Danazol

Danazol is a derivative of the synthetic steroid ethisterone, a modified 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.^[1] Although effective for endometriosis, its use is limited by its masculinizing side-effects.^[2] Its role as a treatment for endometriosis has been largely replaced by the GnRH agonists.

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Chemistry

The agent is fat-soluble. It is an isoxazole of testosterone with isolated weak androgenic activity and no estrogenic or progestagenic effects.^[1]

Method of action

Danazol inhibits ovarian steroidgenesis resulting in decreased secretion of estradiol and may increase androgens. Pituitary hormones are largely unaffected although luteinizing hormone (LH) may be slightly elevated.^[3]

Indications

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

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.^[4] 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.^[5]

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.

References

1. ^ ^{a b} Dmowski WP, Scholer HF, Mahesh VB, Greenblatt RB (1971). "Danazol--a synthetic steroid derivative with interesting physiologic properties". Fertil. Steril. 22 (1): 9–18. PMID 5538758.
2. ^ Selak V, Farquhar C, Prentice A, Singla A (2007). "Danazol for pelvic pain associated with endometriosis". Cochrane database of systematic reviews (Online) (4): CD000068. doi:10.1002/14651858.CD000068.pub2. PMID 17943735.
3. ^ Steingold KA, Lu JK, Judd HL, Meldrum DR (1986). "Danazol inhibits steroidogenesis by the human ovary in vivo.". Fertil Steril 45: 649-54. PMID 3084301.
4. ^ Cottreau CM, Ness RB, Modugno F, Allen GO, Goodman MT (2003). "Endometriosis and Its Treatment with Danazol or Lupron in Relation to Ovarian Cancer". Clinical Cancer Research 9: 5142~5144. PMID 14613992.
5. ^ Velazquez I, Alter BP (2004). "Androgens and liver tumors: Fanconi's anemia and non-Fanconi's conditions". Am. J. Hematol. 77 (3): 257–67. doi:10.1002/ajh.20183. PMID 15495253.