Raynaud J P, Coussediere D, Moguilewsky M, Pottier J, Labrie F
Bull Cancer. 1986;73(1):36-46.
Although orchiectomy, estrogens and LHRH agonists suppress testicular androgens, they are without effect on adrenal androgens which are converted into dihydrotestosterone in the prostate. It is therefore necessary to develop substances able to block the action of all androgens, whatever their source, on target organs. The non-steroid, Anandron (RU 23908), when administered orally, gives rise to a high and sustained plasma level of intact compound that inhibits testosterone binding to its receptor. This inhibition, however, occurs not only in the prostate but also in the pituitary. The negative feedback action of androgens is thus inhibited by Anandron resulting in an increased secretion of testosterone and explaining the necessity of combining Anandron with castration (whether surgical or medical by an LHRH agonist). Anandron opposes, on the one hand, the action of adrenal androgens and, on the one other, of the testosterone surge that occurs during the early days of treatment with the LHRH analog. The efficacy of the combined treatment has been demonstrated experimentally. Clinical trials are presently underway.
虽然睾丸切除术、雌激素和促性腺激素释放激素(LHRH)激动剂可抑制睾丸雄激素,但它们对肾上腺雄激素无效,而肾上腺雄激素会在前列腺中转化为双氢睾酮。因此,有必要研发能够阻断所有来源的雄激素对靶器官作用的物质。非甾体类药物阿南雄(RU 23908)口服给药后,会在血浆中产生高浓度且持续的完整化合物水平,该化合物可抑制睾酮与其受体的结合。然而,这种抑制不仅发生在前列腺,也发生在垂体。因此,阿南雄会抑制雄激素的负反馈作用,导致睾酮分泌增加,这也解释了将阿南雄与去势(无论是手术去势还是使用LHRH激动剂进行药物去势)联合使用的必要性。一方面,阿南雄可对抗肾上腺雄激素的作用,另一方面,它也可对抗在使用LHRH类似物治疗初期出现的睾酮激增。联合治疗的疗效已在实验中得到证实。目前正在进行临床试验。