Hormone therapy for prostate cancer

Hormone therapy is also called androgen deprivation therapy (ADT) or androgen suppressive therapy. The objective of this treatment is to reduce the levels of male hormones called androgens in the body, or prevent these hormones affect cancer cells in the prostate.

Androgens stimulate the growth of cancer cells in the prostate. The main body androgens include testosterone and dihydrotestosterone (DHT). The testes produce most of androgens, although the adrenal glands (glands located above the kidneys) also produce a small amount. Often reducing androgen levels or preventing them from reaching the cells of prostate causes cancer grow more slowly. However, hormone therapy alone does not cure prostate cancer.

When hormone therapy is used

  • If the cancer has spread too far to be cured with surgery or radiation or if you will not be subjected to these treatments for some other reason
  • If cancer remains or comes back after treatment with surgery or radiotherapy
  • Along with radiation therapy as initial treatment if you are at a higher risk of the cancer coming back after treatment (according to a high Gleason score, a high PSA level, and / or growth of cancer outside the prostate)
  • Before radiation to try to shrink the cancer and make the treatment more effective

Various types of hormone therapy can be employed to treat prostate cancer.

Treatments to reduce the levels of androgens

Orchiectomy (castration)

Although it is a type of surgery, its main effect is like a form of hormone therapy. In this operation, the surgeon removes the testicles, where most of androgens (testosterone and DHT) is produced. This causes most prostate cancers stop growing or shrinking for a while.

The operation is performed as an outpatient procedure. It is probably the least expensive and simplest form of hormone therapy. However, unlike some other treatments, this is permanent, and many men have trouble accepting the removal of his testicles.

Some men who undergo this surgery are concerned about how they will look after the procedure. They can be inserted into the scrotum artificial testicles look like normal.

LHRH agonists

Agonists of luteinizing-hormone releasing hormone (also called LHRH analogues or GnRH agonists) are drugs that reduce the amount of testosterone produced by the testes. Treatment with these drugs is sometimes called chemical castration or medical castration, as they reduce androgen levels as well as orchiectomy.

Although LHRH agonists cost more than orchiectomy and require frequent doctor visits, most men prefer this method. These drugs allow the testicles remain in place. However, the testicles will be reduced in size with the passage of time, and may even become so small that they can not be palpated.

LHRH agonists are injected or placed as small implants under the skin. Depending on the used drug can be administered from once per month to once per year. LHRH agonists available in the United States include:

Leuprolide (Lupron, Eligard)

Goserelin (Zoladex)

Triptorelin (Trelstar)

Histrelin (Vantas)

First LHRH agonists briefly increase testosterone levels before declining to low levels. This effect is called exacerbation and results from the complex way in which these drugs act. Men whose cancer has spread to the bones may experience bone pain. If the cancer has spread to the spine, even an increase in tumor growth for a short period of time as a result of the exacerbation could compress the spinal cord and cause pain or paralysis. Exacerbation can be avoided by administering drugs called anti-androgens (discussed below) for several weeks when treatment begins with LHRH agonists.

LHRH Antagonists

The drug degarelix (Firmagon) is an LHRH antagonist that acts as LHRH agonists but reduces testosterone levels faster and does not cause tumor flare as do LHRH agonists. Treatment with this drug may also be considered a form of medical castration.

This medicine is used to treat advanced prostate cancer. It is administered monthly by injection under the skin. The most common side effects are problems at the injection site (pain, redness, and swelling) and increased liver enzymes in laboratory analysis was applied levels. Other side effects are discussed in more detail below.

CYP17 inhibitors

Agonists and antagonists of LHRH can cause the testicles stop producing androgens, although other cells in the body, including the same cancerous prostate cells, can continue production of small quantities, which can stimulate cancer growth. Abiraterone (Zytiga) blocks an enzyme called CYP17 that helps these cells stop producing androgens.

Abiraterone can be used in men with castration resistant prostate cancer (the cancerous tumor that continues to grow despite the low testosterone levels due to either an LHRH agonist, LHRH antagonist or orchiectomy).

This medication is administered orally every day and does not stop the production of testosterone by the testicles so that men who have not undergone an orchiectomy need to continue treatment with an agonist or LHRH antagonist. Since abiraterone also reduces the level of some other hormones in the body, it is also necessary to administer prednisone (a cortisone-like medicine) during treatment to avoid certain side effects.

Drugs that stop the function of androgens

Antiandrogens

Androgens can work only if they bind to a protein in the cell called prostatic androgen receptor. Anti-androgens are drugs that attach to these receptors so that androgens can not.

Some drugs of this type are:

They are administered daily in tablet form.

Antiandrogens are not often used alone in the United States. An antiandrogen may be added to treatment if orchiectomy or an analogue or releasing hormone antagonist of luteinizing hormone is not effective alone. Sometimes an antiandrogen for several weeks are also given when an LHRH agonist was started to prevent exacerbation of the tumor.

An antiandrogen also be combined with orchiectomy or LHRH agonist as first-line hormonal therapy. This is called combined androgen blockade. It is still debating whether this blockade is more effective in this scenario orchiectomy or LHRH agonist alone. If there is any benefit, it appears to be small.

In some men, an antiandrogen is no longer working, simply suspending the antiandrogen can cause the cancer to stop growing for a short time. Doctors call this effect antiandrogen withdrawal, although they are not sure why that happens.

The drug Enzalutamide (Xtandi) is a newer type of antiandrogen. Normally, when androgens bind to the receptor, it sends a signal to the control center of the cell, indicating that grow and divide. Enzalutamide blocks this signal. It is administered orally every day.

Often Enzalutamide may be useful in men with cancer resistant prostate castration. In most studies on this drug, men also received an LHRH agonist, so it is unclear if this drug would be useful in men with normal testosterone levels.

Other androgen-suppressing drugs

Some time ago estrogens (female hormones) were the main alternative to orchiectomy for men with advanced prostate cancer. Because of its potential side effects (including blood clots and increased breast size), estrogens have been replaced by other types of hormone therapy. Still, you can try using estrogen if other hormonal treatments stopped effect.

Ketoconazole (Nizoral), which first used to treat fungal infections, blocks the production of certain hormones, including androgens, similar to abiraterone. It is used most often to treat men who have just been diagnosed with advanced prostate cancer who have a lot of cancer in the body, because it offers a quick way to lower testosterone levels. You can also try if other forms of hormonal therapy ceased to have effect.

Ketoconazole may also block the production of cortisol, a steroid hormone important in the body, so that men treated with this drug often need to take a corticosteroid (such as prednisone or hydrocortisone).

Possible side effects of hormone therapy

Orchiectomy and agonists and antagonists of LHRH can all cause similar side effects due to lower levels of hormones such as testosterone. These side effects may include:

  • Reduction or absence of sexual desire
  • Erectile dysfunction (impotence)
  • Reducing the size of the testicles and penis
  • Hot flashes (hot flushes) that can be alleviated or disappear with time
  • Pain when touching the breasts and breast tissue growth
  • Osteoporosis (thinning of the bones), causing broken bones
  • Anemia (low red blood cell counts)
  • Decreased mental acuity
  • Loss of muscle mass
  • Weight gain
  • Fatigue
  • Increased cholesterol levels
  • Depression

Some researches have suggested that the risk of hypertension, diabetes, strokes, heart attacks, and even death from heart disease is higher in men treated with hormone therapy, although not all studies agree with this.

Antiandrogens have similar side effects. The main difference between agonists and antagonists of LHRH and orchiectomy is that anti-androgens may cause fewer sexual side effects. When these drugs are used alone thay can often maintain sexual desire and erections. Diarrhea is the main side effect when these drugs are administered in men who have already been treated with LHRH agonists. In addition, there may be nausea, liver problems and tiredness.

Abiraterone can cause pain in muscles and joints, high blood pressure, fluid accumulation in the body, hot flashes, upset stomach and diarrhea.

Enzalutamide can cause diarrhea, fatigue, and hot flashes worse. This medicine may also cause some side effects on the nervous system, including dizziness and, rarely, seizures. Men who take this drug are more likely to fall, which may cause injury.

They can prevent or treat many side effects of hormone therapy. For example:

  • The hot flashes often be alleviated with certain antidepressants or other medications.
  • The brief treatment with radiation to the breast can help prevent increase in size, but this is not effective once the breasts have grown.
  • Several medications can 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 loss of bone and muscle mass.

There is growing as to whether the hormone for prostate cancer therapy can cause problems concern reasoning, concentration and / or memory, although this has not been studied thoroughly. Still, it seems that, indeed, hormone therapy causes memory problems in some men. In rare cases, these problems are serious, and most often affect only some types of memory are being carried out further studies to look at this issue.

Current controversies about hormone therapy

Not all doctors agree on many issues related to hormone therapy, such as the best time to start and stop therapy and the best way to manage it. They are conducting studies that are looking at these issues. Some of these issues are discussed below.

Treatment of early stage cancer: Some doctors have used hormone therapy instead of watchful waiting or active surveillance in men with early-stage prostate cancer who do not want to undergo surgery or radiation. Studies have not found that these men live longer than those treated only when the cancer progresses or when symptoms occur. Because of this, hormone treatment usually not recommended for prostate cancer at early stage.

Early treatment or late treatment: in the case of men who need (or will need in the future) hormonal therapy, as men whose PSA levels are increased after surgery or radiation, or men with advanced prostate cancer still no symptoms, do not always know when to begin hormone treatment. Some doctors think that hormone therapy works best if started as soon as possible, even if the man feels well and has no symptoms. Some studies have shown that hormone therapy can slow the disease and perhaps even help men live longer.

However, not all doctors agree with this method. Some doctors expect more evidence that there are benefits. They believe that treatment should not be started until the man has symptoms of cancer, due to side effects of hormone therapy and the possibility of cancer soon become resistant to therapy. This issue is still under study.

Comparison of intermittent hormone therapy with continuous therapy: Most prostate cancers treated with hormone therapy for a period of months or years become resistant to this treatment. Some doctors believe that constant androgen suppression may not be necessary, so that recommend intermittent treatment. The intention is that disruption of androgen suppression also provide men a break of side effects like decreased energy, sexual problems and hot flashes.

In one type of intermittent hormone therapy, the treatment is stopped when the PSA in the blood drops to a very low level. If the PSA level starts to increase, the drugs begin to manage again. Another method uses intermittent therapy hormone therapy during fixed time periods, for example administered for 6 months and resting the next 6 months.

For now it is not known what the benefits of this approach to continuous hormone therapy. Some studies have found that continuous therapy can help men live longer, but other studies have found no such difference.

Combined androgen blockade: Some doctors treat patients with androgen deprivation (orchiectomy or LHRH agonist or antagonist) and an antiandrogen. Some studies have suggested that this may be more useful than androgen deprivation alone, although other studies do not agree with this. Most doctors do not believe there is sufficient evidence that this combination therapy is better to start with a single drug to treat cases of metastatic prostate cancer.

Triple androgen blockade: some doctors have suggested to add an additional step to combination therapy adding a drug called inhibitor of 5-alpha reductase, either finasteride (Proscar, Propecia) or dutasteride (Avodart) to combined androgen blockade. Currently, there is little evidence to support the use of this triple androgen blockade.

Hormone-refractory cancer versus castration-resistant prostate cancer: the two terms are sometimes used to describe prostate cancers that no longer respond to hormones, although there is a difference between the two.

The term castration-resistant means that the cancer continues to grow even when testosterone levels are as low as would be expected if the testicles had been removed (equivalent to castration levels). Low levels could be due to an orchiectomy, an LHRH agonist or antagonist LHRH. Some men feel uncomfortable with this term, but it is intended to refer specifically to these cancers, some of which could benefit from other forms of hormonal therapy, such as Abiraterone and Enzalutamide. Cancers that still respond to some types of hormone therapy are not completely hormone-refractory.

On the other hand, hormone-refractory refers to prostate cancer that no longer benefits from any type of hormone therapy, including more recent medicines.