Hormone therapy for prostate cancer

The goal of hormone therapy (also called androgen deprivation) is to lower the levels of the male hormones (androgens), such as testosterone, or to stop them from reaching prostate cancer cells. Androgens, which are made mostly in the testicles, cause prostate cancer cells to grow. Lowering androgen levels or stopping them from getting into prostate cancer cells often makes prostate cancer shrink or grow more slowly for a time. Hormone therapy alone can control but will not cure the cancer. It does not take the place of treatments aimed at a cure.

Hormone therapy is often used in these cases:

• In men who can’t have surgery or radiation or who can't be cured by these treatments because the cancer has already spread beyond the prostate.
• For men whose cancer remains or has come back after earlier treatment with surgery or radiation.
• Along with radiation as the first treatment in men who are at high risk of having the cancer return after treatment.
• Before radiation to try to shrink the cancer and make treatment more effective.

While hormone therapy does not cure the cancer on its own, it can provide relief from symptoms. Some doctors think that hormone therapy works better if it is started as early as possible after the cancer has reached an advanced stage. But not all doctors agree with this.

Because nearly all prostate cancers become resistant to hormone therapy over time, some doctors use an on-again, off-again approach for men with advanced cancer (this is called intermittent therapy). The drugs are given for a while, then stopped, then started again. One advantage is that some men are able to avoid the side effects (impotence, loss of sex drive, etc.) for a time. Studies are now going on to see whether this new approach is better or worse than giving the drugs non-stop.

Types of hormone therapy

There are several types of hormone therapy.

Orchiectomy: Even though this is a type of surgery, its main effect is as a form of hormone therapy. In this operation, the surgeon removes the testicles where most of the androgens such as testosterone are made. While this is a fairly simple operation and is not as costly as some other options, it is permanent and many men have trouble accepting this operation. Most men who have this surgery lose the desire for sex and cannot have erections.

LHRH analogs (luteinizing hormone-releasing analogs): These drugs lower testosterone levels just as well as orchiectomy. LHRH analogs (also called LHRH agonists) are given as shots or as small pellets of medicine put under the skin. Depending on the drug used, they are given anywhere from once a month to once a year. Even though this treatment costs more and means more doctor visits, most men choose this method over surgery to remove the testicles. These drugs allow the testicles to remain in place, but the testicles will shrink over time, and they may even become too small to feel.

When LHRH analogs are the first given, the testosterone level goes up briefly before going down to low levels. This is called "flare." Men whose cancer has spread to the bones may have bone pain during this flare. To reduce flare, drugs called anti-androgens can be given for a few weeks before starting treatment with LHRH analogs.

LHRH antagonists: Degarelix (Firmagon^®) is an LHRH antagonist to treat advanced prostate cancer. It is given as a monthly shot under the skin. This drug quickly lowers testosterone levels without causing a flare. The most common side effects are pain, redness, and swelling at the place where the shot was given and increased levels of liver enzymes on lab tests.

Anti-androgens: These drugs block the body's ability to use any androgens. Even after the testicles are removed or during LHRH treatment, the adrenal glands still make small amounts of androgens.

Anti-androgens may be used along with orchiectomy or LHRH analogs to provide combined androgen blockade (CAB), or total blocking of all androgens produced by the body. There is still debate about whether CAB is better than using the other treatments alone.

Other drugs to lower androgen levels: At one time estrogens (female hormones) were used to treat men with prostate cancer. Because of side effects, LHRH analogs and anti-androgens are now used more often. But estrogen or some other drugs may be used if other hormone treatments are no longer working.

Ketoconazole (Nizoral^®) blocks androgens. It is most often used to treat patients with recently diagnosed disease and a large amount of cancer, as it is a quick way to lower testosterone levels. It can also be tried if other forms of hormone therapy are no longer working.

Newer forms of hormone therapy

Some newer forms of hormone treatment may prove to be work better than some of those now in use.

Abiraterone (Zytiga^®): Drugs such as LHRH agonists can stop the testicles from making androgens, but other cells in the body, including prostate cancer cells themselves, can still make small amounts, which may fuel cancer growth. Abiraterone blocks an enzyme that helps stop these cells from making certain hormones, including androgens.

Abiraterone can be used in men with advanced castrate-resistant prostate cancer (cancer that is still growing despite low testosterone levels from either LHRH agonists or orchiectomy).

This drug is taken as a pill every day. Since this drug doesn’t stop the testicles from making testosterone, men who haven’t had their testicles removed need to stay on LHRH agonist treatment. Because abiraterone lowers the level of certain other hormones in the body, prednisone (a cortisone-like drug) needs to be taken as well during treatment.

Enzalutamide (Xtandi^®): This drug is a newer type of anti-androgen. It is also known as MDV3100.

Enzalutamide is mainly use in men with castrate-resistant prostate cancer who have already been treated with the chemotherapy drug docetaxel (Taxotere), This drug is also being studied to see if it can help men earlier in treatment.

Possible side effects of hormone therapy

Orchiectomy, LHRH analogs, and LHRH antagonists can all cause side effects because of changes in the levels of hormones. These side effects can include:

• Less sexual desire
• Impotence (not being able to get an erection)
• Hot flashes (which may get better or even go away with time)
• Breast tenderness and growth of breast tissue
• Bone thinning (osteoporosis), which can lead to broken bones
• Low red blood cell counts (anemia)
• Decreased mental sharpness
• Loss of muscle mass
• Weight gain
• Extreme tiredness (fatigue)
• Increased cholesterol
• Depression

Some research has suggested that the risk of high blood pressure, diabetes, strokes, and heart attacks, and even death from heart disease is also higher in men treated with hormone therapy. But not all studies have found this.

Anti-androgens may have fewer sexual side effects than other forms of hormone therapy. When they are used alone, sexual desire and erections can often be maintained. These drugs can also cause diarrhea, nausea, and liver problems.

Abiraterone does not usually cause major side effects, although it can cause joint or muscle pain, high blood pressure, fluid buildup in the body, hot flashes, upset stomach, and diarrhea.

Enzalutamide can cause diarrhea, fatigue, and hot flashes to get worse. This drug can also cause dizziness and, rarely, seizures. Men taking this drug are more likely to have problems with falls, which may lead to injuries.

Many side effects can be prevented or treated. For example, hot flashes can be helped by treatment with certain antidepressants. Brief radiation treatment to the breasts can help prevent their enlargement (but it is not effective once breast enlargement has occurred). Drugs can help prevent and treat osteoporosis. Depression can be treated by antidepressants or counseling. Exercise can help reduce many side effects, including fatigue, weight gain, and the chance of loss of bone and muscle mass.

There is growing concern that hormone therapy for prostate cancer may lead to problems with thinking, concentration, or memory. But this link has not been studied well in men getting hormone therapy for prostate cancer. More studies are being done to look at this issue.

Current issues in hormone therapy

Many issues about hormone therapy are not yet resolved, such as the best time to start and stop it and the best way to give it. Studies looking at these issues are now going on. If you are thinking about hormone therapy, ask your doctor to explain which treatments will be used and what side effects you might expect to have.