Hormonal Therapy for Prostate Cancer

OVERVIEW

Testosterone is a male hormone produced mainly by the testicles. Many organs in the body are composed of cells that respond to or are regulated by exposure to testosterone. Cells in the prostate have testosterone receptors and when exposed to testosterone, are stimulated to grow. When cells that have testosterone receptors become cancerous, the growth of these cancer cells can be increased by exposure to testosterone. The basis of hormone therapy as a treatment for prostate cancer is to block or prevent the cancer cells from being exposed to testosterone. Hormone therapy is primarily cytostatic (it prevents cancer cells from growing) not cytotoxic (kills cancer cells). Chemotherapy and radiation therapy are cytotoxic treatments. There are two methods of delivering hormone therapy: 1) surgical orchiectomy and 2) medical hormone therapy.

ORCHIECTOMY

Bilateral orchiectomy (castration) is surgical operation to remove the testicles. By removing the testicles, the main source of male hormones is removed and hormone levels decrease. Orchiectomy is a common treatment for patients with metastatic (stage IV) prostate cancer who will likely require hormone therapy for life. Patients may experience a benefit in symptoms in a matter of days following surgery.

Orchiectomy can cause side effects such as loss of sexual desire, impotence, hot flashes, weight gain, and bone loss, and may also increase the risk of diabetes and cardiovascular disease.1 The operation itself is relatively safe and not associated with severe complications. Orchiectomy is a convenient and less costly method of hormone therapy; however, it is irreversible.

MEDICAL HORMONE THERAPY

The second method of hormone therapy is to take medicines that reduce exposure to testosterone. Drugs known as LHRH analogues and GnRH antagonists are similar to orchiectomy in that they suppress the production of testosterone. Drugs known as antiandrogens block the effects of testosterone. Female hormones such as estrogens can also reduce male hormone levels, but can also cause serious side effects and are therefore rarely used.

LHRH Analogues: Drugs that act like luteinizing hormone releasing hormone (LHRH) are known as LHRH analogues. These drugs turn off the signal for testosterone production by the testicles. By turning off the signal, hormone levels are reduced and cancer cells are not exposed to male hormones. LHRH analogues are given as a small injection under the skin of the abdomen every month or every three months. These drugs work just as effectively against prostate cancer as bilateral orchiectomy.

LHRH analogues can cause side effects such as loss of sexual desire, impotence, hot flashes and the development of osteoporosis, which increases the risk of bone fractures. These drugs may also increase the risk of diabetes and cardiovascular disease. Because these drugs require an injection every 1 or 3 months, LHRH analogues may not be as convenient as an orchiectomy. Unlike orchiectomy, these drugs can be discontinued, and male hormone levels gradually return to normal.

LHRH analogues may be used to treat patients with any stage of prostate cancer. When first taken, these drugs may increase prostate cancer growth and make a patient’s symptoms worse. This temporary problem is called “tumor flare.” Gradually, these drugs cause hormone deprivation, shrinkage of prostate cancer, and improvement in symptoms. This “tumor flare” can be prevented by taking an antiandrogen medication before LHRH analogues. Antiandrogens are discussed below.

GnRH antagonists: These drugs also turn off the signal for testosterone production by the testicles, but without producing a tumor flare.2 The currently available GnRH antagonist—Firmagon® (degarelix)—is given as a subcutaneous (under-the-skin) injection. Common side effects include injection site reactions, hot flashes, weight gain, fatigue, and increases in certain liver enzymes. GnRH antagonists may also cause bone loss.

Antiandrogens: Not all male hormones are made by the testicles. A small amount of male hormone is made by the adrenal glands, and may not be affected by bilateral orchiectomy or medical castration. An antiandrogen is a medication that can block the effect of the remaining male hormone on prostate cancer cells. Antiandrogens are pills that may be given to patients in addition to orchiectomy or a testosterone-suppressing medication. This combination of treatment is known as total or combined androgen blockade. There is still debate about whether combined androgen blockade is any more effective than surgical or medical castration alone.

Antiandrogens can cause side effects such as loss of sexual desire, diarrhea, enlargement of the breasts and occasional impotence. When used alone, these drugs appear to cause impotence much less often than other forms of hormone therapy. On rare occasion, these drugs can cause liver abnormalities, and blood tests can help detect these problems before serious side effects occur. These drugs can also be discontinued, and male hormone levels gradually return to normal.

WHEN TO START HORMONAL THERAPY

Hormonal therapy is commonly used to treat metastatic prostate cancer (cancer that has spread to other parts of the body) and cancer that has returned or after prior treatment. There is general agreement that men experiencing symptoms from prostate cancer should begin treatment immediately. There has been some disagreement, however, regarding the best time to start hormonal therapy in asymptomatic patients.

Hormonal therapy may also be combined with radiation therapy for men with earlier-stage prostate cancer that is considered locally advanced or high-risk.

STRATEGIES TO IMPROVE TREATMENT

The progress that has been made in the treatment of prostate cancer has resulted from improved development of radiation treatments, surgical techniques, development of hormonal therapies, and participation in clinical trials. Future progress in the treatment of prostate cancer will result from continued participation in appropriate clinical trials.

Intermittent Therapy: Some doctors believe that using medical hormonal therapy intermittently can decrease the cost and reduce the side effects of treatment. When treatment is withheld for a period of time, sexual function and quality of life may improve. It is currently unknown whether intermittent hormonal therapy will provide the same survival benefit as early continuous hormonal therapy.

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