Barbieri R L, Ryan K J
Am J Obstet Gynecol. 1981 Oct 15;141(4):453-63. doi: 10.1016/0002-9378(81)90611-6.
The options for the medical management of endometriosis have been expanded 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 pharmacology of danazol concluded that danazol was a strong antigonadotrophin with mild androgenic effects and no other hormonal properties. 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 gonadally intact human beings; (3) in castrated animals danazol can prevent the compensatory increase in LH and FSH; (4) danazol binds to androgen, progesterone, and glucocorticoid receptors; (5) danazol does not bind to estrogen receptors; (6) danazol binds to sex hormone-binding globulin and corticosteroid-binding globulin; (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 antigonadotrophin."U
合成类固醇达那唑的引入扩展了子宫内膜异位症的药物治疗选择。大型临床研究结果表明，达那唑治疗能使子宫内膜异位症的症状、体征及腹腔镜检查结果得到显著改善。最初关于达那唑药理学的研究得出结论，达那唑是一种强效抗促性腺激素，具有轻度雄激素作用且无其他激素特性。近期强调达那唑分子药理学的研究表明，这种类固醇对下丘脑 - 垂体功能、多类类固醇受体、性腺类固醇生成及内源性类固醇代谢有直接影响。这些研究证明：（1）达那唑可阻止黄体生成素（LH）和卵泡刺激素（FSH）的中期高峰；（2）达那唑对性腺功能正常的人不会显著抑制基础LH或FSH；（3）在去势动物中，达那唑可阻止LH和FSH的代偿性增加；（4）达那唑与雄激素、孕激素和糖皮质激素受体结合；（5）达那唑不与雌激素受体结合；（6）达那唑与性激素结合球蛋白和皮质类固醇结合球蛋白结合；（7）达那唑抑制多种类固醇生成酶；（8）达那唑增加孕酮的代谢清除率；（9）达那唑的代谢产物具有激素活性。鉴于达那唑复杂的药理学特性，继续将其称为“选择性抗促性腺激素”是不合适的。
