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Hormone Therapy Drugs

Hormone Blocking Agents, Hormone Antagonists

About

About hormone therapy

Hormone therapy (HT) is a form of cancer treatment that can slow down or arrest cancers – especially breast cancer and prostate cancer – that depend on hormones to grow and spread. In women, estrogen and progesterone are the hormones that most often contribute to cancer. In men, testosterone is the most likely source of stimulus for the cancer.

A hormone is a substance created in an organ, gland or body part that moves through the bloodstream to another body part. The hormone then chemically stimulates the second body part to increase or decrease either functional activity, or the secretion of another hormone. Hormones occur naturally in the body, but can also be made synthetically.

The body’s sex hormones are responsible for regulating reproduction. They also regulate the development of the male and female sexual characteristics. A person’s gonads (ovaries in women, testes in men) create most sex hormones. These are estrogen and progesterone in females and androgens (testosterone and androsterone) in males.

Hormone therapy (HT) associated with cancer differs from hormone replacement therapy (HRT) used to treat menopause in women or the effects of aging in men. In HRT treatments, medications are designed to boost levels of certain hormones in the body. In essence, hormone replacement therapy (HRT) is the opposite of hormone therapy (HT) used to treat cancer. HRT has been implicated in some studies as possibly contributing to some cancers, including those of the breast and ovaries. However, HRT also may lower the risk of other cancers, such as colorectal cancer. Women should weigh the possible benefits and risk of menopausal hormone therapy and discuss them with a physician.

Hormone treatments for cancer aim to reduce the levels of certain hormones in the body. Hormone therapy attacks hormone-sensitive cancer in two ways:


  • Reducing the level of hormones in the body. As levels of hormones such as estrogen or testosterone fall, the stimulus for cancer growth dissipates. This can be achieved either by having the patient take medications that suppress hormone production, or by surgically removing the glands that produce hormones.
  • Preventing cancer from using hormones. Synthetic hormones can bind to the cancer’s hormone receptors. HT prevents hormones from reaching and binding to the cancer cells. By preventing the hormones from attaching to the cells, the cancer does not receive the signal from the hormones to grow.

In most cases, hormone therapy will not be the only method of treating cancer. Instead, it is likely to be used in combination with chemotherapy, radiation therapy, surgery or another cancer treatment. Hormone therapy can reach all parts of the body and can affect cancer cells that have spread to areas far from the site of the original cancer.

The different ways in which hormone therapy can be used include:


  • Primary treatment. In some cases of advanced (metastatic) cancer, hormone therapy may be used as the main treatment to alleviate symptoms. This occurs most often in patients too ill or elderly to be able to tolerate aggressive therapy.
  • Neoadjuvant therapy. Hormone therapy may be used to shrink a tumor to a more manageable size prior to removing the cancer in surgery.
  • Adjuvant therapy. In some cases, hormone therapy can be used to prevent cancer from recurring after a tumor has been surgically removed.

While hormone therapy can be an effective means of treating cancer, it has its limitations. Most advanced cancers that depend on hormones can become resistant to hormone therapy and find a way to grow without the use of hormones. In such instances, physicians may switch patients to non-hormonal therapy.

Some physicians may prescribe intermittent doses of hormones as a way to keep a patient’s cancer from becoming resistant to hormone therapy. For example, the vast majority of prostate cancers treated with hormone therapy become resistant to the medication over a period of years. By using hormone therapy intermittently (for example, six months on and six months off), many physicians believe they can lessen the chances that this resistance will develop in the patient. In some cases, physicians may switch the patient to a different hormone therapy drug after a period of time. Changing the schedule or drug also may help reduce the incidence and severity of side effects associated with hormone therapy.

Certain rare cancers may cause excessive levels of hormones in a person’s body. This can cause various symptoms, ranging from sweating to high blood pressure. Hormone-blocking drugs may be prescribed to treat such conditions, which can be triggered by cancers such as carcinoid tumors, small cell lung cancer, pheochromocytomas (tumors of the adrenal gland) and other neuroendocrine cancers (small, slow growing tumors found mostly in the gastrointestinal system).

Types

Types and differences of hormone therapy

Various medications are used in hormone therapy to alter a person’s levels of estrogen, progesterone or testosterone, or to prevent cancer cells from binding with hormones. These drugs can be taken orally or by injection, and include:


  • Hormone-blocking agents. Block the ability of cancer cells to bind with hormones that stimulate the growth of certain cancers. They include:
    • Anti-estrogens. Generally given to women to block cancer cells from using estrogen stimulation. However, certain anti-estrogens have been found to block estrogen in some organs, and to act like the hormone in other organs. These are known as selected estrogen receptor modulators (SERMs) or “designer estrogens.” Anti-estrogens include tamoxifen (Nolvadex), toremifene (Fareston) and raloxifene (Evista).

      Estrogen-receptor down regulators (ERDs) are another type of anti-estrogen drug used in hormone therapy. This drug breaks down estrogen receptors and act to slow down the growth of hormone-sensitive cancers. ERDs destroy estrogen receptors and do not act like hormones elsewhere in the body. In the United States, the only ERD approved by the Food and Drug Administration (FDA) is fulvestrant (Faslodex). It is given by injection and approved for treatment of postmenopausal women with certain forms of breast cancer. It is often used after other anti-estrogen drugs or aromatase inhibitors are no longer effective.

    • Anti-androgens. Given to men to block prostate cells from activation by testosterone from the testicles and the adrenal glands. They are taken in pill form, either once a day or several times daily. They may or may not cause the loss of sex drive. They are usually used in combination with agents that block pituitary stimulation of the testicles, which do not cause the loss of sex drive. Anti-androgens include flutamide (Eulexin), bicalutamide (Casodex) and nilutamide (Nilandron).
  • Aromatase inhibitors (AIs). Block enzymes that produce estrogen. Given to postmenopausal women, they are taken in pill form once daily. This limits the amount of estrogen in the body that can be used by cancer to grow and spread. In postmenopausal women, most estrogen in the body no longer comes from the ovaries. Instead, it is produced from the hormone androgen, which is produced in the adrenal glands. Aromatase inhibitors block an enzyme in the body from turning androgen into estrogen. Aromatase inhibitors include letrozole (Femara), anastrozole (Arimidex) and exemestane (Aromasin).

    Research in clinical trials has shown that aromatase inhibitors are more effective than tamoxifen in postmenopausal women with early-stage breast cancer that is hormone receptor positive. In most women, this drug is taken for up to five years but it may be taken for a longer period of time.

  • Luteinizing hormone releasing hormone (LHRH) agonists and antagonists. Alter mechanisms in the brain that tell the body to produce hormones. This lowers hormone levels in the body. They are given by injection. These drugs serve as an alternative to surgical removal of the ovaries in women and testicles in men. In most cases, the effects of these drugs are reversible after the patient stops taking them. Abarelix (Plenaxis) is an LHRH antagonist. LHRH agonists include leuprolide (Lupron, Viadur, Eligard), goserelin acetate (Zoladex) and trelstar (Trelstar).

There are several options for treatment with hormone therapy drugs. Oncologists consider several factors in choosing a drug for a cancer patient. For example, in women, physicians will consider whether she is pre- or postmenopausal. Research has suggested that tamoxifen is the best for premenopausal women whereas aromatase inhibitors appear to be better for postmenopausal women.

In addition, other research has shown that combining or switching drugs in treatment may be more effective.

One study published in 2003 found that women who switched from tamoxifen to an aromatase inhibitor before the end of the standard five years of treatment had lower recurrence of their breast cancer. In another study released in 2005, the National Cancer Institute (NCI) reported the results of a large clinical trial in which women took an aromatase inhibitor following their course of treatment with tamoxifen. The study suggested that survival rates for women with early stage breast cancer improved with the use of an aromatase inhibitor following tamoxifen. Additional research continues on the long-term effects of hormone therapy drugs and their effectiveness in battling cancer.

Patients should discuss the benefits and risks of hormone therapy drugs with their oncologists to determine the best treatment option. After patients are placed on hormone therapy drugs, they will be monitored by their physicians and treatment may change based on individual factors.

Conditions

Conditions treated with hormone therapy

Patients with certain types of cancer are especially likely to benefit from hormone therapy (HT).

Cancer cells have hormone receptors that bind to certain hormones that stimulate their growth. However, not all cancers use hormones for growth. If the cancer uses hormones to grow, the cancer is labeled “receptor positive” or “hormone dependent.” If the cancer does not rely on hormones to grow, it is labeled “receptor negative” or “hormone independent.” Cancers that are receptor positive benefit from hormone-blocking therapy because the drugs block the hormones from stimulating the cancer.

For example, the common hormone-blocking drug tamoxifen is effective in treating breast cancers that are receptor positive. The drug prevents the hormone from stimulating the cancer by blocking its attachment to the cancer cells. Typically, the more estrogen receptors that are present, the more likely the patient will respond to hormone therapy. Tamoxifen is not a treatment for receptor negative cancers because those cancers do not rely on hormones to grow.

Some cancers are more sensitive to hormone therapy than others, and sensitivity can vary even within a particular type of cancer. A sample of a tumor (biopsy) can be analyzed in a laboratory to determine whether or not that tumor is likely to respond to hormone therapy.

Cancers that are often receptive to hormone therapy include:


  • Breast cancer
  • Ovarian cancer
  • Uterine cancer
  • Prostate cancer
Side effects

Potential side effects of hormone therapy

While hormone therapy can be an effective form of cancer treatment, it also carries some risks. Those who have surgery may lose all or part of an organ. Other side effects are more likely to be temporary and differ depending on a patient’s gender, including:

Men (estrogen administration or testosterone deprivation):


  • Decreased sexual desire
  • Enlarged breasts
  • Hot flashes
  • Inability to achieve an erection
  • Incontinence
  • Osteoporosis

Women (estrogen deprivation):


  • Fatigue
  • Hot flashes
  • Mood swings
  • Nausea
  • Osteoporosis
  • Weight gain
  • Decreased sexual desire

Certain uncommon cancers may cause excessive levels of other hormones. Symptoms that may accompany such high hormone levels include:


  • Sweating
  • Flushing
  • High blood pressure
  • Diarrhea

There is also some evidence that taking hormone therapy drugs like tamoxifen over long periods of time may actually cause the patient to become resistant to their benefits. However, this is not the case with all hormone therapy drugs. Patients should speak with their physician about the possible long-term benefits and risks of various hormone therapy medications.

Interactions

Drug or other interactions

Patients who are using hormone therapy drugs should consult their physician before taking any additional prescriptions, over-the-counter medications, nutritional supplements or herbal medications. For example, the combination of some anticoagulants with certain hormone therapy drugs may cause a significant increase in anticoagulation effect. Other drugs, such as diuretics, may increase the risk of clotting. Use of some hormone therapy drugs with estrogens may prevent the hormone therapy drug from working properly.

Women who are pregnant or nursing are generally not advised to take hormone therapy drugs. In addition, some drugs may not be good for patients with various health conditions. Patients should always consult with their physician about all medication and lifestyle conditions (including alcohol and tobacco use) that might affect the use of hormone therapy drugs.

Questions for your doctor

Patients may wish to ask their doctor the following questions about hormone therapy drugs:
  1. Am I a candidate for hormone drug treatment?
  2. How will it work on my cancer?
  3. What is the best type of drug for me?
  4. What are the benefits and risks associated with this drug?
  5. How do I know if the drug is working?
  6. How effective are the drugs in preventing a recurrence of my cancer?
  7. What are the side effects of the drugs?
  8. What can I do to reduce the side effects of the drugs?
  9. Should I undergo any medical tests to monitor my health while taking these drugs?
  10. Will the drugs affect my sexual function and/or fertility?
  11. How long will I have to use the drugs?
  12. Will my drugs be changed during the course of treatment?
  13. Are there any medications or supplements that could interfere with these drugs?
  14. Am I a candidate for any clinical trials?

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