Hormone Therapy

Hormone therapy is also called androgen deprivation therapy (ADT) or androgen suppression therapy. The goal is to reduce levels of male hormones, called androgens, in the body, or to stop them from affecting prostate cancer cells.

The main androgens are testosterone and dihydrotestosterone (DHT). Most of the body’s androgens come from the testicles, but the adrenal glands also make a small amount. Androgens stimulate prostate cancer cells to grow. Lowering androgen levels or stopping them from getting into prostate cancer cells often makes prostate cancers shrink or grow more slowly for a time. But hormone therapy alone does not cure prostate cancer.

Hormone therapy may be used:

  • If the cancer has spread too far to be cured by surgery or radiation, or if you can’t have these treatments for some other reason
  • If your cancer remains or comes back after treatment with surgery or radiation therapy
  • Along with radiation therapy as initial treatment if you are at higher risk of the cancer coming back after treatment (based on a high Gleason score, high PSA level, and/or growth of the cancer outside the prostate)
  • Before radiation to try to shrink the cancer to make treatment more effective

Several types of hormone therapy can be used to treat prostate cancer. Some lower the levels of testosterone or other androgens (male hormones). Others block the action of those hormones.

Treatments to lower androgen levels

Orchiectomy (surgical castration)

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 (testosterone and DHT) are made. With this source removed, most prostate cancers stop growing or shrink for a time.

This is done as an outpatient procedure. It is probably the least expensive and simplest way to reduce androgen levels in the body. But unlike some of the other methods of lowering androgen levels, it is permanent, and many men have trouble accepting the removal of their testicles.

Some men having the procedure are concerned about how it will look afterward. If wanted, artificial silicone sacs can be inserted into the scrotum. These look much like testicles.

Luteinizing hormone-releasing hormone (LHRH) analogs

These drugs lower the amount of testosterone made by the testicles. Treatment with these drugs is sometimes calledchemical castration or medical castration because they lower androgen levels just as well as orchiectomy.

Even though LHRH analogs (also called LHRH agonists or GnRH agonists) cost more than orchiectomy and require more frequent doctor visits, most men choose this method. 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.

LHRH analogs are injected or placed as small implants under the skin. Depending on the drug used, they are given anywhere from once a month up to once a year. The LHRH analogs available in the United States include leuprolide (Lupron®, Eligard®), goserelin (Zoladex®), triptorelin (Trelstar®), and histrelin (Vantas®).

When LHRH analogs are first given, testosterone levels go up briefly before falling to very low levels. This effect is called flare and results from the complex way in which LHRH analogs work. Men whose cancer has spread to the bones may have bone pain. If the cancer has spread to the spine, even a short-term increase in tumor growth as a result of the flare could compress the spinal cord and cause pain or paralysis. Flare can be avoided by giving drugs called anti-androgens for a few weeks when starting treatment with LHRH analogs. (Anti-androgens are discussed further on.)

Degarelix (Firmagon®)

Degarelix is an LHRH antagonist. LHRH antagonists work like LHRH agonists, but they reduce testosterone levels more quickly and do not cause tumor flare like the LHRH agonists do.

This drug is used to treat advanced prostate cancer. It is given as a monthly injection under the skin. The most common side effects are problems at the injection site (pain, redness, and swelling) and increased levels of liver enzymes on lab tests. Other side effects are discussed in detail below.

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 can fuel cancer growth. Abiraterone blocks an enzyme called CYP17, which helps stop these cells from making androgens.

Abiraterone can be used in men with advanced castrate-resistant prostate cancer (cancer that is still growing despite low testosterone levels from an LHRH agonist, LHRH antagonist, or orchiectomy). Abiraterone has been shown to shrink or slow the growth of some of these tumors and help some of these men live longer.

This drug is taken as pills every day. This drug doesn’t stop the testicles from making testosterone, so men who haven’t had an orchiectomy need to continue treatment with an LHRH agonist or antagonist. Because abiraterone also lowers the level of some other hormones in the body, prednisone (a cortisone-like drug) needs to be taken during treatment as well to avoid certain side effects.

Drugs that stop androgens from working

Anti-androgens

Androgens have to bind to a protein in the cell called an androgen receptor to work. Anti-androgens are drugs that bind to these receptors so the androgens can’t.

Drugs of this type, such as flutamide (Eulexin®), bicalutamide (Casodex®), and nilutamide (Nilandron®), are pills taken daily.

Anti-androgens are not often used by themselves in the United States. An anti-androgen may be added to treatment if orchiectomy, an LHRH analog, or LHRH antagonist is no longer working by itself. An anti-androgen is also sometimes given for a few weeks when an LHRH analog is first started to prevent a tumor flare.

Anti-androgen treatment can be combined with orchiectomy or an LHRH analog as first-line hormone therapy. This is called combined androgen blockade (CAB). There is still some debate as to whether CAB is more effective in this setting than using orchiectomy or an LHRH analog alone. If there is a benefit, it appears to be small.

Some doctors are testing the use of anti-androgens instead of orchiectomy or LHRH analogs. Some studies have found no difference in survival rates, but others have found anti-androgens to be slightly less effective.

In some men, if an anti-androgen is no longer working, simply stopping the anti-androgen can cause the cancer to stop growing for a short time. Doctors call this the anti-androgen withdrawal effect, although they are not sure why it happens.

Enzalutamide (Xtandi®)

This drug is a newer type of anti-androgen. When androgens bind to the androgen receptor, the receptor sends a signal to the cell’s control center, telling it to grow and divide. Enzalutamide blocks this signal.

In men with castrate-resistant prostate cancer, enzalutamide can lower PSA levels, shrink or slow the growth of tumors, and help the men live longer.

Enzalutamide is taken as pills each day. In studies of this drug, men stayed on LHRH agonist treatment, so it isn’t clear how helpful this drug would be in men with non-castrate levels of testosterone.

Other androgen-suppressing drugs

Estrogens (female hormones) were once the main alternative to orchiectomy for men with advanced prostate cancer. Because of their possible side effects (including blood clots and breast enlargement), estrogens have been largely replaced by LHRH analogs and anti-androgens. Still, estrogens may be tried if other types of hormone therapy are no longer working.

Ketoconazole (Nizoral®), first used for treating fungal infections, blocks production of certain hormones, including androgens, similarly to abiraterone. It is most often used to treat men just diagnosed with advanced prostate cancer who have a lot of cancer in the body, as it offers a quick way to lower te5stosterone levels. It can also be tried if other forms of hormone therapy are no longer working.

Ketoconazole also can block the production of cortisol, an important steroid hormone in the body. People treated with ketoconazole often need to take a corticosteroid (like hydrocortisone) to prevent the side effects caused by low cortisol levels.