone replacement therapy (TRT)
You may be about to start on your TRT journey and want more information about the potential side effects you could face. Or you might already be on TRT and are noticing some effects that you wanted more information about. Either way, this is an in depth look at different side effects that men experience on TRT and how you can combat them.
What is testosterone replacement therapy?
Testosterone replacement therapy (TRT) is used in men with low natural testosterone levels. It is the use of exogenous (from outside of the body) testosterone in the form of injections, gels, patches or pellets to increase testosterone levels and reduce symptoms.
Modern TRT also incorporates HCG to maintain testicular function, which helps to ensure that natural testosterone production and fertility are maintained whilst on treatment.
TRT may also include other medications to control side effects, depending on the individual and their reaction to the therapy. These are medications such as aromatase inhibitors which may be used in some men to reduce the amount of oestrogen converted from testosterone. This is a common side effect of TRT which causes lots of symptoms if not controlled.
What are common side effects of TRT?
The most common side effects of TRT are usually related to increased levels of oestrogen, DHT and testosterone.
1. Fatigue – counterintuitively, TRT can cause fatigue. This is usually when the dose is too high or someone converts a lot of testosterone into oestrogen. If oestrogen is raised then men often experience fatigue.
2. Nipple itchiness or gynaecomastia – raised oestrogen can also cause the irritation, and later growth, of breast tissue. This process usually starts with sensitive of itchy nipples.
3. Water retention – high oestrogen levels can cause water retention. This is a common side effect of TRT and a good indicator that oestrogen levels are raised. It is often seen by men on TRT as an increase in weight or swollen ankles. This can be a serious side effect if left untreated in men with heart conditions.
4. Increased emotional lability – this means being more emotional than usual. High oestrogen makes men more emotional – crying at things they wouldn’t usually find very emotional is a common complaint.
5. Anxiety – in some men, raised oestrogen can cause anxiety.
6. Low mood – as with anxiety, high oestrogen levels can make men feel down.
How to deal with common oestrogen side effects from TRT
Most side effects from TRT are easily treated, and raised oestrogen is no exception.
There are a few ways to treat this issue, some require medications whereas others use changes to the way testosterone is administered.
1. Prevention is better than a cure – the best way to stop oestrogen related side effects is to use a protocol that prevents oestrogen build up.
2. Higher frequency of injections with a lower dose reduces spikes in oestrogen levels.
3. Smaller doses rather than large ones reduces that amount of oestrogen converted from testosterone.
4. Using compounds such as Cypionate and Enanthate with less fast acting esters which increase oestrogen spikes.
5. Aromatase inhibitors act on the aromatase enzyme to prevent the conversion of testosterone into oestrogen.
6. Tamoxifen may be used in some cases to block the oestrogen receptors in the breast tissue and prevent issues with gynaecomastia and nipple irritation.
7. Lose body fat – body fat contains high levels of aromatase. The more body fat you have, the more conversion of testosterone into oestrogen will occur.
DHT is a metabolite of testosterone – its volume increases with higher testosterone levels. If too high it can cause unwanted side effects.
1. Excess body hair growth – also known as hirsutism, this can be an undesirable side effect of TRT. Other men will want this effect to an extent.
2. Increased spots or acne – TRT can increase sebum production which leads to more spots and acne in some men. This is most common when levels of testosterone and oestrogen are spiking.
3. Prostate growth – It is well known that men who start TRT may get a small amount of prostate growth and a rise in PSA, this usually reduces after the first few months of treatment. This change in the prostate is caused by DHT, which is metabolized by the type II 5-alpha-reductase enzyme.
4. Androgenic alopecia/male pattern baldness – TRT can accelerate certain types of baldness that occur in men.
The DHT in the scalp shrinks the hair follicle and may cause it to stop growing hair over time. DHT affects the hairs primarily at the top and front of the scalp near the temples. Over time these follicles will stop producing hair.
How to deal with common DHT side effects
1. Smaller, more frequent doses may lead to less spikes in testosterone and therefore DHT which means less of these side effects.
2. Finasteride can be used in men to prevent DHT conversion in the scalp – this can cause side effects of its own in men and should be used with caution and consideration.
3. Minoxidil may help to prevent hair loss and grow back some lost hair. DHT blocking shampoos may also help.
4. Ensuring the testosterone dose is not too high will reduce the side effects further.
5. Washing the back and shoulders regularly will reduce build-up of sebum and reduce acne.
All medications have side effects. These side effects are related to the administration route of the medication rather than the testosterone which they contain.
1. Gels – gels can irritate the skin in some men leaving red and sore areas. There is a risk of transfer where the gel can get onto the skin of women, children and other people.
2. Injections – the carrier oil in some injections can cause irritation or allergic reactions. If not injected safely, there is a small risk of infection from injections. Alcohol wipes and a new needle should always be used.
3. Pellets – as with injections, these may lead to irritation or infection in rare cases. As they can’t be easily removed the dose can be too high on insertion.
4. Patches – as with gels, these can cause irritation to the skin.
If you are getting side effects with a particular medication then our specialist doctors can support by recommending new options. There are usually options available to reduce the issues above.
This can include switching from a gel to an injectable or switching the compound used to reduce the irritation.
Will TRT affect my fertility?
Testosterone which is administered from outside of the body affects your natural production of both testosterone and sperm. This leads to reduced fertility.
The testosterone and oestrogen levels in the blood are detected by the pituitary gland which results in a negative feedback loop leading to a reduction in LH (luteinising hormone) and FSH (follicle stimulating hormone).
Together these two hormones stimulate the production of testosterone and sperm in the testicles. If they are reduced, the production of sperm and therefore fertility drops dramatically.
How to maintain fertility whilst on TRT?
There are a few options for maintaining fertility whilst on TRT, reduced fertility can be one of the most concerning side effects so for many this is the deciding factor between starting TRT and living with the symptoms!
1. First off, it is important to note that TRT should not be used instead of contraception. Most men will still be producing sperm and pregnancies are not unheard of in men on TRT.
2. HCG (Human Chorionic Gonadotropin) – This is an analogue of LH which stimulates the normal production of testosterone and sperm in the testicles. This is one of the most effective ways to maintain fertility whilst also maintaining testicular size, normal testosterone production and the production of other hormones which are inhibited by TRT. There are various studies supporting its use.
3. HMG (Human Menopausal Gonadotrophin) – This is a similar compound to HCG but also maintains FSH production unlike LH. It may be used in some men who have issues with HCG alone, although this is rare in our patients. It is also very expensive.
4. Clomifene – This is a SERM (Selective Estrogen Receptor Modulator) which also works to increase the production of LH and FSH by the pituitary. It is rarely used over HCG due to its other side effects. It is a popular treatment for hypogonadism in young men by endocrinologists. It has poor outcomes in most young men despite increasing testosterone levels effectively.
You can read more on this in greater depth here.
Does TRT increase the risk of heart attacks and strokes?
The best answer to this is that the evidence suggests that overall it does not have a major impact.
A very recent cohort study of around 30,000 men (15,000 in each arm of the study) demonstrated that whilst there was a slightly increased risk in the first 2 years of treatment, this risk then returned to normal.
The study also showed that men on TRT had a reduced overall mortality rate compared to men not on TRT over the length of the study!
The only issue with this study is that it is difficult to fully understand the level of monitoring and type of protocol used – it could be that the protocol was not of a good standard, which would make the results less applicable to men on a protocol which resulted in better oestrogen and haematocrit control.
The average TRT protocol provided by the NHS has very poor control of these measures which may lead to increased risk over time.
It is also well established that men with low testosterone are at greater risk from cardiovascular issues than those with normal testosterone levels.
You should discuss these issues with a specialist before starting testosterone replacement therapy, if you are at greater risk of cardiovascular issues such as heart attacks and strokes then TRT may be considered too much of a risk. For those without any issues in this area it is likely to make you healthier and reduce your likelihood of death from disease.
You can read more on this topic with further research studies here.
Does TRT make Obstructive Sleep Apnea worse?
There is no concrete evidence that TRT makes OSA (Obstructive Sleep Apnea) worse. However, it still remains in the guidelines that TRT should not be started in patients with untreated OSA. If true, it is uncertain what causes this effect. It may be due to increased muscle mass around the neck (neck circumference is linked to OSA) or an effect on the tone of the neck.
Interestingly OSA can actually cause low testosterone itself by reducing LH (luteinising hormone) production. Being overweight is another major cause of both low testosterone and Obstructive sleep apnea which may make matters worse.
Testosterone replacement therapy improves the sleep quality of men with low testosterone, so this area clearly needs more research. The main ways to avoid OSA are to be in good shape with a low body fat and to avoid alcohol wherever possible.
Dr Chris Airey
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.