Stovall Dale W
The University of Virginia Health System, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, PO Box 800712, Charlottesville, VA 22908, USA.
Curr Opin Investig Drugs. 2010 Apr;11(4):464-71.
Aprela, in development by Pfizer Inc, is a once-daily, orally administered, tissue-selective estrogen complex that contains the selective estrogen receptor modulator bazedoxifene (BZA) and conjugated equine estrogens (CE). Aprela was designed as an alternative to combination estrogen and progestin therapy to treat the vasomotor symptoms associated with menopause without the potential safety concerns associated with combination estrogen/progestin therapy, and with better tolerability. Both estrogens and BZA bind to estrogen receptors (ER)alpha and beta, but when BZA binds to an ER, the result may be an estrogen agonistic or antagonistic effect. In contrast, progestins antagonize the effects of estrogen in the uterus, but along with estrogen, stimulate breast tissue increasing the risk for breast cancer. In phase III clinical trials, Aprela significantly reduced the number and severity of vasomotor symptoms, reduced vaginal atrophy and increased bone mineral density. However, higher doses of BZA tended to attenuate these positive effects of CE. At the time of publication, there were no clinical data from women taking Aprela for > 2 years, and no definitive trials to determine the effects of Aprela on the risks for cardiovascular events, stroke, breast cancer, venous thromboembolism or cognitive function had been completed. Nevertheless, at the time of publication, Aprela was under consideration by the FDA for approval to treat vasomotor symptoms in postmenopausal women.
阿普雷拉（Aprela）由辉瑞公司研发，是一种每日服用一次的口服组织选择性雌激素复合物，含有选择性雌激素受体调节剂巴泽昔芬（BZA）和结合马雌激素（CE）。阿普雷拉被设计为雌激素和孕激素联合疗法的替代方案，用于治疗与更年期相关的血管舒缩症状，不存在雌激素/孕激素联合疗法相关的潜在安全问题，且耐受性更好。雌激素和BZA均可与雌激素受体（ER）α和β结合，但当BZA与ER结合时，结果可能是雌激素激动或拮抗作用。相比之下，孕激素可拮抗雌激素在子宫中的作用，但与雌激素一起会刺激乳腺组织，增加患乳腺癌的风险。在III期临床试验中，阿普雷拉显著减少了血管舒缩症状的数量和严重程度，减轻了阴道萎缩并增加了骨矿物质密度。然而，较高剂量的BZA往往会减弱CE的这些积极作用。在发表时，尚无服用阿普雷拉超过2年的女性的临床数据，也未完成确定阿普雷拉对心血管事件、中风、乳腺癌、静脉血栓栓塞或认知功能风险影响的确定性试验。尽管如此，在发表时，美国食品药品监督管理局（FDA）正在考虑批准阿普雷拉用于治疗绝经后女性的血管舒缩症状。
