Feature Archive

Hormone Therapy for Prostate Cancer

By R. Morgan Griffin
WebMD Feature

Reviewed By Charlotte Grayson

Hormone therapy for prostate cancer has come a long way in the past few decades. Not so long ago, the only hormonal treatment for this disease was drastic: an orchiectomy, the surgical removal of the testicles.

Now we have a number of medications -- available as pills, injections, and implants -- that can give men the benefits of decreasing male hormone levels without irreversible surgery.

"I think hormonal therapy has done wonders for men with prostate cancer," Stuart Holden, MD, Medical Director of the Prostate Cancer Foundation.

Hormone therapy for prostate cancer does have limitations. Right now, it's usually used only in men whose cancer has recurred or spread elsewhere in the body.

But even in cases where removing or killing the cancer isn't possible, hormone therapy can help slow down cancer growth. Though it isn't a cure, hormone therapy for prostate cancer can help men with prostate cancer feel better and add years to their lives.

On average, hormone therapy can stop the advance of cancer for two to three years. However, it varies from case to case. Some men do well on hormone therapy for much longer.

What Is Hormone Therapy?

The idea that hormones have an effect on prostate cancer is not new. The scientist Charles Huggins first established this over 60 years ago in work that led to his winning the Nobel Prize. Huggins found that removing one of the main sources of male hormones from the body -- the testicles -- could slow the growth of the disease.

"This procedure worked dramatically," says Holden, who is also director of the Prostate Cancer Center at Cedar Sinai Medical Center in Los Angeles. "Before, these men were confined to bed and wracked with pain. Almost immediately afterwards, they improved."

Huggins found that some types of prostate cancer cells need certain male hormones -- called androgens -- to grow. Androgens are responsible for male sexual characteristics, like facial hair, increased muscle mass, and a deep voice. Testosterone is one kind of androgen. About 90% to 95% of all androgens are made in the testicles, while the rest are made in the adrenal glands located on top of the kidneys.

How Does Hormone Therapy Work?

Hormone therapy for prostate cancer works by either preventing the body from making these androgens or by blocking their effects. Either way, the hormone levels drop, and the cancer's growth slows.

"Testosterone and other hormones are like fertilizer for cancer cells," Holden tells WebMD. "If you take them away, the cancer goes into shock, and some of the cells die."

In 85% to 90% of cases of advanced prostate cancer, hormone therapy can shrink the tumor.

However, hormone therapy for prostate cancer doesn't work forever. The problem is that not all cancer cells need hormones to grow. Over time, these cells that aren't reliant on hormones will spread. If this happens, hormone therapy won't help anymore, and your doctor will need to shift to a different treatment approach.

What Types of Hormone Therapy Are There?

There are two basic kinds of hormone therapy for prostate cancer. One class of drugs stops the body from making certain hormones. The other allows the body to make these hormones, but prevents them from attaching to the cancer cells. Some doctors start treatment with both drugs in an effort to achieve a total androgen block. This approach goes by several names: combined androgen blockade, complete androgen blockade, or total androgen blockade.

Here's a rundown of the techniques.

  • Luteinizing hormone-releasing hormone agonists (LHRH agonists.) These are chemicals that stop the production of testosterone in the testicles. Essentially, they provide the benefits of an orchiectomy for men with advanced prostate cancer without surgery. This approach is sometimes called "chemical castration." However, the effects are fully reversible if you stop taking the medication.

    Most LHRH agonists are injected every one to four months. Some examples are Lupron, Trelstar, Vantas, and Zoladex. A new drug, Viadur, is an implant placed in the arm just once a year.

    Side effects can be significant. They include: loss of sex drive, hot flashes, development of breasts (gynecomastia) or painful breasts, loss of muscle, weight gain, fatigue, and decrease in levels of "good" cholesterol.

    Plenaxis is a drug that's similar to LHRH agonists. However, because it can cause serious allergic reactions, it's not used that often.

  • Anti-androgens. LHRH agonists and orchiectomies only affect the androgens that are made in the testicles. Thus they have no effect on the 5% to 10% of a man's "male" hormones that are made in the adrenal glands. Anti-androgens are designed to affect the hormones made in the adrenal glands. They don't stop the hormones from being made, but they stop them from having an effect on the cancer cells.

    The advantage of anti-androgens is that they have fewer side effects than LHRH agonists. Many men prefer them because they are less likely to diminish libido. Side effects include tenderness of the breasts, diarrhea, and nausea. These drugs are also taken as pills each day, which may be more convenient than injections. Examples are Casodex, Eulexin, and Nilandron.

    In some cases, starting treatment with an LHRH agonist can cause a "tumor flare," a temporary acceleration of the cancer's growth due to an initial increase in testosterone before the levels drop. This may cause the prostate gland to enlarge, obstructing the bladder and making it difficult to urinate. It's believed that starting with an anti-androgen drug and then switching to an LHRH agonist can help avoid this problem. In patients with bone metastases, this "flare" can lead to significant complications such as bone pain, fractures, and nerve compression.

    Strangely, if treatment with an anti-androgen doesn't work, stopping it may actually improve symptoms for a short time. This phenomenon is called "androgen withdrawal," and experts aren't sure why it happens.

  • Combined Androgen Blockade. This approach combines anti-androgens with LHRH agonists or an orchiectomy. By using both approaches, you can cut off or block the effects of hormones made by both the adrenal glands and the testicles. However, using both treatments can also increase the side effects. An orchiectomy or an LHRH agonist on its own can cause significant side effects like a loss of libido, impotence, and hot flashes. Adding an anti-androgen can cause diarrhea, and less often, nausea, fatigue, and liver problems.

  • Estrogens. Some synthetic versions of female hormones are used for prostate cancer. In fact, they were one of the early treatments used for the disease. However, because of their serious cardiovascular side effects, they're not used as often anymore. J. Brantley Thrasher, MD, a spokesman for the American Urological Association and chairman of urology at the University of Kansas Medical Center, says they're usually used only after initial hormone treatments have failed. Examples of estrogens are DES (diethylstilbestrol), Premarin, and Estradiol.

  • Other Drugs. Proscar (finasteride) is another drug that indirectly blocks an androgen that helps prostate cancer cells grow. Depending on the case, doctors sometimes use other anticancer drugs like Nizoral (ketoconazole) and Cytadren (aminoglutethimide.)

  • Orchiectomy. The surgical removal of the testicles was the earliest form of hormone therapy for prostate cancer. However, the procedure is permanent. As with LHRH agonists, side effects can be significant. They include: Loss of sex drive, hot flashes, development of breasts (gynecomastia) or painful breasts, loss of muscle, weight gain, fatigue, and decrease in levels of "good" cholesterol.

    "Since we have other options, orchiectomies really aren't done very much anymore," says Holden.



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