• Prostate cancer cells require male hormone for development.
• Treatment to remove male hormone activity can control cancer growth wherever it is in the body.
• Hormone treatment is usually given by injection, but may also include tablets. It may last many years.
• Side effects of hormone treatment can include hot flushes, lack of interest in sex, tiredness and bone loss. Exercise can minimise these effects. It is important to keep up calcium intake and vitamin D levels.
• Drugs called bisphosphonates may help with bone loss.
• Hormone treatment can stop working after some years. Treatment then includes chemotherapy, new types of hormone treatment and new agents.

Hormone treatment controls cancer growth by reducing the effects of male hormones.

Introduction

Hormone treatment is the major treatment option for cancer that has spread beyond the prostate region or has recurred following initial treatment. It is also sometimes used with radiotherapy for the initial treatment of high risk prostate cancer. Here we describe what hormone treatment is, its effects and the long term outcome.

What is the male hormone and what does it do?

Male hormones (also called androgens) are important for the development and functioning of the male reproductive system. Men rely on normal levels of male hormones to have adult sexual function and fertility. The level of male hormone in the body is precisely controlled by several factors, the main one being the normal secretion of stimulatory hormones from the hypothalamus and the pituitary gland, two structures at the base of the brain. Testosterone is the principal male hormone. It is released from the testicles and is important for prostate growth. Both normal and cancerous prostate cells are stimulated to grow in the presence of male hormones.

What is hormone treatment?

Prostate cancer cells that have left the prostate and are growing in other areas of the body (metastases) are stimulated to grow by male hormones. A common treatment for metastatic prostate cancer is to lower the levels of male hormones in the body to control this growth. Prostate cancer cells typically die when the hormone levels are lowered. Unfortunately, not all prostate cancer cells die, and with time, often several years later, the cancer growth returns. Nevertheless, men receiving hormone treatment may get good cancer control and a symptom-free life for many years.

Hormone treatment is also called androgen ablation or androgen deprivation therapy.

The removal of male hormone or its effects means that a man will experience changes in the way he feels, his attitudes and his sex life. While this can be distressing, and it means communication with your partner is particularly important, it does not change who you are. It does not change your identity as an individual and your ability to direct your own life. Some men feel a need for a change in focus in their lives at this stage, and they may take up activities that are more meaningful to them. According to these men, the years that follow can be rewarding and productive.

You may notice changes in energy levels and sexual interest.

Hormone treatment is normally used for men whose cancer has not been cured by surgery or radiotherapy. The timing of hormone treatment in response to a rising PSA level varies. It is based to some extent on the speed of tumour growth and its location.

Hormone treatment is the principal therapy for metastatic prostate cancer – when the prostate cancer cells have escaped from the prostate to grow in other sites of the body. The treatment may be started soon after this diagnosis is made. On occasions a delay in starting does not pose serious risk to the patient.

Hormone treatment may also be used to shrink a tumour before or together with radiotherapy. There is evidence that this hormone therapy is beneficial when used with external beam radiotherapy as a treatment for high risk localised prostate cancers. Once the radiotherapy is complete, the hormone treatment may continue for months to several years. PSA tests are used to check on the tumour control.

There are two ways of reducing male hormones:
• by surgery, where the testicles are removed (orchidectomy)
• by medication, either in the form of regular injections and/or tablets.

Both are effective.

Surgery (orchidectomy)

The testicles provide over 95% of the male hormones and so surgery to remove the testicles reduces the blood hormone levels. This occurs very quickly after the operation.

An advantage of surgery is that the inconvenience and cost of regular medications is avoided.
The operation is usually done as day surgery. The scrotum (pouch of skin that holds the testes) remains and the testes are removed through a small incision. The operation, called an orchidectomy, is permanent.

Medication

Medications are available as an alternative to orchidectomy. Some are injected and others taken as tablets.

Injectable drugs act on the brain to reduce the production of male hormones in the testicles. They currently last from 1–6 months per injection. This means that regular monthly or 6-monthly injections are required to control the cancer cell growth. Should these be stopped in men with metastatic cancer, the cancer will start to grow again when male hormone levels begin to rise (after several months).

Drugs given as tablets are called anti-androgens. They block the action of the male hormone in the reproductive organs and are not as effective as injectables in controlling cancer growth. Treatment with both injectables and tablets is called combined androgen blockade. Sometimes doctors start with a tablet, then 2–4 weeks later give an injectable medication. This is to control a brief increase in testosterone activity (called ‘flare’), which passes with time.

The effectiveness of hormone treatment can be checked with a blood test for testosterone. Its effectiveness in controlling the cancer can be checked with a PSA blood test (see Mr PHIP No. 1 and 2), although this is not always reliable.

Sometimes hormone treatment may be given in cycles (i.e. started and stopped repeatedly). This type of treatment is called intermittent hormone treatment. Typically, the treatment is continued for several months until the PSA has reached a low level, then the hormone treatment is stopped.

The PSA then gradually rises. Once it rises to a particular level (and this can take many months), hormone treatment is restarted. The main benefit of this approach is reduced side effects (see the next section) without a significant reduction in tumour control. Trials suggest that cancer control is similar with both continuous and intermittent therapies.

Table 1: Medications available in Australia

The following drugs and medications are in some way related to, or used in the treatment of Prostate Cancer. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.  http://www.drugs.com/condition/prostate-cancer.html

Many of the side effects of hormone treatment are related to the low levels of male hormone in the body and occur whether you choose orchidectomy or medications. These are summarised in Table 2.

Most men have poor or absent erections (impotence) and a lack of interest in sex (reduced libido). Your voice will not change. Some men notice a change in their body hair: a different texture and growth on previously bald areas. Tiredness is common and is related to the main ‘male fuel’ being suppressed.

Hot flushes are very common in the early stages of treatment but may decline after several months of treatment. Medications can reduce the intensity of this symptom if required. Over many months or years there may be a decline in muscle strength and some tenderness or enlargement in the breast area. Hormone treatment may also increase the risk of diabetes.

Before beginning treatment, it is helpful to discuss the possibility of side effects with your wife or partner. Good communication is important in dealing successfully with these changes and maintaining your close relationship.

What you can do to minimise side effects:

Recent research has shown that exercise, particularly resistance exercise, can reverse some of the side effects of hormone treatment. This kind of exercise builds up muscle mass and muscle strength in the body. Examples include chest presses (‘push-ups’), leg presses and lifting weights. They have been shown to increase muscle strength, reduce fatigue, improve mood and reverse some of the changes in the body that predispose to diabetes (3). Further information is given in the ‘Advanced prostate cancer: A guide for men and their families’ (see Resources). Check with your doctor regarding an exercise program that is suitable for you.

Do not hesitate to discuss distressing symptoms such as hot flushes with your doctor as there are medications and supplements that can help.

Intermittent hormone treatment can also reduce the effects for periods of time off the drugs.

There are non-medical therapies that can help with your quality of life, which we have not covered in this series. Information about these is available from the cancer organisation in your state and prostate cancer support groups (see Resources). Looking after your health through improving your diet, undertaking active exercise and managing stress is a good way to begin. It is wise to advise your medical team if you are taking additional non-conventional therapies.

The ability of hormone treatment to continue controlling your cancer over the years is quite variable. Some men (approximately 1 in 5) have recurrent cancer growth within a year from starting hormone treatment. Others have no sign of recurrent disease after 10 years of treatment.

For men with metastatic disease (cancer present in areas of the body remote from the prostate), the average time to active cancer growth (hormone resistance) is about 3 years. This stage is sometimes called ‘castrate resistance’.

When resistance to hormone treatment occurs, it is usually indicated by rising PSA while testosterone levels remain low. Symptoms typically occur months to years after the rising PSA. Symptoms caused by growth of the cancer in the pelvic region may include blood in the urine and reduced ability to pass urine. Symptoms caused by growth of the cancer at distant sites such as the bones may include pain in the bones, pelvis and back.

Treatment options for hormone-resistant cancer

1. Changing the type of hormone treatment. Even when one type of drug ceases to work, others may remain active. The order in which you have drugs can also change their effectiveness. Consequently different types and combinations of drugs may be effective. This is called ‘secondary hormone manipulation’.

2. Chemotherapy for prostate cancer is an area of research. A range of newer agents and methodologies are showing promise. Docetaxel is a chemotherapy agent used successfully for other cancers. It has been shown to extend life and reduce pain for prostate cancer. Discussion regarding pros and cons of chemotherapy options usually involves a medical oncologist. This should occur early on when considering approaches to treating hormone resistant prostate cancer.

3. Radiotherapy may alleviate pain and control cancer growth at sites away from the prostate. It is usually delivered by external beam although agents which are injected are sometimes used.

4. Steroids such as prednisolone to control pain and reduce tumour growth.

5. New treatments and clinical trials. Trials of drugs including one called ‘Abiraterone’ are currently underway in Australia. You can search for trials on the ANZ Clinical Trials Registry website listed under Resources, or ask your doctor about clinical trials that could be helpful to you.

Protecting the bones

Hormone treatment is known to weaken bones over time and increase the risk of a break or fracture. A DEXA scan for bone strength is a common investigation for men on or beginning hormone treatment. This is safe and readily available.

To maintain bone strength, it is wise to have an active exercise program and to maintain a balanced diet with adequate calcium intake. Exposure to sunlight stimulates the production of vitamin D, which is also important to bone health. A supplement of vitamin D and calcium is often recommended.

Prostate cancer may spread to the bones, where metastases can lead to bone pain and fractures. Your specialist(s) may recommend drugs known as bisphosphonates. Studies show regular use of this drug by men with secondary prostate cancer in the bones reduces bone fractures and bone pain. These drugs help to retain bone density but they have side effects. It is important to talk to your doctor about these.The drugs can be taken orally or by injection.

Radiotherapy is also used to effectively control bone pain and metastases.