Selective Progesterone Receptor Modulators-Mechanisms and Therapeutic Utility.
Selective Progesterone Receptor Modulators-Mechanisms and Therapeutic Utility.
复制标题
DOI：
10.1210/endrev/bnaa012
复制
发表时间：
2020-10-01
影响因子：
20.3
通讯作者：
Segars J
中科院分区：
文献类型：
--
作者：
Islam MS;Afrin S;Jones SI;Segars J
选择性孕激素受体调节剂(SPRM)是一类以孕激素受体(PR)为靶点的新型化合物，兼具激动剂和拮抗剂的特性。基于孕酮在生殖和生殖组织中的关键作用，这些化合物已被引入用于治疗几种妇科疾病。在子宫肌瘤患者中，米非司酮和醋酸利普司坦一直显示出疗效，维拉普兰目前正在研究中，而阿索普利斯尼和替拉普司酮的研究出于安全考虑而暂停。米非司酮显示出对子宫内膜异位症的有效治疗作用，而关于阿司匹尼、醋酸利普利司酮、替拉普司酮和维拉普森治疗这种情况的疗效的数据有限。目前，没有一种SPRM在治疗子宫内膜癌方面显示出成功的疗效。已经评估了多种SPRM治疗PR阳性复发乳腺癌的疗效，体内研究表明米非司酮有好处，多种体外模型表明醋酸利普司通和替拉普司酮的疗效。米非司酮、醋酸利普司坦、维拉普兰和阿索普利尼有效治疗子宫肌瘤患者的月经大出血，但关于SPRM治疗子宫肌瘤的疗效的数据有限。SPRM的一个显著的类别效应是良性的PR调节剂相关的子宫内膜改变(PAECs)，这是由于化合物对子宫内膜的作用。米非司酮和醋酸利普司坦在紧急避孕方面都有效，米非司酮由于具有额外的抗糖皮质激素作用，于2012年被美国食品和药物管理局(FDA)批准用于治疗库欣综合征。根据目前的证据，SPRM在治疗几种妇科疾病方面显示出相当大的前景。
Selective progesterone receptor modulators (SPRMs) are a new class of compounds developed to target the progesterone receptor (PR) with a mix of agonist and antagonist properties. These compounds have been introduced for the treatment of several gynecological conditions based on the critical role of progesterone in reproduction and reproductive tissues. In patients with uterine fibroids, mifepristone and ulipristal acetate have consistently demonstrated efficacy, and vilaprisan is currently under investigation, while studies of asoprisnil and telapristone were halted for safety concerns. Mifepristone demonstrated utility for the management of endometriosis, while data are limited regarding the efficacy of asoprisnil, ulipristal acetate, telapristone, and vilaprisan for this condition. Currently, none of the SPRMs have shown therapeutic success in treating endometrial cancer. Multiple SPRMs have been assessed for efficacy in treating PR-positive recurrent breast cancer, with in vivo studies suggesting a benefit of mifepristone, and multiple in vitro models suggesting the efficacy of ulipristal acetate and telapristone. Mifepristone, ulipristal acetate, vilaprisan, and asoprisnil effectively treated heavy menstrual bleeding (HBM) in patients with uterine fibroids, but limited data exist regarding the efficacy of SPRMs for HMB outside this context. A notable class effect of SPRMs are benign, PR modulator-associated endometrial changes (PAECs) due to the actions of the compounds on the endometrium. Both mifepristone and ulipristal acetate are effective for emergency contraception, and mifepristone was approved by the US Food and Drug Administration (FDA) in 2012 for the treatment of Cushing’s syndrome due to its additional antiglucocorticoid effect. Based on current evidence, SPRMs show considerable promise for treatment of several gynecologic conditions.