Hormone Therapy for Prostate Cancer

Hormone therapy, also known as androgen deprivation therapy (ADT), is a series of medicines or procedures that are intended to lower the level of androgens in the body or prevent androgens from activating their target receptors (thus, making the androgens functionally useless). Androgens are steroid hormones that are present in both males and females during puberty. Prostate cancer tumors are often fueled to grow by androgens, including testosterone.^1-3

Turning off the body’s ability to produce or respond to testosterone can potentially halt tumor growth. Without these critical hormones, it may be possible to starve off tumor cells. Hormone therapy can be curative or palliative in intent, depending on your specific case. When used as a palliative care option, hormone therapy is typically used for pain or symptom management only.^1-3

Hormone therapy can also be used as an initial treatment option in some cases, as well as to treat recurrent prostate cancer when other methods haven’t prevented the cancer’s return.^1-3

Types of hormone therapy

There are three main types of hormone therapy:

• Orchiectomy - Surgical removal of the testicles
• LHRH agonists or antagonists - Medication to stop the testicles from making testosterone
• Anti-androgens - Oral medication that prevents cancer cells from using or responding to testosterone

The goal of hormone therapy is to reduce the amount or functionality of androgens in the body. There are multiple mechanisms by which medications or procedures aim to do this. Several of these options include:

Orchiectomy

An orchiectomy is a surgical procedure that may be performed on men with prostate cancer. However, instead of operating on prostate cancer cells or developed tumors, the surgery involves the removal of the testicles. Removing the testicles can lower overall levels of testosterone in the body.^1-3

Orchiectomies are often inexpensive when compared to other hormonal, surgical, chemotherapy, or radiation treatment options, and the results and side effects are permanent. A man who has had an orchiectomy where the entirety of the testicles are removed may opt to have plastic or reconstructive surgery afterward and have artificial testicles inserted into the scrotum. Although the appearance will remain the same, the artificial testicles will not produce testosterone.^1,2

LNRH agonists or antagonists

LHRH agonists or antagonists are drugs that block the activity of human luteinizing hormone-releasing hormone (LHRH). The most common types of medications in this class include:^1-3

• Gonadotropin-releasing hormone agonists (GnRH agonists, also referred to as LHRH agonists)
• GnRH receptor antagonists
• CYP17 inhibitors

GnRH agonists

GnRH agonists mimic the GnRH receptor’s normal activator, a key component involved in producing testosterone and other androgens. Turning off the body’s ability to produce testosterone, or reducing the amount made can potentially halt tumor growth. These medications continuously activate a key receptor in the pathway for making testosterone, and eventually overwhelms the receptor. When the receptor is overwhelmed, or desensitized, it stops making luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which are key in making testosterone.

However, a major concern with desensitizing the GnRH receptor is that before the receptor becomes overwhelmed, it will be continuously activated for the first few weeks of treatment. This means that more testosterone will be produced than usual, and could potentially cause a surge in tumor growth, known as Tumor Flare Phenomenon, which can cause pain, neurological symptoms, and other reactions. Examples of GnRH agonists include:^1-4

• Goserelin (Zoladex)
• Leuprolide (Lupron Depot, Eligard, Camcevi)
• Triptorelin (Trelstar)

GnRH receptor antagonists

GnRH receptor antagonists block the GnRH receptor, which, as mentioned previously, is a key receptor in the pathway to making testosterone. When this receptor is blocked, it stops making luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which are key in making testosterone. When the making of these hormones is suppressed, testosterone production is decreased as well. These medications are typically able to avoid the Tumor Flare Phenomenon as they decrease androgen levels quicker than GnRH agonists. Examples of GnRH receptor antagonists include degarelix (Firmagon) and relugolix (Orgovyx).

CYP17 inhibitors

CYP17 inhibitors are typically utilized when the cancer is not responding to treatment with androgen receptor antagonists or other first-line androgen deprivation therapies. At this point, the cancer is said to be castrate-resistant. These medications inhibit CYP17, an enzyme critical in the pathways involved in producing androgens, as well as other essential molecules in the body, including steroids. Examples of CYP17 inhibitors include Abiraterone (Zytiga).

Anti-androgens

Anti-androgens, also called androgen receptor inhibitors, block testosterone and other androgens from activating the androgen receptors in the body. These medicines are typically used in combination with GnRH agonists to counter the effects of the Tumor Flare Phenomenon. Although these medicines do not stop the body from making androgens, they do act to turn off the body’s ability to respond to them, thus potentially halting tumor growth. Those taking anti-androgens should be monitored for changes in liver functioning.^1-4

Examples of anti-androgen medications include:^1,2

• Apalutamide (Erleada)
• Nilutamide (Nilandron)
• Flutamide (Eulexin)
• Bicalutamide (Casodex)
• Enzalutamide (Xtandi)
• Darolutamide (Nubeqa)

Other hormone therapies

Other therapies and medicines can alter hormone levels in the body, which may be used to treat prostate cancer.

Antifungals

Ketoconazole (Nizoral) is an antifungal medication that can be used topically to treat athlete’s foot and other minor fungal infections. When prescribed orally in high enough dosages, Nizoral has the capability to prevent the body’s ability to transform cholesterol into other steroid hormones, including testosterone or cortisol. This property of the medicine has led to it being considered an anti-androgen.^1,3

Because the medicine decreases the creation of cortisol, an important glucocorticoid steroid hormone for our everyday functioning, it is often administered with a steroid to prevent glucocorticoid levels from becoming too low in the body. People taking Nizoral should be monitored for changes in the heart’s electrical activity, as well as for liver function changes.^1,3

Corticosteroids

Corticosteroid medications are a class of drugs designed to mimic naturally occurring corticosteroids produced by the adrenal cortex. Glucocorticoids are a class of corticosteroids commonly used in cancer therapy. For prostate cancer treatment, specific corticosteroids can be prescribed alone or in combination with other therapies to stop the adrenal glands from producing testosterone or to aid in symptom or side-effect management.³

Estrogens

Estrogens are commonly known as female sex hormones that regulate the reproductive system, as well as growth and development in females. Estrogens are used for a variety of purposes including birth control, hormone replacement therapy, and can be used to treat prostate cancer. Using estrogens to treat prostate cancer is often used after many other treatment options have failed. When a male is treated with estrogen-containing medications, it can prompt his body to stop making testosterone. This decrease in the important androgen could starve off tumor cells, limiting their ability to grow and spread. Individuals taking estrogen-containing medications should be monitored for blood clots and changes in liver functioning.^1-3

What are the possible side effects?

The side effects of hormone therapies often vary, but typically align with the male body’s natural response to a decrease in testosterone. Some of these symptoms include:^1-3

• Hot flashes
• Swelling of the breast tissue (gynecomastia)
• Thinning of the bones
• Mood changes (mood swings, depression, anxiety)
• Loss of muscle mass
• Fatigue
• Erectile dysfunction
• Decreased sex drive
• Nausea or vomiting
• Swelling of the limbs
• Diarrhea

These are not all the possible side effects of hormone therapy. Talk to your doctor about what to expect or if you experience any changes that concern you during treatment with hormone therapy. Your provider will help you determine what treatment option is right for you based on the goals of your treatment and your quality of life goals.

Combination therapies

In many instances, hormone therapy may be used in addition to surgical, radiation, targeted therapy, and chemotherapy treatment options. Additionally, as mentioned previously with the GnRH agonists and anti-androgens, some of these hormone therapies can be used in conjunction with one another.^1-3

Each person with prostate cancer and the exact characteristics of their case are different, making different options and combinations viable to different people. Your provider will help you determine if a combination treatment approach is appropriate for you, and will help instruct you on how to follow your treatment plan appropriately.