Review of menopausal hormone therapy with estradiol and progesterone versus other estrogens and progestins

Objective: The objective of the present document was to review/summarize reported outcomes compared between menopausal hormone therapy (MHT) containing estradiol (E2) versus other estrogens and MHT with progesterone (P4) versus progestins (defined as synthetic progestogens). Methods: PubMed and EMBASE were systematically searched through February 2021 for studies comparing oral E2 versus oral conjugated equine estrogens (CEE) or P4 versus progestins for endometrial outcomes, venous thromboembolism (VTE), cardiovascular outcomes, breast outcomes, cognition, and bone outcomes in postmenopausal women. Results: A total of 74 comparative publications were identified/summarized. Randomized studies suggested that P4 and progestins are likely equally effective in preventing endometrial hyperplasia/cancer when used at adequate doses. E2- versus CEE-based MHT had a similar or possibly better risk profile for VTE and cardiovascular outcomes, and P4- versus progestin-based MHT had a similar or possibly better profile for breast cancer and cardiovascular outcomes. E2 may potentially protect better against age-related cognitive decline and bone fractures versus CEE; P4 was similar or possibly better versus progestins for these outcomes. Limitations are that many studies were observational and some were not adequately powered for the reported outcomes. Conclusions: Evidence suggests a differential effect of MHT containing E2 or P4 and those containing CEE or progestins, with some evidence trending to a potentially better safety profile with E2 and/or P4.

研究目标：本综述的核心目标为系统梳理并总结已发表的研究结果，对比含雌二醇（estradiol, E2）的绝经激素治疗（menopausal hormone therapy, MHT）与其他雌激素的临床结局，以及含孕酮（progesterone, P4）的MHT与合成孕激素（progestins，即人工合成孕激素）的临床结局。研究方法：截至2021年2月，对PubMed与EMBASE数据库开展系统性检索，纳入对比口服雌二醇与口服结合型雌激素（conjugated equine estrogens, CEE）、口服孕酮与合成孕激素的相关研究，分析绝经后女性的子宫内膜结局、静脉血栓栓塞症（venous thromboembolism, VTE）、心血管结局、乳腺结局、认知功能与骨骼结局。研究结果：最终共纳入74篇对比性研究文献并进行总结分析。随机对照研究显示，当使用足量剂量时，孕酮与合成孕激素在预防子宫内膜增生/癌变方面的临床效果相当。以雌二醇为基础的MHT相较于以结合型雌激素为基础的MHT，在静脉血栓栓塞症与心血管结局的风险特征上相似或更具优势；以孕酮为基础的MHT相较于以合成孕激素为基础的MHT，在乳腺癌与心血管结局的风险特征上相似或更具优势。相较于结合型雌激素，雌二醇可能更有助于抵御年龄相关性认知衰退与骨折；孕酮与合成孕激素在上述结局上效果相似或更优。研究局限性：本研究存在一定局限性：多数研究为观察性研究，且部分研究的统计效力不足以检测所报告的结局差异。研究结论：现有证据表明，含雌二醇或孕酮的MHT与含结合型雌激素或合成孕激素的MHT存在差异化的临床效应，部分证据提示含雌二醇和/或孕酮的MHT可能拥有更优的安全性谱。