The primary strategy of hormonal therapy is to decrease the production of testosterone by the testes or block the actions that testosterone has on the prostate cells. Hormonal therapy cannot cure prostate cancer. Instead, it slows the cancer's growth and reduces the size of the tumor(s).

The types of hormonal therapy may be used in prostate cancer are orchiectomy and hormonal drug therapy.

Orchiectomy

Orchiectomy or surgical castration is the surgical removal of the testes, which produce about 95% of the body’s testosterone. Since the testes are the major source of testosterone in the body, this procedure is a form of hormonal therapy. The goal of an orchiectomy is to deprive the prostate cancer cells of testosterone, thereby causing the cancer to shrink and/or prevent further growth of the tumor. Surgical castration is generally reserved for patients with hormonal-responsive advanced metastatic prostate cancer who do not choose medical castration.

Advantages: Orchiectomy is an effective procedure that is relatively simple. The patient is usually given a local anesthetic and allowed to go home the same day as the surgery.

Disadvantages: The surgery is permanent and the effects cannot be reversed, therefore, many patients prefer a nonsurgical option since the success rates are similar.

Many men find it difficult to accept this type of surgery. Patients will often experience side effects that result from the lack of male hormone in the body.

Following the procedure, men will notice decreased sexual desire as well as impotence. This can be very upsetting for the patient and his significant other.

Many men may experience hot flashes, similar to those experienced by women during menopause. Some men may experience breast tenderness and/or breast growth over time.

Hormonal Drug Therapy

There are drugs that prevent the production or block the action of testosterone and other male hormones. Three classes of drugs most commonly used as hormonal therapy in prostate cancer include:

• LHRH analogs ( luteinizing hormone-releasing hormone analogs) or medical castration – a class of drugs that prevent testosterone production by the testes
  
  
• LHRH antagonists – another class of drugs that prevent testosterone production by the testes (yet work differently than LHRH analogs)
  
  
• Antiandrogens (also called nonsteroidal antiandrogens) – a class of drugs that block the action of testosterone at the prostate

Hormonal therapy is most commonly used to treat locally advanced and advanced metastatic prostate cancer. In locally advanced prostate cancer, hormonal therapy may be used in combination with radiation therapy.

LHRH Analog Therapy

LHRH analog therapy consists of administering a drug called a luteinizing hormone-releasing hormone analog, which prevents testosterone production by the testes.

LHRH analogs may be used alone or in combination with an antiandrogen. This will be discussed in more detail in the ‘combined androgen blockade’ section.

There are currently a number of different LHRH analogs available. Talk to your doctor about which LHRH analog treatment may be right for you. If you are treated with an LHRH analog, your doctor will inform you of how often you need to receive it. Treatment intervals vary from 1 month up to 1 year (depending on which LHRH analog the doctor prescribes).

Advantages: LHRH analogs are generally administered in a doctor’s office or clinic as an injection or a surgical implant. Treatment with LHRH analogs (medical castration) is an effective alternative to orchiectomy (surgical castration). Unlike orchiectomy, where the testes are surgically removed, LHRH analog is minimally invasive. Once the LHRH analog is stopped, its effects may be reversible. Therefore, men generally find it easier to accept treatment with LHRH analogs than surgical castration.

Disadvantages: Patients may experience decreased sexual desire and/or ability to have erections, hot flashes, fatigue, and decreased muscle strength. Other side effects may include anemia, altered lipid levels, decreased cognitive function, and decreased bone mineral density.

When first starting LHRH analog therapy, testosterone levels temporarily increase (called “testosterone surge”). In a small percentage of patients with advanced metastatic prostate cancer, testosterone surge may cause a brief worsening of cancer symptoms (called “flare”) for a few weeks before the testosterone level begins to fall. These symptoms may include bone pain, spinal cord compression, and urinary retention.

LHRH Antagonist Therapy

LHRH antagonists are another class of drugs that also prevent testosterone production by the testes, yet they work differently than LHRH analogs. It is used only in special circumstances to treat metastatic prostate cancer.

Antiandrogen Therapy

Another type of hormonal drug therapy used in prostate cancer is an antiandrogen. Antiandrogens do not prevent testosterone production. Instead, they block the action of male hormones at the prostate.

There are a number of antiandrogens currently available. They are pills taken orally one to three times per day (depending on which antiandrogen the doctor prescribes).

Antiandrogen Withdrawal

Prostate cancer may start to progress after patients have been on combined antiandrogen blockade therapy (therapy with an LHRH analog and an antiandrogen or CAB) for a certain period of time. In other words, the cancer has become resistant to the combined hormonal therapy. When this occurs, the antiandrogen therapy may be stopped (antiandrogen withdrawal) while the LHRH analog is continued. In some cases, stopping the antiandrogen for a while may make the cancer respond to hormonal therapy again.

Combined Androgen Blockade (CAB)

Antiandrogens are used with an LHRH analog or orchiectomy. This combination therapy is called combined androgen blockade (CAB), total androgen blockade (TAB) or maximal androgen blockade (MAB). LHRH analogs and orchiectomy prevent testosterone production from the testes; however, they do not suppress the production of androgens that are secreted by the adrenal glands. Therefore, there is still a small amount of androgen present in the body after LHRH analog administration or orchiectomy. Antiandrogens may be added to block the actions of the remaining androgens.

Advantages: When an LHRH analog or orchiectomy and an antiandrogen are given together (CAB), they work together to reduce the effect of testosterone. An LHRH analog reduces the quantity of testosterone while an antiandrogen works to block the remaining testosterone. Clinical studies in men with advanced prostate cancer suggest that CAB may provide small improvements in survival over LHRH analogs or orchiectomy alone.

The effects of CAB with an LHRH analog (not orchiectomy) and an antiandrogen may be reversible once CAB is stopped. Therefore, most men find it easier to accept treatment with an LHRH analog and an antiandrogen, than treatment with orchiectomy and an antiandrogen. Treatment with an LHRH analog and an antiandrogen is minimally invasive, since LHRH analogs are given as an injection or implant and antiandrogens are given as pills.

Disadvantages: In addition to an LHRH analog or orchiectomy, the patient has to remember to take their antiandrogen every day. CAB treatment is more expensive than medical castration (LHRH analog) or surgical castration (orchiectomy) alone.

There have been reports of liver injury in association with the use of antiandrogens. Therefore, liver function tests should be measured prior to starting treatment with CAB, at regular intervals for the first 4 months of treatment, and periodically thereafter.

Patients may experience any of the side effects associated with LHRH analogs or orchiectomy, as well as side effects related to antiandrogens. Depending on the antiandrogen used, these side effects may include diarrhea, breast tenderness, breast enlargement, and sometimes liver function problems.

Additionally, it is important to remember that if an LHRH analog or orchiectomy is used in combination with an antiandrogen and radiation therapy, it can be difficult to know for sure which component of therapy, if any, is responsible for the side effects that may occur. Sometimes, a worsening of the actual disease may be confused for a side effect of a particular treatment regimen.

Finally, the length of hormonal therapy influences the type and degree of side effects a patient may experience. Patients should always discuss any bothersome symptoms with their doctor or other health care provider. He/she may have some practical recommendations to help alleviate symptoms that are in fact due to treatment regimen.

Hormone Refractory Prostate Cancer

A patient becomes what is referred to as hormone refractory when the majority of hormonal therapies have been exhausted and the patient stops responding to all hormonal therapy, yet the cancer progresses again. The patient’s PSA level rises despite the use of CAB, antiandrogen withdrawal, or other hormonal therapies. When this happens, other treatments may be considered including chemotherapy, investigational therapy, or palliative treatment to relieve symptoms.