Danazol

Potential Health Benefits of Danazol

• Increases free testosterone [1-14]
• Improves body composition [15-22]
• Improves cardiovascular health [22, 23-26]
• Boosts immune system function [27-43]
• Combats cancer [44-60]
• Improves fertility in women and increases pregnancy rate [61-75]
• Treats uterine problems [76-95]
• Treats bleeding disorders [84, 89, 96-98]

What is Danazol?

Danazol is a man-made form of a steroid and is similar to the hormone testosterone. This medication is commonly prescribed for women with pelvic pain and infertility associated with endometriosis, a painful condition in which the lining of the uterus known as the endometrium grows outside the uterus. Other indications for danazol treatment include fibrocystic breast disease (benign breast lumps) and hereditary angioedema (inflammation of the airway, face, arms, and legs).

How Danazol Works

Danazol exerts its beneficial effects through its anti-estrogenic and anti-progestogenic activities. This medication reduces the production of the hormones estrogen and progesterone by suppressing certain receptors in the endometrium, resulting in thinning of the lining of the uterus. Because of this mechanism of action, danazol is often prescribed for the treatment of leiomyoma (a benign smooth muscle tumor in the uterus) and endometriosis (a disorder in which tissue similar to the lining of the uterus grows outside of the uterine cavity). Danazol also causes marked suppression of sex hormone-binding globulin (SHBG) levels in the blood, which in turn increases free testosterone. This ultimately results in androgenic effects such as an increase in muscle mass and fat loss.

Chemical Structure of Danazol

Research on Danazol

Increases Free Testosterone

Free testosterone refers to the small amount of the total testosterone concentration that is not bound to any protein. The ability of danazol to boost testosterone levels via sex hormone-binding globulin suppression results in improved quality of life and is associated with various health benefits. The testosterone-boosting effects of danazol are backed by a number of studies:

1. In women undergoing danazol treatment for endometriosis, a significant increase in free testosterone levels was found. [1]
2. In patients treated with danazol, a greater increase in the percentage of free testosterone in the plasma samples was observed compared with patients treated with gestrinone. [2]
3. A study showed that danazol increased free testosterone levels in normal females. [3]
4. In women undergoing danazol treatment for endometriosis, a marked rise in free testosterone was found during danazol therapy. [4]
5. In patients with endometriosis, danazol treatment resulted in increased free testosterone percentage. [5]
6. A study showed that danazol therapy resulted in increased free testosterone levels by exerting a marked testosterone-displacing activity. [6]
7. In patients treated with danazol, there was a significantly greater increase in the percentage of free testosterone in the blood samples compared to gestrinone-treated patients. [7]
8. A study showed that danazol therapy significantly increased the percentage of free testosterone by about three folds. [8]
9. In patients under danazol therapy, testosterone values increased because of cross-reaction with danazol metabolites. [9]
10. In premenopausal women with endometriosis, the administration of danazol increased the tissue availability of testosterone. [10]
11. In patients with hereditary angioedema, danazol therapy markedly increased blood levels of free testosterone. [11]
12. In women who received danazol treatment, a significant increased in free testosterone levels were observed. [12]
13. In non-obese women with minimal endometriosis, treatment with danazol increased free testosterone levels compared with the gonadotropin-releasing hormone analogue, goserelin. [13]
14. In patients with hereditary angioedema treated with danazol for 10 months, a significant increase in the levels of free testosterone was observed. [14]

Improves Body Composition

By suppressing sex hormone-binding globulin (SHBG), danazol boosts the production of the primary male hormone testosterone. Studies show that this mechanism promotes fat loss and increased production of lean muscle mass:

1. In women with endometriosis, treatment with 200 mg of danazol 3 times daily for 6 months increased the levels of leptin, a hormone that promotes weight loss via reduction of dietary intake and fat storage while modulating energy expenditure and carbohydrate metabolism. [15]
2. In premenopausal women undergoing danazol treatment for endometriosis, a significant reduction in body fat and an increase in lean tissue mass were observed after 6 months. [16]
3. In patients with endometriosis, danazol treatment resulted in fat reduction of the legs. [17]
4. In premenopausal women undergoing danazol treatment for endometriosis, a significant increase in lean tissue mass was observed. [18]
5. In patients with hereditary angioedema, danazol treatment improved body composition by decreasing inflammation in different body parts. [19-22]

Improves Cardiovascular Health

A growing body of evidence also found that danazol is good for the heart and can be beneficial in people with cardiovascular disease:

1. In healthy volunteers and patients with hereditary angioedema, danazol administration improved the dilation of heart blood vessels. [22]
2. In patients with recurrent painful ulcers of the lower extremities, low-dose danazol reduced cardiovascular risk factors by decreasing the levels of lipoprotein a. [23]
3. In mice, injection of danazol induced prolonged cell survival of transplanted hearts. [24]
4. In normal women, danazol treatment reduced the risk of atherosclerosis (plaque build-up within the heart arteries). [25]
5. In patients undergoing dialysis, danazol administration has been found to treat blood clots. [26]

Boosts Immune System Function

Aside from its potent anti-cancer properties, numerous studies suggest that danazol has immune-modulating properties that can help ward off a wide array of diseases:

1. In patients with thrombocytopenia (low platelet count), danazol therapy increased the production of the immune system cell T lymphocytes. [27]
2. A 2013 study published in the Iranian Journal of Basic Medical Sciences found that danazol can treat human T-cell lymphotropic virus type I, an infection that can progress to leukemia. [28]
3. In patients with primary immune thrombocytopenia, a low-to-medium dosage of danazol is better tolerated and resulted in long-term disease remission. [29]
4. In patients with immune thrombocytopenic purpura, a blood clotting disorder, danazol treatment increased the production of white blood cells and reduced the number of abnormal platelets. [30-31]
5. In patients with angio-immunoblastic lymphadenopathy, a cancer of the blood and lymph nodes caused by impaired immune function, danazol treatment showed immune-boosting properties. [32]
6. In an animal model of immune-mediated anemia, danazol treatment reduced the binding of immunoglobulin to the red blood cell’s surface, thus preventing the formation of abnormal RBCs. [33]
7. In older women with autoimmune hemolytic anemia, danazol modified cell membranes which in turn led to specific immune modulations. [34]
8. In patients with hereditary angioedema, danazol exerts its therapeutic effect via the promotion of C4 synthesis and increasing C1 esterase inhibitor production. [35]
9. In patients with IgA nephropathy, a kidney disease characterized by the build-up of the antibody immunoglobulin A (IgA) in the kidneys, danazol administration stabilized the disease. [36]
10. In rats, danazol administration at a dose of 100 mg/kg per day ameliorated the endometrial implant-induced alterations of the immune system. [37]
11. In a mouse model of lupus, a long-term autoimmune disease, danazol administration at an oral dose of 100 mg/kg, significantly prolonged survival. [38]
12. In patients with aplastic anemia (inadequate production of blood cells), danazol therapy improved survival rate and increased T regulatory cells. [39-40]
13. In patients with uterine problems, danazol treatment prevented the formation of antibodies that attack the immune system. [41-42]
14. In patients with bleeding problems, danazol treatment increased platelet count. [43]

Combats Cancer

Evidence also suggests that danazol can help treat various types of malignant cells because of its potent anti-cancer properties:

1. In premenopausal and postmenopausal patients with advanced breast cancer, danazol treatment for periods ranging between 3 days and 30 months resulted in stabilization of the disease. [44]
2. In patients with metastatic breast cancer, danazol treatment at a dose of 200 mg three times daily significantly improved symptoms. [45]
3. In patients with advanced breast cancer, danazol is associated with better treatment outcomes. [46]
4. In breast cancer cells, danazol treatment induced cell cycle dysregulation and programmed cell death (apoptosis). [47]
5. In patients with advanced breast cancer, danazol administration improved the survival rate. [48-49]
6. In a human endometrial cancer cell line, danazol displayed growth-inhibitory effects. [50-51]
7. In women with benign breast disease, danazol treatment reduced the risk of cancer progression. [52]
8. In menopausal and postmenopausal women with uterine tumors, danazol decreased tumor size without further recurrence and/or progression of the disease. [53-54]
9. In women with metastatic breast cancer, danazol has been found to be more effective than other chemotherapeutic drugs such as tamoxifen and fluoxymesterone. [55]
10. A study also found that danazol can induce cell cycle arrest of multi-drug resistant cancer cells. [56]
11. A cell study found that monotherapy with danazol induced apoptosis and cytotoxicity of leukemic cells. [57]
12. A cell study found that danazol increased the sensitivity of cancer cells to chemotherapeutic drugs. [58]
13. A cell study also found that danazol was toxic to human cervical cancer cells. [59]
14. In patients with advanced breast cancer, danazol treatment stabilized the disease. [60]

Improves Fertility in Women and Increases Pregnancy Rate

An overwhelming body of high-quality studies shows that danazol can be a safe and effective therapeutic option in women with endometriosis and infertility:

1. In patients with unsuccessful in vitro fertilization-embryo transfer, danazol treatment (400 mg/d orally for 12 weeks) showed a significant increase in the pregnancy rate. [61]
2. Danazol treatment at 100 mg daily for 3 months is associated with a 40 to 50% pregnancy rate in women with endometriosis. [62]
3. Danazol administration also improved pregnancy outcomes in women with endometriosis who had surgical procedures and those who had non-invasive laser treatment. [63-64]
4. Danazol administration in women with endometriosis for 3-6 months is associated with regression and disappearance of endometriosis and a higher pregnancy rate. [65]
5. A 6-year study assessing the benefits of danazol in infertile women found a higher pregnancy rate for the 800-mg danazol regimen than for the 400-mg regimen. [66]
6. In women with endometriosis-associated infertility, danazol treatment is associated with a 45% pregnancy rate compared to 32% with lynestrenol (a fertility medication). [67]
7. A study also found that danazol is as effective as gestrinone (a drug used for endometriosis) in the treatment of infertility. [68]
8. A 3-year study on infertile women found that danazol therapy improved ovulation with minimal side effects. [69]
9. Postoperative danazol therapy in infertile patients with severe endometriosis is associated with a higher pregnancy rate. [70]
10. Vaginally administered danazol has been found to improve heavy menstrual bleeding and restore fertility in women with endometriosis. [71]
11. A trial of 100mg danazol daily for 3 months in infertile women found that the treatment increased the pregnancy rate by 40-50%. [72]
12. In patients with stage 1 endometriosis, treatment with danazol for 6 months resulted in more pregnancies. [73]
13. In patients with mild or moderate endometriosis who had no previous treatments, administration of danazol increased the pregnancy rate. [74]
14. In patients with severe endometriosis, danazol administration following surgery significantly improved the pregnancy rate. [75]

Treats Uterine Problems

Numerous studies have shown that danazol is highly effective in the treatment of various uterine problems such as uterine fibroids, endometriosis, and other uterine disorders:

1. In patients with pelvic endometriosis, the lower than maximum doses of danazol ameliorated the symptoms. [76]
2. In patients with laparoscopically-diagnosed endometriosis, danazol treatment at 200 mg three times a day for 24 weeks reduced the symptoms. [77]
3. A study reported that danazol and goserline (an anti-cancer drug) were equally effective in symptomatic relief of endometriosis. [78-79]
4. In patients with endometriosis treated with danazol for 6 months, a marked reduction in the size of the endometrium was observed. [80]
5. In a woman with pulmonary endometriosis, a rare form of endometriosis where endometrial-like tissue is found in the lungs, danazol treatment for 6 months allowed the subject to remain symptom-free for 12 months. [81]
6. In women with endometriosis who received danazol treatment, a significant reduction in autoantibodies such as total immunoglobulin levels (IgG, IgM, and IgA) was found. [82]
7. In patients who received danazol vaginally before hysteroscopy (a surgery that allows the surgeon to look inside the uterus), a shorter operating time, lower infusion volume, fewer side effects, and higher surgeon satisfaction were observed. [83]
8. In premenopausal women with dysfunctional uterine bleeding, danazol therapy for 6 weeks resulted in a significant increase in the uterine artery impedance, thus, reducing uterine bleeding. [84]
9. In patients with advanced endometriosis, danazol treatment at a dose of 200 mg 3 times daily significantly alleviated pelvic pain. [85]
10. A study reported that gestrinone is on par with danazol in treating and preventing the recurrence of the symptoms of endometriosis. [86]
11. In patients with advanced endometriosis, the combination therapy of danazol and gonadotropin-releasing hormone agonist induced the regression of fluid. [87]
12. In patients with adenomyosis (a condition in which the endometrium breaks through the muscle wall of the uterus) and myoma (smooth, noncancerous tumors in the uterus), the injection of a danazol suspension into the uterine cervix improved subjective symptoms after 24 weeks. [88]
13. In patients with benign, severe menorrhagias (abnormal vaginal bleeding), danazol was found to be effective in reducing the amount of bleeding. [89]
14. In women with endometriosis, long-term treatment with danazol caused shrinking of the endometrium similar to that induced by gestrinone. [90]
15. Danazol administration in patients with endometriosis was associated with complete disease regression and symptom relief. [91]
16. A cell study found that both danazol and testosterone have inhibitory effects on the growth of human endometrial cells. [92]
17. In patients with mild-moderate endometriosis, the administration of danazol (200 mg 3 times daily) significantly alleviated endometriosis-associated pelvic pain, lower back pain, and defecation pain. [93-95]

Treats Bleeding Disorders

Strong clinical evidence suggests that danazol may help stop significant blood loss in people with bleeding disorders:

1. In premenopausal women with dysfunctional uterine bleeding, danazol therapy for 6 weeks resulted in a significant increase in the uterine artery impedance, thus, reducing uterine bleeding. [84]
2. In patients with abnormal vaginal bleeding, danazol was found to be effective in reducing the bleeding episodes. [89]
3. In patients with chronic idiopathic thrombocytopenic purpura, a blood disorder characterized by abnormally low platelets in the blood and is associated with increased risk of bleeding, danazol therapy reduced the prevalence of bleeding. [96]
4. In women with autoimmune thrombocytopenia (low platelet count), danazol treatment resulted in increased platelet count and eliminated the need for surgery. [97]
5. In patients with chronic idiopathic thrombocytopenic purpura, a very low dose danazol regimen significantly increased CD4 cells (fight infection). [98]

Associated Side Effects of Danazol

Danazol side effects are very uncommon. There have been some side effects associated with the use of this drug wherein the patient had one of the issues listed below at some point while being on danazol. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of danazol. Despite this, it was listed as a side effect associated with danazol even though these associated side effects are very uncommon.

Side effects associated with danazol may include the following:

• Acne
• Changes in the menstrual cycle
• Decrease in breast size
• Flushing
• Irritability
• Nervousness
• Oily skin or hair
• Sweating
• Vaginal dryness, burning, itching, or bleeding

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