Danazol

Danazol is a derivative of the synthetic steroid ethisterone, a modified testosterone. Also known as 17alpha-ethinyl testosterone. Before becoming available as a generic drug, Danazol was marketed as Danocrine in the United States. It was approved by the U.S. Food and Drug Administration (FDA) as the first drug to specifically treat endometriosis in the early 1970s. Although effective for endometriosis, its use is limited by its masculinizing side-effects. Its role as a treatment for endometriosis has been largely replaced by the GnRH agonists.

Chemistry
The agent is fat-soluble. It is an isoxazole of testosterone with isolated weak androgenic activity and no estrogenic or progestagenic effects.

Method of action
Danazol inhibits ovarian steroidogenesis resulting in decreased secretion of estradiol and may increase androgens. Pituitary hormones are largely unaffected although luteinizing hormone (LH) may be slightly elevated.

Indications
Danazol has been used - mostly off-label - for other indications, namely in the management of menorrhagia, fibrocystic breast disease, immune thrombocytopenic purpura, breast pain (mastodynia) and hereditary angioedema. Though danazol prevents pregnancy, it is not licenced for use as a contraceptive agent.

Although not currently a standard treatment for menorrhagia, danazol has resulted in significant relief in young women with menorrhagia in a study, and, because of a lack of significant adverse effects, it was proposed as an alternative treatment.

Side-effects
Androgenic side effects are of concern, because in sensitive female patients, danazol can enhance unwanted hair growth, leading to hirsutism. On rare occasion, it can deepen the voice. Other possible side effects include acne and oily skin. Because danazol is metabolized by the liver, it cannot be used by patients with liver disease, and in patients receiving long-term therapy, liver function must be monitored on a periodic basis. Some patients who use danazol experience weight gain and fluid retention. Due to these limitations, danazol is seldom prescribed continuously beyond six months.

The use of danazol for endometriosis has been linked to an increased risk of ovarian cancer. Patients with endometriosis have specific risk factors for ovarian cancer so this may not apply for other uses.

Danazol has, like most other androgenic agents, been linked with an increased risk of liver tumors. These are generally benign.

Unlike GnRH agonists, danazol does not induce osteoporosis. Also, symptoms of hot flushes tend to be less common or severe.

Contraindications
Danazol is contraindicated in pregnancy because it could masculinize a female fetus.