Prostate cancer grows when it is stimulated by the male hormone testosterone, an androgen that is mainly produced by the testicles. Testosterone is metabolized and converted into dihydrotestosterone (DHT) which stimulates the growth of prostate cells. This leads to normal prostate growth in adolescents but contributes to abnormal cell growth in older men. Therefore, one way to slow prostate cancer growth is to reduce the amount of testosterone or its activity in the body. This form of hormone therapy is called androgen deprivation therapy (ADT) or androgen suppression therapy.
Androgens and their effects may be suppressed in several ways:
- Subcapsular orchidectomy – This is an operation involving the removal of the part of the testicles that produces and releases testosterone. Sometimes both of the testicles are completely removed which is referred to as orchiectomy.
- Medical castration – Sometimes surgery may not be acceptable or possible. In these cases, certain drugs are used to suppress androgens and this form of treatment is termed chemical castration. Some of the agents that are used to suppress the production of androgens include:
Luteinizing hormone-releasing hormone (LHRH) agonist
These drugs reduce the production of testosterone in the testicles. LHRH is responsible for stimulating the pituitary release of LH, which, in turn, stimulates the production of testosterone in the testes.
Due to the prolonged presence of LHRH agonists and the long-term LH release, testosterone levels suddenly rise or “flare” and after several days, LHRH receptors are desensitized and their production is decreased, triggering a drop in LH production and ultimately testosterone.
The drugs are injected or implanted in the form of pellets underneath the skin. Depending on which agent is used, they may be administered anywhere from once a month to once a year. These drugs can be just as effective at lowering testosterone levels as orchiectomy and examples include leuprolide, goserelin and triptorelin.
Luteinizing hormone-releasing hormone (LHRH) antagonists
These drugs act directly by binding to LHRH receptors and inhibiting LH release, therefore preventing the stimulation of testosterone production. This direct method of reducing testosterone levels avoids the testosterone spike seen with the use of LHRH agonists. An example of a drug in this class is degarelix which is used to treat advanced prostate cancer and is administered once a month as a shot under the skin.
Side effects of medical castration
Some of the effects of medical castration include:
- Reduced sexual desire and libido
- Reduced size of testes and penis
- Hot flashes
- Growth of breast tissue (gynaecomastia) and pain across the breasts
- Thinning of the bones or osteoporosis and risk of fracture
- Loss of muscle mass
- Weight gain
- Fatigue and memory problems
- Increased blood cholesterol