Hormone Therapy for Prostate Cancer

July 1, 2024

This page was reviewed under our medical and editorial policy by Tanya Barauskas Dorff, M.D., professor, Department of Medical Oncology & Therapeutics Research, City of Hope^® Cancer Center Duarte

Hormone therapy, also referred to as androgen deprivation therapy (ADT), reduces levels of male hormones in the body. These hormones, called androgens, have been found to encourage prostate cancer growth. By reducing the hormones available to the prostate cancer cells, the amount of cancer is reduced and the growth slows.

The two main androgens in a man’s body are testosterone and dihydrotestosterone (DHT), which are primarily made by the testicles. Adrenal glands and prostate cancer cells can also produce androgens. Using hormone therapy to stop or slow the growth of prostate cancer cells is helpful for a while, but prostate cancer cells tend to become resistant to the treatment over time, so it is necessary to combine it with other treatments to fight the cancer as well.

Why Is Androgen Deprivation Therapy Used?

This type of hormone therapy may be recommended in early- or advanced-stage prostate cancer and is usually combined with other prostate cancer treatments.

It may be used:

• Along with radiation therapy in early-stage prostate cancer, if the cancer is at high risk for recurring after treatment
• Prior to radiation therapy in more advanced prostate cancers to shrink the size of the cancer
• After surgery or radiation therapy for prostate cancer, if the cancer remains or returns (relapsed or recurrent cancer)
• In cases when cancer is widespread and surgery or radiation therapy is not advised

ADT Options for Prostate Cancer

Hormone treatments use medicine or surgery to reduce the body's testicle production of androgen. There are several types.

Orchiectomy

This procedure, also known as surgical castration, is commonly used as a form of ADT and is the simplest and least costly therapy. The testicles are surgically removed, permanently reducing the primary source of androgens. This outpatient procedure stops the growth of prostate cancer and may temporarily shrink it. Orchiectomy may be appropriate if it is used as an initial treatment and combined with another therapy, like radiation.

LHRH Agonists

LHRH (luteinizing hormone-releasing hormone) agonists are medications that reduce testosterone production by the testicles. Also called LHRH analogs or GnRH agonists, these drugs are considered a form of medical castration because they are as successful as surgical removal of the testicles in reducing androgen production. Even though the testicles remain, over time, they may become too small to feel.

LHRH agonists are given by injection or by an implant placed under the skin. The frequency depends on the type. These are used for the palliative treatment of advanced prostate cancer, meaning they are given to help relieve pain. These medications often cause a tumor flare — a temporary rise in testosterone levels before falling to treatment levels.

Leuprolide (Lupron^®, Eligard^®): Depending on the dose, these injections may be given monthly, quarterly, every four months or every six months.

Goserelin (Zoladex^®): This implant is used along with flutamide to treat locally confined prostate cancer. It is placed every 12 weeks under the skin into the abdomen wall, just below the navel.

Triptorelin (Trelstar^®): This is an intramuscular injection administered in either buttock. The frequency depends on the dose and may be given every four, 12 or 24 weeks. This GnRH agonist usually sees an initial rise in testosterone levels, but they lower to castrate levels within four weeks.

LHRH Antagonists

These medications are used to treat advanced prostate cancer. They work slightly different than LHRH agonists, and they lower testosterone levels more quickly and without tumor flare. These medications are also considered a form of medical castration because they result in such low testosterone levels.

Two medications do this in different forms.

Degarelix (Firmagon^®): This injection is given under the skin in the abdomen, usually monthly. It is used in patients with advanced prostate cancer. The most common side effects are pain, redness and swelling at the injection site, which is why some prefer to take an oral form of GnRH medication.

Relugolix (Orgovyx^®): Another type for adults with advanced prostate cancer, this is a tablet taken by mouth. The initial treatment is 360 mg on the first day (three tablets) followed by 120 mg daily (one tablet), taken around the same time each day.

Treatments to Lower Androgen Production Outside the Testicles

While LHRH agonists and antagonists suppress testicular androgen production, other cells in the body, like adrenal glands and prostate cancer cells, may still contribute to male hormone production. Because androgens may encourage cancer growth, some drugs are designed to block androgens originating from these areas.

Abiraterone (Zytiga^®): This is a daily pill to block an enzyme called CYP17. This helps cells in the body stop producing androgens. It may be used by men with advanced prostate cancer who are at high risk, in those whose cancer cells have spread to several areas or for those whose cancer is castration resistant (either by surgery or medication).

Ketoconazole (Nizoral^®): This drug blocks androgen production in the adrenal glands and is most often used for men with advanced prostate cancer. Because ketoconazole also blocks cortisol production, men may need to take a corticosteroid along with this medication.

Anti-Androgens (Androgen Receptor Antagonists)

Prostate cancer cells have a protein called androgen receptors, where androgens attach and fuel the cancer cell. Anti-androgens counteract that process. These drugs may slow the cancer’s progression, but they will not eliminate it.

These anti-androgens come in pill form and are often taken along with other testosterone-lowering treatments. Some common first-generation drugs are:

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

Second generation anti-androgens are newer types and sometimes help when older forms are not successful. These include:

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

How Will Patients Know if Hormone Therapy Is Working?

Every patient is different, and how long hormone therapy remains effective varies. Men taking hormone therapy for several months will have regular prostate-specific antigen (PSA) blood tests to look for any rise or fall in levels.

Androgen levels will also be reviewed at the same time to see whether they remain low. The results help to alert the care team as to whether the cancer is being suppressed or in a growing stage.

Hormone Therapy Side Effects

Hormones affect many organs besides the prostate, so side effects may vary widely. The most common side effects may include:

• Low libido (sexual energy)
• Erectile dysfunction
• Loss of muscle mass/decreased strength
• Insulin resistance
• Hot flashes
• Mood swings
• Weight gain
• Fatigue
• Decreased bone density/fractures
• Enlarged breast tissue (gynecomastia)

LHRH agonists normally cause tumor flares, a temporary increase in blood testosterone levels, and they may result in an initial increase or a new set of symptoms. These may last a few weeks and may include:

• Bone pain
• Neuropathy
• Blood in the urine
• Bladder and ureteral obstructions
• Spinal cord compression

Other symptoms may include high blood glucose levels and diabetes, cardiovascular diseases and convulsions.

Anti-androgens have many of the same side effects as LHRH agonists and antagonists and orchiectomy. However, if these are used alone, they may produce fewer sexual side effects. Other common side effects may include:

• Nausea and diarrhea
• Liver problems
• Fatigue
• Rash
• Some nervous system side effects (dizziness and, rarely, seizures)
• Heart problems

Many of these side effects may be managed with medications and exercise. Side effects may vary from person to person and may require medical attention. Side effects should always be discussed with the patient’s cancer care team.