This page discusses the use of hormonal therapy for the treatment of prostate cancer. For a thorough review of hormonal therapy, please see the ]]>hormonal therapy treatment monograph]]> .

Hormones are chemical messengers that regulate specific body functions. They are produced by various glands in the body and enter the blood stream, where they travel to other tissues and exert their influence. Hormonal therapy is used in cancer treatment to augment or interfere with the activity of certain hormones that can influence the growth of tumors.

How Hormonal Therapy Works for Prostate Cancer

Prostate cancer, at least until its late stages, almost always requires male hormones (androgens, such as testosterone) in order to survive and grow. The aim of hormonal therapy is to reduce the amount of male hormones in your body or block their effects, so that prostate cancer cells are not stimulated to grow, or may even die.

Androgen levels can be lowered either with surgical removal of the testicles or with injections of medicines called LHRH agonists. Hormonal therapies may sometimes be combined to achieve greater effects.

  • Eventually, despite lowering the testosterone level, the prostate cancer will begin to grow again. At that point, so-called “second-line” hormonal treatments may be recommended. These include ketoconazole and female hormones. These treatments have more side effects and are effective in a lower percentage of patients.
  • With time, the disease can progress to the point where all hormonal treatments lose their effectiveness. This is known as androgen-independent or hormone-refractory prostate cancer. At that point, treatment options include care to manage the side effects of prostate cancer and its treatment, radiation therapy to control symptoms, chemotherapy, or experimental therapies in a clinical trial.

When Hormonal Therapy is Most Beneficial

In general, hormone treatments do not have the potential to cure prostate cancer but they can suppress its growth in a large majority of patients, sometimes for years. Eventually, however, the prostate cancer will begin to grow again despite the absence of androgens. Therefore, surgery or radiation are usually recommended as first-line, potentially curative treatments for patients who have no evidence of spread of their cancer to other parts of their bodies.

For patients who do have evidence of spread to lymph nodes, bones, or other locations, or whose prostate cancer returns at some point after surgery or radiation, hormonal therapies are often recommended to suppress the disease and reduce symptoms. These treatments can be very effective at reducing pain from spread of the cancer to the bones, which is very common in prostate cancer. Hormonal therapies can also prevent the progression of the disease for a period of time that varies greatly from one patient to the next, but can often be measured in years.

Types of Hormonal Therapies

Hormonal therapy may be achieved through drugs or surgery.

Surgery for Hormonal Therapy

Surgical removal of the testicles ( ]]>orchiectomy]]> ) can lead to a reduction in androgens.

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Luteinizing Hormone-releasing Hormone (LHRH) Analogs (also called Partial Agonists)

Common names include:

  • Leuprolide (Lupron)
  • Goserelin (Zoladex)

These medications decrease the production of the male hormone, testosterone, from the testicles. These medications are given by injection into a muscle (intramuscularly) or under the skin (subcutaneously). They are available in long-acting formulations that can be given once every three months.

Patients with liver or heart disease, seizures, problems with blood clots, or diabetes should inform their doctor before using leuprolide. Patients with depression or hypertension should inform their doctor before using goserelin.

Within the first several weeks of starting these medications, a brief increase in testosterone—called the “flare effect"—may occur, resulting in an increase in pain and other symptoms. To avoid the flare effect, other medications (anti-androgens) may be given at the same time. Anti-androgens are also given to increase the effectiveness of LHRH analogs.

Possible side effects of LHRH analogs include the following:

  • Impotence
  • Hot flashes
  • Loss of sexual desire
  • Osteoporosis
  • Fatigue
  • Anemia

Anti-androgens

Common names include:

  • Flutamide (Eulexin)
  • Bicalutamide (Casodex)
  • Nilutamide (Nilandron)

Anti-androgens prevent your body from using the male hormones (androgens) that are made by your body. These medications are given by mouth. Patients with kidney, liver, or heart disease should inform their doctor before starting these medications.

Possible side effects of anti-androgens include the following:

  • Nausea
  • Vomiting
  • Diarrhea
  • Breast growth or tenderness
  • Increased sensitivity to sunlight (photosensitivity)
  • Anemia
  • Interference with sperm production
  • Decreased sex drive

Androgen Suppressants

Common name: ketoconazole (Nizoral)

Ketoconazole blocks the production of androgens from the adrenal gland. It is considered a second-line hormonal treatment, and is usually used when other medications are not working. It is taken as a pill, usually with a citrus juice to improve its absorption into the body. Patients on ketoconazole are usually given a steroid hormone pill along with it, since their bodies’ normal production of steroid hormones is reduced by ketoconazole.

Patients with kidney or liver disease, or a sensitivity to sulfites, should inform their doctor before starting this medication. Furthermore, ketoconazole has a long list of drugs with which it can interact adversely; make sure that your doctor reviews your list of medications before starting this treatment.

With long-term use, ketoconazole may cause liver problems.

Possible side effects of ketoconazole include the following:

  • Nausea, vomiting
  • Diarrhea
  • Abdominal pain
  • Headache, dizziness
  • Skin rashes, itching
  • Blood disorders

Female Hormones

Common name: diethylstilbestrol (estrogen)

Female hormones have a dampening effect on the production of male hormones. They are usually given by pill, but may occasionally be administered via intravenous injection.

Patients with congestive heart disease, problems with blood clotting, diabetes, high blood pressure, or high blood fats should inform their doctor before using this type of medication.

These medicines are used infrequently due to the risk of blood clots and heart attacks. Diethylstilbestrol is not currently being manufactured for commercial use in the United States.

Possible side effects of diethylstilbestrol include the following:

  • Nausea, vomiting
  • Shrinking testicle size (testicular atrophy)
  • Increase breast growth (gynecomastia)
  • Headache
  • Heart attack
  • Blood clots in the lungs
  • Stroke

Surgery for Hormonal Therapy – Orchiectomy

Orchiectomy is the removal of the testicles, which are the major producers of male hormones in the body. The surgeon removes the testicles through an incision in the skin of the scrotum.

Orchiectomy is considered a type of hormonal therapy. Prescription hormonal therapies are available as alternatives to orchiectomy. The only reason a surgeon will recommend an orchiectomy or injectable (or oral) hormones is when the prostate cancer is particularly large, involves the lymph nodes, or has spread beyond the pelvis. This treatment should not be offered for early stage cancer; in fact, this surgery is usually reserved for patients with metastatic prostate cancer. In patients with metastases, orchiectomy can be quite effective in reducing symptoms and suppressing the cancer, although it is not curative.

Orchiectomy causes impotence and reduced sexual desire, as well as decreased muscle mass, hot flashes, breast tenderness, and osteoporosis. Furthermore, orchiectomy can be very difficult psychologically.

For more information on hormonal therapy, please see the hormonal therapy treatment monograph]]> .