Hormonal therapy for prostate cancer

The growth of prostate cancer is stimulated by the presence of male hormones or androgens in the body. Hormone therapy is aimed at reducing the amount of androgen present in the blood to prevent the growth and further spread of prostate cancer. The therapy is also called androgen deprivation therapy (ADT) or androgen suppression therapy.

Hormone therapy works either by reducing androgen levels in the body or by preventing these androgens from reaching the prostate cells.

Androgens in prostate cancer

The main androgens in the body that prostate cancer growth depends on are Testosterone and Dihydrotestosterone (DHT).

Testosterone is mainly produced in the testicles and in small amounts by the adrenal gland. Dihydrotestosterone, the converted from of testosterone, is the most important hormone in the growth and spread of prostate cancer. As the levels of testosterone are reduced and less DHT becomes available, the prostate cancer shrinks or grows more slowly. However, agents that reduce the androgens cannot cure prostate cancer; they can only delay its progression.

Uses of hormone therapy

Situations where hormone therapy may be used include:

• In cases where people cannot tolerate surgery or radiotherapy or when these therapies are not suitable because the cancer is too advanced to treat and cure.
• In cases of cancer recurrence after remission
• When the risk of the cancer returning is high, as predicted by high Gleason score, high PSA level or imaging studies revealing cancer spread beyond the prostate.
• Before radiotherapy is begun, hormone therapy may be used to shrink the cancer to increase the effectiveness of the therapy.

Some of the drugs used in hormonal therapy include:

Luteinizing hormone-releasing hormone (LHRH) agonists

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, the testosterone level suddenly rises or “flares” 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 of the agents include leuprolide, goserelin and triptorelin.

Luteinizing hormone-releasing hormone (LHRH) antagonists

These drugs act 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.

Anti-androgens

These drugs do not affect the manufacture of androgens but prevent them from affecting the prostate cancer cells. Normally, androgens bind to androgen receptors in order to exert their effects. Anti-androgens inhibit the actions of androgens by binding to these receptors, before androgens do. Drugs of this class include flutamide, bicalutamide and nilutamide. These agents can be taken in the form of tablets and are usually added to an LHRH agent or surgical orchiectomy and this is called combined androgen blockade (CAB).