About hormone therapyProstate cancer occurs in the prostate gland, which is located just below a male's bladder and surrounds the top portion of the tube that drains urine from the bladder urethra. This illustration shows a normal prostate gland increase free testosterone herbs a prostate with a tumor. Hormone therapy for prostate cancer is treatment to stop the male hormone testosterone from reaching prostate cancer cells in your body. Hormone therapy for prostate cancer is also known as androgen deprivation therapy. Male hormone treatment prostate cancer prostate cancer cells rely on testosterone to help them grow. Hormone therapy cuts off the supply of testosterone or stops testosterone from reaching the cancer cells, causing cancer cells male hormone treatment prostate cancer die or to grow more slowly.
About hormone therapy | Prostate cancer | Cancer Research UK
Hormones are substances made by glands in the body that function as chemical signals. They affect the actions of cells and tissues at various locations in the body, often reaching their targets by traveling through the bloodstream.
Androgens male sex hormones are a class of hormones that control the development and maintenance of male characteristics. Testosterone and dihydrotestosterone DHT are the most abundant androgens in men.
Almost all testosterone is produced in the testicles ; a small amount is produced by the adrenal glands. Prostate cancer cells may also have the ability to produce testosterone.
Androgens are required for normal growth and function of the prostate , a gland in the male reproductive system that helps make semen. Androgens are also necessary for prostate cancers to grow. Androgens promote the growth of both normal and cancerous prostate cells by binding to and activating the androgen receptor , a protein that is expressed in prostate cells 1. Once activated, the androgen receptor stimulates the expression of specific genes that cause prostate cells to grow 2.
Early in their development, prostate cancers need relatively high levels of androgens to grow. Such prostate cancers are referred to as androgen dependent or androgen sensitive because treatments that decrease androgen levels or block androgen activity can inhibit their growth. Most prostate cancers eventually become " castration resistant ," which means that they can continue to grow even when androgen levels in the body are extremely low or undetectable.
Hormone therapy for prostate cancer —also called androgen suppression therapy or androgen deprivation therapy —can block the production and use of androgens 3. Currently available treatments can:. Treatments that reduce androgen production by the testicles are the most commonly used hormone therapies for prostate cancer. Normally, when androgen levels in the body are low, LHRH stimulates the pituitary gland to produce luteinizing hormone , which in turn stimulates the production of androgens by the testicles.
However, the continued presence of high levels of LHRH agonists actually causes the pituitary gland to stop producing luteinizing hormone, which prevents testosterone from being produced.
Treatment with an LHRH agonist is called medical castration sometimes called chemical castration because it uses drugs to lower androgen levels in the body to the same extent as surgical castration orchiectomy.
But, unlike orchiectomy, the effects of these drugs on androgen production are reversible. Once treatment is stopped, androgen production usually resumes. LHRH agonists are given by injection or are implanted under the skin. When patients receive an LHRH agonist for the first time, they may experience a phenomenon called " testosterone flare. The flare may worsen clinical symptoms for example, bone pain, ureter or bladder outlet obstruction , and spinal cord compression , which can be a particular problem in men with advanced prostate cancer.
The increase in testosterone is usually countered by giving another type of hormone therapy called antiandrogen therapy described below along with an LHRH agonist for the first few weeks of treatment. It is given by injection. Antiandrogens that are approved in the United States to treat prostate cancer include flutamide , enzalutamide , bicalutamide , and nilutamide.
Antiandrogens are given as pills to be swallowed. Drugs that prevent the adrenal glands as well as the testicles and prostate cancer cells from making androgens, which are called androgen synthesis inhibitors, can lower testosterone levels in a man's body to a greater extent than any other known treatment.
These drugs block testosterone production by inhibiting an enzyme called CYP This enzyme, which is found in testicular , adrenal , and prostate tumor tissues , plays a central role in allowing the body to produce testosterone from cholesterol.
Three androgen synthesis inhibitors are approved in the United States. All are given as pills to be swallowed. Two of these, ketoconazole and aminoglutethimide , are approved for indications other than prostate cancer but are sometimes used as second-line treatments for castration-resistant prostate cancer. The third, abiraterone acetate , is approved to treat metastatic castration-resistant prostate cancer.
Hormone therapy may be used in several ways to treat prostate cancer , including:. Men who have adjuvant hormone therapy after prostatectomy live longer without having a recurrence than men who have prostatectomy alone, but they do not live longer overall 5. Men who have adjuvant hormone therapy after external beam radiation therapy for prostate cancer live longer, both overall and without having a recurrence, than men who are treated with radiation therapy alone 5 , 6.
Hormone therapy used alone is also the standard treatment for men who have a prostate cancer recurrence documented by CT , MRI , or bone scan after treatment with radiation therapy or prostatectomy. Hormone therapy is often recommended for men who have a "biochemical" recurrence —a rapid rise in prostate-specific antigen PSA level—especially if the PSA level doubles in fewer than 12 months.
However, a rapid rise in PSA level does not necessarily mean that the prostate cancer itself has recurred. The use of hormone therapy in the case of a biochemical recurrence is somewhat controversial. Finally, hormone therapy used alone is also the standard treatment for men who are found to have metastatic disease i.
Whether hormone therapy prolongs the survival of men who have been newly diagnosed with advanced disease but do not yet have symptoms is not clear 10 , Moreover, because hormone therapy can have substantial side effects , some men prefer not to take hormone therapy before symptoms develop. For men with intermediate-risk prostate cancer, hormone therapy is generally given for 4 to 6 months; for men with high-risk disease it is generally given for 2 to 3 years.
Many prostate cancers that initially respond to hormone therapy with LHRH agonists , LHRH antagonists , or orchiectomy eventually stop responding to this treatment. This is referred to as castration-resistant prostate cancer. Castration-resistant prostate cancers need much lower levels of androgen to grow than androgen-sensitive cancers. Several potential mechanisms may allow prostate cancer cells to grow even when androgen levels are very low, including increased production of androgen receptor molecules within the cells either through an increase in the expression of the androgen receptor gene or an increase in the number of copies of the androgen receptor gene per cell , a change in the androgen receptor gene such that it produces a more active protein , and changes in the activities of proteins that help control the function of the androgen receptor 12 , Therefore, men who take hormone therapy for more than a few months will be regularly tested to determine the level of PSA in their blood.
Treatments for castration-resistant prostate cancer include:. Men with castration-resistant prostate cancer who receive these treatments will continue to take first-line hormone therapy e. Randomized clinical trials have demonstrated that treatment with abiraterone acetate or enzalutamide prolongs survival among men with metastatic castration-resistant prostate cancer, whether or not they have previously received chemotherapy 15 — Both medical castration and surgical castration greatly reduce the amount of androgens produced by the body.
Because androgens are used by many other organs besides the prostate , medical or surgical castration can have a wide range of side effects 3 , Antiandrogens can cause diarrhea , breast tenderness, nausea , hot flashes, loss of libido, and erectile dysfunction. The antiandrogen flutamide may damage the liver. Drugs that stop the adrenal glands from making androgens i. Estrogens avoid the bone loss seen with other kinds of hormone therapy , but they increase the risk of cardiovascular side effects, including heart attacks and strokes.
Because of these side effects, estrogens are rarely used today as hormone therapy for prostate cancer. Having adjuvant hormone therapy after radiation therapy worsens some adverse effects of radiotherapy, particularly sexual side effects and vitality Many of the side effects of ongoing hormone therapy also become stronger the longer a man takes hormone therapy Men who lose bone mass during long-term hormone therapy may be prescribed drugs to slow or reverse this loss.
The drugs zoledronic acid and alendronate which belong to a class of drugs called bisphosphonates increase bone mineral density in men who are undergoing hormone therapy 21 , A newer drug, denosumab , which increases bone mass through a different mechanism than bisphosphonates 23 , was approved in for use in men undergoing hormone therapy for prostate cancer.
However, bisphosphonates and denosumab are associated with a rare but serious side effect called osteonecrosis of the jaw Exercise may help reduce some of the side effects of hormone therapy, including bone loss, muscle loss, weight gain, fatigue, and insulin resistance 14 , Several clinical trials are examining whether exercise is an effective strategy to reverse or prevent side effects of hormone therapy for prostate cancer.
The sexual side effects of hormone therapy for prostate cancer can be some of the most difficult to deal with. More information about the sexual side effects of cancer treatment can be found in the NCI booklet Facing Forward: Life After Cancer Treatment. More information about supportive care for other side effects of hormone therapy can be found in the following PDQ summaries:. When most men stop taking a reversible hormone therapy, the sexual and emotional side effects caused by low levels of androgens will eventually go away.
However, if a man has been taking hormone therapy for many years, these side effects may not disappear completely. Some physical changes that have developed over time, such as bone loss, will remain after stopping hormone therapy. Patients should be sure to tell their doctor about all medications they are taking, including over-the-counter herbal medicines. Some herbal medicines interact with drug-metabolizing enzymes in the body, which can adversely affect hormone therapy Researchers have investigated whether a technique called intermittent androgen deprivation can improve the effectiveness of hormone therapy for prostate cancer —that is, whether it delays the development of hormone resistance.
With intermittent androgen deprivation, hormone therapy is given in cycles, with breaks between drug administrations, rather than continuously. Two clinical trials of intermittent versus continuous androgen deprivation found that intermittent therapy reduced some of the side effects of hormone therapy, including those involving sexual function. However, the trials did not show any improvement in overall survival with intermittent therapy 26 , Treatment in a clinical trial is an option for men with any stage of prostate cancer.
Many questions about the best uses of hormone therapy still need to be answered. These include whether hormone therapy added to brachytherapy , a type of internal radiation therapy , can help improve survival for men with early-stage prostate cancer.
Other questions include whether newer intensive hormone therapies may improve the outcome of men who are receiving surgery or radiation therapy for high-risk disease. Researchers are also testing new hormone therapies to treat castration-resistant prostate cancer.
Another question is the possible value of adding chemotherapy to hormone therapy as initial treatment for men with hormone-sensitive metastatic prostate cancer. Currently, chemotherapy is not used in these men until their disease progresses on hormone therapy i.
Early results of an NCI-sponsored trial that was conducted by two cancer cooperative groups—the Eastern Cooperative Oncology Group ECOG and the American College of Radiology Imaging Network ACRIN —suggest that men with hormone-sensitive metastatic prostate cancer who receive the chemotherapy drug docetaxel at the start of standard hormone therapy live longer than men who receive hormone therapy alone.
The trial results suggested that men with the most extensive metastatic disease benefit the most from the early addition of docetaxel. A follow-up analysis will be performed to clarify the effect of this treatment on men with less extensive metastatic disease.
Information about clinical trials can be found on NCI's website. NCI's Drug Information Summaries provide consumer-friendly information about certain drugs that are approved by the FDA to treat cancer or conditions related to cancer, including prostate cancer. For each drug, topics covered include background information, research results, possible side effects , FDA approval information, and ongoing clinical trials.
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