Types of hormone therapy

LHRH agonists are a type of medicine that first tell the pituitary gland - a small gland at the base of the brain that controls hormones - to release more LH (luteinising hormone) and FSH (follicle-stimulating hormone), which then causes the body to make more testosterone.

But if the medicine is used continuously, the pituitary gland starts to respond less. This means it sends out less LH and FSH, so the testicles slowly make less testosterone over time.

Because this treatment lowers testosterone levels significantly, it is often called chemical or medical castration, as it has a similar effect to surgical castration (orchiectomy).

LHRH agonists are given as injections.

• Injections might be given every one, three, six or 12 months.
• Some of the injections are liquid and some are implants.
• Implants are typically a small pellet or rod, injected just under the skin using a specialist applicator or syringe. The implant will then slowly release the medication over a specified period.

Common LHRH agonists are shown below. All drugs have a generic name and a name given by the pharmaceutical company that produces them. This is called a trade name.

• Buserelin – Suprefact®
• Goserelin – Zoladex®, Reseligo®
• Leuprorelin (Leuprolide) – Eligard®, Staladex®, Enanton®, Prostap®, Lucrin®, Lutrate®
• Triptorelin – Decapeptyl SR®, Salvacyl®, Diphereline®, Gonapeptyl®, Pamorelin®

LHRH agonists can cause a range of side effects because they lower testosterone levels, a hormone important for many body functions. 

Below are some of the most common side effects of Leuprorelin, an LHRH agonist used in prostate cancer treatment.

'Very common' (at least 10% of people are affected):

• Hot flushes – a sudden, spontaneous feeling of warmth.
• Lots of sweating.
• Sexual dysfunction:
  • Less interest in sexual activity.
  • Difficulty in getting or keeping an erection.
• Extreme tiredness or fatigue - a constant feeling of tiredness and low energy.
• Skin reaction / irritation at the site of the injection - including firmness, redness or sores.
• Mood changes - this varies widely between people, but can include depression, anxiety, irritability, and emotional instability.
• Penis and testicles shrinking.

Other side effects often seen by professionals:

• Anaemia - where you don't have enough healthy red blood cells to carry oxygen around your body.

It is also common for the body to produce a testosterone surge when you first start LHRH agonist treatment. This is called a 'flare'. For the first 1-2 weeks, flares can make your symptoms worse and may cause the tumour to grow quickly.

Because of this, you will also be given tablets to take, known as anti-androgens. These tablets stop testosterone from reaching the cancer cells, so they cannot grow. Anti-androgens are also a type of hormone therapy in their own right - see later in this section for more detail.

Other significant side effects of LHRH agonists can develop over time and vary in their impact. 

Very common (at least 10% of people are affected):

• Weight gain - especially around the belly.
• Muscle mass loss - muscles getting weaker.

Other side effects often seen by professionals:

• Higher risk of heart problems.
• Bone density loss (osteoporosis) - testosterone helps keep bones strong, so when its levels drop, bones can weaken faster, increasing the risk of osteoporosis. Ask your doctor about having a DEXA scan to monitor your bone strength.

LHRH antagonists are a type of hormone therapy that work by directly stopping the pituitary gland - a small gland at the base of the brain that controls hormones - from releasing two hormones: LH (luteinising hormone) and FSH (follicle-stimulating hormone).

This stops the testicles from making testosterone. Unlike LHRH agonists, they don’t cause a short-term increase in testosterone. Instead, they lower testosterone levels quickly.

This stops the cancer cells from growing and spreading. They can even reverse the growth, causing the cancer to get smaller.

LHRH antagonists are usually given as injections. Injections are usually given as a single dose every month, apart from the very first treatment, which is given as two injections during the same visit.

• Degarelix (Firmagon®) is the LHRH antagonist treatment available in Europe as an injection.
• Antagonists can also be given as a daily tablet - available as Relogulix. 

LHRH antagonists can cause a range of side effects because they lower testosterone levels, a hormone important for many body functions. 

Below are some of the most common side effects of Degarelix, an LHRH antagonist used in prostate cancer treatment.

'Very common' (at least 10% of people affected):

• Hot flushes - a sudden, spontaneous feeling of warmth.
• Skin reaction / irritation at the site of the injection - including pain and redness.
• Lots of sweating.
• Sexual dysfunction:
  • Less interest in sexual activity.
  • Difficulty in getting or keeping an erection.
• Extreme tiredness or fatigue - a constant feeling of tiredness and low energy.
• Mood changes - this varies widely between people, but can include depression, anxiety, irritability, and emotional instability.
• Penis and testicles shrinking.

Other side effects often seen by professionals:

• Anaemia - where you don't have enough healthy red blood cells to carry oxygen around your body.

Other significant side effects of LHRH antagonists can develop over time and vary in their impact.

'Common' (between 1% and 10% of people are affected):

• Weight gain - especially around the belly.

Other side effects often seen by professionals:

• Muscle mass loss - muscles getting weaker.
• Bone density loss (osteoporosis) - testosterone helps keep bones strong, so when its levels drop, bones can weaken faster, increasing the risk of osteoporosis. Ask your doctor about having a DEXA scan to monitor your bone strength.

Anti-androgens stop androgens (like testosterone) from attaching to prostate cancer cells. This stops the cancer cells from growing and spreading. They can even reverse the growth, causing the cancer to get smaller. 

Anti-androgens are often given with salvage radiotherapy, which is radiotherapy given when a person's cancer has returned despite surgery.

Anti-androgens are also given with an initial LHRH agonist injection, to combat the 'flare' (testosterone surge) that the injection causes. (See 'LHRH agonist' section above.)

Anti-androgens are usually given as oral tablets, taken once or twice daily. 

Your doctor will discuss which anti-androgen drug best manages your stage of prostate cancer.

Common anti-androgens are shown below. All drugs have a generic name and a name given by the pharmaceutical company that produces them. This is called a trade name.

• Bicalutamide – Casodex®, Bicalutamid®
• Flutamide – Flutasin®, Flutamid®
• Nilutamide – Anandron®
• Cyproterone – Cyprostat®

Anti-androgens can cause a range of side effects because they affect hormone activity and how the body responds to androgens.

Below are some of the most common side effects of Bicalutamide, an anti-androgen used in prostate cancer treatment.

'Very common' (at least 10% of people are affected):

• Hot flashes - a sudden, spontaneous feeling of warmth.
• Extreme tiredness or fatigue - a constant feeling of tiredness and low energy.
• Sexual dysfunction:
  • Less interest in sexual activity.
  • Difficulty in getting or keeping an erection.
• Breast tenderness and swelling.
• Swelling - particularly in the legs, ankles, feet and hands.
• Feeling dizzy.
• Feeling sick.
• Pain in the abdomen (tummy).
• Constipation - finding it difficult to poo.
• Mood changes - this varies widely between people, but can include depression, anxiety, irritability, and emotional instability.
• Penis and testicles shrinking.

Other side effects often seen by professionals:

• Anaemia - where you don't have enough healthy red blood cells to carry oxygen around your body.

Other significant side effects of anti-androgens can develop over time and vary in their impact.

'Common' (between 1% and 10% of people are affected):

• Weight gain - particularly around the belly.

If you are prescribed anti-androgen tablets, you will also need to have regular blood tests, to check your levels of blood cells and how well your liver and kidneys are working.

ARPIs are newer drugs that target the system in the body that produces and uses androgens such as testosterone. 

Enzalutamide, apalutamide and darolutamide are anti-androgens that stop testosterone from attaching to cancer cells. This stops the cancer cells from growing and spreading. They can even reverse the growth, causing the cancer to get smaller.

Abiraterone works in a different way, by stopping androgens like testosterone from being made in the adrenal glands and within the cancer itself. Again, this stops the cancer cells from growing and spreading, and can even reverse the growth, causing the cancer to get smaller.

ARPIs can be more effective than traditional anti-androgens but can also have more serious side effects.

ARPIs are usually used for people who are also having LHRH agonists (see earlier section).

They can also be given to people who are having chemotherapy for prostate cancer that has spread to other parts of the body, or is at risk of spreading.

ARPIs are usually given as an oral tablet, taken once a day. 

If you are taking abiraterone, you will also have to take other tablets that are a low dose of steroids.

Your doctor will discuss which ARPI is most appropriate, based on medical evidence, your health, and any other medicines you are taking.

Common ARPIs are shown below. All drugs have a generic name and a name given by the pharmaceutical company that produces them. This is called a trade name.

• Abiraterone – Zytiga®
• Apalutamide – Erleada®, Erlyand®
• Darolutamide – Nubeqa®
• Enzalutamide – Xtandi®

ARPIs can cause a range of side effects because they affect hormone activity and how the body responds to androgens.

Below are some of the most common side effects of Enzalutamide (and sometimes to Apalutamide or Darolutamide), an ARPI used in prostate cancer treatment.

'Very common' (at least 10% of people affected):

• Hot flushes – a sudden, spontaneous feeling of warmth.
• Extreme tiredness or fatigue - a constant feeling of tiredness and low energy.
• Bone density loss (osteoporosis) - testosterone helps keep bones strong, so when its levels drop, bones can weaken faster, increasing the risk of osteoporosis. Ask your doctor about having a DEXA scan to monitor your bone strength.

Other side effects often seen by professionals:

• Anaemia - where you don't have enough healthy red blood cells to carry oxygen around your body.
• High blood pressure (hypertension).

Below are some of the most common side effects of Abiraterone, another ARPI used in prostate cancer treatment.

'Very common' (at least 10% of people affected):

• Swelling - particularly in the legs, ankle and feet.
• Urinary tract infection (UTI) - infection in the part of your body that helps you to wee.
• Diarrhoea.

Other side effects often seen by professionals:

• Anaemia - where you don't have enough healthy red blood cells to carry oxygen around your body.
• High blood pressure (hypertension).
• Low levels of potassium - which can cause a range of other problems.

Other significant side effects of ARPIs can develop over time and vary in their impact.

A common longer-term side effect of Enzalutamide is problems with thinking and memory (also called cognitive impairment). This is something doctors often notice, but it’s not usually seen with Apalutamide or Darolutamide.

A common longer-term side effect of Abiraterone is changes in how your liver works. This can show up as higher levels of certain enzymes in your blood, which may mean your liver isn’t working as well as it should

If you are prescribed ARPIs, you will also need to have regular blood tests, to check your levels of blood cells and how well your liver and kidneys are working.

A subcapsular orchiectomy, also called surgical castration, is a treatment where the part of the testicles that makes testosterone (and sperm cells) is removed.

This procedure lowers testosterone levels in the body very quickly because the testicles are the main source of testosterone. Lowering testosterone helps slow down or stop the growth of prostate cancer cells, since they often need testosterone to grow. In some cases, it can even shrink the cancer.

This type of treatment may also be called bilateral orchiectomy, which simply means that the surgery is happening on both testicles.

Subcapsular orchiectomy is a type of surgery that is usually done under local anaesthetic (so you're awake but don’t feel pain), though sometimes general anaesthetic is used. The surgeon makes a small cut in the scrotum, opens the capsula (the protective outer layer of the testicle), and removes the tissue inside that produces testosterone.

The procedure usually requires a hospital stay of up to one day, depending on how well you recover and whether there are any complications.

Once done, an orchiectomy cannot be reversed.

Subcapsular orchiectomy may be offered if:

• You have prostate cancer that doesn't respond to other hormone therapies.
• You cannot have other hormonal therapy.

Subcapsular orchiectomy removes the need for regular injections or hospital visits, and may have a lower risk of heart problems compared to other types of hormone therapy.

Subcapsular orchiectomy can cause a range of side effects because of the sudden and significant drop in testosterone levels.

Below are some of the most common side effects of orchiectomy in prostate cancer treatment, according to Cancer Research UK and Prostate Cancer Research.

• Mood changes - this varies widely between people, but can include depression, anxiety, irritability, and emotional instability.
• Extreme tiredness or fatigue - a constant feeling of tiredness and low energy.
• Hot flushes - a sudden, spontaneous feeling of warmth.
• Sexual dysfunction:
  • Less interest in sexual activity.
  • Difficulty in getting or keeping an erection.
• Smaller testicles - you'll be left with some of the testicle tissue – the 'shell’ of the testicle – which will feel smaller than a normal testicle.

Other side effects often seen by professionals:

• Anaemia - where you don't have enough healthy red blood cells to carry oxygen around your body.

Other significant side effects of subcapsular orchiectomy can develop over time and vary in their impact.

Below are some of the common longer-term side effects of subcapsular orchiectomy in prostate cancer treatment.

'Common' (between 1% and 10% of people are affected):

• Weight gain - especially around the belly.

Longer-term side effects often seen by professionals:

• Muscle mass loss - muscles getting weaker.
• Bone density loss (osteoporosis) - testosterone helps keep bones strong, so when its levels drop, bones can weaken faster, increasing the risk of osteoporosis. Ask your doctor about having a DEXA scan to monitor your bone strength.

When I was initially diagnosed, which was just before I went on holiday, I was put on some Bicalutamide for a month. And then when I actually saw my medical oncologist, I started on the injections that are used. I think my first injection was Prostap and now I'm on Zoladex, a subcutaneous pellet that gets fired into, it's a tummy fat area. So luckily that's only every three months. And then a month after that I started on Enzalutamide tablets, which is four little tablets. And as far as I'm aware, both of those treatments are for life.

The key benefits in my hormone therapy are in the PSA levels that I have, which have gone down to being undetectable, which is fantastic. So that is the key benefit that the prostate cancer cells have effectively gone to sleep. I think the other thing is that it's a surprisingly unobtrusive treatment plan. An injection itself, it's very quick and it's easy, and it's a little bit painful when you get a pellet fired into your tummy fat. But it's bearable and it's worth it. And the Enzalutamide tablets, it's just a matter of very regularly, every morning, I do it every morning, but you just do it at a consistent time every day just swallowing four little tablets with water and that's it.

Bicalutamide - an anti-androgen.

Prostap - an LHRH agonist.

Zoladex - an LHRH agonist.

Enzalutamide - an ARPI (androgen receptor pathway inhibitor).

Subcutaneous - under the skin.

The side effects have been very variable.

The key ones in that way are hot flushes. And with hot flushes, I can't see any real pattern to them. The only thing I would say with my hot flushes is that they don't tend to last very long. Really just a matter of a couple of minutes. They come and they go in their severity, sometimes vary in how much my body they cover. Sometimes they're just restricted to my forehead. Sometimes they go throughout my whole body. Sometimes I'm sort of dripping like I've got out of shower. But they're not. They are just on the surface. I can sort of live with them.

The next side effect perhaps to mention is the fatigue, that perhaps has surprised me. And not always, just at the end of the day, sometimes it's like that first thing in the morning.

And then another one is brain fog. Some days are better than other days. Sometimes a day are better than others. But when it is bad, I can become really quite forgetful.

My other side effects have been a complete loss of libido, but that has been quite a significant change. And it's not one necessarily because of it, the nature of it, that perhaps gets talked about as much as it should. And it's not just about the relationship that you might have, the sexual relationship you might have with your partner. And it does make that difficult, and you do have to think of different ways of doing things and so on. But it's also just about a whole way of being, whole way of seeing the world.

If I have to explain it to people, I sometimes say that it's, it's a bit like walking down the street and seeing someone who in the past you might have thought core, that's a very attractive person, and that's gone. And that's a big, big change. There are various resources to try and help with that, both with the sort of physical side and with the mental side, but it's a big challenge and not easy. Not easy at all.