Hormone therapy in prostate cancer

Hormone therapy is also known as androgen deprivation therapy (ADT) or androgen suppression therapy. The aim is to reduce levels of the male hormones, androgens, in the body. The main androgens are testosterone and dihydrotestosterone (DHT).

Rational:

The growth of some cancer cells originating from the prostate depends on male hormones, androgens.. These types of cancers are known as hormone responsive. Thus, hormone therapy can be used to block or slow down this effect. Almost 95% of all androgens are made in the testicles, while the rest are made in the adrenal glands.

Types:

There are two main types of hormone therapy for prostate cancer.

1. Drugs or surgery to stop the production of male hormones:

• Orchiectomy (surgical castration):

• Pituitary down regulators. Medical castration

2. Drugs that block the androgen growth stimulating effect:

• Anti-androgens.

 1.Drugs or surgery to stop the production of male hormones:

• Orchiectomy (surgical castration):

Surgical removal of the testicles, which represents the main source of male hormones androgens (mostly testosterone), permanently reduce the circulation male hormones. Although it is considered an easy and less expensive technique for hormone therapy in prostate cancer, many men have trouble accepting the removal of their testicles.

• Pituitary down regulators (medical castration):

- Luteinizing hormone-releasing hormone (LHRH) agonists: e.g. Leuprolide and Zoladex.

 LH and FSH are hormones released from the pituitary gland (located in the brain) to regulate the function of the gonads (ovaries in females and tests in males). The term medical castration refers to decrease in circulating LH and FSH in addition to down-regulation of gonadal receptors for LH and FSH. Medical castration with LHRH analogues is used to treat men with hormone sensitive prostste cancer. In such way a complete inhibition of gonadal (testicular) function and a decline in sex hormones occur; androgens (mainly testosterone). Thus, provide the benefits of an orchiectomy without surgery. Most LHRH agonists are injected every one to four months. A new drug, Viadur, is a skin implant placed just once a year.

- Luteinizing hormone-releasing hormone (LHRH) antagonists:

 A newer pure LHRH antagonist, abarelix (Plenaxis) has been approved by the FDA. It lacks the flare effect of LHRH analogues, and it is indicated in men with

impending spinal cord compression and alikes where a

flare could be of serious effects. The main disadvantage is that this drug

must be administered every 2 weeks in the first month and monthly thereafter. Reports showed that fewer than 5% of patients have serious allergic reactions to the drug.

2. Drugs that block the androgen growth stimulating effect:

• Anti-androgens.
Anti-androgens exert their effect by blocking the testosterone receptors in the prostate cells they include:  

1. Bicalutamide (Casodex)

2. Cyproterone acetate (Cyprostat)

3. Flutamide (Drogenil)

4. Nilutamide

Anti-androgens can be used as monotherapy for prostate cancer patients who are in early stages (low risk), in conjunction with either surgical or medical castration to obtain complete hormonal blockade (CAB) or added after gonadal castration (medical or surgical) fails to show adequate response.

• Other androgen-suppressing drugs:

- Estrogens were once used as an alternative to orchiectomy in advanced prostate cancer. New drugs like LHRH analogues replaced its role, and is preferred to avoid side effects from estrogens. It is however one of the options that may be tried if androgen deprivation is no longer working.

- Ketoconazole (Nizoral), a drug used to treat fungal infections, blocks production of androgens and is sometimes used.

The "anti-androgen withdrawal" effect:

Some patients who fail on hormonal treatment may show tumor shrinkage and good response upon withdrawal of the hormone therapy. The "anti-androgen withdrawal" effect is considered one of the rationales in hormone treatment although the explanation of this effect is still not clear.