Hormone therapy in prostate cancer – Part 2

Dr Sithembile Ngidi goes into detail about the three types of hormone therapy for prostate cancer and their side effects.

Luteinizing hormone-releasing hormone (LHRH) agonists 

Also called GnRH agonists, LHRH analogs, are injected as small implants under the skin. Depending on the drug used, they are given anywhere from once a month up to once a year e.g. leuprolide  and goserelin. 

When LHRH agonists are first given, testosterone levels go up briefly before falling to very low levels. This effect is called testosterone flare and results from the complex way in which these drugs work. 

Men who have urinary obstruction or whose cancer has spread to the bones may have worsening symptoms of flare. If the cancer has spread to the spine, even a short-term increase in tumour growth, because of the flare, could press on the spinal cord and cause pain or paralysis (skeletal event). 

Flare can be avoided by giving antiandrogens for a few weeks when starting treatment with LHRH agonists or using an antagonist initially.

Other side effects include hot flushes, loss of libido, weight gain, and fatigue.

LHRH antagonist

Degarelix is an LHRH antagonist. It works like the LHRH agonists but offers more advantages, including rapid reduction in testosterone levels (castrate levels can be reached in just a month), maintenance of castrate levels of testosterone and, most noticeable, it doesn’t cause testosterone flare like the LHRH agonists do.

Often, it’s prescribed for men who have skeletal events where flare needs to be avoided and men with cardiac problems, etc. 

It’s used to treat intermediate or advanced prostate cancer and is given as a monthly injection. 

The most common side effects are problems at the injection site (pain, redness, and swelling) and increased levels of liver enzymes on lab tests. 

Antiandrogens

These are oral drugs that bind to these receptors so that testosterone (androgens) can’t. Types of these drugs are flutamide  and bicalutamide.

An antiandrogen is not often used alone and may be added to treatment, if surgical castration or LHRH agonist/antagonist is no longer working by itself. 

It can also be combined with surgical castration or an LHRH agonist as first-line hormone therapy. This is called combined androgen blockade (CAB). There is still some debate as to whether CAB is more effective in this setting than using surgical castration or an LHRH agonist alone. If there is a benefit, it appears to be small.

An antiandrogen is also sometimes given for a few weeks when an LHRH agonist is first started to prevent a flare.

Castrate resistance

LHRH agonists and antagonists can stop the testicles from making androgens, but other cells in the body, including prostate cancer cells themselves, can still make small amounts, which can fuel cancer growth.

Some men can develop castrate resistance. When this occurs, there are other drugs that can be prescribed. In some men, if an antiandrogen is no longer working, simply stopping the antiandrogen can cause the cancer to stop growing for a short time. This is called antiandrogen withdrawal effect, although the cause as to why it happens is not known.

Possible side effects of hormone therapy

Surgical castration, LHRH agonists and antagonists can all cause similar side effects. It’s important to discuss your treatment with your doctor as side effects may differ with different agents. 

LHRH agonists and antagonists side effects can include:

• Reduced or absent sexual desire
• Erectile dysfunction (impotence)
• Shrinkage of testicles and penis
• Hot flushes (which may get better or go away with time)
• Breast tenderness and growth of breast tissue
• Osteoporosis (bone thinning)
• Anaemia (low red blood cell count)
• Decreased mental sharpness
• Loss of muscle mass
• Weight gain
• Fatigue
• Increased cholesterol levels
• Depression

Some research has suggested that the risk of high blood pressure, diabetes, strokes, heart attacks, and even death from heart disease is higher in men treated with hormone therapy. Although, not all studies have found this.

Antiandrogen side effects

The side effects are similar to the above. The major difference is that antiandrogens may have fewer sexual side effects. When these drugs are used alone, sexual desire and erections can often be maintained. 

When these drugs are given to men already being treated with LHRH agonists, diarrhoea is the major side effect. Nausea, liver problems, and tiredness can also occur.

Treating side effects

Many side effects of hormone therapy can be prevented or treated. 

• Hot flushes can often be treated with certain antidepressants or other drugs.
• Brief radiation treatment to the breasts can help prevent their enlargement. Though, this is not effective once breast enlargement has occurred. 
• Several drugs can help prevent and treat osteoporosis. It’s important for men to take calcium and vitamin D daily.
• Depression can be treated with antidepressants and/or counselling. 
• Exercise can help reduce many side effects, including fatigue, weight gain, and the loss of bone and muscle mass. 

It’s important to discuss possible side effects, and take active preventative measures to stop or manage side effects and improve overall health, well-being and quality of life.