Hormone therapy for advanced prostate cancer

The cornerstone of treatment for advanced prostate cancer is medications that shut off the production and activity of male sex hormones (androgens).

Testosterone is the main male sex hormone responsible for masculine features and the development of male reproductive organs. Testosterone also supports the spread of prostate cancer.

Prostate cancer cells are highly dependent on androgens for survival and growth.

Circulation of androgens throughout the body and around cancer cells in the prostate gland encourages the cancer cells to multiply. A way to slow the growth of the cancer is to drastically reduce or cut off the supply of androgens to cancer cells. This weakens the cells and ultimately leads to their death.

Depriving prostate cancer of androgens is known as hormone therapy, or androgen-deprivation therapy (ADT). To decrease androgen levels, two methods may be used: medications or surgical removal of the testicles. The goal of each approach is to:

• Stop the body’s production of male sex hormones (androgens).

• Block androgens in circulation from getting into cancer cells.

Sometimes, a combination approach may be implemented to try to achieve both. Hormone therapy is usually the first line of treatment for men with advanced prostate cancer. Among most men, medications are preferred to surgical removal of the testicles, what’s called orchiectomy.

Hormone therapy is so effective at shrinking tumors that it also may be used in some early-stage prostate cancers, primarily in combination with other treatments such as cryotherapy and radiation therapy. Hormone therapy can reduce the size of large tumors, making it easier for other treatments to destroy them. After more aggressive treatment, hormone therapy also may help kill stray cells left behind at the tumor site. And it may benefit some men in which cancer is found in nearby lymph nodes during prostatectomy surgery.

It’s important to remember, though, that hormone therapy by itself generally isn’t curative. It must be used in combination with another form of treatment to effectively rid the prostate of cancer. In addition, over time the cancer may become resistant to hormone medications, making them ineffective.

Hormone therapy medications

The specific medication your doctor prescribes to treat your cancer will depend on several factors, including how aggressive the cancer is, its current location outside the prostate gland, how widespread it is, whether you’re experiencing symptoms, side effects of the medication and your personal preferences.

GnRH agonists

These medications, called gonadotropin releasing hormone agonists, act by shutting off the brain’s production of a hormone called luteinizing hormone releasing hormone (LHRH). This action halts the manufacture of male sex hormones within the testicles, thereby starving cancer cells.

More than 90% of male hormones, specifically testosterone, are produced by the testicles. GnRH agonists basically set up a chemical blockade, preventing the testicles from receiving messages from the brain to make testosterone. These messages are carried by special brain chemicals.

GnRH agonists are synthetic hormones similar to your brain’s natural messengers. But instead of turning on the chemical switch to activate the message pathway, they turn it off. Your testicles never get the alert to produce testosterone.

GnRH agonists include:

• Goserelin (Zoladex).

• Histrelin (Supprelin LA).

• Leuprolide (Camcevi, Eligard, Fensolvi, Lupron).

• Triptorelin (Trelstar, Triptodur).

The medications are injected into muscle or under the skin. Their effects last for a month to a year, depending on which medication is used. You may receive an injection of a hormone medication for a few months, a few years or the rest of your life, depending on your situation. The most common dosing schedule calls for an injection once every 3 to 6 months.

GnRH antagonists

The medication degarelix (Firmagon) is known as a gonadotropin-releasing hormone (GnRH) antagonist. It also works in the brain, reducing testosterone levels by blocking signals from the brain to the testicles to produce testosterone. This medication acts more rapidly than GnRH agonists. Degarelix may be prescribed to keep the cancer from progressing until other treatments have time to work. Two injections are given initially, then monthly thereafter.

A newer GnRH antagonist called Relugolix (Orgovyx) works in a similar fashion but is available in pill form, making it more convenient to use. Relugolix also has been shown to cause fewer effects on cardiovascular function.

Testicular surgery

Surgically removing the testicles (orchiectomy) to prevent the production of testosterone was once the standard treatment for advanced prostate cancer. Hormone-blocking drugs that produce a similar effect with use of chemicals have greatly reduced the use of this procedure. Today, orchiectomy is rarely performed. You might consider testicular surgery if:

• You can’t tolerate hormone drug therapy for health reasons unrelated to your prostate cancer.

• You aren’t able to take daily medication as prescribed, or regularly visit the doctor’s office for hormone injections.

• There’s an urgent need to eliminate testosterone from the body — more quickly than medications can act.

Orchiectomy is generally performed as an outpatient procedure using local anesthesia. A small incision is made at the center of the scrotum, the pouch that holds the testicles. Each testicle is clipped from the spermatic cord and removed, with most of the cord left in place. Some men have an artificial implant placed into the scrotum during the operation to maintain a more natural appearance. In a variation of this procedure (subcapsular approach), tissue is removed from within each testicle, but the lining and cord structure are left behind, resulting in near-normal appearing testicles.

Benefits and risks

If your cancer has spread beyond the prostate gland, you may benefit from hormone therapy. You also may be a candidate for hormone therapy if you’re receiving radiation therapy for cancer that hasn’t spread (metastasized) beyond the prostate gland.

The advantages of hormone therapy are:

• It can slow the growth of the cancer and shrink tumors, reducing your symptoms and allowing you to live longer.

• When used in conjunction with other treatments, such as radiation therapy, it may weaken cancer cells, improving the effectiveness of other treatments.

• The medications may be stopped temporarily, allowing the return of normal hormone production.

• Newer medications can be taken orally.

Hormone therapy is associated with several side effects. They include:

• Fatigue.

• Weight gain, often as much as 10 to 15 pounds.

• Loss of bone and muscle mass, increasing risk of a bone fracture.

• Loss of sex drive.

• Impotence and erectile dysfunction.

• Hot flashes.

• Mood changes and depression.

• Breast enlargement, potentially requiring low-dose radiation to the chest.

• Liver damage, generally without symptoms.

• Increased risk of heart attack.

• With testicular surgery, a feeling of reduced masculinity.

Because hormone therapy may pose a higher risk of heart attack the first year or two after starting treatment, your doctor should carefully monitor your heart health and aggressively treat other conditions that may predispose you to a heart attack, such as high blood pressure, high cholesterol and smoking.

–By Mayo Clinic Press Editors