Hormonal Therapies

Hormonal therapy is the first-line treatment for prostate cancers that cannot be treated at a curable stage. It is mainly used in two situations:

  1. when the cancer is at the advanced stage and has spread outside the prostate to other areas of the body, or
  2. when  the cancer has recurred after other treatments.

It can also be used for men with curable cancers prior to radiotherapy or other treatments, which may make the treatment more effective.

In order to grow, most prostate cancers need the male hormones (androgens), the most common of which is testosterone. Most testosterone is produced in the testicles, though a small amount is also produced in the adrenal glands, which lie above the kidneys. By inhibiting the generation of testosterone, the cancer will be starved and shrink. 

The standard methods to control the production of testosterone are:

  1. an operation to remove the testicles, called an orchidectomy. This treatment is effective, but understandably is not favoured by most patients and is rarely performed nowadays.

  2. treatments with hormones, which are designed to control the production of testosterone. These are described below.

Hormone treatment is also called androgen deprivation therapy. Hormone treatment alone does not cure the cancer but may control it for anything from 2 to 10+ years. A marked lowering of the PSA is usually a good indication of the effectiveness of hormone treatment.

However, the cancer will eventually no longer respond to the hormone drugs. This is called Hormone Relapsed prostate cancer (still sometimes referred to by the medical profession as ‘castration resistant’ or ‘hormone resistant’ prostate cancer). A rise in PSA level is the first sign of the treatment becoming ineffective. When this happens, there are several second-line treatments, described later in this section.

There are two main types of hormone treatment: LHRH analogues and anti-androgens.

LHRH analogues

This is short for Luteinising Hormone-Releasing Hormone. These drugs can decrease the amount of testosterone produced by the testicles as effectively as surgical removal. Two common examples of these drugs are Zoladex (Goserelin) and Prostap  (Leuprorelin). They are administered by the injection of a slowly dissolving pellet either monthly or quarterly.

Less common is Decapeptyl or Gonapeptyl (Triptorelin). This is another drug that can be used, especially in cases of aggressive advanced prostate cancer, administered in one-, three- or six-monthly injections.

When first administered, this causes an initial surge of testosterone, which is counteracted by a short course of anti-androgen tablets shortly before and after the first injection. 

Degarelix (Firmagon) works in a slightly different way to LHRH analogues but has been shown to be just as safe and effective. The advantage of this drug (as opposed to others listed above) is that there is no tumour flare and thus no need for an anti-androgen before an LHRH analogue treatment. It is approved by NICE for cases of advanced prostate cancer where it has spread to the spinal column. It is administered by injection under the skin.

Anti-androgens

These drugs do not stop the production of testosterone but block the effects of androgens produced by the testes and adrenal glands. Two common examples of these drugs are Cyprostat (Cyproterone acetate) and Casodex (Bicalutamide).

They are usually taken in pill form, which makes them attractive to those who do not like the thought of regular injections. Anti-androgens can be used as a stand-alone therapy (referred to as ‘anti-androgen monotherapy’), or can be used in combination with LHRH analogues, referred to as ‘combined androgen blockade’. Some men may prefer anti-androgens because of the reduced side effects, but evidence shows that they are not quite as effective as LHRH analogues. 

Intermittent hormone therapy

Intermittent hormone therapy is a process in which the hormone treatment is started and stopped for periods while monitoring the PSA. When the PSA rises, treatment is restarted. The aim is to reduce the side effects of the treatment. Some trials have shown that intermittent treatment can be as effective as continuous treatment, and with fewer side effects.

Side effects of hormone treatments

A common side effect, particularly with LHRH analogues, is hot flushes for short periods, which can occur at night, affecting sleep, for which a short course of low-dose anti-androgens may be prescribed. Eliminating alcohol, tea and coffee (or using decaffeinated drinks) and going on a soya diet (to replace milk) may also help. Weight gain, bone or muscle pain, joint pain, numbness and tingling in hands and feet, and possible hair loss on face, arms, legs or underarm are other listed side effects. Some may find these hard to live with, but with time many will reduce in severity as the body adjusts. Medication can, of course, be changed should these become a problem.

LHRH analogue side effects. The main side effect is that the patient will be impotent and lose his sex drive; but unlike orchidectomy the process is gradually reversed if the patient stops taking the drug. Some men may suffer from decreased size of testicles and some slight penile shrinkage. Initially these drugs can produce a flare in testosterone, which settles after a few weeks.

Anti-androgen side effects. A common side effect of these drugs is tender or enlarged breast tissue (gynaecomastia), which may subside if treatment is ceased. Low doses of Tamoxifen (an anti-oestrogen) can reduce this side effect. Other possible concerns may be nausea, diarrhoea, itching, feeling weak, and problems with the liver. As the drugs affect your hormone levels, this may cause some anxiety or depression. Although there is still a risk of impotence and other adverse sexual side effects with anti-androgens, these are less severe than with LHRH analogues (or with orchidectomy, where it is permanent).