Abstract

PIP: Danazol, a heterocyclic steroid related chemically to 17 alpha-ethinyltestosterone (ethisterone), is currently approved by the FDA for treatment of endometriosis only. However, other clinical applications of the drug may be found for both endocrine and nonendocrine disorders. Hence, the literature of danazol is reviewed. Included are discussions of the chemical structure and biological properties of danazol, which has a basic cyclopentenophenanthrene configuration characteristic of all steroids, and exerts its effects at a subcellular level. Its metabolism and excretion have been studied in animals extensively and in humans via tritiated danazol administration. The drug is well-absorbed from the gastrointestinal system and is rapidly metabolized. Over 60 metaboites have been associated with the metabolic endproduct of tritiated danazol, but only 6 are recognized as metabolites of the drug. Its antigonadotropic effect receives the most attention in the review. In experimental animals various doses of danazol have suppressed gonadal weight (rats), suppressed pituitary gonadotropins (rats and humans), suppressed gonadotropin-releasing hormones (rats and humans), suppressed fertility (rats and rhesus monkeys), and suppressed gonadal steroidogenesis (rats and hamsters). Other biological properties of danazol, besides its primary one of suppression of gonadotropic effect, are related to its androgenicity. Various conceivable clinical applications of danazol are discussed, and its use in therapy of endometriosis is outlined and discussed in detail.