Danazol is a synthetic steroid derived from ethisterone, possessing potent androgenic, anti-estrogenic, and anti-gonadotropic properties. It is primarily indicated for the treatment of endometriosis, fibrocystic breast disease, and hereditary angioedema. As an attenuated androgen, danazol suppresses the pituitary-ovarian axis by inhibiting the output of gonadotropins, leading to a reversible hypoestrogenic and hyperandrogenic state. This mechanism makes it a cornerstone in managing conditions driven by hormonal imbalances or immune-mediated pathways, offering significant symptomatic relief and disease modification where conventional therapies may fall short.

Features

• Synthetic steroid with androgenic and anti-estrogenic activity
• Suppresses pituitary secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
• Redects estrogen receptor binding in target tissues
• Available in 50 mg, 100 mg, and 200 mg oral capsules
• Half-life of approximately 4–5 hours
• Hepatic metabolism via CYP3A4

Benefits

• Effectively reduces pelvic pain and lesion size in endometriosis
• Prevents attacks of hereditary angioedema by increasing C1 esterase inhibitor levels
• Alleviates breast pain and nodularity in fibrocystic disease
• Provides an alternative to surgical intervention in select cases
• Allows for reversible suppression of ovarian function
• May reduce menstrual blood loss in menorrhagia

Common use

Danazol is most frequently prescribed for the management of endometriosis, particularly in cases where pain is refractory to NSAIDs or combined oral contraceptives. It is also a first-line therapy for prophylaxis in hereditary angioedema (HAE), significantly reducing the frequency and severity of attacks. In benign breast diseases such as fibrocystic mastopathy, danazol is used to relieve mastalgia and reduce breast nodularity. Off-label uses include the treatment of autoimmune thrombocytopenia, precocious puberty, and gynecomastia, though evidence supporting these applications is less robust.

Dosage and direction

For endometriosis, the typical starting dose is 200–400 mg twice daily, titrated to the lowest effective dose based on symptom response. Therapy is usually initiated during menstruation. For hereditary angioedema, doses range from 200 mg daily to 600 mg daily, depending on attack frequency and severity. In fibrocystic breast disease, doses of 100–400 mg daily in divided doses are common. Danazol should be taken with food to minimize gastrointestinal upset. Regular monitoring of liver function, lipids, and androgenic effects is advised during treatment.

Precautions

Patients should be monitored for signs of virilization, including acne, hirsutism, clitoromegaly, and voice deepening, which may be irreversible. Liver function tests should be performed periodically due to the risk of hepatotoxicity. Lipid profiles may show elevated LDL and reduced HDL cholesterol. Danazol may cause fluid retention, which can exacerbate hypertension, heart failure, or epilepsy. Use with caution in patients with diabetes due to potential alterations in glucose tolerance. Androgenic effects may be more pronounced in women and children.

Contraindications

Danazol is contraindicated in patients with pregnancy or those who may become pregnant due to potential virilization of the female fetus. It should not be used in patients with undiagnosed abnormal genital bleeding, severe hepatic impairment, or porphyria. Additional contraindications include breast cancer (due to theoretical risk of stimulation), severe cardiac or renal disease, and history of thromboembolic disorders. Concomitant use with simvastatin or lovastatin is contraindicated due to increased risk of rhabdomyolysis.

Possible side effect

Common side effects include weight gain, acne, oily skin, reduced breast size, flushing, sweating, and menstrual irregularities. Androgenic effects such as hirsutism, voice deepening, and clitoral enlargement may occur and can be irreversible. Gastrointestinal disturbances like nausea and vomiting are frequent. Less commonly, danazol may cause hepatotoxicity, headache, dizziness, muscle cramps, emotional lability, and changes in libido. Rare but serious adverse effects include hepatic adenoma, pancreatitis, and intracranial hypertension.

Drug interaction

Danazol is a moderate inhibitor of CYP3A4 and may increase levels of drugs metabolized by this enzyme, including carbamazepine, cyclosporine, and tacrolimus. It may potentiate the effects of warfarin, requiring close INR monitoring. Concomitant use with statins (especially simvastatin and lovastatin) increases the risk of myopathy. Danazol may reduce the efficacy of insulin and oral hypoglycemics. Use with other hepatotoxic drugs should be avoided. Coadministration with corticosteroids may alter their metabolism.

Missed dose

If a dose is missed, it should be taken as soon as remembered unless it is nearly time for the next dose. In that case, the missed dose should be skipped, and the regular dosing schedule resumed. Doubling the dose to make up for a missed one is not recommended. Consistent dosing is important for maintaining therapeutic effect, particularly in hereditary angioedema prophylaxis.

Overdose

Symptoms of overdose may include exaggerated androgenic effects, nausea, vomiting, and dizziness. There is no specific antidote for danazol overdose. Management is supportive and symptomatic, including gastric lavage if ingestion was recent. Monitoring of vital signs, liver function, and electrolyte balance is advised. Hemodialysis is unlikely to be effective due to high protein binding.

Storage

Store danazol capsules at room temperature (15–30°C or 59–86°F) in a tightly closed container, protected from light and moisture. Keep out of reach of children and pets. Do not use after the expiration date printed on the packaging.

Disclaimer

This information is intended for medical professionals and should not replace personalized medical advice. Dosage and treatment decisions must be made by a qualified healthcare provider based on individual patient characteristics. Always verify the latest prescribing information and clinical guidelines before initiating therapy.

Reviews

Clinical studies and long-term use support the efficacy of danazol in endometriosis and hereditary angioedema, though its androgenic side effect profile often limits prolonged use. Many experts consider it a valuable option in specific patient populations, particularly where other treatments have failed or are contraindicated. Patient tolerance varies widely, with some individuals experiencing significant symptomatic improvement and others discontinuing due to adverse effects.