Hormone Therapy for Prostate Cancer

Male hormones, called androgens, cause prostate cancer cells to grow. Androgens include testosterone and dihydrotestosterone (DHT), and are produced primarily by the testicles and in small amounts by the adrenal glands near your kidneys. They support the proper functioning of a healthy prostate gland but can also promote the growth of cancerous prostate cells. 

Hormone therapy for prostate cancer, also called androgen deprivation therapy (ADT) or androgen suppression therapy (AST), does not typically put prostate cancer in remission. Rather, it is used to slow or stop the production of androgens, which should also result in the slowed growth of prostate cancer cells. 

When is Hormone Therapy Used for Prostate Cancer Treatment?

Hormone therapy may be used at various stages throughout the prostate cancer treatment process.

After other treatments (adjuvant therapy) - Given to men who have a higher likelihood of recurrence. This is determined by the cancer’s stage, the grade of the tumor according to the Gleason score, and whether nearby lymph nodes have been affected. Men whose prostate cancer did not respond well to surgery or radiation therapy may also be candidates for hormone therapy.

Before surgery and/or radiation therapy (neoadjuvant therapy) - Sometimes hormone therapy is given before other prostate cancer treatments to reduce the size of the tumor before surgery or radiation therapy begins. Patients who receive hormone therapy before other treatments may also receive it again, after surgery and/or radiation therapy are complete. Your oncologist will provide the specific details about whether this is necessary.

As a stand-alone treatment - Using only hormone therapy for prostate cancer is considered by the oncologist when the patient has a limited life expectancy, an advanced local tumor stage, and/or has other serious health conditions.

Types of Hormone Therapy Used for Prostate Cancer

Several types of hormone therapy are available as part of the prostate cancer treatment process, which can be broken into two basic categories: therapies that lower androgen production and therapies that block androgen production. The most common of the two are those that reduce androgen production in the body. 

Treatments that Slow Androgen Production By the Testicles

• LHRH Agonists
  Luteinizing hormone-releasing hormone (LH-RH) agonists are drugs that prevent the testicles from making testosterone and the secretion of a hormone called luteinizing hormone. When levels of androgens in the body are low, this hormone is secreted to signal to the testicles to start producing androgens. An LHRH agonist will signal to the body to make a lot of androgens, which it will do at first. This is called a flare. Then, the testicles will stop reacting to the signal from LHRH and will significantly slow the production of androgens. When the testosterone level falls, the tumor shrinks, or its growth slows. These drugs are also called gonadotropin-releasing hormone (GnRH) agonists.
  
  LHRH agonists are given by injection or implanted under the skin. LHRH agonists available in the United States that are used to treat prostate cancer can include:

  • Leuprolide (Lupron, Eligard)

  • Goserelin (Zoladex)

  • Histrelin (Vantas)

  • Triptorelin (Trelstar)  

• Orchiectomy (Surgical Castration)
  Orchiectomy is a surgical procedure to remove one or both testicles. Removal of the testicles can reduce the level of testosterone in the blood by 90-95%. This type of treatment is permanent and irreversible.

• LHRH Antagonists
  Luteinizing hormone-releasing hormone (LH-RH) antagonists are drugs considered to be another form of medical castration.
  
  LHRH antagonists act by preventing the luteinizing hormone from binding to its receptors in the pituitary gland. Doing that prevents the signal to the testicles to start producing androgens. The result is a lowered level of androgens in the body without causing the flare that agonists cause.
  
  One LHRH antagonist, degarelix (Firmagon), is currently approved to treat advanced prostate cancer in the United States. It is given by injection.

• CYP17 inhibitor
  While LHRH agonists and antagonists can slow the testicles from making androgens, they cannot block the adrenal glands and prostate cancer cells from producing androgens. Even though the amounts of androgens they produce are small, it can be enough to support the growth of more prostate cancer cells. 
  
  Drugs to help prevent this are called androgen synthesis inhibitors. These drugs block testosterone production by inhibiting an enzyme called CYP17.
  
  Ketoconazole, aminoglutethimide, and abiraterone acetate (Zytiga) are three androgen synthesis inhibitors that are approved in the United States. All are given as pills to be swallowed. 

Antiandrogens Drugs 

Androgens have to bind to a protein in the prostate cell called an androgen receptor to promote cell growth. Antiandrogens drugs can block the action of male hormones and will bind to these receptors so that the androgens cannot. This slows the growth of prostate cancer cells. 

Because antiandrogens do not block androgen production, they are rarely used on their own to treat prostate cancer. Instead, they are used in combination with orchiectomy or an LHRH agonist. Use of an antiandrogen drug in combination with orchiectomy or an LHRH agonist is called combined androgen blockade, complete androgen blockade, or total androgen blockade.

After orchiectomy or treatment with an LH-RH agonist, your body no longer gets testosterone from the testicles, the major source of male hormones. Because the adrenal gland makes small amounts of male hormones, you may receive an antiandrogen to block the action of the male hormones that remain. However, studies have shown that total androgen blockade is no more effective than surgery or an LH-RH agonist alone.

Antiandrogens that are approved in the United States to treat prostate cancer include flutamide, enzalutamide (Xtandi), bicalutamide (Casodex), and nilutamide (Nilandron). Antiandrogens are given as pills to be swallowed.

What are the Possible Side Effects of Prostate Cancer Hormone Therapies?

Orchiectomy and LHRH agonists and antagonists greatly reduce the number of androgens produced by the body. However, because androgens are used by many other organs besides the prostate, there can be a wide range of side effects, including: 

• Loss of interest in sex (lowered libido)
• Erectile dysfunction (ED)
• Hot flashes
• Loss of bone density, which can result in bone fractures
• Loss of muscle mass and physical strength
• Changes in blood lipids
• Insulin resistance
• Weight gain
• Mood swings
• Fatigue
• Growth of breast tissue (gynecomastia)

Antiandrogens can cause diarrhea, breast tenderness, nausea, hot flashes, loss of libido, and erectile dysfunction. The antiandrogen flutamide may damage the liver.

Drugs that stop the adrenal glands from making androgens (i.e., the androgen synthesis CYP17 inhibitors ketoconazole, aminoglutethimide, and abiraterone acetate) can cause diarrhea, itching and rashes, fatigue, erectile dysfunction (with long-term use), and, potentially, liver damage.

For some men, prostate cancer will be controlled for two or three years, but others will have a much shorter response to hormone therapy. In time, most prostate cancers can grow with very little or no male hormones, and hormone therapy alone is no longer helpful. At that time, your doctor may suggest chemotherapy or other forms of prostate cancer treatments. In many cases, the doctor may suggest continuing with hormone therapy because it may still be effective against some of the cancer cells.

Hormone Therapy and The Latest Prostate Cancer Treatment Options at Virginia Oncology Associates

If you or a loved one is seeking prostate cancer treatment in the Hampton Roads and Eastern North Carolina areas, VOA is here to help guide you through your journey. Based on your specific situation, there are a few different treatment options available. We recommend you gather all the information about your diagnosis and options, as treatment is not always immediately required for prostate cancer patients. You have time to work with an oncologist to find out what your options are and choose the one that’s going to be best for you. Find a location near you to request an appointment. Our cancer centers are located in Virginia Beach, Norfolk, Hampton, Williamsburg, Chesapeake, Suffolk, Newport News, and Elizabeth City.