Summary: Danazol is being increasingly used for the treatment of a wide range of disorders, many of which appear to bear little relation to the condition for which the drug was originally marketed – endometriosis. It has been claimed that this drug acts by means of its antigonadotrophic effects on the pituitary; however, a review of the literature reveals that its efficacy in suppressing normal endometrial growth and in causing atrophy of deposits of endometrium cannot be explained solely on this basis. Recent information indicates that, besides acting at the pituitary level, a major mechanism of action may be by a direct inhibitory effect on target tissues. It is suggested that such a mechanism would more readily account for the diverse effects of this drug in the treatment of many disorders, all of which appear to be associated with an imbalanced sensitivity of target organs to steroid hormones. A greater understanding of its mechanism of action could lead to an even wider application of this novel drug.
Shelton and Rajfer (2012) noted that androgen deficiency in aging men is common, and the potential sequelae are numerous. In addition to low libido, erectile dysfunction, decreased bone density, depressed mood, and decline in cognition, studies suggest strong correlations between low testosterone, obesity, and the metabolic syndrome. Because causation and its directionality remain uncertain, the functional and cardiovascular risks associated with androgen deficiency have led to intense investigation of testosterone replacement therapy in older men. Although promising, evidence for definitive benefit or detriment is not conclusive, and treatment of LOH is complicated.
Danazol, an isoxazol derivative of ethinyl testosterone which suppresses gonadotropin levels and acts as a weak androgen, is shown by competition studies to bind rat androgen receptor (Ki 10(-8M) and progestin receptor (Ki 10(-7)M) but not estrogen receptor. Effective antigonadotropin doses to the rat in vivo translocate only androgen receptor to target cell nuclei; nuclear receptor levels remain elevated more than 6 hours. The same translocation occurs when rat uteri are incubated with danazol in vitro, showing that the action of danazol is direct and probably does not require metabolic conversion of the drug.