Danazol is used for the treatment of the following conditions:

• Endometriosis
• Benign breast disorders
• Menorrhagia (heavy menstrual bleeding)
• Gynecomastia
• Preoperative thinning of the endometrium prior to hysteroscopic endometrial ablation

Danazol acts as a gonadotropin inhibitor by suppressing the pituitary–ovarian axis, likely through reducing the release of pituitary gonadotropins. It decreases the preovulatory surge of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which in turn lowers ovarian estrogen production. Danazol may also directly inhibit ovarian steroid production. Additionally, it can bind to androgen, progesterone, and glucocorticoid receptors, as well as to sex hormone-binding globulin and corticosteroid-binding globulin, and it increases the metabolic clearance of progesterone. Another possible mechanism in the treatment of endometriosis involves reducing levels of immunoglobulins (IgG, IgM, IgA) and certain autoantibodies. By suppressing ovarian function, danazol causes both normal and ectopic endometrial tissue to become inactive and atrophic, leading to anovulation and amenorrhea. In fibrocystic breast disease, the exact mechanism is unclear, but it is thought to be related to reduced estrogen stimulation due to decreased ovarian estrogen production. A direct effect on steroid receptors in breast tissue may also contribute. This results in reduced nodularity, relief from pain and tenderness, and possible changes in menstrual patterns. In hereditary angioedema, danazol helps correct the underlying biochemical deficiency by increasing serum levels of C1 esterase inhibitor, which in turn raises the level of the C4 component of the complement system.

Usually given in up to 4 divided doses; in women of child-bearing potential, treatment should start during menstruation, preferably on first day.

Endometriosis: 200-800 mg daily in up to 4 divided doses, adjusted to achieve amenorrhoea, usually for 6 months (up to 9 months in some cases).

Menorrhagia: In menorrhagia daily doses of 100-200 mg have been found effective but 200 mg daily for 3 months is usually sufficient to reduce menstrual blood flow to acceptable levels.

Severe cyclical mastalgia: 100-400 mg daily usuallys for 3-6 months

Benign breast cysts: 300 mg daily usually for 3-6 months

Gynaecomastia: 400 mg daily in up to 4 divided doses for 6 months (adolescents 200 mg daily, increased to 400 mg daily if no response after 2 months).

For pre-operative thinning of endometrium: 400 mg-800 mg daily in up to 4 divided doses for 3-6 weeks

Children: Danazol is not used in children

Insulin: Danazol therapy may lead to increased insulin resistance in patients. The clinical significance is unclear, but careful monitoring is recommended.

Estrogens and progestogens: Danazol may theoretically interact with externally administered estrogens and/or progestogens. It is believed to act by binding to estrogen, progesterone, or androgen receptors at different levels of the hypothalamic–pituitary–ovarian axis. Therefore, women of reproductive age should use reliable non-hormonal contraceptive methods.

Anticonvulsant therapy: Danazol may alter plasma levels of carbamazepine and may affect patient response to carbamazepine and phenytoin. A similar interaction may also occur with phenobarbital.

Antihypertensive therapy: Danazol may reduce the effectiveness of antihypertensive drugs, possibly due to fluid retention.

Cyclosporine: Danazol can increase the plasma concentration of cyclosporine.

Migraine therapy: Danazol may trigger migraine attacks and could also reduce the effectiveness of medications used for migraine prevention.

Common adverse effects of danazol include nausea, dizziness, skin reactions such as rashes, photosensitivity, and exfoliative dermatitis, fever, back pain, nervousness, mood changes, anxiety, altered libido, vertigo, fatigue, epigastric and pleuritic pain, headache, and weight gain. Menstrual irregularities, vaginal dryness and irritation, flushing, and reduced breast size may also occur. Musculoskeletal symptoms such as muscle spasms, joint pain and swelling, and hair loss have been reported. Androgenic effects may include acne, oily skin, edema, hirsutism, voice changes, and rarely clitoral enlargement. Temporary changes in lipid profile and other metabolic parameters, including insulin resistance, may occur. Other reported effects include thrombotic events, leucopenia, thrombocytopenia, eosinophilia, and reversible erythrocytosis or polycythaemia. Headache and visual disturbances may suggest benign intracranial hypertension.

This drug is contraindicated in pregnancy due to the risk of virilization of a female fetus, especially when high doses are used for several weeks. Women receiving this medication should avoid breastfeeding.

Caution is required in patients with cardiac, hepatic, or renal impairment, as well as in the elderly. It should also be used carefully in conditions such as polycythaemia, epilepsy, diabetes mellitus, hypertension, migraine, lipid (lipoprotein) disorders, and a history of thrombosis or thromboembolic disease. If any signs of virilization develop, such as voice deepening or hirsutism, treatment should be discontinued immediately.

Drugs affecting (inhibiting) gonadotrophin

Store at a temperature below 30°C, protected from light and moisture. Keep out of reach of children.