Hormone Therapy for Prostate Cancer

Hormone therapy is used to treat prostate cancer. This treatment is needed to reduce or eliminate the impact that testosterone, an androgen hormone, has on prostate cancer cells. Hormones are chemical messengers secreted by glands.

Hormone therapy for prostate cancer is also referred to as androgen suppression therapy. Your healthcare provider may recommend hormone therapy to you at various times during treatment. Hormone therapy can be a medical or surgical procedure.

This article will provide an in-depth look at the various types of hormone therapies used to combat prostate cancer. It will also discuss possible side effects you may experience, and the goals for each treatment.

Overview of Hormone Therapy for Prostate Cancer

Testosterone, an androgen, fuels the growth of prostate cancer cells. Testosterone is produced primarily in the testicles. Smaller amounts are also produced in the adrenal glands. Once you have prostate cancer, prostate cancer cells may themselves produce testosterone, fueling the disease.

Hormone therapy is usually done to suppress the production of testosterone in the testicles. It may also be needed to block the action of testosterone manufactured in the adrenal glands.

Hormone therapy doesn’t cure prostate cancer. It may, however, shrink prostate cancers, making them easier to treat with radiation. It may also help slow their growth, prolonging survival. You may have hormone therapy in addition to surgery or radiation. It may also be used as a sole treatment.

Hormone therapy may be recommended at various points during prostate cancer treatment, including:

• As an initial treatment along with radiation therapy
• As a first-line therapy to shrink tumors, prior to radiation
• When prostate cancer has metastasized (spread) and can’t be treated surgically or with radiation
• If prostate cancer recurs after surgery or radiation
• If you’re at a high risk of recurrence, based on your Gleason score (a grading system evaluating the prognosis for people with prostate cancer) or prostate-specific antigen (PSA) level (measures the androgen-specific antigen in your blood)

The risks and side effects of hormone therapy vary but typically include:

• Erectile dysfunction (reduced ability to achieve or keep a firm erection)
• Less interest in sexual activity (lowered libido)
• Hot flashes (sudden sweating, usually of the face, neck, and chest) and night sweats (sudden feeling of warmth and extreme sweating while sleeping)
• Reduction in bone density and bone fractures
• Reduced muscle mass and physical strength
• Gynecomastia (enlarged breasts)
• Fatigue
  
• Mood swings
• Impaired cognitive function (thinking, memory, and judgment)
  
• Poor sleep quality
  
• Anemia (low red blood cell count or impairment of their oxygen-carrying capacity)
  

Reducing Testicular Androgen Levels

Testosterone production can be reduced or halted in the testes with medication or surgery. There are several types of treatment.

Orchiectomy (Surgical Castration)

An orchiectomy is a surgical procedure that is sometimes combined with radiation. The two types are: 

• Simple: Your surgeon will remove both testicles (testes) through an incision in the front of the scrotum (the external sac that holds the testes). Saline implants can be placed inside the scrotum after this procedure.
• Subcapsular: Your surgeon will remove the tissue from the lining of the testicles rather than the entire testicle. This tissue is where testosterone is produced.

With this surgery, the penis and scrotum are left intact. Since most androgen production occurs in the testes, orchiectomy is a simple, straightforward form of hormonal therapy. It is also permanent and may be challenging for some people to go through emotionally.

If you opt for this procedure, you can choose to have prosthetic testicles (saline implants) inserted into your scrotum. These are for aesthetic purposes only. They do not restore fertility, libido, or sexual function.

Orchiectomy permanently eliminates your ability to produce sperm. Like all types of hormonal therapy, orchiectomy also impacts the ability to get or maintain erections and lowers libido.

Orchiectomy is not a cure. However, it may prolong survival in people with advanced prostate cancer. It can also help relieve bone pain and shrink existing tumors.

LHRH Agonists (Medical Castration)

Luteinizing hormone-releasing hormone (LHRH) is a chemical messenger released by the body before testosterone is produced. LHRH agonists are medications that block LHRH from being released. This stops the testes from producing testosterone.

LHRH agonists are also referred to as gonadotropin-releasing hormone agonists (GnRHA) or GnRH agonists. These medications are administered via injection or as implants under the skin. LHRH agonists are the most commonly used form of hormone therapy for prostate cancer.

These drugs may be administered monthly or several times a year. Over time, LHRH agonists shrink the testes. In some instances, your testicles may become too small to feel manually.  

In addition to the common side effects of hormone treatments, LHRH agonists can cause surges in testosterone production when they're first administered. These surges are often referred to as tumor flares. Tumor flares can cause serious side effects, including:

• Short-term increase in tumor growth
• Trouble urinating in people with a prostate gland
• Bone pain in people with advanced prostate cancer
• Severe back pain or paralysis in people whose cancer has spread to the spinal cord

These side effects can be avoided by adding antiandrogen medications to LHRH agonist treatment. Antiandrogens block the effects of testosterone on prostate cancer cells.

LHRH Antagonists (Medical Castration)

These medications block the pituitary gland (located in the brain) from making luteinizing hormone (LH). Without LH, the testicles don't produce testosterone.

LHRH antagonists are used to treat advanced prostate cancer. They're taken orally as a daily pill or given as a monthly injection. If you get an LHRH antagonist injection, you may experience short-lived side effects at the injection site, such as redness, swelling, or pain.  

Unlike LHRH agonists, LHRH antagonists don't cause tumor flares to occur. However, they do typically cause the usual side effects associated with all types of hormonal therapy.

Reducing Adrenal Gland Androgen Levels

The adrenal glands and prostate cancer tumors produce testosterone, although in lesser amounts than the testes. Medications that block or prohibit androgen production outside of the testes may be given in addition to other forms of hormonal therapy. They include:

Abiraterone Acetate

Zytiga and Yonsa are brand names for abiraterone acetate. It is a CYP17 inhibitor medication approved by the Food and Drug Administration (FDA). It is taken daily in pill form.

CYP17 inhibitors are sometimes referred to as second-generation antiandrogens. They block CYP17, an enzyme that processes androgens before they are released to circulate throughout the body. CYP17 is made in the testes and in the adrenal glands.

Most patients become resistant to hormonal therapy over time. This results in castration-resistant prostate cancer (CRPC), a condition that is often metastatic (the tumor has spread to other areas).

CRPC is sometimes treated with CYP17 inhibitors. These medications are also used to treat advanced prostate cancer that is considered high-risk.

Abiraterone acetate can cause side effects, including:

• Joint pain
• Muscle pain
• Hot flashes
• Abdominal discomfort
• Diarrhea
• Fluid retention
• High blood pressure

Nizoral (Ketoconazole)

Nizoral (ketoconazole) is an antifungal medication that's sometimes used off-label to treat advanced prostate cancer. Unlike abiraterone acetate, it is not approved by the FDA for this use. Ketoconazole works by blocking the production of androgens in the adrenal glands. It is taken orally in pill form, once or several times daily.

Ketoconazole can cause side effects, such as:

• Liver toxicity
• Abnormal heartbeat or rhythm
• Nausea
• Vomiting
• Abdominal pain or discomfort
• Diarrhea
• Headache

Less common side effects include:

• Tender breasts
• Allergic reactions, which are sometimes severe
• Adrenal insufficiency (the adrenal glands don't produce enough hormones)
  

Drugs That Stop Androgens From Functioning

There are several classes of medication that block the effects of androgens, including testosterone. They include:

Antiandrogens (Androgen Receptor Antagonists)

Antiandrogens attach to proteins in prostate cancer cells, called androgen receptors. This blocks androgens from causing tumors to grow. Antiandrogens are taken in pill form. They include several brands:

• Casodex (bicalutamide)
• Eulexin (flutamide)
• Nilandron (nilutamide)

Antiandrogens are typically used in conjunction with other hormonal treatments. They may also be given to stop tumor flares caused by LHRH agonists.

Newer Antiandrogens

Several types of next-generation antiandrogens are prescribed for people with localized prostate cancer if it is no longer responding well to traditional forms of hormonal therapy. This type of cancer is referred to as nonmetastatic castrate-resistant prostate cancer.

Antiandrogens may also be prescribed for people with metastatic castrate-resistant prostate cancer.

Newer antiandrogens include:

• Erleada (apalutamide)
• Xtandi (enzalutamide)

Other Androgen Suppressors

Estrogens were once prescribed extensively as an alternative to orchiectomy in people with advanced prostate cancer.

Side effects such as blood clots and gynecomastia made the use of estrogens less popular. However, estrogens may still be tried if other hormonal treatments stop working.

Treatment Issues With Hormone Therapy for Prostate Cancer

Hormone therapy is not a cure-all for treating prostate cancer. Side effects can be life-altering as well as physically and emotionally draining.

In addition to side effects, the positive impact of hormone therapy on androgen suppression can fade when a person becomes resistant to it. In some instances, this may mean that hormone therapy should be withheld during early-stage treatment or in people with low-risk prostate cancer.

Currently, there is no medical consensus on when hormone therapy should start. Some doctors believe that early treatment may be beneficial for halting disease progression and prolonging life. Others feel that waiting makes more sense for at least some of their patients.  

You and your healthcare provider can decide together if hormone therapy is your best option, or if active surveillance or watchful waiting are better choices for early-stage prostate cancer. Active surveillance refers to consistent cancer monitoring that includes PSA blood tests and other tests.

Watchful waiting relies more on observing changes in symptoms, plus intermittent testing. For people with slow-growing cancers that may not spread, these strategies may be beneficial for maintaining quality of life, with no sexual or other side effects.

Discuss the benefits of having intermittent vs. continuous hormone therapy with your healthcare provider. Some doctors feel that constant androgen suppression is not necessary for treating prostate cancer. Taking a break from hormone therapy provides symptom-free windows from sexual side effects and fatigue.

Intermittent hormone therapy administration is sometimes based on PSA level drops. Studies have not yet proven conclusively which approach is most beneficial.

You and your doctor may have additional choices to make about hormonal therapy. These include whether you should take antiandrogens along with hormonal treatment. This therapy is referred to as combined androgen blockade (CAB).

Other potential treatment options include the added use of drugs called 5-alpha reductase inhibitors to a CAB regimen. This treatment is referred to as a triple androgen blockade (TAB). There is little evidence indicating that TAB is highly beneficial.

Definitions That May Help

Your doctor may use specific terms to let you know how your cancer is responding to hormone therapy or other treatments. They include:

• Castrate level: When the testicles are removed and testosterone levels plummet, this is referred to as the castrate level. Androgen levels that remain this low are most beneficial for reducing the impact of prostate cancer. Hormone therapy is designed to keep testosterone at castrate level. 
• Castrate-sensitive prostate cancer (CSPC): CSPC refers to prostate cancer that is being controlled successfully with testosterone at castrate level.
• Castrate-resistant prostate cancer (CRPC): CRPC prostate cancer refers to cancer that is not successfully controlled, even though testosterone levels are at or below castrate level. CRPC may require additional medications, such as a CYP-17 inhibitor or one of the newer antiandrogens.
• Hormone-refractory prostate cancer (HRPC): HRPC is prostate cancer that is no longer responsive to any type of hormone therapy, including newer medications.

Summary

Prostate cancer cells grow in response to testosterone. Hormone therapy may be done to reduce the amount of testosterone produced in the testicles. It may also be done to lower the amount of testosterone made in the adrenal glands.

Types of hormonal therapy for prostate cancer include surgical castration (removal of the testes), chemical castration by use of LHRH agonists or LHRH antagonist drugs, drugs that inhibit testosterone production by other glands, and antiandrogen drugs that prevent testosterone from acting on cells.

Hormonal therapy has a variety of side effects, including impacts on sexual functioning. The tumor may also become resistant to the effects of this treatment.

A Word From Verywell

If you have prostate cancer and your doctor has recommended hormone therapy, you may feel a range of emotions at once. This may be a stressful time for you and your loved ones, but it may help to know you’re in good company. About 1 in 8 people with a prostate will get prostate cancer during their lifetime.

Prostate cancer and its treatments can be hard to go through. No matter what the next few weeks, months, or years bring, remember that you are in charge, not your cancer. Advocate for yourself by asking as many questions as you need to about hormone therapy and other treatments. Let your doctor know how you’re feeling physically and mentally.

Stay in the game by eating healthy food, exercising, and caring for your body, brain, and spirit. Even if this time is challenging, you are still you and deserve the very best care and treatments that health care can provide.