Department of Internal Medicine, Endocrine-Metabolic Sciences and Biochemistry, University of Siena, Policlinico Le Scotte 53100-Siena, Italy.
Ther Clin Risk Manag. 2008 Dec;4(6):1229-42. doi: 10.2147/tcrm.s3476.
Bazedoxifene acetate is a novel, chemically distinct selective estrogen receptor modulator (SERM) that has been specifically developed after a stringent preclinical screening in order to obtain favorable effects on the skeleton and lipid metabolism with the additional improvement of a neutral effect on hot flushes and without stimulating the uterus or the breast. In both preclinical and clinical studies this SERM was shown to maintain BMD, prevent fractures, and reduce total cholesterol. Moreover, bazedoxifene also showed an improved uterine profile and demonstrated estrogen antagonistic activity on the endometrium. Importantly, this latter capacity has led to the development of a novel class of menopausal therapy called tissue selective estrogen complex (TSEC), in which bazedoxifene is combined with conjugated estrogen. The rationale for selecting bazedoxifene as the SERM in this TSEC combination is that it may offset estrogen stimulation of endometrial and breast tissue, without the necessity of using a progestin in women with an intact uterus, without aggravating menopausal vasomotor symptoms, but with an additive effect on bone. Preliminary data from phase 3 clinical trials appear to confirm this hypothesis, showing a greater effect of bazedoxifene on BMD with respect to raloxifene, coupled with efficacy on menopausal vasomotor symptoms not achieved by SERM alone. These properties and the safety profile of this combination, if confirmed long-term in ongoing phase 3 trials, might significantly affect the way women and physicians approach menopause and its related disorders.
醋酸巴多昔芬是一种新型、化学结构独特的选择性雌激素受体调节剂（SERM），它是在严格的临床前筛选后专门开发的，旨在获得对骨骼和脂代谢的有利影响，同时改善潮热的中性影响，而不刺激子宫或乳房。在临床前和临床研究中，这种 SERM 被证明可以维持骨密度、预防骨折和降低总胆固醇。此外，巴多昔芬还显示出改善的子宫特征，并表现出对子宫内膜的雌激素拮抗活性。重要的是，这种能力导致了一种新的绝经治疗方法的发展，称为组织选择性雌激素复合物（TSEC），其中将巴多昔芬与结合雌激素结合使用。选择巴多昔芬作为这种 TSEC 组合中的 SERM 的原理是，它可以抵消雌激素对子宫内膜和乳腺组织的刺激，而无需在子宫完整的女性中使用孕激素，不会加重绝经血管舒缩症状，但对骨骼有附加作用。来自 3 期临床试验的初步数据似乎证实了这一假设，与雷洛昔芬相比，巴多昔芬对骨密度的影响更大，并且对绝经血管舒缩症状的疗效是 SERM 单独使用无法达到的。如果在正在进行的 3 期试验中长期证实这些特性和这种组合的安全性概况，可能会显著影响女性和医生处理绝经及其相关疾病的方式。
