Hormone Therapy

Hormone Therapy Drugs

Drugs used in hormone therapy for prostate cancer inhibit the action or block the production of testosterone and other male hormones. This section discusses LHRH analogs, total androgen blockade and their advantages, disadvantages and side effects; estrogen therapy; testing during and after hormone therapy; intermittent hormone therapy; and adjuvant hormone therapy.

LHRH analogs

The most common drugs used in hormone therapy are called LHRH analogs. LHRH is the acronym for luteinizing hormone-releasing hormone, a hormone produced by the brain, whose purpose is to regulate testosterone production. An analog is a synthetic chemical or drug that behaves similarly to a normal chemical in the body. So an LHRH analog is a drug that behaves very much like LHRH; that is, it regulates the production of testosterone. However, when used on a long-term basis, LHRH analogs suppress testosterone production. LHRH analogs are the chemical equivalent of orchiectomy, resulting in a very low level of testosterone in the body.

LHRH is the first in a series of steps leading to the production of testosterone by the testicles. The brain monitors and regulates testosterone levels in the blood. When the brain detects that testosterone levels have fallen below normal, the brain releases a sequence of hormones, which ultimately signal the testicles to produce more testosterone. Conversely, when the brain detects that the body is producing too much testosterone, it stops sending the signals that stimulate testosterone production.

In the first few days of treatment, LHRH analogs send signals that cause the testicles to increase testosterone production. The brain stops sending signals to stimulate hormone production. This results in low levels of testosterone in the body, similar to those achieved with orchiectomy.

The two most common LHRH drugs are leuprolide acetate (Lupron) and goserelin acetate (Zoladex). Lupron is administered by injection into the muscle of the buttocks monthly, every three months, or every four months. Zoladex comes in pellet form and is injected under the skin of the abdomen monthly or every three months. Lupron and Zoladex injections are administered in a doctor’s office. Men who use LHRH analogs for treatment of advanced disease do so for the rest of their lives.


Advantages of LHRH analogs

LHRH analogs perform the same function as orchiectomy without surgery. The patient needs to get an injection only once every month, three months, or four months.

Disadvantages of LHRH analogs

The shots are required every three to four months and are very expensive. Health insurance may not cover the total cost.


Side effects of LHRH analogs

Most side effects of LHRH analogs are similar to those experienced after orchiectomy and result from the dramatic reduction in the body’s testosterone.

• Diminished libido (sexual desire) occurs in 90 percent of men undergoing hormone therapy.
  
  
• Erectile dysfunction (inability to achieve or maintain an erection adequate for intercourse) occurs in 90 percent of men undergoing hormone therapy.
  
  
• Hot flashes are similar to those experienced by women during menopause. They are characterized by a sudden spread of warmth to the face, neck and upper torso, usually followed by profuse sweating. Although uncomfortable, hot flashes pose no health risk. Their effects may be controlled with medication.
  
  
• Weight gain of 10 to 15 pounds is a common occurrence.
  
  
• Mood swings are common with hormone therapy.
  
  
• Depression may occur with hormone therapy. It may be attributed to a variety of causes, including the treatment itself, reaction to side effects, or other cancer-related issues. Symptoms of depression include feelings of hopelessness, loss of interest in usually enjoyable activities, inability to concentrate and changes in appetite and sleeping patterns. Men experiencing depression are advised to speak to their physician or other member of their health care team about available resources for depression.
  
  
• Fatigue is a feeling of extreme tiredness that may not be alleviated by rest or sleep. It is caused by decreased testosterone production.
  
  
• Anemia is a deficiency of red blood cells in the bloodstream, resulting in reduced oxygen to tissues and organs and feelings of tiredness or weakness. Anemia can be treated with medications, vitamins and minerals.
  
  
• Loss of muscle mass may manifest as decreased strength or weakness. A careful exercise program with progressive weight-bearing activities will improve strength.
  
  
• Osteoporosis, a long-term effect of hormone therapy is a loss of bone mineral density where the bones become thinner, more brittle and at increased risk for breaking. It is the same condition experienced by women in menopause. Osteoporosis can be treated with medications, calcium and vitamin D. An exercise program with progressive weight-bearing activities will also help strengthen bones.

Tumor flare

In the first one to two weeks of treatment, LHRH agonists cause an increase in testosterone production. This increase can cause tumor flare, a serious complication that may occur in men whose prostate cancer has metastasized. The initial testosterone increase can create a temporary increase in tumor growth and cause spinal compression, pain, paralysis, ureteral or bladder outlet obstruction, or a rise in PSA. If spinal metastasis or urinary obstruction is suspected, anti-androgens are given before LHRH analogs to prevent tumor flare.

Total androgen blockade

The testicles produce most, but not all, of the body’s androgens (male hormones). A small amount is produced by the adrenal glands, located on top of the kidneys. Drugs called anti-androgens block the action of the remaining male hormones. When anti-androgens are used in conjunction with LHRH analogs, the result is total androgen blockade.

Experts differ about whether blocking these remaining androgens provides more effective treatment for prostate cancer than LHRH analogs or orchiectomy alone.

The most common anti-androgen medications are flutamide (Eulexin), bicalutamide (Casodex) and nilutamide (Nilandron). All are oral medications administered in pill form. Casodex and Nilandron are taken once a day, Eulexin three times a day. Anti-androgens are expensive – hundreds of dollars a month – and may not be covered by insurance.

• Diarrhea, which occurs with Eulexin only, is the most significant side effect.
  
  
• Breast swelling and tenderness is a less common side effect of LHRH analogs in combination with anti-androgen therapy.
  
  
• Liver damage is a rare side effect of anti-androgens. Liver function is monitored through blood tests to make sure no damage is occurring.
  
  
• Nilandron may cause decreased night vision in some men.
  

Estrogen therapy is the use of the female hormone diethylstilbestrol (DES) to suppress the production of testosterone. Pills are taken one to three times a day. Estrogen therapy was once the primary form of hormone therapy for men with prostate cancer. However, its use has declined due to dangerous side effects, including increased risk of blood clots, heart disease and stroke.

Testing during and after hormone therapy

Intermittent hormone therapy is an experimental approach to limit the side effects of continuous hormone therapy. Patients remain on hormone therapy until blood PSA levels drop to their lowest level and stabilize. The therapy is then stopped temporarily until PSA levels begin to rise. The reasoning behind intermittent hormone therapy is that it prevents prostate cancer cells from building up the resistance they otherwise might with continuous hormone therapy.

Early results of intermittent hormone therapy look promising. Long-term, large-scale studies are needed to determine whether this treatment is more effective than continuous hormone therapy.

Researchers are exploring the effectiveness of adding hormone therapy to primary treatments for locally advanced prostate cancers. These are tumors that have spread locally beyond the prostate but have not metastasized to distant locations.

Adjuvant hormonal therapy is started after radiation or surgery. A recent study found improved survival rates and reduced risk of cancer recurrence when immediate hormone therapy was given to men with cancerous lymph nodes after radical prostatectomy¹ .Other studies indicate that adjuvant hormonal therapy improves overall survival in men who received radiation treatment^2,3.

Studies in neoadjuvant hormonal therapy are looking at whether shrinking the prostate gland prior to surgery or radiation improves survival rates and reduces the risk of cancer progression. Early results indicate that neoadjuvant therapy seems to be more effective with radiation than with surgery.

The long-term effectiveness of adjuvant and neoadjuvant hormonal therapies is not yet known.

1 Messing EM, Manola J, Sarsody M, Wilding G, Crawford ED, Trump D. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med 1999;341:1781-88.

2 Bolla M, Gonzales D, Warde P, et al. Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N Engl J Med 1997;337:295-300.

3 DeWeese TL, Song DY. Current evidence for the role of combined androgen suppression and radiation in the treatment of adenocarcinoma of the prostate. Urology 2000;55:169-174.

The Prostate Cancer pages of this Web site are part of the Comprehensive Prostate Cancer Awareness Program (CPCAP), a major regional effort to reduce the rates of death and illness caused by prostate cancer in southwestern Pennsylvania. Funding for CPCAP is provided by a grant from the Commonwealth of Pennsylvania.

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