Danazol: Endocrine pharmacology and therapeutic applications

Abstract

The options for the medical management of endometriosis have been expended by the introduction of the synthetic steroid, danazol. The results of large clinical studies suggest that danazol treatment produces significant improvement in the symptoms, signs, and laparoscopic findings of endometriosis. The original studies of the phamacology of danazol concluded that danazol was a strong antigonadotropin with mild androgenic effects and no other hormonal proparties. Recent studies which emphasize the molecular pharmacology of danazol suggest that this steroid has direct effects on hypothalamic-pituitary function, multiple classes of steroid receptors, gonadal steroidogenesis, and endogenous steroid metabolism. These studies demonstrate that: (1) danazol prevents the midcycle surge of luteinizing hormone (LH) and follicle-stimulating hormone (FSH): (2) danazol does not significantly suppress basal LH or FSH in gonadalfy intact human beings; (3) in castrated animals danazol can prevent the compensatory increase in LH and FSH; (4) danazol binds to androgen, progesterone, and glucocorticold receptors; (5) danazol does not bind to estrogen receptors; (6) danazol binds to sex hormone-binding globulin and corticosteroid-binding glubulin; (7) danazol inhibits multiple enzymes of steroidogenesis; (8) danazol increases the metabolic clearance rate of progesterone; and (9) metabolites of danazol are hormonally active. Given the complex pharmacology of danazol it is inappropriate to continue to refer to danazol as a “selective antigonadotropin.”