Side Effects of Testosterone Replacement Therapy

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All medications have side effects, but luckily most of the side effects of TRT can be controlled. Learn more about the common side effects and how we manage them in this article.

Side effects of TRT that you should look out for

Are you 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. Remember that just because there is the potential for these side effects (as with any medication) it does not mean that you will get them on treatment. Additionally, lots of these side effects are easily controlled or avoided with sensible protocols.

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The ADAM questionnaire has been shown to have 88% sensitivity in testing for low testosterone.

Common side effects of TRT - oestrogen

The most common side effects of TRT are usually related to increased levels of oestrogen, DHT and testosterone.

Oestrogen related side effects of TRT

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 side effects of oestrogen 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 reduce 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 side effects and TRT

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.

side effects of TRT DHT hair loss

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.

Contact us for more information on medications to control DHT related side effects.

Medication related side effects

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. Cypionate is used in our clinic, this has low levels of irritable benzyl alcohols and therefore avoids most of these issues.

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.

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Will TRT affect my fertility?

Yes, but this can be offset with the use of HCG.

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).

side effects of TRT infertile
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.

Read more about fertility on TRT.

Does TRT increase the risk of heart attacks and strokes?

Side-effects-TRT-blood-pressure

The best answer to this is that the evidence suggests that overall it does not have a major impact over the long term although for those already at risk it may be best avoided.

A very recent cohort study of around 30,000 men (15,000 in each arm of the study, one arm on TRT, the other with low testosterone and no treatment) 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. This means that the effect on cardiac health from two different TRT protocols may be very different.

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.

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.

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What are the Benefits of TRT?

  • Improved mood – reduced anxiety
  • Improved libido (sex drive)
  • Improved assertiveness
  • Improved confidence
  • Better erection quality
  • Better sleep quality
  • Increased muscle mass and strength
  • Improved beard growth
  • Better vascularity and blood supply (which reduces risk of diabetes and can even reverse mild type 2 diabetes).
  • Deeper and more stable voice
  • Improved bone density
  • Improved cognition including memory and mental acuity
  • Reduced all-cause mortality (Loo et al. 2019) (deaths over a time period compared to men not on testosterone replacement therapy)

Does TRT increase your lifespan and health?

Regardless of the potential side effects listed previously, if taken properly, TRT can improve your health and lifespan.

In a recent, large study, TRT was shown to reduce the number of men who died from all causes compared to controls who weren’t taking TRT and had low testosterone. Evidence shows that testosterone is cardioprotective and good for heart health.

Goodale et al even state that ‘ there currently is no credible evidence that T therapy increases CV risk and substantial evidence that it does not.’

They go on to talk about the various benefits of that TRT has been demonstrated to have on the heart and general health:

‘Testosterone replacement therapy (TRT) has been shown to improve myocardial ischemia in men with CAD, improve exercise capacity in patients with CHF, and improve serum glucose levels, HbA1c, and insulin resistance in men with diabetes and prediabetes.’

Testosterone is also converted into oestrogen in men. If men have low testosterone they often also have low oestrogen. Oestrogen is really important in men, it is protects the cardiovascular system, joints and other connective tissue, whilst helping with healing.

It is also well established that men with low testosterone are at greater risk from cardiovascular issues than those with normal testosterone levels.

Improved mood and cognition

Jung and Shin (2016) demonstrated that the benefits of testosterone replacement therapy improved various aspects of mental health in men with testosterone deficiency.

They noted improvements in memory, mental acuity and mood.

In this study there were very few side effects, and none were serious. It is common for men who start treatment to notice a return to normal levels of brain function, where before they suffered from ‘brain fog’. Brain fog is when men struggle to perform simple mental arithmetic, remember things that happened recently, and find concentrating difficult.

They noted that men may also find that their motivation and drive is reduced:

‘The effect of testosterone administration on cognitive function and depression in hypogonadal men is believed to be related to the enhancement of brain perfusion, which is supported by the fact that there are androgen receptors in the brain, suggesting that steroid hormones play a role in neuronal function.’

Interestingly they go on to hypothesise the potential benefits this could have on men with other mental health conditions. In particular, they refer to a study on men with mild alzheimer’s.

‘The effects of TRT in men with mild cognitive impairment or Alzheimer’s disease have been evaluated in small placebo-controlled trials. For example, Cherrier et al (2005) evaluated a sample of 32 subjects, which included 17 men with mild cognitive impairment and 15 with Alzheimer’s disease. At the 6-week follow-up, patients who received TRT showed significantly better scores regarding spatial memory, constructional abilities, and verbal memory compared to those noted in the placebo group. Taken together, these results suggest that TRT has a beneficial effect on cognitive function.’

This is clearly a very interesting finding and something that needs further research. There is some evidence that low testosterone reduces perfusion (supply of blood to tissues) in various areas of the body. Improving testosterone levels often provides relief from conditions such as diabetes that have the side effect of reducing blood supply to regions.

ADAM Questionnaire

Low Testosterone Test

The ADAM questionnaire has been shown to have 88% sensitivity in testing for low testosterone.

Improved libido (sex drive) on TRT

Hackett et al. (2017)  found that men with type 2 diabetes and low testosterone saw large improvements in sexual desire and erection quality after starting testosterone replacement therapy.

Khera et al. (2011) showed that TRT with a testosterone gel significantly improved sexual function including libido in a large study of 840 men.

This is a common benefit we see in our patients with improvements seen by the first 6 months of TRT.

Learn more about low testosterone and low sex drive.

Does TRT improve erectile dysfunction?

There are many medical treatments for erectile dysfunction. Most are very effective for men who have mechanical issues preventing an erection.

However, in some men, the issue isn’t as much an inability to get an erection, which can be a mechanical or biochemical issue but more of a combination of a lack of desire and willingness to engage in sexual activity. This can often be a cause of erectile dysfunction which stems from low testosterone.

In men with low testosterone, improving these levels to normal often results in a return to normal erectile function. As above the general sexual function of men (including erectile function) is improved on TRT.

Does TRT improve muscle muscle mass, strength and reduce body fat?

There are lots of studies which demonstrate the impressive effects of testosterone on men’s muscle mass, strength and body fat levels.

It is something that most men who start testosterone notice – a dramatic change in their physique.

Testosterone is an effective mass builder by increasing the protein synthesis required for growth. It also improves neuromuscular function which results in strength increases. This is part of the androgenic effect of testosterone and includes the effects of DHT (dihydrotestosterone).

Men with higher testosterone levels tend to have lower overall visceral and abdominal body fat levels. Both of these things (when raised) are bad for overall health and lead to increased mortality rates.

However, TRT is not a magic bullet, whilst is does increase muscle very effectively, it will not shed body fat effectively on its own. A consistent workout regime and a healthy diet are paramount to improving this – testosterone does make the dieting process much easier for those who struggle to lose bodyfat.

Does TRT improve bone density in men?

A common effect of low testosterone is reduced bone density. This is partly due to low testosterone and partly due to the reduction in oestrogen that results (as oestrogen is converted from testosterone in men).

Increasing testosterone levels improves bone density, particularly in the spine where older men often suffer from compression fractures.

The main effect on bone density is most likely driven by oestradiol levels, however this is mainly a by-product of testosterone in men as it is converted by the aromatase enzyme.

As a result, men with low testosterone will have lower bone density, and increasing testosterone will improve oestrogen levels.

How long does it take for TRT to start working?

In most patients, the benefits of TRT take from 3 to 6 months to be fully realised. Some benefits, such as bone density, fat loss and muscle mass increases, will continue to improve for longer than 6 months.

Whilst most men notice some improvements early on in their TRT journey, there are lots of factors that affect the rate of progress.

Benefits-of-TRT-when-will-I-notice-benefits

Adapted from Saad et al. (2011)

Firstly, and most importantly, TRT is a process.

Optimising testosterone replacement therapy takes time and you should work with your doctor to monitor blood results and adjust dosages. Often the dose you start on will cause testosterone and oestrogen levels to rise. This will dampen any benefits and may feel like testosterone is still low. Occasionally (much more rare) the dose is too low and patients need to increase it further to get levels into the optimal range. In both situations, a blood test is important to ensure careful adjustment of your dose by a specialist doctor.

Secondly, the type of testosterone preparation will cause variations in the time it takes for men to notice improvements. A testosterone ester like propionate will have a faster effect than something like Nebido which takes longer to act in the body due to a longer ester attachment.

Optimale doctors primarily recommend medium acting esters such as testosterone cypionate and testosterone enanthate which can take around 6 weeks to build up to their full testosterone levels in the blood. However, the benefits of testosterone replacement therapy for men who have lower levels may be seen before this build-up happens.

Thirdly, some of these improvements take a while to be seen in the body. Usually, mood and libido improvements take a few weeks to a couple of months to appear if the dosage is optimised and oestrogen levels are good. Other physique changes can take a lot longer.

Saad et al. (2011) researched the timescales for the effects of testosterone replacement therapy and found that:

  • Effects on sexual interest appear after 3 weeks plateauing at 6 weeks, with no further increments expected beyond.
  • Changes in erections/ejaculations may require up to 6 months.
  • Effects on quality of life manifest within 3–4 weeks, but maximum benefits take longer.
  • Effects on depressive mood become detectable after 3–6 weeks with a maximum after 18–30 weeks.

Read more on the timescales of TRT improvements.

Finally, there are individual factors that influence how long it takes for testosterone to show benefits.

The individual’s testosterone levels before starting treatment. If very low then the impact of adding testosterone may be felt more quickly.

Androgen receptor differences. Some men have less sensitive androgen receptors, often due to previous steroid abuse. Others naturally have more androgen receptors which will improve the response rate to testosterone levels increasing. Read more about the differences that can be seen in CAG length.

Unknown factors. Some men are more sensitive to increases in testosterone and oestrogen. Others are genetically more susceptible to converting testosterone into oestrogen as they have more aromatase in their bodies. This can mean that the benefits of testosterone replacement therapy are less obvious.

Conclusion

Side effects are a part of all medications. Some are mild and some can be more severe.

With TRT, if blood results are monitored carefully and a sensible dose is used, most side effects are easily controlled and generally avoided.

There are some medications which can be used to control side effects, such as HCG for fertility and aromatase inhibitors for oestrogen. In other cases, a change in dose or frequency can also reduce the symptoms. This is the preferable route to improving common side effects on testosterone replacement therapy. As with all medicine, the least number of medications you can use to solve a problem, the better.

Optimale uses the Gold Standard of TRT which is adapted to you as an individual to reduce side effects. This takes into account your circumstances, lifestyle and physiology to provide the best treatment options with the least possible side effects. Each patient’s protocol is adapted to their personal situation to provide bespoke TRT solutions.

If you’re interested in further treatment options then please contact us here to find out more information about how you can get treatment.

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References
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