Antiandrogen drugs are a diverse group of medications given to counteract the effects of androgens (male sex hormones) on various body organs and tissues. Some medications in this category work by lowering the body's production of androgens while others work by blocking the body's ability to make use of the androgens that are produced. The first group of antiandrogens includes such medications as leuprolide (Lupron, Viadur, or Eligard), goserelin (Zoladex), triptorelin (Trelstar Depot), and abarelix (Plenaxis). The second group includes flutamide (Eulexin), nilutamide (Nilandron), cyproterone acetate (Cyprostat, Androcur, Cyproterone), and bicalutamide (Casodex). Flutamide, nilutamide, and bicalutamide are nonsteroidal antiandrogen drugs while cyproterone acetate is a steroidal medication.
Some drugs that were originally developed to treat other conditions are sometimes categorized as antiandrogens because their off-label uses include some of the disorders listed below. These drugs include medroxyprogesterone (Depo-Provera ), a derivative of the female sex hormone progesterone that is used as a contraceptive and treatment for abnormal uterine bleeding; ketoconazole (Nizoral), an antifungal drug; and spironolactone (Aldactone), a diuretic.
Antiandrogen drugs may be given for any of several conditions or disorders, ranging from skin problems to mental disorders:
- Prostate cancer. Antiandrogen medications may be used to treat both early-stage and advanced prostate cancer by lowering or blocking the supply of male sex hormones that encourage the growth and spread of the cancer.
- Androgenetic alopecia. Androgenetic alopecia is a type of hair loss that is genetically determined and affects both men and women. It is sometimes called pattern baldness.
- Acne. Acne is the end result of several factors, one of which is excessive production of sebum, a whitish semiliquid greasy substance produced by certain glands in the skin. Antiandrogens may help to clear acne by slowing down the secretion of sebum, which depends on androgen production.
- Amenorrhea. Amenorrhea, or the absence of menstrual periods in females of childbearing age, is sometimes caused by excessively high levels of androgens in the blood. Antiandrogen medications may help to restore normal menstrual periods.
- Hirsutism. Hirsutism is a condition in which women develop excessive facial and body hair in a distribution pattern usually associated with adult males. It results from abnormally high levels of androgens in the bloodstream or from increased sensitivity of the hair follicles to normal levels of androgens. Hirsutism may be a sign of polycystic ovary syndrome (PCOS), a condition in which the ovaries develop multiple large cysts and produce too much androgen.
- Gender reassignment. Antiandrogen drugs are often prescribed for male-to-female (MTF) transsexuals as part of the hormonal treatment that precedes gender reassignment surgery.
- Paraphilias. Paraphilias are a group of mental disorders characterized by intense and recurrent sexual urges or behaviors involving nonhuman objects, children or nonconsenting adults, or pain and humiliation. Antiandrogen drugs have been prescribed for men diagnosed with paraphilias in order to lower blood serum levels of testosterone and help them control their sexual urges.
- Virilization. Virilization is an extreme form of hyperandrogenism in females, marked by such changes as development of male pattern baldness, voice changes, and overdevelopment of the skeletal muscles. Antiandrogens may be given to correct this condition.
- Leuprolide. Leuprolide is classified as a luteinizing hormone-releasing hormone (LHRH) agonist, which means that it resembles a chemical produced by the hypothalamus (a gland located in the brain) that lowers the level of testosterone in the bloodstream. It also reduces levels of estrogen in girls and women, and may be used to treat endometriosis or tumors in the uterus. It is presently under investigation as a possible treatment for the paraphilias.
- Goserelin. Goserelin is also an LHRH agonist, and works in the same way as leuprolide.
- Triptorelin. Triptorelin is an LHRH agonist, and works in the same way as leuprolide. It is not usually given to women, however.
- Abarelix. Abarelix is a newer drug that works by blocking hormone receptors in the pituitary gland. It is recommended for the treatment of prostate cancer in men with advanced disease who refuse surgery, cannot take other hormonal treatments, or are poor candidates for surgery.
- Ketoconazole. Ketoconazole is an antifungal drug available in tablets to be taken by mouth. Its use in treating hirsutism is off-label.
- Flutamide. Flutamide is a nonsteroidal antiandrogen medication that blocks the use of androgen by the body.
- Nilutamide. Nilutamide is another nonsteroidal antiandrogen drug that works by blocking the body's use of androgens.
- Bicalutamide. Bicalutamide is a nonsteroidal antiandrogen medication that works in the same way as flutamide.
- Cyproterone acetate. Cyproterone acetate is a steroidal antiandrogen drug that works by lowering testosterone production as well as blocking the body's use of androgens.
- Medroxyprogesterone. Medroxyprogesterone is a synthetic derivative of progesterone that prevents ovulation and keeps the lining of the uterus from breaking down, thus preventing uterine bleeding.
- Spironolactone. Spironolactone is a potassiumsparing diuretic that may be given to treat androgen excess in women.
- Leuprolide. Leuprolide is available in an injectable form and as an implant. The implant form, used to treat prostate cancer, contains 22.5 mg of leuprolide and is inserted under the skin every three months. This type of slow-release medication is called depot form. A longer-acting implant that lasts 12 months is also available. Injectable leuprolide is injected once a day in a 1-mg dose to treat prostate cancer. The dosage for endometriosis or uterine tumors is 3.75 mg injected into a muscle once a month for three to six months.
- Goserelin. Goserelin is implanted under the skin of the upper abdomen. The dosage for treating cancer of the prostate is one 3.6-mg implant every 28 days or one 10.8-mg implant every 12 weeks. For treating endometriosis, the dosage is one 3.6-mg implant every 28 days for six months.
- Triptorelin. Triptorelin is given as a long-lasting injection for treatment of prostate cancer or paraphilias. The usual dose for either condition is 3.75 mg, injected into a muscle once a month.
- Abarelix. Abarelix is given in 100-mg doses by deep injection into the muscles of the buttocks. It is given on days 1, 15, and 29 of treatment, then every four weeks for a total treatment duration of 12 weeks.
- Ketoconazole. For treatment of hirsutism, 400 mg by mouth once per day.
- Flutamide. Flutamide is available in capsule as well as tablet form. For treatment of prostate cancer, 250 mg by mouth three times a day. For virilization or hyperandrogenism in women, 250 mg by mouth three times a day. It should be used in women, however, only when other treatments have proved ineffective.
- Nilutamide. To treat prostate cancer, nilutamide is taken in a single 300-mg daily dose by mouth for the first 30 days of therapy, then a single daily dose of 150 mg.
- Bicalutamide. Bicalutamide is taken by mouth in a single daily dose of 50 mg to treat prostate cancer.
- Cyproterone acetate. Cyproterone is taken by mouth three times a day in 100-mg doses to treat prostate cancer. The dose for treating hyperandrogenism or virilization in women is one 50-mg tablet by mouth each day for the first ten days of the menstrual cycle. Cyproterone acetate given to treat acne is usually given in the form of an oral contraceptive (Diane-35) that combines the drug (2 mg) with ethinyl estradiol (35 mg). Diane-35 is also taken as hormonal therapy by MTF transsexuals. The dose for treating paraphilias is 200-400 mg by injection in depot form every 1-2 weeks, or 50-200 mg by mouth daily.
- Medroxyprogesterone. For the treatment of paraphilias, given as an intramuscular 150-mg injection daily, weekly, or monthly, depending on the patient's serum testosterone levels, or as an oral dose of 100-400 mg daily. As hormonal therapy for MTF transsexuals, 10-40 mg per day. For polycystic ovary syndrome, 10 mg daily for 10 days.
- Spironolactone. For hyperandrogenism in women, 100-200 mg per day by mouth; for polycystic ovary syndrome, 50-200 mg per day. For the treatment of acne, 200 mg per day. For hormonal therapy for MTF transsexuals, 200-400 mg per day. A topical form of spironolactone is available for the treatment of androgenetic alopecia.
- Leuprolide. Leuprolide should not be used by pregnant or nursing women, by patients diagnosed with spinal compression, or by patients allergic to the drug. Women taking leuprolide should not try to become pregnant, and should use methods of birth control that do not contain hormones.
- Goserelin. Goserelin should not be used during pregnancy or lactation, or by patients known to be allergic to it. As with leuprolide, women taking goserelin should use methods of contraception that do not contain hormones.
- Triptorelin. Patients using triptorelin should see their doctor at regular intervals for monitoring of side effects.
- Abarelix. Abarelix should not be given to children or women. Because of the severity of this drug's possible side effects, doctors who prescribe it for men must be certified following successful completion of a safety program for its proper use.
- Ketoconazole. Ketoconazole should not be given to alcoholic patients or those allergic to the drug. In addition, patients using ketoconazole should have their liver function monitored by their doctor.
- Flutamide. Flutamide should not be used by pregnant women. Patients taking flutamide should have their liver function monitored carefully. They should notify their doctor at once if they have pain in the upper right side of the abdomen or a yellowish discoloration of the eyes and skin, as these are signs of liver damage. In addition, patients using this drug should not discontinue taking it without telling their doctor.
- Nilutamide. This drug should not be given to patients who are allergic to it, have severe respiratory problems, or have been diagnosed with a liver disorder. Patients taking this drug should discontinue using alcoholic beverages while they are being treated with it.
- Bicalutamide. The precautions while using this drug are the same as those for flutamide.
- Cyproterone acetate. This drug has not been approved by the Food and Drug Administration (FDA) for use in the United States, but is approved for use in Canada and the United Kingdom. It should not be used during pregnancy or lactation, or by patients with liver disease. Men who are taking this drug for treatment of paraphilias should not use alcohol.
- Medroxyprogesterone. This drug should not be given to patients with a history of blood clot formation in their blood vessels. It should be used with caution in patients with asthma, seizure disorders, migraine headaches, liver or kidney disorders, or heart disease.
- Spironolactone. This drug should not be given to patients with overly high levels of potassium in the blood or to patients with liver disease or kidney failure. It should also not be given to pregnant or lactating women.
- Leuprolide. Side effects of leuprolide in men may include pains in the chest, groin, or legs; hot flashes, loss of interest in sex, or impotence ; bone pain; sleep disturbances; and mood changes. Side effects in women may include amenorrhea or light and irregular menstrual periods; loss of bone density; mood changes; burning or itching sensations in the vagina; or pelvic pain.
- Goserelin. The side effects of goserelin may include nausea and vomiting ; they are otherwise the same as for leuprolide.
- Triptorelin. Side effects of triptorelin include pain in the bladder, difficulty urinating, or bloody or cloudy urine; pain in the side or lower back; hot flashes or headache ; loss of interest in sex or impotence; vomiting or diarrhea ; unusual bleeding or bruising; pain at the injection site; unusual tiredness or sleep disturbances; depression or rapid mood changes. It may also cause a temporary enlargement of the tumor; this side effect is known as tumor flare.
- Abarelix. This drug may cause immediate life-threatening allergic reactions following any dose. May also cause a loss of bone mineral density, irregular heartbeat, hot flashes, sleep disturbances, gynecomastia, or pain in the breasts and nipples.
- Ketoconazole. The side effects of ketoconazole include nausea and vomiting, loss of appetite, abdominal pain, skin rash or itching, uterine bleeding, breast pain, gynecomastia, hair loss, loss of interest in sex, and decline in sperm production.
- Flutamide. Flutamide has been reported to cause breast tenderness and gynecomastia in men as well as fatigue, nausea, flu-like symptoms, and runny nose; darkened urine; indigestion, constipation, diarrhea, or gas; bluish-colored or dry skin; dizziness ; and liver damage. These side effects may be intensified in patients who smoke.
- Nilutamide. The side effects of nilutamide are the same as those for flutamide. In addition, this drug may affect the ability of the eyes to adjust to sudden changes in light intensity or may make the eyes unusually sensitive to light. Another potential side effect is difficulty breathing; this is more likely to occur in Asian patients taking this drug than in Caucasians.
- Bicalutamide. The side effects of this drug are the same as those for flutamide.
- Cyproterone acetate. Cyproterone has been reported to cause gynecomastia, impotence, loss of interest in sex, deep venous thrombosis, and possible damage to the cardiovascular system.
- Medroxyprogesterone. The side effects of this drug include high blood pressure, headache, nausea and vomiting, changes in menstrual flow, breakthrough bleeding, puffy skin (edema ), weight gain, and sore or swollen breasts.
- Spironolactone. Spironolactone may cause fatigue, headache, and drowsiness; gynecomastia and impotence in men; abdominal cramps, nausea, vomiting, diarrhea, or loss of appetite; and skin rashes or itching.
- Leuprolide. No interactions with other medications have been reported.
- Goserelin. No interactions have been reported.
- Triptorelin. No interactions have been reported.
- Abarelix. Abarelix may interact with other medications that affect heart rhythm, including procainamide, amiodarone, sotalol, and dofetilde.
- Ketoconazole. Ketoconazole interacts with a number of drugs, including rifampin, warfarin, phenytoin, antacids, cyclosporine, terfenadine, and astemizole. It may cause a sunburn-like skin reaction if used together with alcohol.
- Flutamide. This drug has been reported to intensify the effects of warfarin (Coumadin) and other blood-thinning medications. It has also been reported to intensify the effects of phenytoin (Dilantin), a drug given to control seizures.
- Nilutamide. Reported interactions are the same as for flutamide; in addition, nilutamide has been reported to intensify the effects of theophylline (Theo-Dur), a drug given to treat asthma.
- Bicalutamide. Reported interactions are the same as for flutamide.
- Cyproterone acetate. Patients taking oral medications to control diabetes may require dosage adjustments while taking this drug.
- Medroxyprogesterone. Patients taking phenobarbital, phenothiazine tranquilizers (chlorpromazine, perphenazine, fluphenazine, etc.), or oral medications to control diabetes should consult their doctor about dosage adjustments.
- Spironolactone. Spironolactone is reported to decrease the effectiveness of aspirin and anticoagulants (blood thinners). It may also interact with potassium supplements to increase the patient's blood potassium level.
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Antiandrogens, including flutamide (brand name Eulexin or Euflex), bicalutamide (brand name Casodex), and nilutamide (brand name Nilandron), are medicines used in the treatment of advanced prostate cancer .
Antiandrogen therapy stops or blocks the effect androgen presence has on tumor cells of the prostate. Antiandrogens are combined with either surgery or drug therapy that shuts down male hormone production. The common drugs used with antiandrogens are known as leuteinizing hormone releasing hormone (LHRH) agonists, referred to by the brand names Lupron or Zoladex. The LHRH agonists produce side effects that the antiandrogens can keep under control and the combination of the two agents has improved survival in prostate cancer patients.
Antiandrogens will not cure prostate cancer, but they will help improve some of the disease's symptoms. They may also increase survival time.
Androgens are made naturally in the body and include the hormone testosterone and its related compound, dihydrotestosterone. The testes produce the majority of testosterone. The adrenal glands also produce androgens in smaller amounts. Prostate cancer cells grow due to normal levels of androgens produced by the body. Some patients have prostate tumors that are extra-sensitive to androgens in the blood. The androgens attach to receptors on the tumor cells and send a signal to the tumor cells causing them to grow and multiply. Antiandrogen drugs block the receptors on the prostate cancer cell that are sensitive to the androgen hormones. By blocking these receptors, known as androgen-receptors, the cancer cells cannot be instructed to grow and multiply. Antiandrogens also cause the body to decrease production of androgens and, as a result, their effects.
Flutamide is an oral capsule dosed at 250 mg three times a day in combination with the LHRH agonist or surgical removal of the testis.
Bicalutamide is an oral tablet dosed at 50 mg once a day in combination with the LHRH agonist. The dose may need to be decreased in patients with decreased liver function.
Nilutamide is an oral tablet dosed at 300 mg once a day for 30 days then 150 mg once a day in combination with surgical removal of the testis.
Although antiandrogens are primarily given to men, women taking them should avoid pregnancy. Antiandrogens block the male hormone called testosterone and, as a result, can adversely affect the developing fetus. Blood counts will be monitored while on antiandrogen therapy.
The most common side effects from all antiandrogens are due to the decreased levels of hormones. These commonly include hot flashes, loss of sex drive, and impotence (the inability of males to have sexual intercourse).
Antiandrogens can cause mild nausea, vomiting, diarrhea , loss of appetite, enlarged breasts or breast tenderness, skin reactions, muscle aches, liver problems, blood in the urine and generalized pain and decrease in blood counts. Nilutamide may cause visual disturbances, with patients having difficulty with the dark. Rarely, lung problems have occurred due to nilutamide or bicalutamide, including cough and shortness of breath.
Use with caution in patients who are receiving the blood-thinning drug warfarin or the drugs phenytoin and theophylline. Combining these drugs with antiandrogen therapy may increase the effects or side effects of these agents.
Patients should tell their doctors if they have a known allergic reaction to antiandrogens or any other medications or substances, such as foods and preservatives. Before taking any new medications, including non-prescription medications, vitamins , and herbal medications, the patients should notify their doctors.
Nancy J. Beaulieu, RPh., BCOP
—Small organ located above the kidneys that produce hormones.
—A government agency that oversees public safety in relation to drugs and medical devices. The FDA gives approval to pharmaceutical companies for commercial marketing of their products
—Luteinizing hormone-releasing hormone drugs that initially stimulate the testes to make and release testosterone. With time, as the amount of testosterone in the blood rises, it stops the production of luteinizing hormone, which results in stopping overall production of testosterone.