Danazol is a synthetic androgen hormone that the Federal Drug Administration (FDA) approved in 1976. It is also known by its trade name, Danocrine.
Danazol is approved for use in the treatment of endometriosis, fibrocystic breast changes, and in the prevention of hereditary angioedema. In addition, it has shown promise in the treatment of certain cytopenias.
Endometriosis is a condition in which endometrial tissue, normally found in the uterus, implants itself in other areas of the body. The tissue continues to respond to hormones estrogen and progesterone during menstruation as it does in the uterus, but because the tissue cannot exit the body through the vagina during menstruation, it builds up, causing pain and inflammation. Danazol does not cure endometriosis, but renders the endometrial tissue located outside the uterus inactive. In most cases that are amenable to hormonal treatment, the endometrial lesions completely resolve, but can return within six months of stopping treatment.
Fibrocystic breast changes
Many women experience benign lumps or cystic changes in the breast. Most often, supportive bras and over-the-counter pain medication relieves symptoms. However, in some women, pain and discomfort may be so great that medical treatment is warranted. Danazol is the only drug approved by the FDA for fibrocystic breast disease, and in this patient population usually results in complete resolution of nodularity and pain. However, symptoms usually return when medication is stopped.
Hereditary angioedema is a condition in which parts of the body, most dangerously the airway, develop episodic swelling. Danazol is used to prevent these rare, but potentially fatal, attacks.
In addition to the aforementioned indications, there are other, unlabeled uses for danazol. The drug may be used to treat precocious puberty (premature sexual development), menorrhagia (excessively long menstrual periods), and gynecomastia (excess breast development in males).
Because it stimulates erythropoiesis (the production of red blood cells), it is sometimes administered to treat certain types of anemia. However, the use of danazol to combat anemia has declined since the recent developments in the synthetic production of erythropoeitin, a hormone naturally produced by the kidney that promotes the formation of red blood cells in bone marrow. In cancer patients, danazol may be used for its ability to stimulate erythropoiesis in individuals with types of thrombocytopenia (decreased platelets), often associated with HIV, or anemia. Danazol has shown promise in the management of autoimmune hemolytic anemia, a group of conditions in which the body produces antibodies that attack red blood cells. Myelodysplastic syndrome (MDS), a term that describes a group of hematologic cancers that often develop into acute leukemia, has shown some response to danazol treatment. However, more research is needed to better evaluate its potential in these patient populations.
The pituitary gland produces hormones necessary for reproduction-follicle stimulating hormone (FSH) and luteinizing hormone (LH). Danazol suppresses the production of these and other hormones (estrogen and progesterone), inhibiting ovulation as a result. The effects are usually reversible. Approximately 60 to 90 days after treatment is stopped, ovulation and cyclic bleeding usually return.
The lowest therapeutic dose possible should be administered to minimize side effects. In some cases, doctors may periodically stop treatment or decrease dosages. In women, danazol should be started during menstruation or after tests to ensure the woman is not pregnant. Patients should be careful not to miss a dose, and if they do, should not take a double dose.
Severe cases of endometriosis are initially treated with 800 milligrams (mg) of danazol, given in two divided doses. Gradually, the amount of medication is reduced to a level that is sufficient to suppress menstruation. Mild cases of endometriosis respond to lower doses of danazol. Typically, a doctor will first prescribe 200 to 400 mg a day, in two divided doses. Treatment should continue for three to six months, but in some cases, may last up to nine months.
Fibrocystic breast changes
Treatment for fibrocystic breast changes ranges from 100 to 400 mg given in two divided doses. Up to six months of danazol treatment may be needed to reduce breast nodularity and pain. However, in half of women treated with danazol, symptoms recur within a year. In these cases, treatment can be restarted.
Treatment for hereditary angioedema usually starts with a 200 mg dose given two or three times a day. Further adjustments are made based on the patient's response. If episodes are prevented, the amount may be decreased by half. If an attack occurs, the dose can be increased by up to 200 mg.
Treatment of anemia in myelodysplastic syndrome usually begins with a dose of 200 mg three times a day.
The use of danazol requires that liver and kidney function be routinely tested, as it can cause damage to these organs. In fact, with long-term use, there have been reported incidents of cancerous tumors in the liver.
Breast cancer should be ruled out prior to starting treatment. This may be difficult when there are multiple nodules in the breast. Any lumps that persist once danazol has started warrant consideration for breast cancer. Although danazol is effective in managing dysfunctional uterine bleeding, it should not be used in cases where endometrial cancer has not been ruled out.
Danazol should be used cautiously in people with high cholesterol. Danazol may cause a decrease in high-density lipoproteins (HDL; "good cholesterol"), which in, high levels, remove cholesterol from the arteries. At the same time, danazol can cause an increase in the low density lipoproteins (LDL; "bad cholesterol"), which act to move cholesterol into the arteries.
Danazol can cause androgenic effects on the fetus, and should not be used during pregnancy. Effects on a female fetus can include genital abnormalities such as clitoral enlargement, labia fusion, or vaginal closure. Treatment should not be initiated until pregnancy is ruled out. Throughout therapy, non-hormonal methods of birth control should be used to prevent pregnancy. If pregnancy does occur, the drug should be stopped and a doctor notified immediately.
Danazol is rarely associated with a condition called benign intracranial hypertension, symptoms of which include headache, nausea, vomiting, and visual disturbances. Should these symptoms occur, patients should stop taking the drug and see a neurologist.
When men, particularly adolescent men, take danazol, semen should be tested for volume, viscosity, sperm-count, and sperm motility every three to four months. Any changes may indicate a need to stop treatment.
Conditions that are worsened by swelling, a possible side effect of danazol, should be carefully monitored. This is particularly relevant in patients with epilepsy or cardiac problems.
Long-term effects of danazol are unknown. Androgenic side effects may result, and may be an effect of decreased estrogen. These symptoms may include acne, swelling, abnormal hair growth, decreased breast size, deepening of voice, oily skin or hair, weight gain, enlargement of the clitoris, or reduction in the size of the testicles. Flushing, sweating, vaginitis, nervousness or emotional lability (instability) may also develop. Danazol may cause liver damage. In addition to routine lab testing, patients should be monitored for yellowing of the skin or whites of the eyes due to jaundice.
The effects of oral anticoagulants, such as coumadin, may be increased in patients taking danazol, and should be used with caution. Individuals taking insulin for diabetes should carefully monitor their blood sugars. Taken in conjunction with danazol, insulin's effects are reduced. Danazol is also known to increase effects of the medications carbamazepine and cyclosporine.
- A steroid that produces masculine characteristics.
- Deficiencies of certain elements in blood, such as red blood cells, white blood cells and/or platelets.
- Excessive menstrual bleeding.