HORMONE THERAPY FOR PROSTATE CANCER

Hormone therapy for prostate cancer is the term used to describe the application of a number of pharmacologic agents (drugs) to reduce testosterone in the male to very low levels. But how can decreasing the activity of natural androgens—sex hormones like testosterone—curb symptoms or even shrink a tumor? The summary below should help explain how hormonal therapy can control localized prostate cancer tumors and even control those that have spread to other parts of the body.

What are androgens?
Androgens is the term used to describe a group of male sex hormones responsible for characteristics such as facial hair, a deepened voice and increased muscle bulk. They come from two sources: the testicles (accounting for 90 to 95 percent of the male hormones) and the adrenal glands that produce several other androgens (accounting for 5 to 10 percent of male hormones).

Testosterone is the most potent of these androgens. It is the product of a controlled process that begins when the hypothalamus, a cherry-sized control mechanism in the brain, releases a substance called luteinizing hormone-releasing hormone (LH-RH). It, in turn, stimulates the pituitary gland, also located in the brain, to manufacture and secrete luteinizing hormone (LH). Lutinizing hormone activates the testicles to produce testosterone.

What causes prostate cancer?
The prostate may be no bigger than a walnut, but it is a major male sex gland. It facilitates reproduction along with another sex gland, the seminal vesicles, by providing the fluid necessary for successful transport of sperm from the testicle to the urethra via a tube system called the ejaculatory duct.

Prostate cancer occurs when abnormal cells, supported by male hormones such as testosterone, begin to grow uncontrollably to form tumors. Since prostate cancer frequently produces no symptoms in its earliest stages, a man may only become aware of the cancer during routine screening. The tumor eventually interferes with normal bladder and sexual function, producing both ejaculatory and urinary problems.

Diagnosis can be made using any or all of a variety of tests: digital rectal examination (DRE), prostate-specific antigen (PSA), biopsy, X-ray and other imaging techniques such as transrectal ultrasound andCT scan. But the most important and productive methods for early detection are the prostate exam (DRE) and the PSA blood test . As men age, the risk for prostate cancer increases. Other known risk factors are African-American ancestry and a family history of prostate cancer.

What is hormone therapy for prostate cancer?
If detected early, prostate cancer is curable. Treatment options are based on the stage and grade of the disease. Surgical removal and radiation treatment are the most frequently applied therapies. The decision for one or the other involves a thorough discussion of the pros and cons of each. When the prostate cancer is more advanced, and has spread to other parts of the body, treatment includes reducing the testosterone (male hormone) that supports the prostate and its tumors. Hormone therapy reduces symptoms and prevents further growth. While hormonal manipulation causes prostate cancer to shrink in 85 to 90 percent of a prostate cancer patients, total and durable eradication of disease is unlikely.

Scientists believe that prostate cancer contains genetically different cells, some of which may respond to hormone deprivation, while others do not. It is those androgen-insensitive cells that scientists believe eventually grow, reproduce and ultimately cause disease progression. The good news is that hormone therapy may control prostate cancer for many years.

Hormone therapy, or as it is sometimes called androgen deprivation is achieved by either surgery or medication. Testosterone can be reduced by removing the testes the operation is called a bilateral orchiectomy. It involves surgically opening the scrotum, and freeing blood vessels and nerves before cutting the testicles away from surrounding tissue. The other commonly used option, however, is chemical castration—injecting synthetic LH-RH analogs every three to four months to suppress the natural production of testosterone.

An additional option focuses on interfering with the effects of both adrenal hormones and testicular testosterone. Referred to as complete androgen blockade (CAB), this treatment choice combines anorchiectomy or LH-RH analogist with anti-androgens. Anti-androgens block the effects of adrenal gland hormones as well as testicular androgens by interfering with a receptor in the nucleus of the prostate cancer cell. These medications include flutamide, bicalutamide and nilutamide. Some urologists add a third drug, finasteride, which blocks the conversion of testosterone to a more potent androgen, dihydrosterstosterone (DHT). In doing so, it deprives the cancer cells of an element needed for growth. Using a number of medications, attempts to nullify as much as possible all male hormone affect on prostate cancer cells.

How effective is hormone therapy for prostate cancer?
While scientists and urologists agree on many aspects of hormone deprivation in the treatment of prostate cancer, there is still controversy concerning when and how to use these options. For instance, research continues in the debate over:

Monotherapy vs. complete androgen blockade (CAB): CAB has not yielded dramatic increases in survival for advanced prostate cancer but there is evidence that it may be more advantageous than monotherapy. This should be discussed between the patient and his urologist.

Early vs. late hormonal deprivation: Research has not provided a clear indication that early, compared to delayed, hormonal therapy improves survival. There is little argument, however, that a person with prostate cancer that has distant spread (e.g. to their bones) should be treated promptly to prevent potentially crippling effects like bone fractures and spinal cord paralysis. There is also evidence that prostate cancer patients whose disease has spread to the lymph nodes will encounter prolonged progressive-free survival and a better quality of life with early hormonal therapy. In fact, research suggests that men suffering from prostate cancer that has spread without symptoms experience fewer serious complications if they undergo hormonal therapy earlier, rather than later.

Continuous vs. intermittent androgen deprivation: The current hormonal therapy standard of care is, once initiated, to continue hormone therapy for life. In fact, most physicians prescribe testosterone-suppressing therapy even after other second-line hormonal agents or chemotherapiesare introduced. Recent research has focused on intermittent androgen deprivation (IAD). Alternating cycles of hormone therapy possibly inhibit the molecular pathways that allow cells to escape or modal control. The idea is that by stopping and starting therapy, IAD delays that transformation and may improve quality of life. But until a large current randomized National Cancer Institute trial yields its findings, scientists will not know which method of administration offers patients the best survival with the least complications—IAD or continuous hormonal therapy.

What can be expected after hormone therapy for prostate cancer?
While hormonal therapy can put your cancer in check, there are unpleasant side effects: nausea and vomiting, hot flashes, anemia, lethargy, osteoporosis, swollen and tender breasts and erectile dysfunction.

Also, if your cancer is resistant to hormonal treatments, your doctor may order chemotherapy, which consists of single drugs or a cocktail of several medications aimed at killing the cancer cells, even though this regimen causes numerous side effects.

Evidence indicates that hormonal treatment when combined with radiation increases survival duration.

Frequently asked question:

Can prostate cancer be cured with hormonal therapy?

The future is bright with regard to new agents that can deliver hormone therapy more effectively. A number of agents are now being tested in clinical trials and soon will be positioned for FDA approval. They are more reliable and reducing the effect of androgens in the blood and tissue and do so with few added side effects.

Where can I get more information?

Know Your Stats About Prostate Cancer Treatment Options: Hormonal Therapy

Hormone Health Network’s Osteoporosis and Men’s Health Fact Sheet.