- How is prostate cancer treated?
- Expectant management, watchful waiting, and active surveillance for prostate cancer
- Surgery for prostate cancer
- Radiation therapy for prostate cancer
- Cryosurgery for prostate cancer
- Hormone (androgen deprivation) therapy for prostate cancer
- Chemotherapy for prostate cancer
- Vaccine treatment for prostate cancer
- Preventing and treating prostate cancer spread to bones
- Clinical trials for prostate cancer
- Complementary and alternative therapies for prostate cancer
- Considering prostate cancer treatment options
- Initial treatment of prostate cancer by stage
- Following PSA levels during and after treatment
- Prostate cancer that remains or recurs after treatment
- More prostate cancer treatment information
Hormone (androgen deprivation) therapy for prostate cancer
Hormone therapy is also called androgen deprivation therapy (ADT) or androgen suppression therapy. The goal is to reduce levels of male hormones, called androgens, in the body, or to stop them from affecting prostate cancer cells.
The main androgens are testosterone and dihydrotestosterone (DHT). Most of the body’s androgens come from the testicles, but the adrenal glands also make a small amount. Androgens stimulate prostate cancer cells to grow. Lowering androgen levels or stopping them from getting into prostate cancer cells often makes prostate cancers shrink or grow more slowly for a time. But hormone therapy alone does not cure prostate cancer.
Hormone therapy may be used:
- If the cancer has spread too far to be cured by surgery or radiation, or if you can’t have these treatments for some other reason
- If your cancer remains or comes back after treatment with surgery or radiation therapy
- Along with radiation therapy as initial treatment if you are at higher risk of the cancer coming back after treatment (based on a high Gleason score, high PSA level, and/or growth of the cancer outside the prostate)
- Before radiation to try to shrink the cancer to make treatment more effective
Several types of hormone therapy can be used to treat prostate cancer. Some lower the levels of testosterone or other androgens (male hormones). Others block the action of those hormones.
Treatments to lower androgen levels
Orchiectomy (surgical castration)
Even though this is a type of surgery, its main effect is as a form of hormone therapy. In this operation, the surgeon removes the testicles, where most of the androgens (testosterone and DHT) are made. With this source removed, most prostate cancers stop growing or shrink for a time.
This is done as an outpatient procedure. It is probably the least expensive and simplest way to reduce androgen levels in the body. But unlike some of the other methods of lowering androgen levels, it is permanent, and many men have trouble accepting the removal of their testicles.
Some men having the procedure are concerned about how it will look afterward. If wanted, artificial silicone sacs can be inserted into the scrotum. These look much like testicles.
Luteinizing hormone-releasing hormone (LHRH) analogs
These drugs lower the amount of testosterone made by the testicles. Treatment with these drugs is sometimes called chemical castration or medical castration because they lower androgen levels just as well as orchiectomy.
Even though LHRH analogs (also called LHRH agonists or GnRH agonists) cost more than orchiectomy and require more frequent doctor visits, most men choose this method. These drugs allow the testicles to remain in place, but the testicles will shrink over time, and they may even become too small to feel.
LHRH analogs are injected or placed as small implants under the skin. Depending on the drug used, they are given anywhere from once a month up to once a year. The LHRH analogs available in the United States include leuprolide (Lupron®, Eligard®), goserelin (Zoladex®), triptorelin (Trelstar®), and histrelin (Vantas®).
When LHRH analogs are first given, testosterone levels go up briefly before falling to very low levels. This effect is called flare and results from the complex way in which LHRH analogs work. Men whose cancer has spread to the bones may have bone pain. If the cancer has spread to the spine, even a short-term increase in tumor growth as a result of the flare could compress the spinal cord and cause pain or paralysis. Flare can be avoided by giving drugs called anti-androgens for a few weeks when starting treatment with LHRH analogs. (Anti-androgens are discussed further on.)
Degarelix is an LHRH antagonist. LHRH antagonists work like LHRH agonists, but they reduce testosterone levels more quickly and do not cause tumor flare like the LHRH agonists do.
This drug is used to treat advanced prostate cancer. It is given as a monthly injection under the skin. The most common side effects are problems at the injection site (pain, redness, and swelling) and increased levels of liver enzymes on lab tests. Other side effects are discussed in detail below.
Drugs such as LHRH agonists can stop the testicles from making androgens, but other cells in the body, including prostate cancer cells themselves, can still make small amounts, which can fuel cancer growth. Abiraterone blocks an enzyme called CYP17, which helps stop these cells from making androgens.
Abiraterone can be used in men with advanced castrate-resistant prostate cancer (cancer that is still growing despite low testosterone levels from an LHRH agonist, LHRH antagonist, or orchiectomy). Abiraterone has been shown to shrink or slow the growth of some of these tumors and help some of these men live longer.
This drug is taken as pills every day. This drug doesn’t stop the testicles from making testosterone, so men who haven’t had an orchiectomy need to continue treatment with an LHRH agonist or antagonist. Because abiraterone also lowers the level of some other hormones in the body, prednisone (a cortisone-like drug) needs to be taken during treatment as well to avoid certain side effects.
Drugs that stop androgens from working
Androgens have to bind to a protein in the cell called an androgen receptor to work. Anti-androgens are drugs that bind to these receptors so the androgens can’t.
Drugs of this type, such as flutamide (Eulexin®), bicalutamide (Casodex®), and nilutamide (Nilandron®), are pills taken daily.
Anti-androgens are not often used by themselves in the United States. An anti-androgen may be added to treatment if orchiectomy, an LHRH analog, or LHRH antagonist is no longer working by itself. An anti-androgen is also sometimes given for a few weeks when an LHRH analog is first started to prevent a tumor flare.
Anti-androgen treatment can be combined with orchiectomy or an LHRH analog as first-line hormone therapy. This is called combined androgen blockade (CAB). There is still some debate as to whether CAB is more effective in this setting than using orchiectomy or an LHRH analog alone. If there is a benefit, it appears to be small.
Some doctors are testing the use of anti-androgens instead of orchiectomy or LHRH analogs. Some studies have found no difference in survival rates, but others have found anti-androgens to be slightly less effective.
In some men, if an anti-androgen is no longer working, simply stopping the anti-androgen can cause the cancer to stop growing for a short time. Doctors call this the anti-androgen withdrawal effect, although they are not sure why it happens.
This drug is a newer type of anti-androgen. When androgens bind to the androgen receptor, the receptor sends a signal to the cell’s control center, telling it to grow and divide. Enzalutamide blocks this signal.
In men with castrate-resistant prostate cancer, enzalutamide can lower PSA levels, shrink or slow the growth of tumors, and help the men live longer.
Enzalutamide is taken as pills each day. In studies of this drug, men stayed on LHRH agonist treatment, so it isn’t clear how helpful this drug would be in men with non-castrate levels of testosterone.
Other androgen-suppressing drugs
Estrogens (female hormones) were once the main alternative to orchiectomy for men with advanced prostate cancer. Because of their possible side effects (including blood clots and breast enlargement), estrogens have been largely replaced by LHRH analogs and anti-androgens. Still, estrogens may be tried if other types of hormone therapy are no longer working.
Ketoconazole (Nizoral®), first used for treating fungal infections, blocks production of certain hormones, including androgens, similarly to abiraterone. It is most often used to treat men just diagnosed with advanced prostate cancer who have a lot of cancer in the body, as it offers a quick way to lower testosterone levels. It can also be tried if other forms of hormone therapy are no longer working.
Ketoconazole also can block the production of cortisol, an important steroid hormone in the body. People treated with ketoconazole often need to take a corticosteroid (like hydrocortisone) to prevent the side effects caused by low cortisol levels.
Possible side effects of hormone therapy
Orchiectomy, LHRH analogs, and LHRH antagonists can all cause similar side effects due to changes in the levels of hormones such as testosterone and estrogen. These side effects can include:
- Reduced or absent libido (sexual desire)
- Impotence (erectile dysfunction)
- Shrinkage of testicles and penis
- Hot flashes, which may get better or even go away with time
- Breast tenderness and growth of breast tissue
- Osteoporosis (bone thinning), which can lead to broken bones
- Anemia (low red blood cell counts)
- Decreased mental sharpness
- Loss of muscle mass
- Weight gain
- Increased cholesterol
Some research has suggested that the risk of high blood pressure, diabetes, strokes, heart attacks, and even death from heart disease is higher in men treated with hormone therapy, although not all studies have found this.
Anti-androgens have similar side effects. The major difference from LHRH agonists and orchiectomy is that anti-androgens may have fewer sexual side effects. When these drugs are used alone, libido and erections can often be maintained. When these drugs are given to men already being treated with LHRH agonists, diarrhea is the major side effect. Nausea, liver problems, and tiredness can also occur.
Abiraterone cause joint or muscle pain, high blood pressure, fluid buildup in the body, hot flashes, upset stomach, and diarrhea.
Enzalutamide can cause diarrhea, fatigue, and worsening of hot flashes. This drug can also cause some neurologic side effects, including dizziness and, rarely, seizures. Men taking this drug are more likely to fall, which may lead to injuries.
Many side effects of hormone therapy can be prevented or treated. For example:
- Hot flashes can often be helped by treatment with certain antidepressants or other drugs.
- Brief radiation treatment to the breasts can help prevent their enlargement, but it is not effective once breast enlargement has occurred.
- Several drugs are available to help prevent and treat osteoporosis.
- Depression can be treated with antidepressants and/or counseling.
- Exercise can help reduce many side effects, including fatigue, weight gain, and the loss of bone and muscle mass.
There is growing concern that hormone therapy for prostate cancer may lead to problems thinking, concentrating, and/or with memory, but this has not been studied thoroughly. Studying the possible effects of hormone therapy on brain function is hard, because other factors can also affect how the brain works. Still, hormone therapy does seem to lead to memory problems in some men. These problems are rarely severe, and most often affect only some types of memory. More studies are being done to look at this issue.
Current issues in hormone therapy
There are many issues around hormone therapy that not all doctors agree on, such as the best time to start and stop it and the best way to give it. Studies are now looking at these issues. A few of them are discussed here.
Treating early stage cancer: Some doctors have used hormone therapy instead of watchful waiting or active surveillance in men with early (stage I or II) prostate cancer who do not want surgery or radiation. Studies have not found that these men live any longer than those who don’t get any treatment until the cancer progresses or symptoms develop. Because of this, hormone treatment is not usually advised for early stage prostate cancer.
Early versus delayed treatment: For men who need (or will eventually need) hormone therapy, such as men whose PSA levels are rising after surgery or radiation or men with advanced prostate cancer who don’t yet have symptoms, it’s not always clear when it is best to start hormone treatment. Some doctors think that hormone therapy works better if it’s started as soon as possible, even if a man feels well and is not having any symptoms. Some studies have shown that hormone treatment may slow the disease down and perhaps even help men live longer.
But not all doctors agree with this approach. Some are waiting for more evidence of benefit. They feel that because of the side effects of hormone therapy and the chance that the cancer could become resistant to therapy sooner, treatment shouldn’t be started until a man has symptoms from the cancer. Studies looking at this issue are now under way.
Intermittent versus continuous hormone therapy: Nearly all prostate cancers treated with hormone therapy become resistant to this treatment over a period of months or years. Some doctors believe that constant androgen suppression might not be needed, so they advise intermittent (on-again, off-again) treatment. The hope is that giving men a break from androgen suppression will also give them a break from side effects like decreased energy, impotence, hot flashes, and loss of sex drive.
In one form of intermittent therapy, hormone treatment is stopped once the PSA drops to a very low level. If the PSA level begins to rise, the drugs are started again. Another form of intermittent therapy uses hormone therapy for fixed periods of time – for example, 6 months on followed by 6 months off.
At this time, it isn’t clear that this approach is better than continuous hormone therapy, and it may even be worse in some ways. In one study of men with advanced prostate cancer, it wasn’t clear that intermittent therapy helped men live as long as continuous therapy. While the men getting intermittent therapy did report fewer problems with impotence and sex drive 3 months into the study, there was no difference later on.
Combined androgen blockade (CAB): Some doctors treat patients with both androgen deprivation (orchiectomy or an LHRH agonist or antagonist) plus an anti-androgen. Some studies have suggested this may be more helpful than androgen deprivation alone, but others have not. Most doctors are not convinced there’s enough evidence that this combined therapy is better than starting with one drug alone when treating metastatic prostate cancer.
Triple androgen blockade (TAB): Some doctors have suggested taking combined therapy one step further, by adding a drug called a 5-alpha reductase inhibitor – either finasteride (Proscar) or dutasteride (Avodart) – to the combined androgen blockade. There is very little evidence to support the use of this triple androgen blockade at this time.
Castrate-resistant and hormone-refractory prostate cancer: These terms are both sometimes used to describe prostate cancers that are no longer responding to hormones, although there is a difference between the two.
Castrate-resistant means the cancer is still growing even when the testosterone levels are as low as what would be expected if the testicles were removed (called castrate levels). Levels this low could be from an orchiectomy, an LHRH agonist, or an LHRH antagonist. Some men might be uncomfortable with this term, but it is specifically meant to refer to these cancers, some of which might still be helped by other forms of hormone therapy, such as the drugs abiraterone and enzalutamide. Cancers that still respond to some type of hormone therapy are not completely hormone-refractory, so that term can’t be used.
Hormone-refractory refers to prostate cancer that is no longer helped by any type of hormone therapy, including the newer medicines.
Last Medical Review: 12/22/2014
Last Revised: 03/12/2015