Male hormones (androgens) cause prostate cancer cells to grow. Androgens include testosterone and dihydrotestosterone (DHT), which are produced primarily by the testicles and in small amounts by the adrenal glands, near your kidneys. While androgens support the proper functioning of a healthy prostate gland, they can also promote the growth of cancerous prostate cells.
Hormone therapy for prostate cancer is called androgen deprivation therapy (ADT) or androgen suppression therapy (AST). The goal is to slow or stop the production of androgens, which should then result in the slowed growth of prostate cancer cells.
When is Hormone Therapy Used for Prostate Cancer Treatment?
There are various stages throughout the prostate cancer treatment process in which hormone therapy may be used.
Before surgery and/or radiation therapy (neoadjuvant therapy): Some patients may be given hormone therapy before other prostate cancer treatments to reduce the size of the tumor before surgery or radiation therapy begins. Those who receive hormone therapy before other treatments may also receive it again once surgery and/or radiation therapy are complete. Your oncologist will provide specific details about whether this is necessary.
After other treatments (adjuvant therapy): This is typically given to men who have a higher likelihood of recurrence. The risk of recurrence 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.
As a stand-alone treatment: The oncologist may consider using only hormone therapy for prostate cancer 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. These therapies can be broken into two basic categories: therapies that lower androgen production and therapies that block androgen production. Those that reduce androgen production in the body are the most common of the two.
Treatments that Slow Androgen Production By the Testicles
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 Agonists: Luteinizing hormone-releasing hormone (LHRH) agonists are drugs that prevent the secretion of the luteinizing hormone. The secretion of this hormone signals the testicles to start producing androgens when levels of androgens in the body are low. 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. After that, the testicles will stop reacting to the signal from LHRH and will significantly slow the production of androgens.
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)
- Histrelin (Vantas)
- Triptorelin (Trelstar)
- Goserelin (Zoladex)
LHRH Antagonists: Luteinizing hormone-releasing hormone (LHRH) 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. This prevents the signal to the testicles to start producing androgens. The result is a lowered level of androgens in the body, but without the flare, that is caused by agonists.
One LHRH antagonist, degarelix (Firmagon), is currently approved to treat advanced prostate cancer in the United States. It is given by injection.
CYP17 inhibitor: LHRH agonists and antagonists can slow the testicles from making androgens. However, they cannot block the adrenal glands and prostate cancer cells from producing androgens. Although the amounts of androgens they produce are small, it can still be enough to support the growth of more prostate cancer cells.
Drugs to help prevent that from happening 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 taken orally.
In order to promote cell growth, androgens have to bind to a protein in the prostate cell called an androgen receptor. Antiandrogens drugs will bind to these receptors so that the androgens cannot. This slows the growth of prostate cancer cells.
Antiandrogens do not block androgen production. Because of this, 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.
Flutamide, enzalutamide (Xtandi), bicalutamide (Casodex), and nilutamide (Nilandron) are antiandrogens that are approved in the United States. 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
- Weight gain
- Mood swings
- The growth of breast tissue (gynecomastia)
- Changes in blood lipids
- Insulin resistance
Diarrhea, breast tenderness, nausea, hot flashes, loss of libido, and erectile dysfunction are some side effects that can be caused by antiandrogens. 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 side effects such as diarrhea, itching and rashes, fatigue, erectile dysfunction (with long-term use), and, potentially, liver damage.