Department of Obstetrics & Gynecology, Division of Midlife Health, University of Virginia Health System, Charlottesville, VA, United States.
Department of Obstetrics & Gynecology, Division of Midlife Health, University of Virginia Health System, Charlottesville, VA, United States.
J Steroid Biochem Mol Biol. 2014 Jul;142:142-54. doi: 10.1016/j.jsbmb.2013.12.011. Epub 2013 Dec 25.
Selective estrogen receptor modulators (SERMs) are synthetic non-steroidal agents which have varying estrogen agonist and antagonist activities in different tissues, most likely due to the receptor conformation changes associated with that SERM's binding and the subsequent effect on transcription. Clinical trials aim to differentiate amongst SERMs on selected target tissues for use in postmenopausal women including effects on breast, bone, cardiovascular venous thrombosis risk, endometrium, vagina, vasomotor symptoms, and brain. This paper describes differences in clinical effects on selected target tissues of SERMs that are approved, discontinued or in development. FDA approved SERMs include tamoxifen and toremifene used for prevention and treatment of breast cancer, raloxifene approved for prevention and treatment of osteoporosis and prevention of invasive breast cancer, and ospemifene approved for treatment of dyspareunia from menopausal vaginal atrophy. The FDA approved first tissue selective estrogen complex (TSEC) a pairing of conjugated equine estrogens with the SERM, bazedoxifene. This pairing reduces the risk of endometrial hyperplasia that can occur with the estrogenic component of the TSEC without the need for a progestogen in women with a uterus. It also allows for the estrogenic benefits on relief of hot flashes and prevention of bone loss without stimulating the breast or the endometrium. In clinical practice, the tissue-selective actions of SERMs, alone or paired with estrogens, allow for individualization in meeting the treatment needs of postmenopausal women by providing targeted tissue effects. This article is part of a Special Issue entitled 'Menopause'.
选择性雌激素受体调节剂（SERMs）是一种合成的非甾体类药物，在不同组织中具有不同的雌激素激动剂和拮抗剂活性，这很可能是由于该 SERM 结合后受体构象的变化以及随后对转录的影响。临床试验旨在区分不同的 SERMs 在绝经后妇女选定的靶组织中的作用，包括对乳房、骨骼、心血管静脉血栓形成风险、子宫内膜、阴道、血管舒缩症状和大脑的影响。本文描述了已批准、已停用或正在开发的 SERMs 在选定靶组织的临床效应差异。美国食品和药物管理局（FDA）批准的 SERMs 包括用于预防和治疗乳腺癌的他莫昔芬和托瑞米芬、用于预防和治疗骨质疏松症以及预防浸润性乳腺癌的雷洛昔芬，以及用于治疗绝经后阴道萎缩引起的性交困难的奥昔布芬。FDA 批准的第一个组织选择性雌激素复合物（TSEC）是结合了雌激素和 SERM 巴多昔芬的共轭马雌激素。这种组合降低了 TSEC 中雌激素成分引起子宫内膜增生的风险，而无需在有子宫的妇女中使用孕激素。它还允许雌激素对缓解热潮红和预防骨质流失的益处，而不会刺激乳房或子宫内膜。在临床实践中，SERMs 的组织选择性作用，无论是单独使用还是与雌激素联合使用，都可以通过提供针对特定组织的效应，实现个体化满足绝经后妇女的治疗需求。本文是题为“更年期”的特刊的一部分。
