Androgen ablation therapy is a well established form of treatment for various stages of prostate cancer. Also known as hormone deprivation therapy, the intent of a therapy using androgen ablation is to slow the growth of prostate cancer by removing male, or androgen, hormones, such as testosterone, because these hormones stimulate the growth of cancerous cells.
If you are considering ablation androgen therapy, your doctor will most likely tell you that, while it can be used as primary form of treatment in selected cases, ablation therapy is most effective when used in combination with other more definitive measures, such as radical prostatectomy (surgery), cryosurgery, and radiation therapy. Studies have suggested that pre-treatment with androgen ablation therapy can lead to a better long-term outcome for the other prostate cancer therapies.
Why Androgen Ablation Therapy Is Effective
Androgens are made primarily made in the testicles, with a small amount produced in the adrenal glands (located above each kidney). Androgens, especially testosterone, are responsible for male features that appear after you go through puberty, such as male hair patterns, a lower voice, and male libido. They are also responsible for the development and growth of your prostate gland. When testosterone is present, it attaches to the receptors of both normal and cancerous prostate cells and stimulates them to grow, which is why removing the hormone through androgen ablation therapy is so effective.
To understand ablation therapy, you first need to understand how your body maintains a tight control over your testosterone levels. There are other hormones created in a small area in your brain, or the hypothalamus, which act like a monitoring and maintenance system for levels of androgen. Hormone therapy focuses on this system.
Similar to a thermostat, your hypothalamus senses when testosterone levels are too high or too low. If it senses your testosterone too low, your hypothalamus causes a chain reaction, starting with the production of what is called a luteinizing hormone-releasing hormone (LHRH). This hormone causes the pituitary gland at the base of your brain to release another hormone called luteinizing hormone (LH). LH then travels through the bloodstream to the testicles, where it stimulates them to make more testosterone, which in turn travels to other parts of the body, such as the prostate, where prostate cells, both normal and cancerous, are then stimulated to grow. The principle behind androgen ablation therapy is to interrupt or prevent this chain reaction.
The Three Main Methods of Androgen Ablation Therapy
There are several methods of ablation therapy. The three main androgen hormonal therapy options are:
- Orchiectomy- Surgical castration is the original and most direct approach of ablation therapy. This method eliminates any access to testosterone by prostate cancer cells. Performed as an outpatient procedure, you are able to go home several hours later. If you opt for this androgen ablation therapy, you will be put under anesthesia while your doctor makes a small incision, about 1 to 2 inches long, in front of your scrotum. The testicles are then removed through this incision, and the blood vessels clamped and sutured.
-
LHRH Analog – A third method of ablation therapy reduces testosterone by cutting off the luteinizing hormones (LH) that stimulate the testicles to produce testosterone. As you may recall from earlier, LH is produced as part of the chain reaction that is started in the hypothalamus. When the pituitary gland gets the message from the hypothalamus that testosterone (androgen) levels are low, it sends LH to the testicles to make more of the androgen. This ablation therapy uses drugs called luteinizing hormone –releasing hormone (LHRH) agonists and antagonists to fool the hypothalamus ’ monitoring system into sensing that there is no need for additional testosterone. As a result, the pituitary gland does not send LH to the testicles to produce testosterone, thereby cutting of the prostate cancer cells ability to thrive and grow. In this ablation therapy process, LHRH antagonists and agonists are administered by injection, usually in the buttock, either once a month or every 3 months. Leuprolide (lupron) and goserelin (Zoladex) are examples of LHRH agonists, and abarleix (Plenaxis) is an example of an LHRH antagonist. Lupron can be injected every 4 months. Viadur, which is a different formulation of leuprolide, is implanted under the skin and lasts for a year. Abarelix given only to men who cannot take the other drugs because of serious side effects, but the results are the same.
-
Androgen Blockade - This androgen ablation therapy method uses drugs, or antiandrogens, to block testosterone from reaching prostate cancer cells. Some experts believe that antiandrogens are more effective at keeping prostate cancer in check than orchiectomy or LHRH analog injections. Examples of antiandrogens are bicalutamide (Casodex) and flutamide (Eulexin).
There are other types of androgen ablation therapy, such as the taking estrogens (female hormones), and drugs, such ketoconozole and aminoglutehamide, which affect the adrenal glands. Although lesser known, such hormonal therapies are often reserved for men whose prostate cancers are no longer responding to the other, main ablation therapy options.
The Side Effects of Androgen Ablation Therapy
There is no question that ablation therapy has the potential for serious side effects. If you are considering a therapy using androgen ablation, you should discuss with your doctor the complications and side effects that may arise from prolonged hormonal treatment. The most significant side effects to consider are the following:
- Decreased sexual desire – One of the most prominent side effects of ablation therapy is the elimination of a man’s libido, or sex drive. Although most men lose their desire and interest for sexual activity, they are still able foster and maintain loving and nurturing with their spouses or partners.
- Erectile Dysfunction – Difficult obtaining and maintaining an erection occurs in almost all men who undergo androgen ablation therapy, especially in those men who undergo orchiectomy or LHRH analog treatment. Impotence appears less frequently in men undergoing androgen blockade, especially in the first few months of their treatment when they are still producing testosterone.
- Hot Flashes – The most common complaint from men undergoing androgen ablation therapy is hot flashes, sometimes called hot flushes. These sudden rushes of body heat cause reddening and sweating. About 10% to 15% of men receiving androgen hormone therapy injections experience this side effect, while those who undergo orchitectomy experience it less. Similar to the hot flashes experienced by women going through menopause, they vary from mild flushing to drenching perspiration and may last from a minute to an hour. In most men, hot flashes seem to come and go. They may gradually become less frequent and less overwhelming and disabling. For most men who undergo ablation therapy, these hot flashes are a minor nuisance. However, for a few men, they can be quite severe and bothersome. Some men take soy to help alleviate these symptoms, although there are no definitive medical studies that have proven its effectiveness in reducing the frequency or intensity of hot flashes. Drugs such as megestrol (Megace), low-dose estrogen compounds, venlafaxine (Effexor), gabapetin (Neurontin) and paxoxetine (Paxil) may provide relief.
- Breast Enlargement or Tenderness - Breast tenderness and fullness can occur in some men after starting ablation therapy. In many cases, these side effects eventually go away. They occur in approximately a third of men undergoing androgen ablation therapy. They appear more common in men who undergo the ablation therapy using antiandrogens alone (or an androgen blockade) or with other drugs such as finasteride (Proscar), and especially after being on the antiandrogen for several months. Men who undergo orchiectomy and LHRH analog therapies do not commonly experience these side effects. Some doctors believe these side effects be prevented by small doses of radiation to the breast before treatment starts.
- Osteoporosis –Long-term hormonal therapy with a LHRH analog or orchiectomy sometimes results in decreased muscle mass and strength, which can accelerate the loss of bone mineral density and lead to osteoporosis, or bone thinning and weakness. Men who expect to undergo hormone therapy for several years should have baseline bone mineral density scan. Osteoporosis is one of the most serious side effects of ablation therapy. Its incidence in men, who have had some form of androgen ablation therapy, increases with time. Studies have shown that men on ablation therapy loses 8% to 10% of their bone mass in the first 2 years of treatment, then approximately 2% per year thereafter. Because of this about 20% of men who are on long-term hormone treatment, or ablation therapy, experience a bone fracture within five years. To minimize this side effect, most doctors recommend regular exercise along with calcium and vitamin D supplements. Intermittent hormonal therapy may also lessen or eliminated these side effects. Your doctor may also prescribe medications called bisphosphonates to help counterbalance the effects of ablation therapy and rebuild bones.
- Fatigue – Approximately half of men undergoing ablation therapy, particularly men who receive LHRH treatments, experience fatigue and weakness. The cause may be a loss of muscle mass or anemia, both of which may be from the androgen hormone therapy. Regular exercise can help in both cases.
- Worsening of Cancer Symptoms – With ablation therapy using LHRH analog, when the drugs are first introduced into the body, they produce a brief outpouring of testosterone that can temporarily worsen prostate cancer symptoms. This can be a serious issue, especially if the prostate cancer has begun to spread into the bones. Referred to as a flair, this temporary worsening of symptoms can be blocked by first undergoing antiandrogen treatments for at least a week, before the first injection of LHRH drugs.
- Other side effects –Other side effects of ablation therapy that can occur are weight gain (particularly in around the mid-section), elevation of cholesterol, diarrhea (with flutamide), impairment of night vision (with nilutamide) and increased moodiness or depression. Men on androgen ablation therapy may find relief from some of these side effects with regular exercise and a balanced diet.
