Hormone Therapy for Prostate Cancer

Hormone therapy is also called androgen deprivation therapy (ADT). This treatment lowers levels of male hormones called androgens, or stops them from fueling prostate cancer cell growth. Several types of hormone therapy can be used to treat prostate cancer.

How does hormone therapy work?

Instead of affecting cancer cells directly, hormone therapy works on androgens, which help prostate cancer cells grow. The main androgens in the body are testosterone and dihydrotestosterone (DHT). The testicles make most androgens, but the adrenal glands (small glands that sit above the kidneys) and prostate cancer cells themselves can also make androgens.

Hormone therapy works by lowering androgen levels or blocking them from reaching prostate cancer cells. This often shrinks prostate cancer or slows its growth for a time. But hormone therapy alone doesn’t cure prostate cancer, and many cancers become resistant to it over time.

When is hormone therapy used?

Doctors may use hormone therapy:

• Along with radiation therapy as the first treatment for cancer that’s still in or around the prostate, if the cancer has a higher risk of coming back after treatment
• Before radiation, to shrink the cancer and make treatment more effective
• If the cancer remains or comes back after surgery or radiation therapy, especially if it has spread or its location isn’t clear
• If the cancer has spread too far for surgery or radiation to cure, of if these treatments aren’t an option for other reasons

Learn more: 

• Initial Treatment of Prostate Cancer, by Stage and Risk Group
• Treating Prostate Cancer That Doesn’t Go Away or Comes Back After Treatment

Treatment to lower testicular androgen levels

Some hormone treatments use surgery or medicines to lower the levels of androgens made by the testicles.

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.

This treatment is called medical castration because these drugs lower androgen levels about as well as orchiectomy. Although the testicles are not removed, they shrink over time, and they may even become too small to feel.

LHRH agonists are given as injections or small implants placed under the skin. Depending on the drug used, they are given anywhere from once a month up to once every 6 months. The LHRH agonists available in the United States include:

• Leuprolide (Lupron, Eligard) and leuprolide mesylate (Camcevi)
• Goserelin (Zoladex)
• Triptorelin (Trelstar)

When LHRH agonists are first given, testosterone levels go up briefly before falling to very low levels. This effect is called androgen flare. It results from the complex way these drugs work and can cause certain temporary side effects. Some men whose cancer has spread to the bones may have bone pain during this time. Men whose prostate has not been removed may have trouble urinating. If the cancer has spread to the spine, a short-term rise in tumor growth from the flare could, in very rare cases, press on the spinal cord and cause pain or paralysis.

A flare can be avoided by taking medicines called anti-androgens (discussed below) for a few weeks when starting treatment with LHRH agonists.

LHRH antagonists

LHRH antagonists can be used to treat advanced prostate cancer. They work somewhat differently from LHRH agonists. They lower testosterone levels faster and don’t cause tumor flare like the LHRH agonists do. Treatment with these drugs can also be considered a form of medical castration.

• Degarelix (Firmagon) is given as a monthly injection under the skin. Some men may notice problems at the injection site, such as pain, redness, and swelling.
• Relugolix (Orgovyx) is taken as daily pills, which may allow for less frequent office visits.

Orchiectomy (surgical castration)

Although orchiectomy is a type of surgery, its main effect is as a form of hormone therapy. The surgeon removes the testicles, which make most of the body’s androgens, including testosterone and DHT. This causes most prostate cancers to stop growing or shrink for a time.

Orchiectomy is rarely used today, because drug treatments like LHRH agonists and antagonists can lower testosterone just as effectively without surgery. When it is used, it is usually an outpatient procedure and is probably the least expensive and simplest form of hormone therapy. Unlike other hormone treatments, it is permanent, and many men have trouble accepting the removal of their testicles. Because of this, some may choose drug treatment instead, such as an LHRH agonist or antagonist (see below).

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 placed in the scrotum.

Possible side effects

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

Some research suggests that men treated with hormone therapy have a higher risk of high blood pressure, diabetes, stroke, heart attack, and death from heart disease, though not all studies agree.

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

• Certain antidepressants and other drugs can often help with hot flashes.
• 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.
• Antidepressants and/or counseling can treat depression.
• 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 with thinking, concentrating, and memory, though this hasn’t been studied thoroughly. 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 made elsewhere in the body

LHRH agonists and antagonists 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 that can fuel cancer growth. Some drugs block the formation of androgens.

Abiraterone (Zytiga)

Abiraterone blocks an enzyme called CYP17, which cells throughout the body need to make androgens.

Abiraterone can treat advanced prostate cancer in either of these situations:

• High-risk androgen pathway modulation-sensitive prostate cancer, high-risk APMS (previously called high-risk castration-sensitive prostate cancer): The cancer has spread, and it still responds to low testosterone levels. But it's considered high-risk because it also has at least one of these features: a high Gleason score, several spots of cancer in the bones, or spread to other organs.

• Androgen pathway modulation-resistant prostate cancer, APMR (also called castration-resistant prostate cancer): The cancer keeps growing even though testosterone stays low, from an LHRH agonist, LHRH antagonist, or orchiectomy.

This drug is taken as pills every day.

Abiraterone doesn’t stop the testicles from making testosterone, so men need another treatment to lower testosterone made by the testicles, usually an LHRH agonist or antagonist. Because abiraterone also lowers other hormone levels in the body, men need to take a low dose of prednisone, a corticosteroid drug, during treatment to avoid certain side effects.

Possible side effects: Abiraterone can cause joint or muscle pain, high blood pressure, fluid buildup in the body, hot flashes, upset stomach, and diarrhea.

Drugs that stop androgens from working

For most prostate cancer cells to grow, androgens must attach to a protein in the prostate cancer cell called an androgen receptor.

Anti-androgens, also called androgen receptor antagonists, are drugs that connect to androgen receptors, which stops the androgens from fueling tumor growth.

First-generation anti-androgens

These drugs were the first anti-androgens to become available, and they are often still used:

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

These drugs are taken as pills every day.

In the United States, anti-androgens are most often used along with treatments that lower testosterone levels. An anti-androgen may be:

• Added to treatment if orchiectomy or an LHRH agonist or antagonist is no longer working by itself.
• Given for a few weeks when an LHRH agonist is first started to help prevent a tumor flare.
• Combined with orchiectomy or an LHRH agonist as first-line hormone therapy. This is called combined androgen blockade (CAB).

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 it is not clear why it happens.

Possible side effects: Anti-androgens have similar side effects to LHRH agonists, LHRH antagonists, and orchiectomy. When these drugs are used alone, they may have fewer sexual side effects. 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 (second-generation) anti-androgens

Newer types of anti-androgens can sometimes be helpful even when older anti-androgens are not. These drugs are:

• Enzalutamide (Xtandi)
• Apalutamide (Erleada)
• Darolutamide (Nubeqa)

Any of these drugs may be used for:

• Non-metastatic androgen pathway modulation-resistant prostate cancer (nmAPMR), also called non-metastatic castration-resistant prostate cancer (nmCRPC), meaning cancer that has not spread but is no longer responding to other forms of hormone therapy.
• Metastatic androgen pathway modulation-sensitive prostate cancer (mAPMS), also called metastatic castration-sensitive prostate cancer (mCSPC), meaning cancer that has spread but is still responding to other forms of hormone therapy.

Enzalutamide can also be used for:

• Non-metastatic androgen pathway modulation-sensitive prostate cancer (nmAPMS), also called non-metastatic castration-sensitive prostate cancer (nmCSPC), that appears to have come back after treatment based on a high PSA level (a biochemical recurrence), and that is thought to be at high risk for spreading to other parts of the body.
• Metastatic androgen pathway modulation-resistant prostate cancer (mAPMR), also called metastatic castration-resistant prostate cancer (mCRPC).

These drugs are taken as pills each day.

Side effects can include high blood pressure, 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 have also had heart problems when taking 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. Rarely, estrogens may be tried if other hormone treatments are no longer working.

Current issues in hormone therapy

Not all doctors agree on when the best time is to start and stop hormone therapy or the best way to give it. Studies are now looking at these issues.

Terms to describe hormone therapy response

These terms are sometimes used to describe how well a man’s prostate cancer is responding to hormone therapy. Doctors have started using newer terms that avoid the word "castration," so you may hear either set from your care team.

• Androgen pathway modulation-sensitive prostate cancer (APMS), also called castration-sensitive prostate cancer (CSPC) or hormone-sensitive prostate cancer (HSPC), means the cancer is being controlled by keeping the testosterone level as low as what would be expected if the testicles were removed by castration. Levels can be kept this low with an orchiectomy, or by taking an LHRH agonist or an LHRH antagonist.
• Androgen pathway modulation-resistant prostate cancer (APMR), also called castration-resistant prostate cancer (CRPC), means the cancer is still growing even when the testosterone levels are at or below the level that would be expected with castration. Some of these cancers might still be helped by other forms of hormone therapy, such as abiraterone or one of the newer anti-androgens.