Hormone Therapy for Prostate Cancer

Hormone therapy is also called androgen suppression therapy. The goal is to reduce levels of male hormones, called androgens, in the body, to stop them from fueling prostate cancer cells.

Androgens stimulate prostate cancer cells to grow. The main androgens in the body are testosterone and dihydrotestosterone (DHT). Most androgen is made by the testicles, but the adrenal glands (glands that sit above your kidneys) as well as the prostate cancer itself, can also make a fair amount. 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.

When is hormone therapy used?

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 the cancer remains or comes back after treatment with surgery or radiation therapy
  • Along with radiation therapy as the 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

Types of hormone therapy

Several types of hormone therapy can be used to treat prostate cancer.

Treatment to lower testicular androgen levels

Androgen deprivation therapy, also called ADT, uses surgery or medicines to lower the levels of androgens made in the testicles.

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. This causes most prostate cancers to stop growing or shrink for a time.

This is done as an outpatient procedure. It is probably the least expensive and simplest form of hormone therapy. But unlike some of the other treatments, it is permanent, and many men have trouble accepting the removal of their testicles.

Some men having this surgery are concerned about how it will look afterward. If wanted, artificial testicles that look much like normal ones can be inserted into the scrotum.

LHRH agonists

Luteinizing hormone-releasing hormone (LHRH) agonists (also called LHRH analogs or GnRH agonists) are drugs that lower the amount of testosterone made by the testicles. Treatment with these drugs is sometimes called medical castration because they lower androgen levels just as well as orchiectomy.

Even though LHRH agonists cost more than orchiectomy and require more frequent doctor visits, most men choose this method. With these drugs, the testicles stay in place, but they will shrink over time, and they may even become too small to feel.

LHRH agonists 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 agonists available in the United States include:

  • Leuprolide (Lupron, Eligard)
  • Goserelin (Zoladex)
  • Triptorelin (Trelstar)
  • Histrelin (Vantas)

When LHRH agonists are first given, testosterone levels go up briefly before falling to very low levels. This effect is called a flare and results from the complex way in which these drugs work. Men whose cancer has spread to the bones may have bone pain. Men whose prostate gland has not been removed may have trouble urinating. If the cancer has spread to the spine, even a short-term increase in tumor growth as a result of the flare could press on the spinal cord and cause pain or paralysis. A flare can be avoided by giving drugs called anti-androgens (discussed below) for a few weeks when starting treatment with LHRH agonists.

LHRH antagonists

Degarelix (Firmagon) is an LHRH antagonist. It works like the LHRH agonists, but it lowers testosterone levels more quickly and doesn’t cause tumor flare like the LHRH agonists do. Treatment with this drug can also be considered a form of medical castration.

This drug is used to treat advanced prostate cancer. It is given as a monthly injection under the skin. The most common side effect are problems at the injection site (pain, redness, and swelling).

Possible side effects: Orchiectomy and LHRH agonists and antagonists can all cause similar side effects from lower levels of hormones such as testosterone. These side effects can include:

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

Many side effects of hormone therapy can be prevented or treated. For example:

  • Hot flashes can often be helped by treatment with certain antidepressants or other drugs.
  • Brief radiation treatment to the breasts can help prevent their enlargement, but this is not effective once breast enlargement has occurred.
  • Several drugs can help prevent and treat osteoporosis.
  • Depression can be treated with antidepressants and/or counseling.
  • Exercise can help reduce many side effects, including fatigue, weight gain, and the loss of bone and muscle mass.

There is growing concern that hormone therapy for prostate cancer may lead to problems thinking, concentrating, and/or with memory, but this has not been studied thoroughly. Still, hormone therapy does seem to lead to memory problems in some men. These problems are rarely severe, and most often affect only some types of memory. More studies are being done to look at this issue.

Treatment to lower androgen levels from the adrenal glands

LHRH agonists and antagonists can stop the testicles from making androgens, but cells in other parts of the body, such as the adrenal glands, and prostate cancer cells themselves, can still make male hormones, which can fuel cancer growth. Drugs are available that block the formation of androgens made by these cells.

Abiraterone (Zytiga) blocks an enzyme (protein) called CYP17, which helps stop these cells from making androgens.

Abiraterone can be used in men with advanced prostate cancer that is either:

  • High risk (cancer with a high Gleason score, spread to several spots in the bones, or spread to other organs) 
  • Castrate-resistant (cancer that is still growing despite low testosterone levels from an LHRH agonist, LHRH antagonist, or orchiectomy)

This drug is taken as pills every day. It 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 corticosteroid drug) needs to be taken during treatment as well to avoid certain side effects.

Ketoconazole (Nizoral), first used for treating fungal infections, also blocks production of androgens made in the adrenal glands, much like abiraterone. It's 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 testosterone 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, so men treated with this drug often need to take a corticosteroid (such as prednisone or hydrocortisone).

Possible side effects: Abiraterone can cause joint or muscle pain, high blood pressure, fluid buildup in the body, hot flashes, upset stomach, and diarrhea. Ketoconazole can cause elevated liver blood tests, nausea, vomiting, gynecomastia (enlargement of breast tissue in men) and a skin rash.

Drugs that stop androgens from working

Anti-androgens

For most prostate cancer cells to grow, androgens have to attach to a protein in the prostate cancer cell called an androgen receptor. Anti-androgens are drugs that also connect to these receptors, keeping the androgens from causing tumor growth. Anti-androgens are also sometimes called androgen receptor antagonists.

Drugs of this type include:

  • Flutamide (Eulexin)
  • Bicalutamide (Casodex)
  • Nilutamide (Nilandron)

They are taken daily as pills.

In the United States, anti-androgens are not often used by themselves:

  • An anti-androgen may be added to treatment if orchiectomy or an LHRH agonist or antagonist is no longer working by itself.
  • An anti-androgen is also sometimes given for a few weeks when an LHRH agonist is first started to prevent a tumor flare.
  • An anti-androgen can also be combined with orchiectomy or an LHRH agonist 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 agonist alone. If there is a benefit, it appears to be small.
  • 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. This is called the anti-androgen withdrawal effect, although they are not sure why it happens.

Possible side effects: Anti-androgens have similar side effects to LHRH agonists, LHRH antagonists and orchiectomy but may have fewer sexual side effects. When these drugs are used alone, sexual desire and erections can often be maintained. When these drugs are given to men already being treated with LHRH agonists, diarrhea is the major side effect. Nausea, liver problems, and tiredness can also occur.

Newer anti-androgens

Enzalutamide (Xtandi), apalutamide (Erleada) and darolutamide (Nubeqa) are newer types of anti-androgens. These drugs can often be helpful in men with cancer that has not spread but is no longer responding to other forms of hormone therapy (known as non-metastatic castrate-resistant prostate cancer (CRPC), described below). Enzalutamide can also be used for metastatic CRPC, whereas apalutamide can also be used for metastatic castrate-sensitive prostate cancer (cancer that has spread but is still responding to other forms of hormone therapy).

These drugs are taken as pills each day.

Side effects can include diarrhea, fatigue, rash, and worsening of hot flashes. These drugs can also cause some nervous system side effects, including dizziness and, rarely, seizures. Men taking one of these drugs are more likely to fall, which may lead to injuries. Some men also had heart problems related to these newer types of anti-androgens.

Other androgen-suppressing drugs

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

Current issues in hormone therapy

There are many issues around hormone therapy that not all doctors agree on, such as the best time to start and stop it and the best way to give it. Studies are now looking at these issues. A few of them are discussed here.

Treating early-stage cancer

Some doctors have used hormone therapy instead of observation or active surveillance in men with early-stage prostate cancer who do not want surgery or radiation. Studies have not found that these men live any longer than those who don’t get any treatment until the cancer progresses or symptoms develop. Because of this, hormone treatment is not usually advised for early-stage prostate cancer.

Early versus delayed treatment

For men who need (or will eventually need) hormone therapy, such as men whose PSA levels are rising after surgery or radiation or men with advanced prostate cancer who don’t yet have symptoms, it’s not always clear when it is best to start hormone treatment. Some doctors think that hormone therapy works better if it’s started as soon as possible, even if a man feels well and is not having any symptoms. Some studies have shown that hormone treatment may slow the disease down and perhaps even help men live longer.

But not all doctors agree with this approach. Some are waiting for more evidence of benefit. They feel that because of the side effects of hormone therapy and the chance that the cancer could become resistant to therapy sooner, treatment shouldn’t be started until a man has symptoms from the cancer. This issue is being studied.

Intermittent versus continuous hormone therapy

Most prostate cancers treated with hormone therapy become resistant to this treatment over a period of months or years. Some doctors believe that constant androgen suppression might not be needed, so they advise intermittent (on-again, off-again) treatment. The hope is that giving men a break from androgen suppression will also give them a break from side effects like decreased energy, sexual problems, and hot flashes.

In one form of intermittent hormone therapy, treatment is stopped once the PSA drops to a very low level. If the PSA level begins to rise, the drugs are started again. Another form of intermittent therapy uses hormone therapy for fixed periods of time – for example, 6 months on followed by 6 months off.

At this time, it isn’t clear how this approach compares to continuous hormone therapy. Some studies have found that continuous therapy might help men live longer, but other studies have not found such a difference.

Combined androgen blockade (CAB)

Some doctors treat patients with both androgen deprivation (orchiectomy or an LHRH agonist or antagonist) plus an anti-androgen. Some studies have suggested this may be more helpful than androgen deprivation alone, but others have not. Most doctors are not convinced there’s enough evidence that this combined therapy is better than starting with one drug alone when treating prostate cancer that has spread to other parts of the body.

Triple androgen blockade (TAB):

Some doctors have suggested taking combined therapy one step further, by adding a drug called a 5-alpha reductase inhibitor – either finasteride (Proscar) or dutasteride (Avodart) – to the combined androgen blockade. There is very little evidence to support the use of this triple androgen blockade at this time.

Castrate-resistant versus hormone-refractory prostate cancer

Both these terms are sometimes used to describe prostate cancers that are no longer responding to hormones, although there is a difference between the two.

  • Castrate-resistant means the cancer is still growing even when the testosterone levels are as low as what would be expected if the testicles were removed (called castrate levels). Levels this low could be from an orchiectomy, an LHRH agonist, or an LHRH antagonist. Some men might be uncomfortable with this term, but it’s specifically meant to refer to these cancers, some of which might still be helped by other forms of hormone therapy, such as the drugs abiraterone, enzalutamide, and apalutamide. Cancers that still respond to some type of hormone therapy are not completely hormone-refractory.
  • Hormone-refractory refers to prostate cancer that is no longer helped by any type of hormone therapy, including the newer medicines.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

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Last Medical Review: August 1, 2019 Last Revised: November 11, 2019

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