The Role of Hormone Therapy in Prostate Cancer—Who Get’s It, How It Works, and What Are the Side Effects?

Posted by Medical Board on October 1, 2017 in Hormones Men
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According to the American Cancer Society, one in seven men will be diagnosed with prostate cancer in his lifetime. Most will not die from the disease, however treatment can render a man impotent or incontinent. Depending on the persistence or severity of cancerous tumors, hormone therapy may be a viable option for some males. Whether alone, or together with another prostate regimen, therapies that act on androgens play an important role in cancer treatment.[4]

Though most prostate cancers originate in the fluid production cells of the small gland just below the bladder, they can sometimes metastasize beyond the localized tissue, eventually ravaging organs and bones.[2]

Fortunately, about 85 percent of prostate cancers are slow growing and can successfully be treated if diagnosed in the early stages, while still encapsulated in the prostate gland.[6]

Current Treatment Options

The decision to treat prostate cancer is an important one that should be considered only after serious investigation. All treatment options are fraught with possible side effects and some may be irreversible.

Possible effects of prostate treatment include:

Urinary incontinence
Bowel disturbances or dysfunction
Erectile dysfunction
Infertility

*Chemotherapy and hormone therapy may cause individual side effects.

Hormone Therapy For Prostate Cancer

Over the past 70 years hormone therapy has played an important role in the treatment of prostate cancer.[5] In general, it is presented as a viable option for recurrent prostate cancer, cancer that is resistant to other treatments, and cancer that has metastasized. Doctors however, often conflict about when to initiate hormone therapy in patients, when treatment is to cease, and whether or not to combine therapies for maximum efficacy.

Hormone Therapy—How It Works

Androgens, known as male sex hormones not only help develop and maintain male characteristics, but also promote cell growth in the prostate, including cancerous prostate cells. In the beginning, high levels of androgens are necessary for cancer to grow, rendering it “androgen sensitive” or “androgen dependent”.[2] Hormone therapy, also referred to as androgen deprivation therapy (ADT), or androgen suppression therapy essentially reduces male hormones that can affect prostate cancer cells. Androgens including testosterone and dihydrotestosterone (DHT) are mainly produced in the testicles, though adrenal glands do manufacture small amounts as well.

While hormone therapy alone does not completely cure prostate cancer, it can shrink the cancer or slow its growth altogether.

When To Use Hormone Therapy

Hormone therapy may not be recommended as a course of treatment for all prostate cancers. It has been known to be effective under the following circumstances:

When surgery or radiation is not an option because cancer has spread.

If cancer is recurrent after previous radiation therapy or surgical treatment.

If cancer is not responsive to radiation or surgery.

As a combined treatment with radiation for patients who are at-risk for recurrent prostate cancer, or cancer likely to spread outside of the prostate.

Prior to radiation, in order to shrink cancer so that other therapies or treatments may be more effective.

Types of Hormone Therapy

Hormone therapies vary depending on the type and stage of prostate cancer.

These include:

Orchiectomy

This surgical option, performed in an outpatient medical center removes the testicles entirely to drastically reduce androgen levels. This often shrinks prostate cancer and slows growth. Many men forgo the orchiectomy in favor of less dramatic anatomy-changing treatment, however.

LHRH agonists

Luteinizing hormone-releasing hormone (LHRH) agonists (also referred to as LHRH analogs or GnRH agonists) lower the amount of testosterone produced by the testicles. This treatment process is often referred to as “chemical castration” because androgen levels are lowered to the point of surgical castration. This hormone treatment option is chosen more often than physical removal of testicles.

LHRH agonists are delivered through injections or implanted under the skin. These are administered monthly (sometimes yearly) depending on the specific drug to be injected.

LHRH agonists include the following:

Leuprolide (Lupron, Eligard)
Goserelin (Zoladex)
Triptorelin (Trelstar)
Histrelin (Vantas)

In the initial period of administration of LHRH, testosterone levels briefly rise before falling dramatically. This may result in short-term tumor growth in men. Anti-androgen drugs given at the onset of treatment can reduce the effects of “tumor flare”.

LHRH antagonists

The drug, Degarelix (Firmagon) is one LHRH antagonist that lowers testosterone quickly without the side effect of tumor flare. The treatment is only used for advanced prostate cancer and is administered monthly. Side effects consist of pain, swelling, or redness at the injection site, as well as an increase in liver enzymes.

CYP17 inhibitor

While LHRH agonists and antagonists inhibit cancer growth by stopping the production of androgens in the testicles, cells (including cancer cells) can produce small amounts of androgen, enough to fuel cancer itself.
Abiraterone (Zytiga) is a drug that blocks the CYP17 enzyme, helping prevent theses cells from androgen production. This treatment may be effective in men considered, “castrate-resistant” whose cancer continues to grow despite treatment with an LHRH agonist, LHRH antagonist, or orchiectomy. Abiraterone is taken daily in pill form, but because it doesn’t stop testosterone production in men with testicles in tact, it must be further supplemented with an LHRH agonist or antagonist. Because the CYP17 inhibitor also lowers levels of other hormones as well, the drug must be taken with the cortisone-like medication, prednisone to avoid particular side effects.

Anti-androgens

Since androgens must bind to androgen receptors to work effectively in the male body, anti-androgen drugs essentially bind to receptors in their place. These may be taken daily in pill form.

Anti-androgen drugs include:

Flutamide (Eulexin)
Bicalutamide (Casodex)
Nilutamide (Nilandron)
Enzalutamide (Xtandi) 
Enzalutamide

In the United States, anti-androgen drugs are not used exclusively for prostate cancer treatment. They may be used in conjunction with an LHRH agonist during initial treatment to prevent tumor flare, or used in cases where an orchiectomy or LHRH treatment fails.

Other androgen-suppressing drugs include:

Estrogens (female hormones)

These are no longer used as frequently as other hormone therapies, however they may be used if other treatments are not effective.

Ketoconazole (Nizoral)

This medication blocks androgen production and lowers testosterone quickly. It is most often used in cases of advanced prostate cancer, or when other hormone therapies are ineffective. Ketoconazole may also block cortisol production, so a corticosteroid will likely be administered as well.

Hormone Therapy Side Effects

Orchiectomy and LHRH agonists, and antagonist side effects may include:

Loss of libido
Impotence
Testicles/penis shrinkage
Hot flashes
Breast tenderness/growth
Osteoporosis
Anemia
Mental confusion
Decrease in muscle mass
Weight gain
Lack of energy
High cholesterol
Depression

Anti-androgen drugs impact the body in similar ways, with the exception of sexual side effects. In combination with LHRH agonists, anti-androgens may result in diarrhea, nausea, liver problems and fatigue. 
Abiraterone can lead to joint or muscle pain, hypertension, fluid retention, hot flashes, nausea and diarrhea. Enzalutamide side effects may include diarrhea, fatigue, hot flashes and dizziness. Seizures are rare, but possible.[3]

Hormone therapy may be an effective treatment option for some men with prostate cancer, depending on their individual circumstances. Several challenges in hormone therapy treatment remain, however. These include issues involving timing and duration of treatment, whether to combine therapies, androgen resistance, and prevention of side effects.[1]

Talk with your doctor to discuss whether hormone therapy can benefit you.

References

1Publishing, Harvard Health. “Hormone therapy for prostate cancer.” Harvard Health, www.health.harvard.edu/newsletter_article/hormone-therapy-for-prostate-cancer. Accessed 30 Sept. 2017. 
2“Hormone Therapy for Prostate Cancer.” American Cancer Society, www.cancer.org/cancer/prostate-cancer/treating/hormone-therapy.html. Accessed 30 Sept. 2017. 
3“Hormone Therapy for Prostate Cancer.” National Cancer Institute, www.cancer.gov/types/prostate/prostate-hormone-therapy-fact-sheet. Accessed 30 Sept. 2017. 
4“Key Statistics for Prostate Cancer | Prostate Cancer Facts.” American Cancer Society, www.cancer.org/cancer/prostate-cancer/about/key-statistics.html. Accessed 30 Sept. 2017. 
5Namiki, Mikio, et al. “Role of hormonal therapy for prostate cancer: perspective from Japanese experiences.” Translational Andrology and Urology, AME Publishing Company, Sept. 2012, www.ncbi.nlm.nih.gov/pmc/articles/PMC4708248/. Accessed 30 Sept. 2017. 
6“The prostate cancer predicament.” News, 9 Jan. 2014, www.hsph.harvard.edu/news/magazine/the-prostate-cancer-predicament/. Accessed 30 Sept. 2017.

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