Profile of estetrol, a promising native estrogen for oral contraception and the relief of climacteric symptoms of menopause
Profile of estetrol, a promising native estrogen for oral contraception and the relief of climacteric symptoms of menopause
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DOI：
10.1080/17512433.2022.2054413
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发表时间：
2022-03-28
影响因子：
4.4
通讯作者：
Foidart, Jean-Michel
中科院分区：
文献类型：
--
作者：
Gerard, Celine;Arnal, Jean-Francois;Foidart, Jean-Michel
在妇女保健中使用的雌激素与静脉血栓栓塞（VTE）和乳腺癌的风险增加有关。Estetrol （E4）是一种由人类胎儿肝脏产生的雌激素，最近首次被批准作为一种新型联合口服避孕药（E4/drospirenone [DRSP]）的新的雌激素成分，已有十多年的历史。在3期研究中，E4/DRSP显示出良好的避孕效果、可预测的出血模式、良好的安全性和耐受性。涉及领域：这篇叙述性综述讨论了E4MODIFIER LETTER PRIMEs的药理学特征、作用方式，以及避孕、更年期和肿瘤的临床前和临床研究结果。专家意见：广泛的研究已经阐明了E4的特性，奠定了其良好的安全性。经典雌激素（如雌二醇）通过激活核和膜雌激素受体α (ER α)来发挥作用，而E4呈现出ER α激活的特殊特征：E4结合并激活核ER α，但不诱导特定组织中膜ER α信号通路的激活。E4对正常乳腺组织增殖影响较小，对肝脏参数影响最小。这种独特的内质网α激活，解耦核和膜激活，是独一无二的。
Introduction: Estrogens used in women's healthcare have been associated with increased risks of venous thromboembolism (VTE) and breast cancer. Estetrol (E4), an estrogen produced by the human fetal liver, has recently been approved for the first time as a new estrogenic component of a novel combined oral contraceptive (E4/drospirenone [DRSP]) for over a decade. In phase 3 studies, E4/DRSP showed good contraceptive efficacy, a predictable bleeding pattern, and a favorable safety and tolerability profile.Areas covered: This narrative review discusses E4MODIFIER LETTER PRIMEs pharmacological characteristics, mode of action, and the results of preclinical and clinical studies for contraception, as well as for menopause and oncology.Expert opinion: Extensive studies have elucidated the properties of E4 that underlie its favorable safety profile. While classical estrogens (such as estradiol) exert their actions via both activation of nuclear and membrane estrogen receptor alpha (ER alpha), E4 presents a specific profile of ER alpha activation: E4 binds and activates nuclear ER alpha but does not induce the activation of membrane ER alpha signaling pathways in specific tissues. E4 has a small effect on normal breast tissue proliferation and minimally affects hepatic parameters. This distinct profile of ER alpha activation, uncoupling nuclear and membrane activation, is unique.