女性内分泌平衡(专业版)
平衡激素水平,包括孕酮、雌激素、脱氢表雄酮(DHEA)、睾酮和孕烯醇酮,对女性健康很重要。不幸的是,随着年龄的增长,女性体内的激素水平会下降。
其他名称:女性荷尔蒙恢复,生物相同激素替代疗法
英文名称:Female Hormone Restoration,Bioidentical HRT
传统的激素替代疗法(HRT,即妊马雌酮和合成黄体酮)已被证明具有严重的不良后果,包括癌症、血栓和冠心病等风险。幸运的是,生物相同激素替代疗法(HRT)以及植物雌激素等天然替代品,可能为女性提供安全有效的选择,以促进年轻激素水平恢复。
生物相同HRT使用与体内自然产生的激素相同的激素。生物同质激素与传统HRT的风险无关。它们可以在美国FDA批准的制剂中获得,可通过口服、透皮或阴道途径给药。
因支持健康女性荷尔蒙信号,植物雌激素受到广泛重视和大量研究。这些雌激素样化合物存在于许多植物中,研究最深入的是异黄酮(主要来自大豆)和木脂素(主要来自亚麻籽)。植物雌激素可以在体内发挥雌激素样作用,并可能为一些女性提供替代HRT的方法。植物雌激素与降低癌症风险、改善心血管健康、减少更年期症状等益处有关。
心脏病是美国女性死亡的主要原因1,女性的冠心病发病率在绝经后急剧增加2,3。与绝经前妇女相比,绝经后妇女的血压更高,低密度脂蛋白(LDL)胆固醇、总胆固醇、甘油三酯和同型半胱氨酸水平更高,以及慢性炎症和代谢紊乱的标志物4,5,6。此外,绝经后高密度脂蛋白(HDL)胆固醇水平显著下降4,5。雌激素活性对于维持血管内皮的完整性至关重要,而血管内皮正是动脉粥样硬化发生的地方7。激素替代疗法(HRT)可能会对抗其中的一些变化。在一项临床试验中,75名围绝经期和绝经后妇女接受复合透皮(局部)生物相同雌激素治疗,无论是否使用孕酮,在36个月内心血管风险和炎症标志物都有所改善8。
更年期和围绝经期与骨质流失有关,骨质流失会导致骨质疏松和骨折风险增加。雌激素信号传导不足会导致促炎细胞因子的产生增加,从而扰乱骨形成和骨分解之间的平衡,并导致骨丢失9,10。
激素损失也与神经元变性和痴呆、阿尔茨海默病和帕金森病风险增加有关11-13。雌激素不足会刺激β淀粉样蛋白形成,从而导致阿尔茨海默病14。孕烯醇酮和DHEA都是神经保护激素,它们的缺失也与阿尔茨海默病相关的记忆问题和脑细胞死亡有关15,16。这两种激素似乎在调节与学习和记忆、压力、情绪和动机有关的神经递质系统中发挥着重要作用17-20。
更年期通常会导致睡眠紊乱和相关症状,如盗汗21。重要的是,睡眠紊乱与更年期妇女心血管风险增加有关。一项研究表明,更年期女性的睡眠障碍与动脉硬化有关—僵硬、不灵活的动脉不太健康22。一项观察性队列研究的证据表明,生物相同的HRT可以减少绝经后妇女的睡眠障碍,但还需要更多的研究23。
附:什么是雌激素优势
“雌激素优势(Estrogen dominance)”是整合医学(Integrative Health)从业者用来描述相对于孕酮水平的高雌激素水平的术语24。然而,这个词在整合医学界的普遍使用不应被解释为雌激素天生就不好。相反,重点应该是保持性激素的适当平衡(例如,雌激素相对于孕激素)。不平衡的水平,包括高雌激素水平,可能会导致不愉快的症状,如情绪波动、性欲改变、腹胀、焦虑等。雌激素优势也可能意味着在接受无对抗雌激素治疗的女性中出现的激素环境,例如仅使用雌激素而不使用孕激素(黄体酮)的HRT25。例如,接受无对抗雌激素治疗的绝经后妇女可能会出现雌激素优势的迹象和症状26。
还没有广泛接受的诊断标准或特定的雌激素和孕激素水平将女性归类为雌激素优势。事实上,高水平和低水平的雌激素都会导致急性和慢性疾病27。确定性别失衡或其他类型的类固醇激素是否可能导致症状,需要一种个性化的方法,包括实验室测试以评估激素水平,以及临床评估,以确定任何失衡是否与特定症状相关。最终目标是仔细调整激素环境,通常使用生物相同HRT,以实现特定女性的最佳平衡。“最佳”激素范围总是相对于其他激素的平衡,必须考虑到特定女性的感受,并且会因个人而异。
平衡类固醇激素水平—包括黄体酮、雌激素(雌酮、雌二醇、雌三醇)、DHEA、睾酮、孕烯醇酮,有时还有皮质醇—对于在激素影响下保持健康很重要。激素水平及其平衡不仅影响生殖健康和某些癌症的风险,还影响情绪和心理健康2、肌肉骨骼健康29、自身免疫30,31、胃肠健康32等。
所有类固醇激素都是在代谢级联过程中由胆固醇产生的。级联反应中的第一种激素是孕烯醇酮,它随后可以转化为所有其他类固醇激素,包括DHEA、孕酮、睾酮和各种形式的雌激素33。这些激素是相互关联的,但每种激素都具有独特的生理功能。生物学上合理的激素疗法应旨在协调对全身不断发生的激素信号环境的生理反应。
传统HRT的一个问题是,与女性身体产生的内源性雌激素相比,妊马雌酮(CEE)在身体的某些部位刺激更明显的雌激素信号,可能导致不良后果34。CEE是从怀孕母马的尿液中获得的35,通常与合成的孕激素联合使用。然而,CEE和合成黄体酮不能在女性体内复制由各种激素及其代谢产物在自然条件下刺激的复杂信号网络。
传统HRT的另一个问题是,CEE制剂含有其他激素,如雄激素和黄体酮,这些激素与人类自然产生的激素不同36。此外,由于CEE与体内雌激素的形式和比例不同,其使用可能导致与内源性激素代谢产生的激素代谢物不同且不成比例37。口服马雌激素引起的这种不同激素代谢的一个表现是凝血风险增加,这是众所周知的CEE副作用34。
1.关于孕酮:
在健康的育龄妇女中,孕酮(黄体酮)和雌激素在月经周期中处于动态平衡状态。孕酮在排卵、着床、妊娠、乳房发育和功能方面具有独特而重要的功能38,39,以及在大脑中40。
孕酮可以在缓解更年期症状方面发挥重要作用。几项研究报告称,与合成孕激素醋酸甲羟孕酮相比,使用黄体酮的女性更年期症状和生活质量得到了类似或更大的减轻,雌激素治疗相关的副作用也更少41-44。在一项研究中,与合成孕激素的使用者相比,黄体酮使用者的睡眠问题症状得分低30%,焦虑症状得分低50%以上,抑郁症状得分低60%,认知困难症状得分低40%,性功能得分高30%。此外,80%使用生物相同黄体酮的女性报告对其激素治疗总体满意45。
在心血管健康方面,黄体酮已被证明比合成黄体酮更安全。已发现某些合成孕激素,但不是孕酮,会加重口服雌激素治疗对血栓风险的负面影响46,47。在一项大型病例对照研究中发现,共轭马雌激素和合成孕激素醋酸甲羟孕酮的组合可使静脉血栓形成的风险增加一倍以上48。单独使用黄体酮已证明绝经后妇女的心血管安全性(2015年以前)。在一项研究中,黄体酮增强了雌激素对心肌血流的积极作用:当添加到雌激素治疗中时,在有心脏病发作或冠状动脉疾病史的女性在跑步机运动中,黄体酮显著改善了冠状动脉血流量,但合成的黄体酮没有效果49。
黄体酮在调节认知功能、社交行为和情绪方面发挥作用,并在神经系统中表现出神经保护和抗炎特性50,51。由于一些黄体酮代谢产物具有抗焦虑作用,人们认为黄体酮耗竭可能导致更年期早期焦虑和情绪障碍的发生率增加52。
2.关于雌激素:
雌激素有许多天然存在的形式。人类的主要雌激素是雌酮、雌二醇和雌三醇53,54。雌激素在生殖期由卵巢产生,在一生中由肾上腺和其他组织产生少量。雌激素的非卵巢来源在绝经后变得更加重要55,56。
2.1.雌二醇:在未怀孕、育龄女性中是最有效的形式,主要有助于卵子从卵巢循环释放(排卵)57,58。雌二醇对心脏、骨骼、大脑和结肠有有益作用59。雌二醇水平的波动和总体下降会导致常见的围绝经期和绝经后症状,如潮热、情绪波动和阴道萎缩60,61,绝经后雌二醇耗竭会影响全身组织,导致一系列疾病风险和虚弱62,63。雌酮是绝经后妇女的主要雌激素,它是由脂肪组织产生的64;雌三醇是一种相对较弱的雌激素,由于雌三醇是由胎盘分泌的,它是妊娠期的主要雌激素65,66。
雌激素的三种主要类型可以转化为许多代谢产物。例如,雌酮可转化为以下代谢产物67:
一些证据表明,雌激素代谢为2-羟基形式可能对绝经后妇女的乳腺癌具有预防作用67,68。然而,在得出各种雌激素代谢产物的比例在乳腺癌风险中的作用的确切结论之前,还需要更多的研究。
2.2.雌三醇:雌三醇的雌激素效应比其他形式的雌激素弱。研究表明,雌三醇能有效治疗更年期潮热、盗汗和失眠。此外,一些研究表明,雌三醇可以对抗绝经前骨质流失66。当与雌二醇一起服用时,雌三醇会对抗雌二醇更强的雌激素作用69。雌三醇用于阴道,是治疗更年期泌尿系统和阴道症状的极佳药物34。
雌三醇已经在一系列慢性疾病的背景下进行了研究。日本的研究人员进行了大量试验,表明雌三醇可以改善血压、血管功能和血脂70-74。
新兴研究表明,雌三醇在治疗自体免疫疾病多发性硬化症和其他神经退行性疾病中具有潜在作用,部分是通过调节免疫功能。这一理论源于观察到多发性硬化症在妊娠期间和妊娠后不久的缓解和复发与胎盘分泌雌三醇有关66。
附:什么是异源性雌激素?
异源性雌激素(Xenoestrogens,或称外源性雌激素)是与体内雌激素信号通路相互作用的外源性化合物,可能导致激素失衡的某些表现。异源性雌激素模仿雌激素对雌激素受体的作用。它们是一大类被称为内分泌干扰物的化合物的一部分,这些化合物可以干扰正常的激素信号传导75。外源雌激素存在于塑料、杀虫剂、除草剂和许多其他来源中76,77。
全身的组织和器官系统对雌激素信号敏感,并可能受到外源性雌激素的影响。事实上,研究表明,除了乳腺癌外,外源性雌激素暴露也可能导致肺癌、肾癌和生殖系统肿瘤78,79。截至2022年初,一项大型研究正在进行中,目的是了解这些污染物和其他污染物对患乳腺癌风险的影响80。外源性雌激素暴露也被证明会改变免疫细胞功能81,导致肾功能下降82,增加子宫肌瘤的风险83,对分娩结果产生负面影响84,可能增加肥胖和糖尿病的风险85,并可能影响良性乳腺疾病和乳腺组织变化86,87。
由于外源性雌激素实际上不是雌激素,因此通过测量雌激素水平的测试不会发现它们。为了限制外源性雌激素的暴露和潜在的不良影响,尽量少用塑料,彻底清洗农产品,避免使用包括对羟基苯甲酸酯和邻苯二甲酸酯在内的产品。也可以考虑在饮食中添加更多的植物雌激素(在大豆和亚麻籽中大量存在)和十字花科蔬菜,因为有一些初步数据表明它们可以阻断外源性雌激素的作用88-91。
2.3.其他重要激素
除了雌激素和孕激素,重要的是要考虑激素孕烯醇酮、DHEA和睾酮的作用。理想的生物相同HRT包括对所有下降的激素水平的综合评估。
2.3.1.脱氢表雄酮(DHEA):
这是一种由肾上腺、性腺和大脑分泌的甾体激素92。男性和女性都经历了与年龄相关的DHEA下降93。女性通常在30多岁时达到峰值水平,之后开始每年损失约2%94。更年期后DHEA和DHEA-硫酸盐(DHEA-s,DHEA的一种循环形式)水平降低会影响认知、情绪和性行为95,并被认为会导致癌症、胰岛素抵抗、免疫防御降低和精神疾病96。
DHEA已被证明会影响情绪和神经功能97、免疫功能98、能量和幸福感99、血管健康100、胰岛素抵抗和炎症标志物水平101以及肌肉和骨量的维持102,103。此外,DHEA已被发现可增强性功能,尤其是阴道内DHEA的使用已被证明是治疗绝经后外阴阴道萎缩的有效方法104,105。
2.3.2.睾酮:
与DHEA一样,女性的睾酮水平随着年龄的增长而逐渐降低106。睾酮的丧失会影响性欲、骨骼和肌肉质量、血管舒缩症状、心血管健康、情绪和幸福感107-110。
女性的睾酮治疗已被证明可以改善生活质量、情绪、注意力、骨骼健康、心血管风险标志物、认知功能和外阴阴道萎缩111,112。此外,睾酮,无论是单独使用还是与雌激素治疗联合使用,已被证明在治疗女性性欲低下和提高性满意度方面是有效的113-115。由于DHEA可以转化为睾酮,因此使用DHEA可能会获得睾酮的一些好处110,116。
2.3.3.孕烯醇酮:
与其他一些激素的情况一样,孕烯醇酮的显著减少始于女性30岁出头117。孕烯醇酮作为整个类固醇激素级联中的初始激素,主要来源于肾上腺、性腺、大脑和其他组织中的胆固醇。除了作为其他激素的前体外,孕烯醇酮似乎对神经功能的调节有直接影响16,20。孕烯醇酮可能对与年龄相关的睡眠和认知变化特别重要118,并且缺失与大脑功能下降和痴呆症有关119。
附:关于激素与癌症风险
尽管许多因素影响乳腺癌风险,但众所周知,高雌激素水平和一生中雌激素暴露量的增加,尤其是由于青春期提前,与乳腺癌风险的增加有关120。建立适当的激素平衡,并加入支持健康激素代谢的食物和补充剂,可能有助于减轻雌激素的乳腺癌诱因。
目前的证据表明,虽然CEE似乎不会增加癌症风险,但传统HRT中使用的合成孕激素(主要是醋酸甲羟孕酮)与风险增加有关34。在妇女健康倡议(WHI)中,仅CEE不会增加癌症风险,而CEE加醋酸甲羟孕酮与风险增加相关121-123。
尚未发现将生物相同孕酮与雌激素联合使用与增加癌症风险有关124。事实上,体外研究表明,黄体酮实际上可能会减少雌激素引发的细胞增殖125。尽管需要更多的研究来明确确定孕酮治疗乳腺癌症的风险和安全性,但迄今为止的证据表明,它比合成孕酮更安全,尤其是醋酸甲羟孕酮126,127。
此外,研究表明,睾酮对乳腺组织具有抗增殖作用,对抗雌激素的致癌作用128。在一项研究中,发现患有癌症的女性唾液睾酮水平低于无癌女性129。在另一项研究中,包括雌激素、孕激素和睾酮的绝经后激素替代疗法与癌症的发生率显著低于使用不含睾酮的激素替代疗法的历史数据预测的发生率130。
随着时间的推移,这种风险很大程度上归因于醋酸甲羟孕酮(安宫黄体酮),这是WHI研究中使用的合成孕激素132。随着人们对传统的口服HRT相关风险的认识和传播,许多女性开始担心使用传统HRT。因此,在美国传统HRT的使用急剧下降133。2003年在50岁以上妇女中观察到的乳腺癌发病率的急剧下降与传统HRT使用的减少有关134。
研究中使用的共轭马雌激素和合成孕激素在化学结构上与女性体内产生的天然激素不同135。许多研究表明,合成孕激素(醋酸甲羟黄体酮)会带来多种健康风险,包括增加乳腺癌、中风和认知功能障碍132。而生物相同的HRT疗法使用与体内自然产生的激素相同的激素(分子结构一致)136,137。
生物相同(Bioidentical,或称生物同质)HRT使用与体内自然产生的激素相同的激素。生物相同激素与常规的激素治疗的风险无关。它们可以依据美国FDA批准的制剂获得,可通过口服、透皮或阴道途径给药;或者,高质量的复合药物可以制备常规制剂可能无法获得的浓度。
生物相同HRT比传统HRT产生更少的副作用。与传统HRT中使用的口服马雌激素相比,生物相同的局部应用雌激素似乎造成的血栓风险更小,可能还有总体心血管病风险降低34。这在一项大型病例对照研究中得到证实,该研究表明,与对照组相比,单独使用口服马雌激素(不与合成孕激素联合使用)导致静脉血栓的风险增加约50%。当马雌激素与合成孕激素联合使用时,风险比对照组参与者高出约90%138。此外,与最广泛使用的合成孕酮不同,生物相同的孕酮不会增加心血管或乳腺癌风险69。事实上,生物相同激素疗法的吸引力并没有在公众或医学界消失:现在使用激素疗法的女性中,近三分之一使用生物相同激素139。
许多美国FDA批准的商业制剂现在使用生物相同激素,这有助于在传统观念的医生中推广生物相同HRT的接受度。美国FDA批准的生物相同激素制剂,包括:戊酸雌二醇(Estrace)、戊酸雌二醇阴道乳霜、雌二醇透皮贴剂(Climara)、雌二醇乳液(Estrasorb),以及微粉化黄体酮…等。
此外,补充经过科学研究的当归和甘草等草药,可以进一步促进女性激素的健康代谢,并补充生物相同HRT的作用。
植物雌激素一类在一些植物中发现的与雌激素结构相似的膳食生物活性物质和天然化合物。尽管有几种类型的植物化合物被归类为植物雌激素140,但研究最多的是异黄酮和木脂素(或木酚素)141。植物中的植物雌激素在很大程度上是无活性的,但被肠道细菌代谢成活性化合物142,143。一旦被吸收,活化的植物雌激素在体内发挥雌激素样作用,对一些女性来说可能是生物相同的HRT的替代品144,140。
一些支持使用植物雌激素的最佳证据来自亚洲,那里的更年期症状较轻,不太常见,乳腺癌症发病率低于欧洲和北美地区。一种解释可能是在亚洲饮食中常见的大豆和其他植物产品中发现的植物雌激素145-147。
植物雌激素与雌激素受体结合并帮助调节雌激素活性148,149,142。植物雌激素的雌激素作用各不相同,但通常相对于雌二醇较弱;在雌二醇存在的情况下,它们似乎具有抗雌激素作用,因为它们与雌二醇竞争雌激素受体结合位点149,150。植物雌激素已被证明可以减轻更年期症状,并可能降低患某些慢性疾病的风险,包括心血管疾病、骨质疏松症和乳腺癌142,146,151-154。
有趣的是,植物雌激素似乎优先结合雌激素受体ER-β,而不是ER-α,后者被雌二醇和其他一些哺乳动物雌激素更强烈地激活144,153。ER-β激活已被认为是预防衰老和更年期的情绪和神经方面的机制155,并似乎可以预防乳腺、卵巢和可能的其他组织的癌症变化156-159。
饮食和补充植物雌激素为女性提供了一种在不使用激素治疗的情况下获得有限激素支持的方法,其健康益处包括如下:
1.1.心血管益处:
传统HRT已被证明会增加绝经后妇女心脏病发作的风险,与此不同,植物雌激素似乎对心脏有积极影响143,144。1999年,美国FDA授权在食品标签上使用健康声明,将大豆消费量的增加与冠状动脉疾病风险的降低相联系160。
有许多研究检测植物雌激素对心血管的影响。总体而言,研究表明,异黄酮可以降低高血压161,153,改善脂质紊乱,降低同型半胱氨酸水平162,改善血管健康,预防动脉粥样硬化143,153。类似地,木脂素与降低血压163、改善脂质代谢143和降低心脏风险有关164,140。
除了弱激活雌激素受体的能力外,植物雌激素还具有强烈的抗炎和降低氧化应激作用,这可能有助于其心血管益处143,140。
1.2.大脑保护:
雌激素和雌激素样化合物保护脑细胞免受衰老、氧化应激和中风诱导的损伤引起的退行性变化的影响165-167,35。几项研究表明,植物雌激素的染料木素(金雀异黄酮)保护实验动物免受脑缺血的影响,这种损伤见于中风168-170。此外,金雀异黄酮还表现出抗凋亡活性,保护培养的脑细胞免受时间的破坏171。
骨质疏松症与骨骼健康:已经对植物雌激素和骨骼健康进行了许多研究。临床试验发现,植物雌激素可以增加骨矿化,减少骨吸收,增强骨形成,改善骨代谢标志物。总之,他们的研究结果表明,植物雌激素(主要是大豆食品和异黄酮)可能有助于缓解更年期后的骨质流失153,172,173。
1.3.癌症预防:
许多研究已经注意到异黄酮消耗与乳腺癌风险降低之间的关联性174-176。大豆异黄酮对乳腺癌高危女性(包括乳腺癌幸存者)是安全的176,153,不会增加患子宫癌的风险177。此外,木脂素含量高的亚麻籽已被证明可降低乳腺癌风险并减少乳腺肿瘤生长178,179。
植物雌激素可以部分通过改善雌激素代谢来预防癌症。在一项试验中发现,每天含有113–202mg(取决于体重)染料木素和大豆黄酮的饮食可以增加绝经前妇女尿液中保护性2-羟基雌激素与有害的16-羟基雌激素的比例,这可能有助于降低乳腺癌的长期风险180。此外,新出现的证据表明,植物雌激素抑制芳香化酶,芳香化酶是催化睾酮转化为雌激素的酶,这种作用可能有助于降低其与乳腺癌风险的关系181。
木脂素是一种植物雌激素,主要存在于亚麻籽中,少量存在于芝麻、一些豆芽和许多其他植物性食物中。一项对21项研究的综合综述发现,木脂素摄入量较高的绝经后妇女患乳腺癌的可能性显著降低182。
在一项临床试验中,32名等待乳腺癌手术的女性被随机分配接受一块含有或不含有25g亚麻籽的松饼(对照组)。手术后对癌组织的分析显示,亚麻籽组的肿瘤生长标志物减少了30-71%,但对照组没有183。2010年发表的一项研究发现,木脂素、吲哚3甲醇(I3C)、D葡糖酸钙和其他草药的组合有利于改变47名绝经前和49名绝经后妇女的雌激素代谢产物比例184。
1.4.更年期症状:
多项研究表明,天然植物雌激素可以改善更年期症状144,尤其是潮热141。一项包括17项临床试验结果的综合荟萃分析发现,在6周至12个月的时间里,平均每天服用54mg染料木素,可安全地将潮热频率降低20.6%,潮热严重程度降低26.2%185。
2.改善更年期症状的草药:
2.1.黑升麻:
黑升麻根用于治疗妇科疾病有着悠久的历史,并已成为缓解更年期综合征的流行草药186。随机对照试验已证明其在治疗更年期症状(如潮热、性欲低下、睡眠障碍和其他身体和情绪症状)方面的疗效187-190。黑升麻具有安全性记录,大量证据支持其用于治疗更年期症状191-194。黑升麻和密切相关的物种在实验室中对癌症细胞产生了抗增殖作用195,196,并且黑升麻的使用与癌症风险或复发率的增加无关176。来自一项临床试验和几项动物研究的数据表明,在预防骨质流失方面,它与雌二醇和另一种抗骨质疏松药物相当197-200。
2.2.西伯利亚大黄:
数十年来,西伯利亚大黄的一种特殊提取物已在德国用于治疗与女性激素失衡有关的问题,包括月经少或不规律,以及围绝经期和绝经后症状201。
在使用该补充剂的第一项随机对照临床试验中,109名有症状的围绝经期妇女服用肠溶片,每天提供4mg标准化西伯利亚大黄提取物或安慰剂,持续12周。四周后,与安慰剂相比,西伯利亚大黄组的更年期相关症状明显减轻,到第12周,这种差异更加明显,试验中考虑的11种症状中的每一种都可以测量到。接受提取物治疗的54名女性中有45名(83%)和接受安慰剂治疗的55名女性中的1名(不到2%)报告症状有临床意义的减轻。此外,对西伯利亚大黄提取物可能产生的不良影响进行的广泛调查没有发现任何不良影响201。然后,一组参与者在开放标签试验中使用相同的提取物,持续48至96周。总的来说,妇女的更年期症状持续改善,没有不良副作用202。
另一项使用初步试验数据的研究发现,标准化西伯利亚大黄提取物比安慰剂更有效,特别是在缓解更年期相关焦虑症和改善总体健康方面。39名接受大黄治疗的女性中,有33名在试验开始时焦虑程度为“严重”或“中度”(85%),12周后焦虑程度降至“轻微”。该研究还注意到焦虑减少和潮热减少之间的相关性203。
其他研究已经证实了西伯利亚大黄提取物的益处:在一项为期六个月的363名参与者的开放标签研究204和一项为期12周的112名参与者的随机对照试验205中,使用该提取物治疗导致整体更年期症状评分降低,以及所有个体症状的减少。
实验室研究表明,西伯利亚大黄提取物及其活性成分选择性激活ER-β,对ER-α没有影响206。ER-β激活已被认为是预防衰老和更年期的情绪和神经方面的机制207,并似乎可以预防乳腺、卵巢和可能的其他组织的癌症变化156-159。
2.3.当归:
当归在传统中医中用于治疗妇科症状,如月经痛或盆腔痛、分娩或疾病后恢复以及疲劳/活力低下,因此被称为“女参”208-210。随机对照试验表明,当归与其他植物提取物联合使用可以缓解更年期症状211,212,在一项动物研究中,当归在预防骨质流失方面与雌二醇一样有效213。
2.4.甘草:
甘草根通过选择性激活ERβ发挥雌激素样作用214。实验室研究表明,甘草成分抑制血清素再摄取,这种作用可能有助于其对更年期症状的积极影响215,149。在一项随机对照试验中,在治疗的八周和治疗结束后的两周内,每天三次服用330mg甘草根,比安慰剂更能降低更年期潮热的频率和严重程度216。甘草根成分也已在实验室中显示出支持动脉和骨骼健康,从而降低心血管疾病和骨质疏松症的风险217,218。
2.5.圣洁莓:
含有圣洁莓果的草药配方已被证明可以改善更年期症状,如睡眠障碍、潮热和心理健康219-221。圣洁莓树的干果提取物几个世纪以来一直被用于妇女健康方面。在几项小型研究中,它已被证明可以调节激素和神经递质信号传导,并缓解经前症状。实验室研究表明,卵黄中的化合物可以结合雌激素受体并调节激素反应基因222。
了解有关更年期症状管理的详细内容,可点击:更年期综合征 >>
3.支持健康雌激素代谢的营养素:
3.1.维生素D:维生素D似乎对预防乳腺癌有显著的保护作用。在一项研究中,与维生素D水平最低的女性相比,维生素D水平较高的女性患乳腺癌的风险降低了近70%223,而另一项研究将维生素D水平较低与乳腺癌患者的生存率降低联系起来224。实验室研究表明,维生素D通过以下方式抑制乳腺癌的生长和发展:
3.2. 吲哚3甲醇:
十字花科蔬菜,如菜花、甘蓝、甘蓝和芽甘蓝,含有可能有助于对促进癌症生长的雌激素分解产物进行解毒的化合物228-230。一种这样的化合物是吲哚3甲醇(I3C),其防止雌激素转化为促乳腺癌的代谢物16-α-羟基雌酮,并同时增加向抗癌代谢物2-羟雌酮形式的转化231-233。
3.3.欧米伽3脂肪酸:
鱼油所含的ω-3脂肪酸(EPA和DHA),通过多种机制降低癌症风险。鱼油可减少氧化应激并抑制许多导致癌症发展的炎症介质的产生234,235。即使存在转移,它也可以使肿瘤细胞对化疗效果敏感,潜在地减少治疗所需的化疗剂量236。在乳腺癌动物模型中,补充鱼油可减少骨转移237。
3.4.绿茶:
绿茶多酚,特别是表没食子儿茶素没食子酸盐(EGCG),在实验室中抑制了人类乳腺癌症细胞的生长和繁殖,并减少了该疾病动物模型中乳腺肿瘤的数量238-240。绿茶还抑制了肿瘤血管的产生,同时下调了致癌雌激素受体并增加了细胞凋亡240-243。
3.5.石榴:
石榴因其抗氧化特性和抗癌潜力而被广泛研究244-246。就乳腺癌而言,石榴是一种特别有前途的药物,因为它能够抑制致癌酶芳香化酶并抑制肿瘤血管的生成247,248。
参考文献:
1. CDC. Centers for Disease Control and Prevention. Women and Heart Disease Fact Sheet. http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_women_heart.htm. Last updated 8/23/17. Accessed 10/24/2017.
2. Tandon VR. Prevalence of cardiovascular risk factors in postmenopausal women: A rural study. Journal of mid-life health. Jan 2010;1(1):26-29.
3. Clearfield M. Coronary heart disease risk reduction in postmenopausal women: the role of statin therapy and hormone replacement therapy. Preventive cardiology. Summer 2004;7(3):131-136.
4. Saha KR et al. Changes in lipid profile of postmenopausal women. Mymensingh medical journal: MMJ. Oct 2013;22(4):706-711.
5. Fonseca MIH et al. Impact of menopause and diabetes on atherogenic lipid profile: is it worth to analyse lipoprotein subfractions to assess cardiovascular risk in women? Diabetol Metab Syndr. 2017;9:22.
6. Lee CG et al. Adipokines, inflammation, and visceral adiposity across the menopausal transition: a prospective study. The Journal of clinical endocrinology and metabolism. Apr 2009;94(4):1104-1110.
7. Arnal JF et al. Estrogen receptor actions on vascular biology and inflammation: implications in vascular pathophysiology. Climacteric. 2009;12 Suppl 1: 12-17.
8. Stephenson K et al. The effects of compounded bioidentical transdermal hormone therapy on hemostatic, inflammatory, immune factors; cardiovascular biomarkers; quality-of-life measures; and health outcomes in perimenopausal and postmenopausal women. Int J Pharm Compd. Jan-Feb 2013;17(1):74-85.
9. Pietschmann P et al. Immunology of Osteoporosis: A Mini-Review. Gerontology. 2016;62(2):128-137.
10. Weitzmann MN et al. Estrogen deficiency and bone loss: an inflammatory tale. J Clin Invest. 2006 May;116(5):1186-94.
11. Depypere H et al. Alzheimer's disease, apolipoprotein E and hormone replacement therapy. Maturitas. Dec 2016;94:98-105.
12. Blair JA et al. Hypothalamic-pituitary-gonadal axis involvement in learning and memory and Alzheimer's disease: more than "just" estrogen. Frontiers in endocrinology. 2015 Mar 25:6:45.
13. Rocca WA et al. Increased risk of parkinsonism in women who underwent oophorectomy before menopause. Neurology. 2008 Jan 15;70(3):200-9.
14. Liang K et al. Estrogen stimulates degradation of beta-amyloid peptide by up-regulating neprilysin. J Biol Chem. 2010;285(2): 935-942.
15. Vallee M. Neurosteroids and potential therapeutics: Focus on pregnenolone. The Journal of steroid biochemistry and molecular biology. Jun 2016;160:78-87.
16. Yao Z-X et al. 22R-Hydroxycholesterol protects neuronal cells from β-amyloid-induced cytotoxicity by binding to β-amyloid peptide. J Neurochemistry. 2002 Dec;83(5):1110-19.
17. Maayan R et al. The effect of DHEA complementary treatment on heroin addicts participating in a rehabilitation program: a preliminary study. European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology. Jun 2008;18(6):406-413.
18. Zaluska M et al. [Dehydroepiandrosteron (DHEA) in the mechanisms of stress and depression]. Psychiatria polska. May-Jun 2009;43(3):263-274.
19. Vallée M et al. Role of pregnenolone, dehydroepiandrosterone and their sulfate esters on learning and memory in cognitive aging. Brain Res Brain Res Rev. 2001 Nov;37(1-3):301-12.
20. Zheng P. Neuroactive steroid regulation of neurotransmitter release in the CNS: action, mechanism and possible significance. Progress in neurobiology. Oct 2009;89(2):134-152.
21. Jehan S et al. Sleep Disorders in Postmenopausal Women. Journal of sleep disorders & therapy. Aug 2015;4(5).
22. Zhou Y et al. Sleep disorder, an independent risk associated with arterial stiffness in menopause. Sci Rep. May 15 2017;7(1):1904.
23. Ruiz AD et al. The effectiveness of sublingual and topical compounded bioidentical hormone replacement therapy in postmenopausal women: an observational cohort study. Int J Pharm Compd. Jan-Feb 2014;18(1):70-77.
24. Kolan A. Estrogen Dominance. U.S. Department of Veterans Affairs. Accessed 3/17/2022, https://www.va.gov/WHOLEHEALTHLIBRARY/tools/estrogen-dominance.asp
25. Cleveland Clinic. High Estrogen. Updated 2/9/2022. Accessed 3/18/2022, https://my.clevelandclinic.org/health/diseases/22363-high-estrogen
26. Valdes A, Bajaj T. Estrogen Therapy. StatPearls. 2022.
27. Patel S et al. Estrogen: The necessary evil for human health, and ways to tame it. Biomedicine & Pharmacotherapy. 2018;102:403-411.
28. Borrow AP et al. Estrogenic mediation of serotonergic and neurotrophic systems: Implications for female mood disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2014;54:13-25.
29. Gao WL et al. Measurement of serum estrogen and estrogen metabolites in pre- and postmenopausal women with osteoarthritis using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Braz J Med Biol Res. Feb 2015;48(2):146-53.
30. Chen Y et al. A Higher Ratio of Estradiol to Testosterone Is Associated with Autoimmune Thyroid Disease in Males. Thyroid. Jul 2017;27(7):960-966.
31. Avila M et al. The Role of Sex Hormones in Multiple Sclerosis. European neurology. 2018;80(1-2):93-99.
32. Chen C et al. The roles of estrogen and estrogen receptors in gastrointestinal disease. Oncology letters. Dec 2019;18(6):5673-5680.
33. Hu J et al. Cellular cholesterol delivery, intracellular processing and utilization for biosynthesis of steroid hormones. Nutrition & metabolism. Jun 01 2010;7:47.
34. L'Hermite M. Bioidentical menopausal hormone therapy: registered hormones (non-oral estradiol +/- progesterone) are optimal. Climacteric: the journal of the International Menopause Society. Aug 2017;20(4):331-338.
35. Bhavnani BR. Estrogens and menopause: pharmacology of conjugated equine estrogens and their potential role in the prevention of neurodegenerative diseases such as Alzheimer's. J Steroid Biochem Mol Biol. 2003; 85(2–5):473–482.
36. Notelovitz M. Clinical opinion: the biologic and pharmacologic principles of estrogen therapy for symptomatic menopause. MedGenMed: Medscape general medicine. Mar 28 2006;8(1):85.
37. Bhavnani BR. Pharmacokinetics and pharmacodynamics of conjugated equine estrogens: chemistry and metabolism. Proc Soc Exp Biol Med. Jan 1998;217(1):6-16.
38. Ismail PM et al. Progesterone involvement in breast development and tumorigenesis--as revealed by progesterone receptor "knockout" and "knockin" mouse models. Steroids. Nov 2003;68(10-13):779-787.
39. Al-Asmakh M. Reproductive functions of progesterone. Middle East Fertility Society Journal. 2007;12(3):147-152.
40. Mani SK et al. Progesterone signaling mechanisms in brain and behavior. Frontiers in endocrinology. 2012 Jan 30:3:7.
41. Hargrove JT et al. Menopausal hormone replacement therapy with continuous daily oral micronized estradiol and progesterone. Obstet Gynecol. 1989;73(4): 606-612.
42. Montplaisir J et al. Sleep in menopause: differential effects of two forms of hormone replacement therapy. Menopause. 2001;8(1): 10-16.
43. Ryan N et al. Quality of life and costs associated with micronized progesterone and medroxyprogesterone acetate in hormone replacement therapy for nonhysterectomized, postmenopausal women. Clin Ther. 2001;23(7): 1099-1115.
44. Lindenfeld EA et al. Bleeding patterns of the hormone replacement therapies in the postmenopausal estrogen and progestin interventions trial. Obstet Gynecol. 2002;100(5 Pt 1): 853-863.
45. Fitzpatrick LA et al. Comparison of regimens containing oral micronized progesterone or medroxyprogesterone acetate on quality of life in postmenopausal women: a cross-sectional survey. J Womens Health Gend Based Med. 2000;9(4): 381-387.
46. Binkowska M. Menopausal hormone therapy and venous thromboembolism. Przeglad menopauzalny = Menopause review. Oct 2014;13(5):267-272.
47. Scarabin PY. Hormone therapy and venous thromboembolism among postmenopausal women. Frontiers of hormone research. 2014;43:21-32.
48. Vinogradova Y et al. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ (Clinical research ed.). Jan 9 2019;364:k4810.
49. Rosano GM et al. Natural progesterone, but not medroxyprogesterone acetate, enhances the beneficial effect of estrogen on exercise-induced myocardial ischemia in postmenopausal women. J Am Coll Cardiol. 2000;36(7): 2154-2159.
50. Giatti S et al. The other side of progestins: effects in the brain. Journal of molecular endocrinology. Aug 2016;57(2):R109-126.
51. Arbo BD et al. Astrocytes as a target for neuroprotection: Modulation by progesterone and dehydroepiandrosterone. Progress in neurobiology. Sep 2016;144:27-47.
52. Toriizuka K et al. [Menopause and anxiety: focus on steroidal hormones and GABAA receptor]. Nihon Yakurigaku Zasshi. Jan 2000;115(1):21-28.
53. Taioli E et al. Comparison of estrogens and estrogen metabolites in human breast tissue and urine. Reprod Biol Endocrinol. 2010 Aug 2;8:93.
54. Samavat H et al. Estrogen metabolism and breast cancer. Cancer letters. Jan 28 2015;356(2 Pt A):231-243.
55. Rettberg JR et al. Estrogen: a master regulator of bioenergetic systems in the brain and body. Frontiers in neuroendocrinology. Jan 2014;35(1):8-30.
56. Simpson ER. Sources of estrogen and their importance. The Journal of steroid biochemistry and molecular biology. Sep 2003;86(3-5):225-230.
57. Barbieri RL. The endocrinology of the menstrual cycle. Methods in molecular biology (Clifton, N.J.). 2014;1154:145-169.
58. Chai NC et al. Migraine and estrogen. Current opinion in neurology. Jun 2014;27(3):315-324.
59. Cui J et al. Estrogen synthesis and signaling pathways during aging: from periphery to brain. Trends in molecular medicine. Mar 2013;19(3):197-209.
60. Freedman RR. Menopausal hot flashes: mechanisms, endocrinology, treatment. The Journal of steroid biochemistry and molecular biology. Jul 2014;142:115-120.
61. Finch CE. The menopause and aging, a comparative perspective. The Journal of steroid biochemistry and molecular biology. Jul 2014;142:132-141.
62. Dalal PK et al. Postmenopausal syndrome. Indian journal of psychiatry. Jul 2015;57(Suppl 2):S222-232.
63. Nedergaard A et al. Menopause, estrogens and frailty. Gynecological endocrinology: the official journal of the International Society of Gynecological Endocrinology. May 2013;29(5):418-423.
64. Wharton W et al. Neurobiological Underpinnings of the Estrogen - Mood Relationship. Current psychiatry reviews. Aug 01 2012;8(3):247-256.
65. Liang J et al. Estrogen and cancer. Annual review of physiology. 2013;75:225-240.
66. Ali ES et al. Estriol: emerging clinical benefits. Menopause (New York, N.Y.). 2017 Sep;24(9):1081-1085.
67. Ziegler RG et al. Epidemiologic studies of estrogen metabolism and breast cancer. Steroids. 2015;99(Pt A):67-75.
68. Moore SC et al. Endogenous Estrogens, Estrogen Metabolites, and Breast Cancer Risk in Postmenopausal Chinese Women. Journal of the National Cancer Institute. Oct 2016;108(10).
69. Holtorf K. The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy? Postgrad Med. 2009;121(1): 73-85.
70. Takahashi K et al. Safety and efficacy of oestriol for symptoms of natural or surgically induced menopause. Hum Reprod. 2000;15(5): 1028-1036.
71. Hayashi T et al. Estriol (E3) replacement improves endothelial function and bone mineral density in very elderly women. J Gerontol A Biol Sci Med Sci. 2000;55(4): B183-190; discussion B191-183.
72. Kano H et al. Estriol retards and stabilizes atherosclerosis through an NO-mediated system. Life Sci. 2002;71(1): 31-42.
73. Itoi H et al. Comparison of the long-term effects of oral estriol with the effects of conjugated estrogen on serum lipid profile in early menopausal women. Maturitas. 2000;36(3): 217-222.
74. Yamanaka Y et al. Effects of combined estriol/pravastatin therapy on intima-media thickness of common carotid artery in hyperlipidemic postmenopausal women. Gynecol Obstet Invest. 2005;59(2): 67-69.
75. Singleton DW et al. Xenoestrogen exposure and mechanisms of endocrine disruption. Front Biosci. 2003;8:s110-s118.
76. Brotons JA et al. Xenoestrogens released from lacquer coatings in food cans. Environmental health perspectives. 1995;103(6):608-612.
77. Sultan C et al. Environmental xenoestrogens, antiandrogens and disorders of male sexual differentiation. Molecular and cellular endocrinology. 2001;178(1-2):99-105.
78. Fucic A et al. Environmental exposure to xenoestrogens and oestrogen related cancers: reproductive system, breast, lung, kidney, pancreas, and brain. Environmental Health. 2012;11(1):1-9.
79. Wang X et al. Exploring the Biological Activity and Mechanism of Xenoestrogens and Phytoestrogens in Cancers: Emerging Methods and Concepts. International journal of molecular sciences. 2021 Aug 16;22(16):8798.
80. Amadou A et al. Chronic low-dose exposure to xenoestrogen ambient air pollutants and breast cancer risk: XENAIR protocol for a case-control study nested within the French E3N cohort. JMIR research protocols. 2020;9(9):e15167.
81. Nowak K et al. Methylparaben-induced regulation of estrogenic signaling in human neutrophils. Molecular and cellular endocrinology. Oct 1 2021;538:111470.
82. Chen CY et al. Xenoestrogen exposure and kidney function in the general population: Results of a community-based study by laboratory tests and questionnaire-based interviewing. Environ Int. Oct 2021;155:106585.
83. Katz TA et al. Endocrine-disrupting chemicals and uterine fibroids. Fertility and sterility. Sep 15 2016;106(4):967-77.
84. Bjerregaard-Olesen C et al. Associations of fetal growth outcomes with measures of the combined xenoestrogenic activity of maternal serum perfluorinated alkyl acids in Danish pregnant women. Environmental health perspectives. 2019;127(01):017006.
85. Pérez-Bermejo M et al. The Role of the Bisphenol A in Diabetes and Obesity. Biomedicines. 2021;9(6):666.
86. Abeer F et al. FREQUENCY OF SOME ENVIRONMENTAL FACTORS WITH POTENTIAL RELATIONS TO BREAST DISEASES AMONG A GROUP OF EGYPTIAN FEMALES. Journal of Environmental Science. 2018;43(1):29-47.
87. Trentham-Dietz A et al. Phenol xenoestrogens and mammographic breast density. Cancer Epidemiology and Prevention Biomarkers. 2012;21(3):561-562.
88. Maharjan CK et al. Natural and Synthetic Estrogens in Chronic Inflammation and Breast Cancer. Cancers. 2021;14(1):206.
89. Chavarro JE et al. Soy Intake Modifies the Relation Between Urinary Bisphenol A Concentrations and Pregnancy Outcomes Among Women Undergoing Assisted Reproduction. J Clin Endocrinol Metab. Mar 2016;101(3):1082-90.
90. Lee GA et al. Treatment with Phytoestrogens Reversed Triclosan and Bisphenol A-Induced Anti-Apoptosis in Breast Cancer Cells. Biomolecules & therapeutics. Sep 1 2018;26(5):503-511.
91. Williams DE. Indoles Derived From Glucobrassicin: Cancer Chemoprevention by Indole-3-Carbinol and 3,3'-Diindolylmethane. Frontiers in nutrition. 2021;8:734334.
92. Maninger N et al. Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS). Front Neuroendocrinol. 2009 Jan;30(1):65-91.
93. Labrie F. DHEA, important source of sex steroids in men and even more in women. Prog Brain Res. 2010;182:97-148.
94. Fouany MR et al. Is there a role for DHEA supplementation in women with diminished ovarian reserve? Journal of assisted reproduction and genetics. Sep 2013;30(9):1239-1244.
95. Pluchino N et al. Neurobiology of DHEA and effects on sexuality, mood and cognition. The Journal of steroid biochemistry and molecular biology. Jan 2015;145:273-280.
96. Genazzani AR et al. DHEA therapy in postmenopausal women: the need to move forward beyond the lack of evidence. Climacteric. 2010 Aug;13(4):314-6.
97. Dong Y et al. Dehydroepiandrosterone sulphate: action and mechanism in the brain. Journal of neuroendocrinology. Jan 2012;24(1):215-224.
98. Bauer ME et al. Psychoneuroendocrine interventions aimed at attenuating immunosenescence: a review. Biogerontology. Feb 2013;14(1):9-20.
99. Rutkowski K et al. Dehydroepiandrosterone (DHEA): hypes and hopes. Drugs. Jul 2014;74(11):1195-1207.
100. Weiss EP et al. Dehydroepiandrosterone replacement therapy in older adults improves indices of arterial stiffness. Aging Cell. Oct 2012;11(5):876-884.
101. Weiss EP et al. Dehydroepiandrosterone (DHEA) replacement decreases insulin resistance and lowers inflammatory cytokines in aging humans. Aging (Albany NY). May 2011;3(5):533-542.
102. Weiss EP et al. Dehydroepiandrosterone replacement therapy in older adults: 1- and 2-y effects on bone. Am J Clin Nutr. 2009 May;89(5):1459-67.
103. Kenny AM et al: Dehydroepiandrosterone combined with exercise improves muscle strength and physical function in frail older women. J Am Geriatr Soc.2010 Sep;58(9):1707-14.
104. Pluchino N et al. Neurobiology of DHEA and effects on sexuality, mood and cognition. The Journal of steroid biochemistry and molecular biology. Jan 2015;145:273-280.
105. Archer DF. Dehydroepiandrosterone intra vaginal administration for the management of postmenopausal vulvovaginal atrophy. The Journal of steroid biochemistry and molecular biology. Jan 2015;145:139-143.
106. Schneider HP. Androgens and antiandrogens. Ann NY Acad Sci. 2003;997:292-306.
107. Bain J. The many faces of testosterone. Clinical interventions in aging. 2007;2(4):567-576.
108. Simon JA. Safety of estrogen/androgen regimens. J Reprod Med. 2001 Mar;46(3 Suppl):281-90.
109. Watt PJ et al. A holistic programmatic approach to natural hormone replacement. Fam Community Health. 2003;25(1):53-63.
110. Cameron DR et al. Androgen replacement therapy in women. Fertil Steril. 2004;82(2):273-289.
111. Braunstein GD. Androgen insufficiency in women: summary of critical issues. Fertil Steril. 2002;77(Suppl 4):S94–S99.
112. Davis SR et al. Testosterone in women--the clinical significance. The lancet. Diabetes & endocrinology. Dec 2015;3(12):980-992.
113. Bolour S et al. Testosterone therapy in women: a review. International journal of impotence research. Sep-Oct 2005;17(5):399-408.
114. Achilli C et al. Efficacy and safety of transdermal testosterone in postmenopausal women with hypoactive sexual desire disorder: a systematic review and meta-analysis. Fertility and sterility. Feb 2017;107(2):475-482.e415.
115. Cappelletti M et al. Increasing women's sexual desire: The comparative effectiveness of estrogens and androgens. Hormones and behavior. Feb 2016;78:178-193.
116. Labrie F et al. Androgens in women are essentially made from DHEA in each peripheral tissue according to intracrinology. The Journal of steroid biochemistry and molecular biology. Apr 2017;168:9-18.
117. Havlikova H et al. Sex- and age-related changes in epitestosterone in relation to pregnenolone sulfate and testosterone in normal subjects. J Clin Endocrinol Metab. 2002 May;87(5):2225-31.
118. Mayo W et al. Individual differences in cognitive aging: implication of pregnenolone sulfate. Progress in neurobiology. Sep 2003;71(1):43-48.
119. Mellon SH. Neurosteroid regulation of central nervous system development. Pharmacol Ther. 2007 Oct;116(1):107-24.
120. Dall GV, Britt KL. Estrogen Effects on the Mammary Gland in Early and Late Life and Breast Cancer Risk. Frontiers in oncology. 2017 May 26:7:110
121. Chlebowski RT et al. WHI Investigators. Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. JAMA. 2010 Oct 20;304(15):1684-92.
122. Zhao S et al. Sex hormone associations with breast cancer risk and the mediation of randomized trial postmenopausal hormone therapy effects. Breast cancer research: BCR. Mar 26 2014;16(2):R30.
123. Shah NR et al. Current breast cancer risks of hormone replacement therapy in postmenopausal women. Expert opinion on pharmacotherapy. Dec 2006;7(18):2455-2463.
124. Fournier A et al. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat. Jan 2008;107(1):103-111.
125. Mohammed H et al. Progesterone receptor modulates ERalpha action in breast cancer. Nature. Jul 16 2015;523(7560):313-317.
126. Asi N et al. Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis. Syst Rev. 2016 Jul 26;5(1):121.
127. Prior JC. Progesterone or progestin as menopausal ovarian hormone therapy: recent physiology-based clinical evidence. Current opinion in endocrinology, diabetes, and obesity. Dec 2015;22(6):495-501.
128. Glaser R et al. Testosterone and breast cancer prevention. Maturitas. Nov 2015;82(3):291-295.
129. Dimitrakakis C et al. Low salivary testosterone levels in patients with breast cancer. BMC cancer. 2010;10:547.
130. Dimitrakakis C et al. Breast cancer incidence in postmenopausal women using testosterone in addition to usual hormone therapy. Menopause (New York, N.Y.). Sep-Oct 2004;11(5):531-535.
131. NAMS. The North American Menopause Society. Hormone Therapy: Benefits & Risks. 2017. http://www.menopause.org/for-women/menopauseflashes/menopause-symptoms-and-treatments/hormone-therapy-benefits-risks. Accessed 7/26/2017.
132. Stanczyk FZ et al. Reprint of "Use of medroxyprogesterone acetate for hormone therapy in postmenopausal women: Is it safe?". The Journal of steroid biochemistry and molecular biology. Sep 2015;153:151-159.
133. Schonberg MA et al. After the Women's Health Initiative: decision making and trust of women taking hormone therapy. Womens Health Issues. 2005;15(4): 187-195.
134. Ravdin PM et al. The decrease in breast-cancer incidence in 2003 in the United States. The New England journal of medicine. Apr 19 2007;356(16):1670-1674.
135. Samaras N et al. Off-label use of hormones as an antiaging strategy: a review. Clinical interventions in aging. 2014;9:1175-1186.
136. Moskowitz D. A comprehensive review of the safety and efficacy of bioidentical hormones for the management of menopause and related health risks. Altern Med Rev. 2006 Sep;11(3):208-23.
137. Whelan AM et al. Defining bioidentical hormones for menopause-related symptoms. Pharm Pract (Granada). Jan 2011;9(1):16-22.
138. Vinogradova Y et al. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ (Clinical research ed.). Jan 9 2019;364:k4810.
139. Gass ML et al. Use of compounded hormone therapy in the United States: report of The North American Menopause Society Survey. Menopause (New York, N.Y.). Dec 2015;22(12):1276-1284.
140. Landete JM et al. Bioactivation of Phytoestrogens: Intestinal Bacteria and Health. Critical reviews in food science and nutrition. Aug 17 2016;56(11):1826-1843.
141. Chen MN et al. Efficacy of phytoestrogens for menopausal symptoms: a meta-analysis and systematic review. Climacteric: the journal of the International Menopause Society. Apr 2015;18(2):260-269.
142. Vitale DC et al. Isoflavones: estrogenic activity, biological effect and bioavailability. European journal of drug metabolism and pharmacokinetics. Mar 2013;38(1):15-25.
143. Gencel VB et al. Vascular effects of phytoestrogens and alternative menopausal hormone therapy in cardiovascular disease. Mini reviews in medicinal chemistry. Feb 2012;12(2):149-174.
144. Sirotkin AV et al. Phytoestrogens and their effects. European journal of pharmacology. Oct 15 2014;741:230-236.
145. Aso T. Equol improves menopausal symptoms in Japanese women. J Nutr. 2010 Jul;140(7):1386S-9S.
146. Cho YA et al. Effect of dietary soy intake on breast cancer risk according to menopause and hormone receptor status. Eur J Clin Nutr. 2010 Sep;64(9):924-32.
147. Sarkar FH et al. Soy isoflavones and cancer prevention. Cancer Invest. 2003;21(5):744–757.
148. Zittermann A. [Phytoestrogens]. Zentralbl Gynakol. 2003;125(6):195–201.
149. Hajirahimkhan A et al. Botanical modulation of menopausal symptoms: Mechanisms of action? Planta Med. May 2013;79(7):538-553.
150. Ko KP. Isoflavones: chemistry, analysis, functions and effects on health and cancer. Asian Pacific journal of cancer prevention: APJCP. 2014;15(17):7001-7010.
151. Bawa S. The significance of soy protein and soy bioactive compounds in the prophylaxis and treatment of osteoporosis. J Osteoporos. 2010 Mar 8 2010:891058.
152. Miyake A et al. Repressive effect of the phytoestrogen genistein on estradiol-induced uterine leiomyoma cell proliferation. Gynecol Endocrinol. 2009 Jun;25(6):403-9.
153. Messina M. Soy foods, isoflavones, and the health of postmenopausal women. The American journal of clinical nutrition. Jul 2014;100 Suppl 1:423s-430s.
154. Mainini G et al. Nonhormonal management of postmenopausal women: effects of a red clover based isoflavones supplementation on climacteric syndrome and cardiovascular risk serum profile. Clinical and experimental obstetrics & gynecology. 2013;40(3):337-341.
155. Vargas KG et al. The functions of estrogen receptor beta in the female brain: A systematic review. Maturitas. Nov 2016;93:41-57.
156. Gallo D et al. Estrogen receptor beta in cancer: an attractive target for therapy. Current pharmaceutical design. 2012;18(19):2734-2757.
157. Bardin A et al. Loss of ERbeta expression as a common step in estrogen-dependent tumor progression. Endocr Relat Cancer. 2004 Sep;11(3):537-51.
158. Bossard C et al. Potential role of estrogen receptor beta as a tumor suppressor of epithelial ovarian cancer. PloS one. 2012;7(9):e44787.
159. Omoto Y et al. Clinical significance of estrogen receptor beta in breast and prostate cancer from biological aspects. Cancer science. Apr 2015;106(4):337-343.
160. Vincent A et al. Soy isoflavones: are they useful in menopause? Mayo Clin Proc. 2000;75(11):1174–1184.
161. Sureda A et al. Hypotensive effects of genistein: From chemistry to medicine. Chem Biol Interact. Apr 25 2017;268:37-46.
162. Li J et al. Does genistein lower plasma lipids and homocysteine levels in postmenopausal women? A meta-analysis. Climacteric: the journal of the International Menopause Society. Oct 2016;19(5):440-447.
163. Khalesi S et al. Flaxseed consumption may reduce blood pressure: a systematic review and meta-analysis of controlled trials. The Journal of nutrition. Apr 2015;145(4):758-765.
164. Chun JN et al. The protective effects of Schisandra chinensis fruit extract and its lignans against cardiovascular disease: a review of the molecular mechanisms. Fitoterapia. Sep 2014;97:224-233.
165. Nabavi SF et al. Genistein: A Boon for Mitigating Ischemic Stroke. Current topics in medicinal chemistry. 2015;15(17):1714-1721.
166. Evsen MS et al. Effects of estrogen, estrogen/progesteron combination and genistein treatments on oxidant/antioxidant status in the brain of ovariectomized rats. European review for medical and pharmacological sciences. Jul 2013;17(14):1869-1873.
167. Linford NJ et al. 17beta-estradiol and the phytoestrogen genistein attenuate neuronal apoptosis induced by the endoplasmic reticulum calcium ATPase inhibitor thapsigargin. Steroids. 2002;67(13-14):1029-1040.
168. Schreihofer DA et al. Soy phytoestrogens are neuroprotective against stroke-like injury in vitro. Neuroscience. 2009;158(2): 602-609.
169. Donzelli A et al. Neuroprotective effects of genistein in mongolian gerbils: estrogen receptor-beta involvement. J Pharmacol Sci. 2010;114(2): 158-167.
170. Ma Y et al. Dietary genistein and equol (4', 7 isoflavandiol) reduce oxidative stress and protect rats against focal cerebral ischemia. Am J Physiol Regul Integr Comp Physiol. 2010;299(3): R871-877.
171. Yu HL et al. Neuroprotective effects of genistein and folic acid on apoptosis of rat cultured cortical neurons induced by beta-amyloid 31-35. Br J Nutr. 2009;102(5): 655-662.
172. Abdi F et al. Effects of phytoestrogens on bone mineral density during the menopause transition: a systematic review of randomized, controlled trials. Climacteric: the journal of the International Menopause Society. Dec 2016;19(6):535-545.
173. Chiang SS et al. Beneficial effects of phytoestrogens and their metabolites produced by intestinal microflora on bone health. Appl Microbiol Biotechnol. Feb 2013;97(4):1489-1500.
174. Wada K et al. Soy isoflavone intake and breast cancer risk in Japan: from the Takayama study. International journal of cancer. Journal international du cancer. Aug 15 2013;133(4):952-960.
175. Dong JY et al. Soy isoflavones consumption and risk of breast cancer incidence or recurrence: a meta-analysis of prospective studies. Breast Cancer Res Treat. Jan 2011;125(2):315-323.
176. Fritz H et al. Soy, red clover, and isoflavones and breast cancer: a systematic review. PloS one. 2013;8(11):e81968.
177. Parazzini F et al. Dietary components and uterine leiomyomas: a review of published data. Nutr Cancer. 2015;67(4):569-579.
178. Mason JK et al. Flaxseed and its lignan and oil components: can they play a role in reducing the risk of and improving the treatment of breast cancer? Applied physiology, nutrition, and metabolism. Jun 2014;39(6):663-678.
179. Flower G et al. Flax and Breast Cancer: A Systematic Review. Integrative cancer therapies. May 2014;13(3):181-192.
180. Lu LJ et al. Increased urinary excretion of 2-hydroxyestrone but not 16alpha-hydroxyestrone in premenopausal women during a soya diet containing isoflavones. Cancer Res. 2000;60(5):1299–1305.
181. Lephart ED. Modulation of Aromatase by Phytoestrogens. Enzyme Res. 2015;2015:594656.
182. Buck K et al. Meta-analyses of lignans and enterolignans in relation to breast cancer risk. Am J Clin Nutr. 2010 Jul;92(1):141-53.
183. Thompson LU et al. Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer. Clin Cancer Res. 2005;11(10): 3828-3835.
184. Laidlaw M et al. Effects of A Breast-Health Herbal Formula Supplement on Estrogen Metabolism in Pre- and Post-Menopausal Women not Taking Hormonal Contraceptives or Supplements: A Randomized Controlled Trial. Breast Cancer (Auckl). 2010 Dec 16;4:85-95.
185. Taku K et al. Extracted or synthesized soybean isoflavones reduce menopausal hot flash frequency and severity: systematic review and meta-analysis of randomized controlled trials. Menopause (New York, N.Y.). Jul 2012;19(7):776-790.
186. NIH. National Institutes of Health. Black Cohosh. https://ods.od.nih.gov/factsheets/BlackCohosh-HealthProfessional/. Last updated 3/3/2017. Accessed 10/24/2017.
187. Jiang K et al. Black cohosh improves objective sleep in postmenopausal women with sleep disturbance. Climacteric: the journal of the International Menopause Society. Aug 2015;18(4):559-567.
188. Shahnazi M et al. Effect of black cohosh (cimicifuga racemosa) on vasomotor symptoms in postmenopausal women: a randomized clinical trial. Journal of caring sciences. Jun 2013;2(2):105-113.
189. Mohammad-Alizadeh-Charandabi S et al. Efficacy of black cohosh (Cimicifuga racemosa L.) in treating early symptoms of menopause: a randomized clinical trial. Chinese medicine. Nov 01 2013;8(1):20.
190. Ross SM. Menopause: a standardized isopropanolic black cohosh extract (remifemin) is found to be safe and effective for menopausal symptoms. Holistic nursing practice. Jan-Feb 2012;26(1):58-61.
191. Shams T et al. Efficacy of black cohosh-containing preparations on menopausal symptoms: a meta-analysis. Altern Ther Health Med. 2010 Jan-Feb;16(1):36-44.
192. Beer AM et al. Efficacy of black cohosh (Cimicifuga racemosa) medicines for treatment of menopausal symptoms - comments on major statements of the Cochrane Collaboration report 2012 "black cohosh (Cimicifuga spp.) for menopausal symptoms (review)". Gynecological endocrinology. Dec 2013;29(12):1022-1025.
193. Czuczwar P et al. The safety and tolerance of phytotherapies in menopausal medicine – a review of the literature. Przeglad menopauzalny = Menopause review. Mar 2017;16(1):8-11.
194. Sarri G et al. Vasomotor symptoms resulting from natural menopause: a systematic review and network meta-analysis of treatment effects from the National Institute for Health and Care Excellence guideline on menopause. BJOG: an international journal of obstetrics and gynaecology. Sep 2017;124(10):1514-1523.
195. Fang ZZ et al. Cycloartane triterpenoids from Cimicifuga yunnanensis induce apoptosis of breast cancer cells (MCF7) via p53-dependent mitochondrial signaling pathway. Phytother Res. 2011 Jan;25(1):17-24.
196. Hostanska K et al. Evaluation of cell death caused by triterpene glycosides and phenolic substances from Cimicifuga racemosa extract in human MCF-7 breast cancer cells. Biol Pharm Bull. 2004;27(12):1970–1975.
197. Nisslein T et al. Effects of an isopropanolic extract of Cimicifuga racemosa on urinary crosslinks and other parameters of bone quality in an ovariectomized rat model of osteoporosis. J Bone Miner Metab. 2003;21(6):370–376.
198. Seidlova-Wuttke D et al. Effects of estradiol-17beta, testosterone and a black cohosh preparation on bone and prostate in orchidectomized rats. Maturitas. Jun 16 2005;51(2):177-186.
199. Wuttke W et al. The Cimicifuga preparation BNO 1055 vs. conjugated estrogens in a double-blind placebo-controlled study: effects on menopause symptoms and bone markers. Maturitas. Mar 14 2003;44 Suppl 1:S67-77.
200. Seidlova-Wuttke D et al. Pharmacology of Cimicifuga racemosa extract BNO 1055 in rats: bone, fat and uterus. Maturitas. Mar 14 2003;44 Suppl 1:S39-50.
201. Heger M et al. Efficacy and safety of a special extract of Rheum rhaponticum (ERr 731) in perimenopausal women with climacteric complaints: a 12-week randomized, double-blind, placebo-controlled trial. Menopause (New York, N.Y.). Sep-Oct 2006;13(5):744-759.
202. Hasper I et al. Long-term efficacy and safety of the special extract ERr 731 of Rheum rhaponticum in perimenopausal women with menopausal symptoms. Menopause (New York, N.Y.). Jan-Feb 2009;16(1):117-131.
203. Kaszkin-Bettag M et al. The special extract ERr 731 of the roots of Rheum rhaponticum decreases anxiety and improves health state and general well-being in perimenopausal women. Menopause (New York, N.Y.). Mar-Apr 2007;14(2):270-283.
204. Kaszkin-Bettag M et al. Efficacy of the special extract ERr 731 from rhapontic rhubarb for menopausal complaints: a 6-month open observational study. Altern Ther Health Med. Nov-Dec 2008;14(6):32-38.
205. Kaszkin-Bettag M et al. Confirmation of the efficacy of ERr 731 in perimenopausal women with menopausal symptoms. Altern Ther Health Med. Jan-Feb 2009;15(1):24-34.
206. Wober J et al. Activation of estrogen receptor-beta by a special extract of Rheum rhaponticum (ERr 731), its aglycones and structurally related compounds. The Journal of steroid biochemistry and molecular biology. Nov-Dec 2007;107(3-5):191-201.
207. Vargas KG et al. The functions of estrogen receptor beta in the female brain: A systematic review. Maturitas. Nov 2016;93:41-57.
208. Al-Bareeq RJ et al. Dong Quai (angelica sinensis) in the treatment of hot flashes for men on androgen deprivation therapy: results of a randomized double-blind placebo controlled trial. Canadian Urological Association journal. Feb 2010;4(1):49-53.
209. Goh SY et al. Gynaecomastia and the herbal tonic "Dong Quai". Singapore Med J. 2001;42(3, pp. 115–116.
210. Hardy ML. Herbs of special interest to women. J Am Pharm Assoc (Wash). 2000;40(2):234–242.
211. Trimarco V et al. Effects of a new combination of nutraceuticals on postmenopausal symptoms and metabolic profile: a crossover, randomized, double-blind trial. International journal of women's health. 2016;8:581-587.
212. Kupfersztain C et al. The immediate effect of natural plant extract, Angelica sinensis and Matricaria chamomilla (Climex) for the treatment of hot flushes during menopause. A preliminary report. Clinical and experimental obstetrics & gynecology. 2003;30(4):203-206.
213. Lim DW et al. Anti-osteoporotic effects of Angelica sinensis (Oliv.) Diels extract on ovariectomized rats and its oral toxicity in rats. Nutrients. Oct 16 2014;6(10):4362-4372.
214. Hajirahimkhan A et al. Evaluation of estrogenic activity of licorice species in comparison with hops used in botanicals for menopausal symptoms. PloS one. 2013;8(7):e67947.
215. Ofir R et al. Inhibition of serotonin re-uptake by licorice constituents. J Mol Neurosci. 2003;20(2):135-140.
216. Nahidi F et al. Effects of licorice on relief and recurrence of menopausal hot flashes. Iranian journal of pharmaceutical research: IJPR. Spring 2012;11(2):541-548.
217. Somjen D et al. Estrogen-like activity of licorice root constituents: glabridin and glabrene, in vascular tissues in vitro and in vivo. J Steroid Biochem Mol Biol. 2004;91(3):147–155.
218. Somjen D et al. Estrogenic activity of glabridin and glabrene from licorice roots on human osteoblasts and prepubertal rat skeletal tissues. The Journal of steroid biochemistry and molecular biology. Aug 2004;91(4-5):241-246.
219. De Franciscis P et al. Adding Agnus Castus and Magnolia to Soy Isoflavones Relieves Sleep Disturbances Besides Postmenopausal Vasomotor Symptoms-Long Term Safety and Effectiveness. Nutrients. 2017 Feb 13;9(2):129.
220. van Die MD et al. Vitex agnus-castus (Chaste-Tree/Berry) in the treatment of menopause-related complaints. Journal of alternative and complementary medicine. Aug 2009;15(8):853-862.
221. Rotem C et al. Phyto-Female Complex for the relief of hot flushes, night sweats and quality of sleep: randomized, controlled, double-blind pilot study. Gynecological endocrinology. Feb 2007;23(2):117-122.
222. Dietz BM et al. Botanicals and Their Bioactive Phytochemicals for Women's Health. Pharmacol Rev. Oct 2016;68(4):1026-1073.
223. Abbas S et al. Serum 25-hydroxyvitamin D and risk of post-menopausal breast cancer—results of a large case-control study. Carcinogenesis. 2008 Jan;29(1):93-9.
224. Vrieling A et al. Serum 25-hydroxyvitamin D and postmenopausal breast cancer survival: a prospective patient cohort study. Breast cancer research: BCR. Jul 26 2011;13(4):R74.
225. Welsh J. Vitamin D and breast cancer: Past and present. The Journal of steroid biochemistry and molecular biology. 2018 Mar:177:15-20.
226. Thyer L et al. A novel role for a major component of the vitamin D axis: vitamin D binding protein-derived macrophage activating factor induces human breast cancer cell apoptosis through stimulation of macrophages. Nutrients. Jul 08 2013;5(7):2577-2589.
227. Fleet JC et al. Vitamin D and cancer: a review of molecular mechanisms. The Biochemical journal. Jan 01 2012;441(1):61-76.
228. Marconett CN et al. Indole-3-carbinol disrupts estrogen receptor-alpha dependent expression of insulin-like growth factor-1 receptor and insulin receptor substrate-1 and proliferation of human breast cancer cells. Molecular and cellular endocrinology. Nov 05 2012;363(1-2):74-84.
229. Lampe JW. Interindividual differences in response to plant-based diets: implications for cancer risk. Am J Clin Nutr. 2009 May;89(5):1553S-1557S.
230. Ambrosone CB et al. Breast cancer risk in premenopausal women is inversely associated with consumption of broccoli, a source of isothiocyanates, but is not modified by GST genotype. J Nutr. 2004;134(5): 1134-1138.
231. Acharya A et al. Chemopreventive properties of indole-3-carbinol, diindolylmethane and other constituents of cardamom against carcinogenesis. Recent Pat Food Nutr Agric. 2010 Jun;2(2):166-77.
232. Weng JR et al. Indole-3-carbinol as a chemopreventive and anti-cancer agent. Cancer Lett. 2008 Apr 18;262(2):153-63.
233. Muti P et al. Estrogen metabolism and risk of breast cancer: a prospective study of the 2:16alpha-hydroxyestrone ratio in premenopausal and postmenopausal women. Epidemiology. 2000;11(6):635–640.
234. Saoudi M et al. Protective effects of oil of Sardinella pilchardis against subacute chlorpyrifos-induced oxidative stress in female rats. Archives of environmental & occupational health. 03 May 2017, 73(2):128-135
235. Kansal S et al. Evaluation of the role of oxidative stress in chemopreventive action of fish oil and celecoxib in the initiation phase of 7,12-dimethyl benz(alpha)anthracene-induced mammary carcinogenesis. Tumour Biol. 2011;32(1):167-77.
236. Bougnoux P et al. Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial. Br J Cancer. 2009;101(12): 1978-1985.
237. Mandal CC et al. Fish oil prevents breast cancer cell metastasis to bone. Biochem Biophys Res Commun. 2010 Nov 26;402(4):602-7.
238. Thangapazham RL et al. Green tea polyphenol and epigallocatechin gallate induce apoptosis and inhibit invasion in human breast cancer cells. Cancer Biol Ther. 2007;6(12): 1938-1943.
239. Thangapazham RL et al. Green tea polyphenols and its constituent epigallocatechin gallate inhibits proliferation of human breast cancer cells in vitro and in vivo. Cancer Lett. 2007;245(1-2): 232-241.
240. Leong H et al. Inhibition of mammary tumorigenesis in the C3(1)/SV40 mouse model by green tea. Breast Cancer Res Treat. 2008;107(3): 359-369.
241. Masuda M et al. Epigallocatechin-3-gallate decreases VEGF production in head and neck and breast carcinoma cells by inhibiting EGFR-related pathways of signal transduction. J Exp Ther Oncol. 2002;2(6): 350-359.
242. Farabegoli F et al. (-)-Epigallocatechin-3-gallate downregulates estrogen receptor alpha function in MCF-7 breast carcinoma cells. Cancer Detect Prev. 2007;31(6): 499-504.
243. Hsuuw YD et al. Epigallocatechin gallate dose-dependently induces apoptosis or necrosis in human MCF-7 cells. Ann N Y Acad Sci. 2007;1095: 428-440.
244. Taheri Rouhi SZ et al. The effect of pomegranate fresh juice versus pomegranate seed powder on metabolic indices, lipid profile, inflammatory biomarkers, and the histopathology of pancreatic islets of Langerhans in streptozotocin-nicotinamide induced type 2 diabetic Sprague-Dawley rats. BMC complementary and alternative medicine. Mar 14 2017;17(1):156.
245. Li Y et al. Dietary Natural Products for Prevention and Treatment of Breast Cancer. Nutrients. 2017 Jul 8;9(7):728.
246. Panth N et al. Anticancer Activity of Punica granatum (Pomegranate): A Review. Phytotherapy research: PTR. Apr 2017;31(4):568-578.
247. Toi M et al. Preliminary studies on the anti-angiogenic potential of pomegranate fractions in vitro and in vivo. Angiogenesis. 2003;6(2):121-8.
248. Sturgeon SR et al. Pomegranate and breast cancer: possible mechanisms of prevention. Nutr Rev. 2010 Feb;68(2):122-8.
http://www.womenshealth.gov
美国更年期学会
http://www.menopause.org
美国FDA官网
https://www.fda.gov/
加拿大女性健康网站
http://www.womenshealthmatters.ca
免责声明和安全信息
英文名称:Female Hormone Restoration,Bioidentical HRT
概述
平衡激素水平,包括孕酮、雌激素、脱氢表雄酮(DHEA)、睾酮和孕烯醇酮,对女性健康很重要。不幸的是,随着年龄的增长,女性体内的激素水平会下降。绝经后妇女患多种疾病的风险增加,包括心血管疾病、老年痴呆和骨质疏松症。更年期也经常引起睡眠障碍。传统的激素替代疗法(HRT,即妊马雌酮和合成黄体酮)已被证明具有严重的不良后果,包括癌症、血栓和冠心病等风险。幸运的是,生物相同激素替代疗法(HRT)以及植物雌激素等天然替代品,可能为女性提供安全有效的选择,以促进年轻激素水平恢复。
生物相同HRT使用与体内自然产生的激素相同的激素。生物同质激素与传统HRT的风险无关。它们可以在美国FDA批准的制剂中获得,可通过口服、透皮或阴道途径给药。
因支持健康女性荷尔蒙信号,植物雌激素受到广泛重视和大量研究。这些雌激素样化合物存在于许多植物中,研究最深入的是异黄酮(主要来自大豆)和木脂素(主要来自亚麻籽)。植物雌激素可以在体内发挥雌激素样作用,并可能为一些女性提供替代HRT的方法。植物雌激素与降低癌症风险、改善心血管健康、减少更年期症状等益处有关。
荷尔蒙下降带来健康问题
在绝经后时期,女性性激素水平显著下降,与绝经前女性相比,老年女性患心血管病、骨质疏松症、阿尔茨海默病和痴呆症等多种疾病的风险增加。心脏病是美国女性死亡的主要原因1,女性的冠心病发病率在绝经后急剧增加2,3。与绝经前妇女相比,绝经后妇女的血压更高,低密度脂蛋白(LDL)胆固醇、总胆固醇、甘油三酯和同型半胱氨酸水平更高,以及慢性炎症和代谢紊乱的标志物4,5,6。此外,绝经后高密度脂蛋白(HDL)胆固醇水平显著下降4,5。雌激素活性对于维持血管内皮的完整性至关重要,而血管内皮正是动脉粥样硬化发生的地方7。激素替代疗法(HRT)可能会对抗其中的一些变化。在一项临床试验中,75名围绝经期和绝经后妇女接受复合透皮(局部)生物相同雌激素治疗,无论是否使用孕酮,在36个月内心血管风险和炎症标志物都有所改善8。
更年期和围绝经期与骨质流失有关,骨质流失会导致骨质疏松和骨折风险增加。雌激素信号传导不足会导致促炎细胞因子的产生增加,从而扰乱骨形成和骨分解之间的平衡,并导致骨丢失9,10。
激素损失也与神经元变性和痴呆、阿尔茨海默病和帕金森病风险增加有关11-13。雌激素不足会刺激β淀粉样蛋白形成,从而导致阿尔茨海默病14。孕烯醇酮和DHEA都是神经保护激素,它们的缺失也与阿尔茨海默病相关的记忆问题和脑细胞死亡有关15,16。这两种激素似乎在调节与学习和记忆、压力、情绪和动机有关的神经递质系统中发挥着重要作用17-20。
更年期通常会导致睡眠紊乱和相关症状,如盗汗21。重要的是,睡眠紊乱与更年期妇女心血管风险增加有关。一项研究表明,更年期女性的睡眠障碍与动脉硬化有关—僵硬、不灵活的动脉不太健康22。一项观察性队列研究的证据表明,生物相同的HRT可以减少绝经后妇女的睡眠障碍,但还需要更多的研究23。
附:什么是雌激素优势
“雌激素优势(Estrogen dominance)”是整合医学(Integrative Health)从业者用来描述相对于孕酮水平的高雌激素水平的术语24。然而,这个词在整合医学界的普遍使用不应被解释为雌激素天生就不好。相反,重点应该是保持性激素的适当平衡(例如,雌激素相对于孕激素)。不平衡的水平,包括高雌激素水平,可能会导致不愉快的症状,如情绪波动、性欲改变、腹胀、焦虑等。雌激素优势也可能意味着在接受无对抗雌激素治疗的女性中出现的激素环境,例如仅使用雌激素而不使用孕激素(黄体酮)的HRT25。例如,接受无对抗雌激素治疗的绝经后妇女可能会出现雌激素优势的迹象和症状26。
还没有广泛接受的诊断标准或特定的雌激素和孕激素水平将女性归类为雌激素优势。事实上,高水平和低水平的雌激素都会导致急性和慢性疾病27。确定性别失衡或其他类型的类固醇激素是否可能导致症状,需要一种个性化的方法,包括实验室测试以评估激素水平,以及临床评估,以确定任何失衡是否与特定症状相关。最终目标是仔细调整激素环境,通常使用生物相同HRT,以实现特定女性的最佳平衡。“最佳”激素范围总是相对于其他激素的平衡,必须考虑到特定女性的感受,并且会因个人而异。
平衡类固醇激素水平—包括黄体酮、雌激素(雌酮、雌二醇、雌三醇)、DHEA、睾酮、孕烯醇酮,有时还有皮质醇—对于在激素影响下保持健康很重要。激素水平及其平衡不仅影响生殖健康和某些癌症的风险,还影响情绪和心理健康2、肌肉骨骼健康29、自身免疫30,31、胃肠健康32等。
了解激素替代疗法及激素作用
激素替代疗法(HRT)的原理是,替代随着年龄的增长而丢失的激素可能有助于防止激素水平下降的表现。尽管这一历史上促使传统HRT出现的基本前提在理论上是正确的,但我们现在知道,最佳激素恢复要微妙和复杂得多。所有类固醇激素都是在代谢级联过程中由胆固醇产生的。级联反应中的第一种激素是孕烯醇酮,它随后可以转化为所有其他类固醇激素,包括DHEA、孕酮、睾酮和各种形式的雌激素33。这些激素是相互关联的,但每种激素都具有独特的生理功能。生物学上合理的激素疗法应旨在协调对全身不断发生的激素信号环境的生理反应。
传统HRT的一个问题是,与女性身体产生的内源性雌激素相比,妊马雌酮(CEE)在身体的某些部位刺激更明显的雌激素信号,可能导致不良后果34。CEE是从怀孕母马的尿液中获得的35,通常与合成的孕激素联合使用。然而,CEE和合成黄体酮不能在女性体内复制由各种激素及其代谢产物在自然条件下刺激的复杂信号网络。
传统HRT的另一个问题是,CEE制剂含有其他激素,如雄激素和黄体酮,这些激素与人类自然产生的激素不同36。此外,由于CEE与体内雌激素的形式和比例不同,其使用可能导致与内源性激素代谢产生的激素代谢物不同且不成比例37。口服马雌激素引起的这种不同激素代谢的一个表现是凝血风险增加,这是众所周知的CEE副作用34。
1.关于孕酮:
在健康的育龄妇女中,孕酮(黄体酮)和雌激素在月经周期中处于动态平衡状态。孕酮在排卵、着床、妊娠、乳房发育和功能方面具有独特而重要的功能38,39,以及在大脑中40。
孕酮可以在缓解更年期症状方面发挥重要作用。几项研究报告称,与合成孕激素醋酸甲羟孕酮相比,使用黄体酮的女性更年期症状和生活质量得到了类似或更大的减轻,雌激素治疗相关的副作用也更少41-44。在一项研究中,与合成孕激素的使用者相比,黄体酮使用者的睡眠问题症状得分低30%,焦虑症状得分低50%以上,抑郁症状得分低60%,认知困难症状得分低40%,性功能得分高30%。此外,80%使用生物相同黄体酮的女性报告对其激素治疗总体满意45。
在心血管健康方面,黄体酮已被证明比合成黄体酮更安全。已发现某些合成孕激素,但不是孕酮,会加重口服雌激素治疗对血栓风险的负面影响46,47。在一项大型病例对照研究中发现,共轭马雌激素和合成孕激素醋酸甲羟孕酮的组合可使静脉血栓形成的风险增加一倍以上48。单独使用黄体酮已证明绝经后妇女的心血管安全性(2015年以前)。在一项研究中,黄体酮增强了雌激素对心肌血流的积极作用:当添加到雌激素治疗中时,在有心脏病发作或冠状动脉疾病史的女性在跑步机运动中,黄体酮显著改善了冠状动脉血流量,但合成的黄体酮没有效果49。
黄体酮在调节认知功能、社交行为和情绪方面发挥作用,并在神经系统中表现出神经保护和抗炎特性50,51。由于一些黄体酮代谢产物具有抗焦虑作用,人们认为黄体酮耗竭可能导致更年期早期焦虑和情绪障碍的发生率增加52。
2.关于雌激素:
雌激素有许多天然存在的形式。人类的主要雌激素是雌酮、雌二醇和雌三醇53,54。雌激素在生殖期由卵巢产生,在一生中由肾上腺和其他组织产生少量。雌激素的非卵巢来源在绝经后变得更加重要55,56。
2.1.雌二醇:在未怀孕、育龄女性中是最有效的形式,主要有助于卵子从卵巢循环释放(排卵)57,58。雌二醇对心脏、骨骼、大脑和结肠有有益作用59。雌二醇水平的波动和总体下降会导致常见的围绝经期和绝经后症状,如潮热、情绪波动和阴道萎缩60,61,绝经后雌二醇耗竭会影响全身组织,导致一系列疾病风险和虚弱62,63。雌酮是绝经后妇女的主要雌激素,它是由脂肪组织产生的64;雌三醇是一种相对较弱的雌激素,由于雌三醇是由胎盘分泌的,它是妊娠期的主要雌激素65,66。
雌激素的三种主要类型可以转化为许多代谢产物。例如,雌酮可转化为以下代谢产物67:
- 2-羟基雌酮
- 4-羟基雌酮
- 16α-羟基雌酮
一些证据表明,雌激素代谢为2-羟基形式可能对绝经后妇女的乳腺癌具有预防作用67,68。然而,在得出各种雌激素代谢产物的比例在乳腺癌风险中的作用的确切结论之前,还需要更多的研究。
2.2.雌三醇:雌三醇的雌激素效应比其他形式的雌激素弱。研究表明,雌三醇能有效治疗更年期潮热、盗汗和失眠。此外,一些研究表明,雌三醇可以对抗绝经前骨质流失66。当与雌二醇一起服用时,雌三醇会对抗雌二醇更强的雌激素作用69。雌三醇用于阴道,是治疗更年期泌尿系统和阴道症状的极佳药物34。
雌三醇已经在一系列慢性疾病的背景下进行了研究。日本的研究人员进行了大量试验,表明雌三醇可以改善血压、血管功能和血脂70-74。
新兴研究表明,雌三醇在治疗自体免疫疾病多发性硬化症和其他神经退行性疾病中具有潜在作用,部分是通过调节免疫功能。这一理论源于观察到多发性硬化症在妊娠期间和妊娠后不久的缓解和复发与胎盘分泌雌三醇有关66。
附:什么是异源性雌激素?
异源性雌激素(Xenoestrogens,或称外源性雌激素)是与体内雌激素信号通路相互作用的外源性化合物,可能导致激素失衡的某些表现。异源性雌激素模仿雌激素对雌激素受体的作用。它们是一大类被称为内分泌干扰物的化合物的一部分,这些化合物可以干扰正常的激素信号传导75。外源雌激素存在于塑料、杀虫剂、除草剂和许多其他来源中76,77。
全身的组织和器官系统对雌激素信号敏感,并可能受到外源性雌激素的影响。事实上,研究表明,除了乳腺癌外,外源性雌激素暴露也可能导致肺癌、肾癌和生殖系统肿瘤78,79。截至2022年初,一项大型研究正在进行中,目的是了解这些污染物和其他污染物对患乳腺癌风险的影响80。外源性雌激素暴露也被证明会改变免疫细胞功能81,导致肾功能下降82,增加子宫肌瘤的风险83,对分娩结果产生负面影响84,可能增加肥胖和糖尿病的风险85,并可能影响良性乳腺疾病和乳腺组织变化86,87。
由于外源性雌激素实际上不是雌激素,因此通过测量雌激素水平的测试不会发现它们。为了限制外源性雌激素的暴露和潜在的不良影响,尽量少用塑料,彻底清洗农产品,避免使用包括对羟基苯甲酸酯和邻苯二甲酸酯在内的产品。也可以考虑在饮食中添加更多的植物雌激素(在大豆和亚麻籽中大量存在)和十字花科蔬菜,因为有一些初步数据表明它们可以阻断外源性雌激素的作用88-91。
2.3.其他重要激素
除了雌激素和孕激素,重要的是要考虑激素孕烯醇酮、DHEA和睾酮的作用。理想的生物相同HRT包括对所有下降的激素水平的综合评估。
2.3.1.脱氢表雄酮(DHEA):
这是一种由肾上腺、性腺和大脑分泌的甾体激素92。男性和女性都经历了与年龄相关的DHEA下降93。女性通常在30多岁时达到峰值水平,之后开始每年损失约2%94。更年期后DHEA和DHEA-硫酸盐(DHEA-s,DHEA的一种循环形式)水平降低会影响认知、情绪和性行为95,并被认为会导致癌症、胰岛素抵抗、免疫防御降低和精神疾病96。
DHEA已被证明会影响情绪和神经功能97、免疫功能98、能量和幸福感99、血管健康100、胰岛素抵抗和炎症标志物水平101以及肌肉和骨量的维持102,103。此外,DHEA已被发现可增强性功能,尤其是阴道内DHEA的使用已被证明是治疗绝经后外阴阴道萎缩的有效方法104,105。
2.3.2.睾酮:
与DHEA一样,女性的睾酮水平随着年龄的增长而逐渐降低106。睾酮的丧失会影响性欲、骨骼和肌肉质量、血管舒缩症状、心血管健康、情绪和幸福感107-110。
女性的睾酮治疗已被证明可以改善生活质量、情绪、注意力、骨骼健康、心血管风险标志物、认知功能和外阴阴道萎缩111,112。此外,睾酮,无论是单独使用还是与雌激素治疗联合使用,已被证明在治疗女性性欲低下和提高性满意度方面是有效的113-115。由于DHEA可以转化为睾酮,因此使用DHEA可能会获得睾酮的一些好处110,116。
2.3.3.孕烯醇酮:
与其他一些激素的情况一样,孕烯醇酮的显著减少始于女性30岁出头117。孕烯醇酮作为整个类固醇激素级联中的初始激素,主要来源于肾上腺、性腺、大脑和其他组织中的胆固醇。除了作为其他激素的前体外,孕烯醇酮似乎对神经功能的调节有直接影响16,20。孕烯醇酮可能对与年龄相关的睡眠和认知变化特别重要118,并且缺失与大脑功能下降和痴呆症有关119。
附:关于激素与癌症风险
尽管许多因素影响乳腺癌风险,但众所周知,高雌激素水平和一生中雌激素暴露量的增加,尤其是由于青春期提前,与乳腺癌风险的增加有关120。建立适当的激素平衡,并加入支持健康激素代谢的食物和补充剂,可能有助于减轻雌激素的乳腺癌诱因。
目前的证据表明,虽然CEE似乎不会增加癌症风险,但传统HRT中使用的合成孕激素(主要是醋酸甲羟孕酮)与风险增加有关34。在妇女健康倡议(WHI)中,仅CEE不会增加癌症风险,而CEE加醋酸甲羟孕酮与风险增加相关121-123。
尚未发现将生物相同孕酮与雌激素联合使用与增加癌症风险有关124。事实上,体外研究表明,黄体酮实际上可能会减少雌激素引发的细胞增殖125。尽管需要更多的研究来明确确定孕酮治疗乳腺癌症的风险和安全性,但迄今为止的证据表明,它比合成孕酮更安全,尤其是醋酸甲羟孕酮126,127。
此外,研究表明,睾酮对乳腺组织具有抗增殖作用,对抗雌激素的致癌作用128。在一项研究中,发现患有癌症的女性唾液睾酮水平低于无癌女性129。在另一项研究中,包括雌激素、孕激素和睾酮的绝经后激素替代疗法与癌症的发生率显著低于使用不含睾酮的激素替代疗法的历史数据预测的发生率130。
传统HRT对比生物相同HRT
直到2002年,主流医生还通常开出激素替代疗法(HRT)药方来缓解更年期症状。常规的HRT包括从怀孕母马尿液中提取的口服共轭雌激素(倍美力)和合成黄体酮(激活孕激素受体的化合物),如醋酸甲羟孕酮131。然而,在2002年,具有里程碑意义的妇女健康倡议(WHI)项目研究发现了与传统口服激素替代疗法相关的重大风险:随着时间的推移,这种风险很大程度上归因于醋酸甲羟孕酮(安宫黄体酮),这是WHI研究中使用的合成孕激素132。随着人们对传统的口服HRT相关风险的认识和传播,许多女性开始担心使用传统HRT。因此,在美国传统HRT的使用急剧下降133。2003年在50岁以上妇女中观察到的乳腺癌发病率的急剧下降与传统HRT使用的减少有关134。
研究中使用的共轭马雌激素和合成孕激素在化学结构上与女性体内产生的天然激素不同135。许多研究表明,合成孕激素(醋酸甲羟黄体酮)会带来多种健康风险,包括增加乳腺癌、中风和认知功能障碍132。而生物相同的HRT疗法使用与体内自然产生的激素相同的激素(分子结构一致)136,137。
生物相同(Bioidentical,或称生物同质)HRT使用与体内自然产生的激素相同的激素。生物相同激素与常规的激素治疗的风险无关。它们可以依据美国FDA批准的制剂获得,可通过口服、透皮或阴道途径给药;或者,高质量的复合药物可以制备常规制剂可能无法获得的浓度。
生物相同HRT比传统HRT产生更少的副作用。与传统HRT中使用的口服马雌激素相比,生物相同的局部应用雌激素似乎造成的血栓风险更小,可能还有总体心血管病风险降低34。这在一项大型病例对照研究中得到证实,该研究表明,与对照组相比,单独使用口服马雌激素(不与合成孕激素联合使用)导致静脉血栓的风险增加约50%。当马雌激素与合成孕激素联合使用时,风险比对照组参与者高出约90%138。此外,与最广泛使用的合成孕酮不同,生物相同的孕酮不会增加心血管或乳腺癌风险69。事实上,生物相同激素疗法的吸引力并没有在公众或医学界消失:现在使用激素疗法的女性中,近三分之一使用生物相同激素139。
许多美国FDA批准的商业制剂现在使用生物相同激素,这有助于在传统观念的医生中推广生物相同HRT的接受度。美国FDA批准的生物相同激素制剂,包括:戊酸雌二醇(Estrace)、戊酸雌二醇阴道乳霜、雌二醇透皮贴剂(Climara)、雌二醇乳液(Estrasorb),以及微粉化黄体酮…等。
此外,补充经过科学研究的当归和甘草等草药,可以进一步促进女性激素的健康代谢,并补充生物相同HRT的作用。
自然疗法
1.植物雌激素:植物雌激素一类在一些植物中发现的与雌激素结构相似的膳食生物活性物质和天然化合物。尽管有几种类型的植物化合物被归类为植物雌激素140,但研究最多的是异黄酮和木脂素(或木酚素)141。植物中的植物雌激素在很大程度上是无活性的,但被肠道细菌代谢成活性化合物142,143。一旦被吸收,活化的植物雌激素在体内发挥雌激素样作用,对一些女性来说可能是生物相同的HRT的替代品144,140。
一些支持使用植物雌激素的最佳证据来自亚洲,那里的更年期症状较轻,不太常见,乳腺癌症发病率低于欧洲和北美地区。一种解释可能是在亚洲饮食中常见的大豆和其他植物产品中发现的植物雌激素145-147。
植物雌激素与雌激素受体结合并帮助调节雌激素活性148,149,142。植物雌激素的雌激素作用各不相同,但通常相对于雌二醇较弱;在雌二醇存在的情况下,它们似乎具有抗雌激素作用,因为它们与雌二醇竞争雌激素受体结合位点149,150。植物雌激素已被证明可以减轻更年期症状,并可能降低患某些慢性疾病的风险,包括心血管疾病、骨质疏松症和乳腺癌142,146,151-154。
有趣的是,植物雌激素似乎优先结合雌激素受体ER-β,而不是ER-α,后者被雌二醇和其他一些哺乳动物雌激素更强烈地激活144,153。ER-β激活已被认为是预防衰老和更年期的情绪和神经方面的机制155,并似乎可以预防乳腺、卵巢和可能的其他组织的癌症变化156-159。
饮食和补充植物雌激素为女性提供了一种在不使用激素治疗的情况下获得有限激素支持的方法,其健康益处包括如下:
1.1.心血管益处:
传统HRT已被证明会增加绝经后妇女心脏病发作的风险,与此不同,植物雌激素似乎对心脏有积极影响143,144。1999年,美国FDA授权在食品标签上使用健康声明,将大豆消费量的增加与冠状动脉疾病风险的降低相联系160。
有许多研究检测植物雌激素对心血管的影响。总体而言,研究表明,异黄酮可以降低高血压161,153,改善脂质紊乱,降低同型半胱氨酸水平162,改善血管健康,预防动脉粥样硬化143,153。类似地,木脂素与降低血压163、改善脂质代谢143和降低心脏风险有关164,140。
除了弱激活雌激素受体的能力外,植物雌激素还具有强烈的抗炎和降低氧化应激作用,这可能有助于其心血管益处143,140。
1.2.大脑保护:
雌激素和雌激素样化合物保护脑细胞免受衰老、氧化应激和中风诱导的损伤引起的退行性变化的影响165-167,35。几项研究表明,植物雌激素的染料木素(金雀异黄酮)保护实验动物免受脑缺血的影响,这种损伤见于中风168-170。此外,金雀异黄酮还表现出抗凋亡活性,保护培养的脑细胞免受时间的破坏171。
骨质疏松症与骨骼健康:已经对植物雌激素和骨骼健康进行了许多研究。临床试验发现,植物雌激素可以增加骨矿化,减少骨吸收,增强骨形成,改善骨代谢标志物。总之,他们的研究结果表明,植物雌激素(主要是大豆食品和异黄酮)可能有助于缓解更年期后的骨质流失153,172,173。
1.3.癌症预防:
许多研究已经注意到异黄酮消耗与乳腺癌风险降低之间的关联性174-176。大豆异黄酮对乳腺癌高危女性(包括乳腺癌幸存者)是安全的176,153,不会增加患子宫癌的风险177。此外,木脂素含量高的亚麻籽已被证明可降低乳腺癌风险并减少乳腺肿瘤生长178,179。
植物雌激素可以部分通过改善雌激素代谢来预防癌症。在一项试验中发现,每天含有113–202mg(取决于体重)染料木素和大豆黄酮的饮食可以增加绝经前妇女尿液中保护性2-羟基雌激素与有害的16-羟基雌激素的比例,这可能有助于降低乳腺癌的长期风险180。此外,新出现的证据表明,植物雌激素抑制芳香化酶,芳香化酶是催化睾酮转化为雌激素的酶,这种作用可能有助于降低其与乳腺癌风险的关系181。
木脂素是一种植物雌激素,主要存在于亚麻籽中,少量存在于芝麻、一些豆芽和许多其他植物性食物中。一项对21项研究的综合综述发现,木脂素摄入量较高的绝经后妇女患乳腺癌的可能性显著降低182。
在一项临床试验中,32名等待乳腺癌手术的女性被随机分配接受一块含有或不含有25g亚麻籽的松饼(对照组)。手术后对癌组织的分析显示,亚麻籽组的肿瘤生长标志物减少了30-71%,但对照组没有183。2010年发表的一项研究发现,木脂素、吲哚3甲醇(I3C)、D葡糖酸钙和其他草药的组合有利于改变47名绝经前和49名绝经后妇女的雌激素代谢产物比例184。
1.4.更年期症状:
多项研究表明,天然植物雌激素可以改善更年期症状144,尤其是潮热141。一项包括17项临床试验结果的综合荟萃分析发现,在6周至12个月的时间里,平均每天服用54mg染料木素,可安全地将潮热频率降低20.6%,潮热严重程度降低26.2%185。
2.改善更年期症状的草药:
2.1.黑升麻:
黑升麻根用于治疗妇科疾病有着悠久的历史,并已成为缓解更年期综合征的流行草药186。随机对照试验已证明其在治疗更年期症状(如潮热、性欲低下、睡眠障碍和其他身体和情绪症状)方面的疗效187-190。黑升麻具有安全性记录,大量证据支持其用于治疗更年期症状191-194。黑升麻和密切相关的物种在实验室中对癌症细胞产生了抗增殖作用195,196,并且黑升麻的使用与癌症风险或复发率的增加无关176。来自一项临床试验和几项动物研究的数据表明,在预防骨质流失方面,它与雌二醇和另一种抗骨质疏松药物相当197-200。
2.2.西伯利亚大黄:
数十年来,西伯利亚大黄的一种特殊提取物已在德国用于治疗与女性激素失衡有关的问题,包括月经少或不规律,以及围绝经期和绝经后症状201。
在使用该补充剂的第一项随机对照临床试验中,109名有症状的围绝经期妇女服用肠溶片,每天提供4mg标准化西伯利亚大黄提取物或安慰剂,持续12周。四周后,与安慰剂相比,西伯利亚大黄组的更年期相关症状明显减轻,到第12周,这种差异更加明显,试验中考虑的11种症状中的每一种都可以测量到。接受提取物治疗的54名女性中有45名(83%)和接受安慰剂治疗的55名女性中的1名(不到2%)报告症状有临床意义的减轻。此外,对西伯利亚大黄提取物可能产生的不良影响进行的广泛调查没有发现任何不良影响201。然后,一组参与者在开放标签试验中使用相同的提取物,持续48至96周。总的来说,妇女的更年期症状持续改善,没有不良副作用202。
另一项使用初步试验数据的研究发现,标准化西伯利亚大黄提取物比安慰剂更有效,特别是在缓解更年期相关焦虑症和改善总体健康方面。39名接受大黄治疗的女性中,有33名在试验开始时焦虑程度为“严重”或“中度”(85%),12周后焦虑程度降至“轻微”。该研究还注意到焦虑减少和潮热减少之间的相关性203。
其他研究已经证实了西伯利亚大黄提取物的益处:在一项为期六个月的363名参与者的开放标签研究204和一项为期12周的112名参与者的随机对照试验205中,使用该提取物治疗导致整体更年期症状评分降低,以及所有个体症状的减少。
实验室研究表明,西伯利亚大黄提取物及其活性成分选择性激活ER-β,对ER-α没有影响206。ER-β激活已被认为是预防衰老和更年期的情绪和神经方面的机制207,并似乎可以预防乳腺、卵巢和可能的其他组织的癌症变化156-159。
2.3.当归:
当归在传统中医中用于治疗妇科症状,如月经痛或盆腔痛、分娩或疾病后恢复以及疲劳/活力低下,因此被称为“女参”208-210。随机对照试验表明,当归与其他植物提取物联合使用可以缓解更年期症状211,212,在一项动物研究中,当归在预防骨质流失方面与雌二醇一样有效213。
2.4.甘草:
甘草根通过选择性激活ERβ发挥雌激素样作用214。实验室研究表明,甘草成分抑制血清素再摄取,这种作用可能有助于其对更年期症状的积极影响215,149。在一项随机对照试验中,在治疗的八周和治疗结束后的两周内,每天三次服用330mg甘草根,比安慰剂更能降低更年期潮热的频率和严重程度216。甘草根成分也已在实验室中显示出支持动脉和骨骼健康,从而降低心血管疾病和骨质疏松症的风险217,218。
2.5.圣洁莓:
含有圣洁莓果的草药配方已被证明可以改善更年期症状,如睡眠障碍、潮热和心理健康219-221。圣洁莓树的干果提取物几个世纪以来一直被用于妇女健康方面。在几项小型研究中,它已被证明可以调节激素和神经递质信号传导,并缓解经前症状。实验室研究表明,卵黄中的化合物可以结合雌激素受体并调节激素反应基因222。
了解有关更年期症状管理的详细内容,可点击:更年期综合征 >>
3.支持健康雌激素代谢的营养素:
3.1.维生素D:维生素D似乎对预防乳腺癌有显著的保护作用。在一项研究中,与维生素D水平最低的女性相比,维生素D水平较高的女性患乳腺癌的风险降低了近70%223,而另一项研究将维生素D水平较低与乳腺癌患者的生存率降低联系起来224。实验室研究表明,维生素D通过以下方式抑制乳腺癌的生长和发展:
- 阻断刺激癌症细胞生长的信号
- 增强抑制癌细胞生长的信号
- 调节乳腺对致癌作用的敏感性225
- 诱导癌症细胞死亡(细胞凋亡)226,227
3.2. 吲哚3甲醇:
十字花科蔬菜,如菜花、甘蓝、甘蓝和芽甘蓝,含有可能有助于对促进癌症生长的雌激素分解产物进行解毒的化合物228-230。一种这样的化合物是吲哚3甲醇(I3C),其防止雌激素转化为促乳腺癌的代谢物16-α-羟基雌酮,并同时增加向抗癌代谢物2-羟雌酮形式的转化231-233。
3.3.欧米伽3脂肪酸:
鱼油所含的ω-3脂肪酸(EPA和DHA),通过多种机制降低癌症风险。鱼油可减少氧化应激并抑制许多导致癌症发展的炎症介质的产生234,235。即使存在转移,它也可以使肿瘤细胞对化疗效果敏感,潜在地减少治疗所需的化疗剂量236。在乳腺癌动物模型中,补充鱼油可减少骨转移237。
3.4.绿茶:
绿茶多酚,特别是表没食子儿茶素没食子酸盐(EGCG),在实验室中抑制了人类乳腺癌症细胞的生长和繁殖,并减少了该疾病动物模型中乳腺肿瘤的数量238-240。绿茶还抑制了肿瘤血管的产生,同时下调了致癌雌激素受体并增加了细胞凋亡240-243。
3.5.石榴:
石榴因其抗氧化特性和抗癌潜力而被广泛研究244-246。就乳腺癌而言,石榴是一种特别有前途的药物,因为它能够抑制致癌酶芳香化酶并抑制肿瘤血管的生成247,248。
参考文献:
1. CDC. Centers for Disease Control and Prevention. Women and Heart Disease Fact Sheet. http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_women_heart.htm. Last updated 8/23/17. Accessed 10/24/2017.
2. Tandon VR. Prevalence of cardiovascular risk factors in postmenopausal women: A rural study. Journal of mid-life health. Jan 2010;1(1):26-29.
3. Clearfield M. Coronary heart disease risk reduction in postmenopausal women: the role of statin therapy and hormone replacement therapy. Preventive cardiology. Summer 2004;7(3):131-136.
4. Saha KR et al. Changes in lipid profile of postmenopausal women. Mymensingh medical journal: MMJ. Oct 2013;22(4):706-711.
5. Fonseca MIH et al. Impact of menopause and diabetes on atherogenic lipid profile: is it worth to analyse lipoprotein subfractions to assess cardiovascular risk in women? Diabetol Metab Syndr. 2017;9:22.
6. Lee CG et al. Adipokines, inflammation, and visceral adiposity across the menopausal transition: a prospective study. The Journal of clinical endocrinology and metabolism. Apr 2009;94(4):1104-1110.
7. Arnal JF et al. Estrogen receptor actions on vascular biology and inflammation: implications in vascular pathophysiology. Climacteric. 2009;12 Suppl 1: 12-17.
8. Stephenson K et al. The effects of compounded bioidentical transdermal hormone therapy on hemostatic, inflammatory, immune factors; cardiovascular biomarkers; quality-of-life measures; and health outcomes in perimenopausal and postmenopausal women. Int J Pharm Compd. Jan-Feb 2013;17(1):74-85.
9. Pietschmann P et al. Immunology of Osteoporosis: A Mini-Review. Gerontology. 2016;62(2):128-137.
10. Weitzmann MN et al. Estrogen deficiency and bone loss: an inflammatory tale. J Clin Invest. 2006 May;116(5):1186-94.
11. Depypere H et al. Alzheimer's disease, apolipoprotein E and hormone replacement therapy. Maturitas. Dec 2016;94:98-105.
12. Blair JA et al. Hypothalamic-pituitary-gonadal axis involvement in learning and memory and Alzheimer's disease: more than "just" estrogen. Frontiers in endocrinology. 2015 Mar 25:6:45.
13. Rocca WA et al. Increased risk of parkinsonism in women who underwent oophorectomy before menopause. Neurology. 2008 Jan 15;70(3):200-9.
14. Liang K et al. Estrogen stimulates degradation of beta-amyloid peptide by up-regulating neprilysin. J Biol Chem. 2010;285(2): 935-942.
15. Vallee M. Neurosteroids and potential therapeutics: Focus on pregnenolone. The Journal of steroid biochemistry and molecular biology. Jun 2016;160:78-87.
16. Yao Z-X et al. 22R-Hydroxycholesterol protects neuronal cells from β-amyloid-induced cytotoxicity by binding to β-amyloid peptide. J Neurochemistry. 2002 Dec;83(5):1110-19.
17. Maayan R et al. The effect of DHEA complementary treatment on heroin addicts participating in a rehabilitation program: a preliminary study. European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology. Jun 2008;18(6):406-413.
18. Zaluska M et al. [Dehydroepiandrosteron (DHEA) in the mechanisms of stress and depression]. Psychiatria polska. May-Jun 2009;43(3):263-274.
19. Vallée M et al. Role of pregnenolone, dehydroepiandrosterone and their sulfate esters on learning and memory in cognitive aging. Brain Res Brain Res Rev. 2001 Nov;37(1-3):301-12.
20. Zheng P. Neuroactive steroid regulation of neurotransmitter release in the CNS: action, mechanism and possible significance. Progress in neurobiology. Oct 2009;89(2):134-152.
21. Jehan S et al. Sleep Disorders in Postmenopausal Women. Journal of sleep disorders & therapy. Aug 2015;4(5).
22. Zhou Y et al. Sleep disorder, an independent risk associated with arterial stiffness in menopause. Sci Rep. May 15 2017;7(1):1904.
23. Ruiz AD et al. The effectiveness of sublingual and topical compounded bioidentical hormone replacement therapy in postmenopausal women: an observational cohort study. Int J Pharm Compd. Jan-Feb 2014;18(1):70-77.
24. Kolan A. Estrogen Dominance. U.S. Department of Veterans Affairs. Accessed 3/17/2022, https://www.va.gov/WHOLEHEALTHLIBRARY/tools/estrogen-dominance.asp
25. Cleveland Clinic. High Estrogen. Updated 2/9/2022. Accessed 3/18/2022, https://my.clevelandclinic.org/health/diseases/22363-high-estrogen
26. Valdes A, Bajaj T. Estrogen Therapy. StatPearls. 2022.
27. Patel S et al. Estrogen: The necessary evil for human health, and ways to tame it. Biomedicine & Pharmacotherapy. 2018;102:403-411.
28. Borrow AP et al. Estrogenic mediation of serotonergic and neurotrophic systems: Implications for female mood disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2014;54:13-25.
29. Gao WL et al. Measurement of serum estrogen and estrogen metabolites in pre- and postmenopausal women with osteoarthritis using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Braz J Med Biol Res. Feb 2015;48(2):146-53.
30. Chen Y et al. A Higher Ratio of Estradiol to Testosterone Is Associated with Autoimmune Thyroid Disease in Males. Thyroid. Jul 2017;27(7):960-966.
31. Avila M et al. The Role of Sex Hormones in Multiple Sclerosis. European neurology. 2018;80(1-2):93-99.
32. Chen C et al. The roles of estrogen and estrogen receptors in gastrointestinal disease. Oncology letters. Dec 2019;18(6):5673-5680.
33. Hu J et al. Cellular cholesterol delivery, intracellular processing and utilization for biosynthesis of steroid hormones. Nutrition & metabolism. Jun 01 2010;7:47.
34. L'Hermite M. Bioidentical menopausal hormone therapy: registered hormones (non-oral estradiol +/- progesterone) are optimal. Climacteric: the journal of the International Menopause Society. Aug 2017;20(4):331-338.
35. Bhavnani BR. Estrogens and menopause: pharmacology of conjugated equine estrogens and their potential role in the prevention of neurodegenerative diseases such as Alzheimer's. J Steroid Biochem Mol Biol. 2003; 85(2–5):473–482.
36. Notelovitz M. Clinical opinion: the biologic and pharmacologic principles of estrogen therapy for symptomatic menopause. MedGenMed: Medscape general medicine. Mar 28 2006;8(1):85.
37. Bhavnani BR. Pharmacokinetics and pharmacodynamics of conjugated equine estrogens: chemistry and metabolism. Proc Soc Exp Biol Med. Jan 1998;217(1):6-16.
38. Ismail PM et al. Progesterone involvement in breast development and tumorigenesis--as revealed by progesterone receptor "knockout" and "knockin" mouse models. Steroids. Nov 2003;68(10-13):779-787.
39. Al-Asmakh M. Reproductive functions of progesterone. Middle East Fertility Society Journal. 2007;12(3):147-152.
40. Mani SK et al. Progesterone signaling mechanisms in brain and behavior. Frontiers in endocrinology. 2012 Jan 30:3:7.
41. Hargrove JT et al. Menopausal hormone replacement therapy with continuous daily oral micronized estradiol and progesterone. Obstet Gynecol. 1989;73(4): 606-612.
42. Montplaisir J et al. Sleep in menopause: differential effects of two forms of hormone replacement therapy. Menopause. 2001;8(1): 10-16.
43. Ryan N et al. Quality of life and costs associated with micronized progesterone and medroxyprogesterone acetate in hormone replacement therapy for nonhysterectomized, postmenopausal women. Clin Ther. 2001;23(7): 1099-1115.
44. Lindenfeld EA et al. Bleeding patterns of the hormone replacement therapies in the postmenopausal estrogen and progestin interventions trial. Obstet Gynecol. 2002;100(5 Pt 1): 853-863.
45. Fitzpatrick LA et al. Comparison of regimens containing oral micronized progesterone or medroxyprogesterone acetate on quality of life in postmenopausal women: a cross-sectional survey. J Womens Health Gend Based Med. 2000;9(4): 381-387.
46. Binkowska M. Menopausal hormone therapy and venous thromboembolism. Przeglad menopauzalny = Menopause review. Oct 2014;13(5):267-272.
47. Scarabin PY. Hormone therapy and venous thromboembolism among postmenopausal women. Frontiers of hormone research. 2014;43:21-32.
48. Vinogradova Y et al. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ (Clinical research ed.). Jan 9 2019;364:k4810.
49. Rosano GM et al. Natural progesterone, but not medroxyprogesterone acetate, enhances the beneficial effect of estrogen on exercise-induced myocardial ischemia in postmenopausal women. J Am Coll Cardiol. 2000;36(7): 2154-2159.
50. Giatti S et al. The other side of progestins: effects in the brain. Journal of molecular endocrinology. Aug 2016;57(2):R109-126.
51. Arbo BD et al. Astrocytes as a target for neuroprotection: Modulation by progesterone and dehydroepiandrosterone. Progress in neurobiology. Sep 2016;144:27-47.
52. Toriizuka K et al. [Menopause and anxiety: focus on steroidal hormones and GABAA receptor]. Nihon Yakurigaku Zasshi. Jan 2000;115(1):21-28.
53. Taioli E et al. Comparison of estrogens and estrogen metabolites in human breast tissue and urine. Reprod Biol Endocrinol. 2010 Aug 2;8:93.
54. Samavat H et al. Estrogen metabolism and breast cancer. Cancer letters. Jan 28 2015;356(2 Pt A):231-243.
55. Rettberg JR et al. Estrogen: a master regulator of bioenergetic systems in the brain and body. Frontiers in neuroendocrinology. Jan 2014;35(1):8-30.
56. Simpson ER. Sources of estrogen and their importance. The Journal of steroid biochemistry and molecular biology. Sep 2003;86(3-5):225-230.
57. Barbieri RL. The endocrinology of the menstrual cycle. Methods in molecular biology (Clifton, N.J.). 2014;1154:145-169.
58. Chai NC et al. Migraine and estrogen. Current opinion in neurology. Jun 2014;27(3):315-324.
59. Cui J et al. Estrogen synthesis and signaling pathways during aging: from periphery to brain. Trends in molecular medicine. Mar 2013;19(3):197-209.
60. Freedman RR. Menopausal hot flashes: mechanisms, endocrinology, treatment. The Journal of steroid biochemistry and molecular biology. Jul 2014;142:115-120.
61. Finch CE. The menopause and aging, a comparative perspective. The Journal of steroid biochemistry and molecular biology. Jul 2014;142:132-141.
62. Dalal PK et al. Postmenopausal syndrome. Indian journal of psychiatry. Jul 2015;57(Suppl 2):S222-232.
63. Nedergaard A et al. Menopause, estrogens and frailty. Gynecological endocrinology: the official journal of the International Society of Gynecological Endocrinology. May 2013;29(5):418-423.
64. Wharton W et al. Neurobiological Underpinnings of the Estrogen - Mood Relationship. Current psychiatry reviews. Aug 01 2012;8(3):247-256.
65. Liang J et al. Estrogen and cancer. Annual review of physiology. 2013;75:225-240.
66. Ali ES et al. Estriol: emerging clinical benefits. Menopause (New York, N.Y.). 2017 Sep;24(9):1081-1085.
67. Ziegler RG et al. Epidemiologic studies of estrogen metabolism and breast cancer. Steroids. 2015;99(Pt A):67-75.
68. Moore SC et al. Endogenous Estrogens, Estrogen Metabolites, and Breast Cancer Risk in Postmenopausal Chinese Women. Journal of the National Cancer Institute. Oct 2016;108(10).
69. Holtorf K. The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy? Postgrad Med. 2009;121(1): 73-85.
70. Takahashi K et al. Safety and efficacy of oestriol for symptoms of natural or surgically induced menopause. Hum Reprod. 2000;15(5): 1028-1036.
71. Hayashi T et al. Estriol (E3) replacement improves endothelial function and bone mineral density in very elderly women. J Gerontol A Biol Sci Med Sci. 2000;55(4): B183-190; discussion B191-183.
72. Kano H et al. Estriol retards and stabilizes atherosclerosis through an NO-mediated system. Life Sci. 2002;71(1): 31-42.
73. Itoi H et al. Comparison of the long-term effects of oral estriol with the effects of conjugated estrogen on serum lipid profile in early menopausal women. Maturitas. 2000;36(3): 217-222.
74. Yamanaka Y et al. Effects of combined estriol/pravastatin therapy on intima-media thickness of common carotid artery in hyperlipidemic postmenopausal women. Gynecol Obstet Invest. 2005;59(2): 67-69.
75. Singleton DW et al. Xenoestrogen exposure and mechanisms of endocrine disruption. Front Biosci. 2003;8:s110-s118.
76. Brotons JA et al. Xenoestrogens released from lacquer coatings in food cans. Environmental health perspectives. 1995;103(6):608-612.
77. Sultan C et al. Environmental xenoestrogens, antiandrogens and disorders of male sexual differentiation. Molecular and cellular endocrinology. 2001;178(1-2):99-105.
78. Fucic A et al. Environmental exposure to xenoestrogens and oestrogen related cancers: reproductive system, breast, lung, kidney, pancreas, and brain. Environmental Health. 2012;11(1):1-9.
79. Wang X et al. Exploring the Biological Activity and Mechanism of Xenoestrogens and Phytoestrogens in Cancers: Emerging Methods and Concepts. International journal of molecular sciences. 2021 Aug 16;22(16):8798.
80. Amadou A et al. Chronic low-dose exposure to xenoestrogen ambient air pollutants and breast cancer risk: XENAIR protocol for a case-control study nested within the French E3N cohort. JMIR research protocols. 2020;9(9):e15167.
81. Nowak K et al. Methylparaben-induced regulation of estrogenic signaling in human neutrophils. Molecular and cellular endocrinology. Oct 1 2021;538:111470.
82. Chen CY et al. Xenoestrogen exposure and kidney function in the general population: Results of a community-based study by laboratory tests and questionnaire-based interviewing. Environ Int. Oct 2021;155:106585.
83. Katz TA et al. Endocrine-disrupting chemicals and uterine fibroids. Fertility and sterility. Sep 15 2016;106(4):967-77.
84. Bjerregaard-Olesen C et al. Associations of fetal growth outcomes with measures of the combined xenoestrogenic activity of maternal serum perfluorinated alkyl acids in Danish pregnant women. Environmental health perspectives. 2019;127(01):017006.
85. Pérez-Bermejo M et al. The Role of the Bisphenol A in Diabetes and Obesity. Biomedicines. 2021;9(6):666.
86. Abeer F et al. FREQUENCY OF SOME ENVIRONMENTAL FACTORS WITH POTENTIAL RELATIONS TO BREAST DISEASES AMONG A GROUP OF EGYPTIAN FEMALES. Journal of Environmental Science. 2018;43(1):29-47.
87. Trentham-Dietz A et al. Phenol xenoestrogens and mammographic breast density. Cancer Epidemiology and Prevention Biomarkers. 2012;21(3):561-562.
88. Maharjan CK et al. Natural and Synthetic Estrogens in Chronic Inflammation and Breast Cancer. Cancers. 2021;14(1):206.
89. Chavarro JE et al. Soy Intake Modifies the Relation Between Urinary Bisphenol A Concentrations and Pregnancy Outcomes Among Women Undergoing Assisted Reproduction. J Clin Endocrinol Metab. Mar 2016;101(3):1082-90.
90. Lee GA et al. Treatment with Phytoestrogens Reversed Triclosan and Bisphenol A-Induced Anti-Apoptosis in Breast Cancer Cells. Biomolecules & therapeutics. Sep 1 2018;26(5):503-511.
91. Williams DE. Indoles Derived From Glucobrassicin: Cancer Chemoprevention by Indole-3-Carbinol and 3,3'-Diindolylmethane. Frontiers in nutrition. 2021;8:734334.
92. Maninger N et al. Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS). Front Neuroendocrinol. 2009 Jan;30(1):65-91.
93. Labrie F. DHEA, important source of sex steroids in men and even more in women. Prog Brain Res. 2010;182:97-148.
94. Fouany MR et al. Is there a role for DHEA supplementation in women with diminished ovarian reserve? Journal of assisted reproduction and genetics. Sep 2013;30(9):1239-1244.
95. Pluchino N et al. Neurobiology of DHEA and effects on sexuality, mood and cognition. The Journal of steroid biochemistry and molecular biology. Jan 2015;145:273-280.
96. Genazzani AR et al. DHEA therapy in postmenopausal women: the need to move forward beyond the lack of evidence. Climacteric. 2010 Aug;13(4):314-6.
97. Dong Y et al. Dehydroepiandrosterone sulphate: action and mechanism in the brain. Journal of neuroendocrinology. Jan 2012;24(1):215-224.
98. Bauer ME et al. Psychoneuroendocrine interventions aimed at attenuating immunosenescence: a review. Biogerontology. Feb 2013;14(1):9-20.
99. Rutkowski K et al. Dehydroepiandrosterone (DHEA): hypes and hopes. Drugs. Jul 2014;74(11):1195-1207.
100. Weiss EP et al. Dehydroepiandrosterone replacement therapy in older adults improves indices of arterial stiffness. Aging Cell. Oct 2012;11(5):876-884.
101. Weiss EP et al. Dehydroepiandrosterone (DHEA) replacement decreases insulin resistance and lowers inflammatory cytokines in aging humans. Aging (Albany NY). May 2011;3(5):533-542.
102. Weiss EP et al. Dehydroepiandrosterone replacement therapy in older adults: 1- and 2-y effects on bone. Am J Clin Nutr. 2009 May;89(5):1459-67.
103. Kenny AM et al: Dehydroepiandrosterone combined with exercise improves muscle strength and physical function in frail older women. J Am Geriatr Soc.2010 Sep;58(9):1707-14.
104. Pluchino N et al. Neurobiology of DHEA and effects on sexuality, mood and cognition. The Journal of steroid biochemistry and molecular biology. Jan 2015;145:273-280.
105. Archer DF. Dehydroepiandrosterone intra vaginal administration for the management of postmenopausal vulvovaginal atrophy. The Journal of steroid biochemistry and molecular biology. Jan 2015;145:139-143.
106. Schneider HP. Androgens and antiandrogens. Ann NY Acad Sci. 2003;997:292-306.
107. Bain J. The many faces of testosterone. Clinical interventions in aging. 2007;2(4):567-576.
108. Simon JA. Safety of estrogen/androgen regimens. J Reprod Med. 2001 Mar;46(3 Suppl):281-90.
109. Watt PJ et al. A holistic programmatic approach to natural hormone replacement. Fam Community Health. 2003;25(1):53-63.
110. Cameron DR et al. Androgen replacement therapy in women. Fertil Steril. 2004;82(2):273-289.
111. Braunstein GD. Androgen insufficiency in women: summary of critical issues. Fertil Steril. 2002;77(Suppl 4):S94–S99.
112. Davis SR et al. Testosterone in women--the clinical significance. The lancet. Diabetes & endocrinology. Dec 2015;3(12):980-992.
113. Bolour S et al. Testosterone therapy in women: a review. International journal of impotence research. Sep-Oct 2005;17(5):399-408.
114. Achilli C et al. Efficacy and safety of transdermal testosterone in postmenopausal women with hypoactive sexual desire disorder: a systematic review and meta-analysis. Fertility and sterility. Feb 2017;107(2):475-482.e415.
115. Cappelletti M et al. Increasing women's sexual desire: The comparative effectiveness of estrogens and androgens. Hormones and behavior. Feb 2016;78:178-193.
116. Labrie F et al. Androgens in women are essentially made from DHEA in each peripheral tissue according to intracrinology. The Journal of steroid biochemistry and molecular biology. Apr 2017;168:9-18.
117. Havlikova H et al. Sex- and age-related changes in epitestosterone in relation to pregnenolone sulfate and testosterone in normal subjects. J Clin Endocrinol Metab. 2002 May;87(5):2225-31.
118. Mayo W et al. Individual differences in cognitive aging: implication of pregnenolone sulfate. Progress in neurobiology. Sep 2003;71(1):43-48.
119. Mellon SH. Neurosteroid regulation of central nervous system development. Pharmacol Ther. 2007 Oct;116(1):107-24.
120. Dall GV, Britt KL. Estrogen Effects on the Mammary Gland in Early and Late Life and Breast Cancer Risk. Frontiers in oncology. 2017 May 26:7:110
121. Chlebowski RT et al. WHI Investigators. Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. JAMA. 2010 Oct 20;304(15):1684-92.
122. Zhao S et al. Sex hormone associations with breast cancer risk and the mediation of randomized trial postmenopausal hormone therapy effects. Breast cancer research: BCR. Mar 26 2014;16(2):R30.
123. Shah NR et al. Current breast cancer risks of hormone replacement therapy in postmenopausal women. Expert opinion on pharmacotherapy. Dec 2006;7(18):2455-2463.
124. Fournier A et al. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat. Jan 2008;107(1):103-111.
125. Mohammed H et al. Progesterone receptor modulates ERalpha action in breast cancer. Nature. Jul 16 2015;523(7560):313-317.
126. Asi N et al. Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis. Syst Rev. 2016 Jul 26;5(1):121.
127. Prior JC. Progesterone or progestin as menopausal ovarian hormone therapy: recent physiology-based clinical evidence. Current opinion in endocrinology, diabetes, and obesity. Dec 2015;22(6):495-501.
128. Glaser R et al. Testosterone and breast cancer prevention. Maturitas. Nov 2015;82(3):291-295.
129. Dimitrakakis C et al. Low salivary testosterone levels in patients with breast cancer. BMC cancer. 2010;10:547.
130. Dimitrakakis C et al. Breast cancer incidence in postmenopausal women using testosterone in addition to usual hormone therapy. Menopause (New York, N.Y.). Sep-Oct 2004;11(5):531-535.
131. NAMS. The North American Menopause Society. Hormone Therapy: Benefits & Risks. 2017. http://www.menopause.org/for-women/menopauseflashes/menopause-symptoms-and-treatments/hormone-therapy-benefits-risks. Accessed 7/26/2017.
132. Stanczyk FZ et al. Reprint of "Use of medroxyprogesterone acetate for hormone therapy in postmenopausal women: Is it safe?". The Journal of steroid biochemistry and molecular biology. Sep 2015;153:151-159.
133. Schonberg MA et al. After the Women's Health Initiative: decision making and trust of women taking hormone therapy. Womens Health Issues. 2005;15(4): 187-195.
134. Ravdin PM et al. The decrease in breast-cancer incidence in 2003 in the United States. The New England journal of medicine. Apr 19 2007;356(16):1670-1674.
135. Samaras N et al. Off-label use of hormones as an antiaging strategy: a review. Clinical interventions in aging. 2014;9:1175-1186.
136. Moskowitz D. A comprehensive review of the safety and efficacy of bioidentical hormones for the management of menopause and related health risks. Altern Med Rev. 2006 Sep;11(3):208-23.
137. Whelan AM et al. Defining bioidentical hormones for menopause-related symptoms. Pharm Pract (Granada). Jan 2011;9(1):16-22.
138. Vinogradova Y et al. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ (Clinical research ed.). Jan 9 2019;364:k4810.
139. Gass ML et al. Use of compounded hormone therapy in the United States: report of The North American Menopause Society Survey. Menopause (New York, N.Y.). Dec 2015;22(12):1276-1284.
140. Landete JM et al. Bioactivation of Phytoestrogens: Intestinal Bacteria and Health. Critical reviews in food science and nutrition. Aug 17 2016;56(11):1826-1843.
141. Chen MN et al. Efficacy of phytoestrogens for menopausal symptoms: a meta-analysis and systematic review. Climacteric: the journal of the International Menopause Society. Apr 2015;18(2):260-269.
142. Vitale DC et al. Isoflavones: estrogenic activity, biological effect and bioavailability. European journal of drug metabolism and pharmacokinetics. Mar 2013;38(1):15-25.
143. Gencel VB et al. Vascular effects of phytoestrogens and alternative menopausal hormone therapy in cardiovascular disease. Mini reviews in medicinal chemistry. Feb 2012;12(2):149-174.
144. Sirotkin AV et al. Phytoestrogens and their effects. European journal of pharmacology. Oct 15 2014;741:230-236.
145. Aso T. Equol improves menopausal symptoms in Japanese women. J Nutr. 2010 Jul;140(7):1386S-9S.
146. Cho YA et al. Effect of dietary soy intake on breast cancer risk according to menopause and hormone receptor status. Eur J Clin Nutr. 2010 Sep;64(9):924-32.
147. Sarkar FH et al. Soy isoflavones and cancer prevention. Cancer Invest. 2003;21(5):744–757.
148. Zittermann A. [Phytoestrogens]. Zentralbl Gynakol. 2003;125(6):195–201.
149. Hajirahimkhan A et al. Botanical modulation of menopausal symptoms: Mechanisms of action? Planta Med. May 2013;79(7):538-553.
150. Ko KP. Isoflavones: chemistry, analysis, functions and effects on health and cancer. Asian Pacific journal of cancer prevention: APJCP. 2014;15(17):7001-7010.
151. Bawa S. The significance of soy protein and soy bioactive compounds in the prophylaxis and treatment of osteoporosis. J Osteoporos. 2010 Mar 8 2010:891058.
152. Miyake A et al. Repressive effect of the phytoestrogen genistein on estradiol-induced uterine leiomyoma cell proliferation. Gynecol Endocrinol. 2009 Jun;25(6):403-9.
153. Messina M. Soy foods, isoflavones, and the health of postmenopausal women. The American journal of clinical nutrition. Jul 2014;100 Suppl 1:423s-430s.
154. Mainini G et al. Nonhormonal management of postmenopausal women: effects of a red clover based isoflavones supplementation on climacteric syndrome and cardiovascular risk serum profile. Clinical and experimental obstetrics & gynecology. 2013;40(3):337-341.
155. Vargas KG et al. The functions of estrogen receptor beta in the female brain: A systematic review. Maturitas. Nov 2016;93:41-57.
156. Gallo D et al. Estrogen receptor beta in cancer: an attractive target for therapy. Current pharmaceutical design. 2012;18(19):2734-2757.
157. Bardin A et al. Loss of ERbeta expression as a common step in estrogen-dependent tumor progression. Endocr Relat Cancer. 2004 Sep;11(3):537-51.
158. Bossard C et al. Potential role of estrogen receptor beta as a tumor suppressor of epithelial ovarian cancer. PloS one. 2012;7(9):e44787.
159. Omoto Y et al. Clinical significance of estrogen receptor beta in breast and prostate cancer from biological aspects. Cancer science. Apr 2015;106(4):337-343.
160. Vincent A et al. Soy isoflavones: are they useful in menopause? Mayo Clin Proc. 2000;75(11):1174–1184.
161. Sureda A et al. Hypotensive effects of genistein: From chemistry to medicine. Chem Biol Interact. Apr 25 2017;268:37-46.
162. Li J et al. Does genistein lower plasma lipids and homocysteine levels in postmenopausal women? A meta-analysis. Climacteric: the journal of the International Menopause Society. Oct 2016;19(5):440-447.
163. Khalesi S et al. Flaxseed consumption may reduce blood pressure: a systematic review and meta-analysis of controlled trials. The Journal of nutrition. Apr 2015;145(4):758-765.
164. Chun JN et al. The protective effects of Schisandra chinensis fruit extract and its lignans against cardiovascular disease: a review of the molecular mechanisms. Fitoterapia. Sep 2014;97:224-233.
165. Nabavi SF et al. Genistein: A Boon for Mitigating Ischemic Stroke. Current topics in medicinal chemistry. 2015;15(17):1714-1721.
166. Evsen MS et al. Effects of estrogen, estrogen/progesteron combination and genistein treatments on oxidant/antioxidant status in the brain of ovariectomized rats. European review for medical and pharmacological sciences. Jul 2013;17(14):1869-1873.
167. Linford NJ et al. 17beta-estradiol and the phytoestrogen genistein attenuate neuronal apoptosis induced by the endoplasmic reticulum calcium ATPase inhibitor thapsigargin. Steroids. 2002;67(13-14):1029-1040.
168. Schreihofer DA et al. Soy phytoestrogens are neuroprotective against stroke-like injury in vitro. Neuroscience. 2009;158(2): 602-609.
169. Donzelli A et al. Neuroprotective effects of genistein in mongolian gerbils: estrogen receptor-beta involvement. J Pharmacol Sci. 2010;114(2): 158-167.
170. Ma Y et al. Dietary genistein and equol (4', 7 isoflavandiol) reduce oxidative stress and protect rats against focal cerebral ischemia. Am J Physiol Regul Integr Comp Physiol. 2010;299(3): R871-877.
171. Yu HL et al. Neuroprotective effects of genistein and folic acid on apoptosis of rat cultured cortical neurons induced by beta-amyloid 31-35. Br J Nutr. 2009;102(5): 655-662.
172. Abdi F et al. Effects of phytoestrogens on bone mineral density during the menopause transition: a systematic review of randomized, controlled trials. Climacteric: the journal of the International Menopause Society. Dec 2016;19(6):535-545.
173. Chiang SS et al. Beneficial effects of phytoestrogens and their metabolites produced by intestinal microflora on bone health. Appl Microbiol Biotechnol. Feb 2013;97(4):1489-1500.
174. Wada K et al. Soy isoflavone intake and breast cancer risk in Japan: from the Takayama study. International journal of cancer. Journal international du cancer. Aug 15 2013;133(4):952-960.
175. Dong JY et al. Soy isoflavones consumption and risk of breast cancer incidence or recurrence: a meta-analysis of prospective studies. Breast Cancer Res Treat. Jan 2011;125(2):315-323.
176. Fritz H et al. Soy, red clover, and isoflavones and breast cancer: a systematic review. PloS one. 2013;8(11):e81968.
177. Parazzini F et al. Dietary components and uterine leiomyomas: a review of published data. Nutr Cancer. 2015;67(4):569-579.
178. Mason JK et al. Flaxseed and its lignan and oil components: can they play a role in reducing the risk of and improving the treatment of breast cancer? Applied physiology, nutrition, and metabolism. Jun 2014;39(6):663-678.
179. Flower G et al. Flax and Breast Cancer: A Systematic Review. Integrative cancer therapies. May 2014;13(3):181-192.
180. Lu LJ et al. Increased urinary excretion of 2-hydroxyestrone but not 16alpha-hydroxyestrone in premenopausal women during a soya diet containing isoflavones. Cancer Res. 2000;60(5):1299–1305.
181. Lephart ED. Modulation of Aromatase by Phytoestrogens. Enzyme Res. 2015;2015:594656.
182. Buck K et al. Meta-analyses of lignans and enterolignans in relation to breast cancer risk. Am J Clin Nutr. 2010 Jul;92(1):141-53.
183. Thompson LU et al. Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer. Clin Cancer Res. 2005;11(10): 3828-3835.
184. Laidlaw M et al. Effects of A Breast-Health Herbal Formula Supplement on Estrogen Metabolism in Pre- and Post-Menopausal Women not Taking Hormonal Contraceptives or Supplements: A Randomized Controlled Trial. Breast Cancer (Auckl). 2010 Dec 16;4:85-95.
185. Taku K et al. Extracted or synthesized soybean isoflavones reduce menopausal hot flash frequency and severity: systematic review and meta-analysis of randomized controlled trials. Menopause (New York, N.Y.). Jul 2012;19(7):776-790.
186. NIH. National Institutes of Health. Black Cohosh. https://ods.od.nih.gov/factsheets/BlackCohosh-HealthProfessional/. Last updated 3/3/2017. Accessed 10/24/2017.
187. Jiang K et al. Black cohosh improves objective sleep in postmenopausal women with sleep disturbance. Climacteric: the journal of the International Menopause Society. Aug 2015;18(4):559-567.
188. Shahnazi M et al. Effect of black cohosh (cimicifuga racemosa) on vasomotor symptoms in postmenopausal women: a randomized clinical trial. Journal of caring sciences. Jun 2013;2(2):105-113.
189. Mohammad-Alizadeh-Charandabi S et al. Efficacy of black cohosh (Cimicifuga racemosa L.) in treating early symptoms of menopause: a randomized clinical trial. Chinese medicine. Nov 01 2013;8(1):20.
190. Ross SM. Menopause: a standardized isopropanolic black cohosh extract (remifemin) is found to be safe and effective for menopausal symptoms. Holistic nursing practice. Jan-Feb 2012;26(1):58-61.
191. Shams T et al. Efficacy of black cohosh-containing preparations on menopausal symptoms: a meta-analysis. Altern Ther Health Med. 2010 Jan-Feb;16(1):36-44.
192. Beer AM et al. Efficacy of black cohosh (Cimicifuga racemosa) medicines for treatment of menopausal symptoms - comments on major statements of the Cochrane Collaboration report 2012 "black cohosh (Cimicifuga spp.) for menopausal symptoms (review)". Gynecological endocrinology. Dec 2013;29(12):1022-1025.
193. Czuczwar P et al. The safety and tolerance of phytotherapies in menopausal medicine – a review of the literature. Przeglad menopauzalny = Menopause review. Mar 2017;16(1):8-11.
194. Sarri G et al. Vasomotor symptoms resulting from natural menopause: a systematic review and network meta-analysis of treatment effects from the National Institute for Health and Care Excellence guideline on menopause. BJOG: an international journal of obstetrics and gynaecology. Sep 2017;124(10):1514-1523.
195. Fang ZZ et al. Cycloartane triterpenoids from Cimicifuga yunnanensis induce apoptosis of breast cancer cells (MCF7) via p53-dependent mitochondrial signaling pathway. Phytother Res. 2011 Jan;25(1):17-24.
196. Hostanska K et al. Evaluation of cell death caused by triterpene glycosides and phenolic substances from Cimicifuga racemosa extract in human MCF-7 breast cancer cells. Biol Pharm Bull. 2004;27(12):1970–1975.
197. Nisslein T et al. Effects of an isopropanolic extract of Cimicifuga racemosa on urinary crosslinks and other parameters of bone quality in an ovariectomized rat model of osteoporosis. J Bone Miner Metab. 2003;21(6):370–376.
198. Seidlova-Wuttke D et al. Effects of estradiol-17beta, testosterone and a black cohosh preparation on bone and prostate in orchidectomized rats. Maturitas. Jun 16 2005;51(2):177-186.
199. Wuttke W et al. The Cimicifuga preparation BNO 1055 vs. conjugated estrogens in a double-blind placebo-controlled study: effects on menopause symptoms and bone markers. Maturitas. Mar 14 2003;44 Suppl 1:S67-77.
200. Seidlova-Wuttke D et al. Pharmacology of Cimicifuga racemosa extract BNO 1055 in rats: bone, fat and uterus. Maturitas. Mar 14 2003;44 Suppl 1:S39-50.
201. Heger M et al. Efficacy and safety of a special extract of Rheum rhaponticum (ERr 731) in perimenopausal women with climacteric complaints: a 12-week randomized, double-blind, placebo-controlled trial. Menopause (New York, N.Y.). Sep-Oct 2006;13(5):744-759.
202. Hasper I et al. Long-term efficacy and safety of the special extract ERr 731 of Rheum rhaponticum in perimenopausal women with menopausal symptoms. Menopause (New York, N.Y.). Jan-Feb 2009;16(1):117-131.
203. Kaszkin-Bettag M et al. The special extract ERr 731 of the roots of Rheum rhaponticum decreases anxiety and improves health state and general well-being in perimenopausal women. Menopause (New York, N.Y.). Mar-Apr 2007;14(2):270-283.
204. Kaszkin-Bettag M et al. Efficacy of the special extract ERr 731 from rhapontic rhubarb for menopausal complaints: a 6-month open observational study. Altern Ther Health Med. Nov-Dec 2008;14(6):32-38.
205. Kaszkin-Bettag M et al. Confirmation of the efficacy of ERr 731 in perimenopausal women with menopausal symptoms. Altern Ther Health Med. Jan-Feb 2009;15(1):24-34.
206. Wober J et al. Activation of estrogen receptor-beta by a special extract of Rheum rhaponticum (ERr 731), its aglycones and structurally related compounds. The Journal of steroid biochemistry and molecular biology. Nov-Dec 2007;107(3-5):191-201.
207. Vargas KG et al. The functions of estrogen receptor beta in the female brain: A systematic review. Maturitas. Nov 2016;93:41-57.
208. Al-Bareeq RJ et al. Dong Quai (angelica sinensis) in the treatment of hot flashes for men on androgen deprivation therapy: results of a randomized double-blind placebo controlled trial. Canadian Urological Association journal. Feb 2010;4(1):49-53.
209. Goh SY et al. Gynaecomastia and the herbal tonic "Dong Quai". Singapore Med J. 2001;42(3, pp. 115–116.
210. Hardy ML. Herbs of special interest to women. J Am Pharm Assoc (Wash). 2000;40(2):234–242.
211. Trimarco V et al. Effects of a new combination of nutraceuticals on postmenopausal symptoms and metabolic profile: a crossover, randomized, double-blind trial. International journal of women's health. 2016;8:581-587.
212. Kupfersztain C et al. The immediate effect of natural plant extract, Angelica sinensis and Matricaria chamomilla (Climex) for the treatment of hot flushes during menopause. A preliminary report. Clinical and experimental obstetrics & gynecology. 2003;30(4):203-206.
213. Lim DW et al. Anti-osteoporotic effects of Angelica sinensis (Oliv.) Diels extract on ovariectomized rats and its oral toxicity in rats. Nutrients. Oct 16 2014;6(10):4362-4372.
214. Hajirahimkhan A et al. Evaluation of estrogenic activity of licorice species in comparison with hops used in botanicals for menopausal symptoms. PloS one. 2013;8(7):e67947.
215. Ofir R et al. Inhibition of serotonin re-uptake by licorice constituents. J Mol Neurosci. 2003;20(2):135-140.
216. Nahidi F et al. Effects of licorice on relief and recurrence of menopausal hot flashes. Iranian journal of pharmaceutical research: IJPR. Spring 2012;11(2):541-548.
217. Somjen D et al. Estrogen-like activity of licorice root constituents: glabridin and glabrene, in vascular tissues in vitro and in vivo. J Steroid Biochem Mol Biol. 2004;91(3):147–155.
218. Somjen D et al. Estrogenic activity of glabridin and glabrene from licorice roots on human osteoblasts and prepubertal rat skeletal tissues. The Journal of steroid biochemistry and molecular biology. Aug 2004;91(4-5):241-246.
219. De Franciscis P et al. Adding Agnus Castus and Magnolia to Soy Isoflavones Relieves Sleep Disturbances Besides Postmenopausal Vasomotor Symptoms-Long Term Safety and Effectiveness. Nutrients. 2017 Feb 13;9(2):129.
220. van Die MD et al. Vitex agnus-castus (Chaste-Tree/Berry) in the treatment of menopause-related complaints. Journal of alternative and complementary medicine. Aug 2009;15(8):853-862.
221. Rotem C et al. Phyto-Female Complex for the relief of hot flushes, night sweats and quality of sleep: randomized, controlled, double-blind pilot study. Gynecological endocrinology. Feb 2007;23(2):117-122.
222. Dietz BM et al. Botanicals and Their Bioactive Phytochemicals for Women's Health. Pharmacol Rev. Oct 2016;68(4):1026-1073.
223. Abbas S et al. Serum 25-hydroxyvitamin D and risk of post-menopausal breast cancer—results of a large case-control study. Carcinogenesis. 2008 Jan;29(1):93-9.
224. Vrieling A et al. Serum 25-hydroxyvitamin D and postmenopausal breast cancer survival: a prospective patient cohort study. Breast cancer research: BCR. Jul 26 2011;13(4):R74.
225. Welsh J. Vitamin D and breast cancer: Past and present. The Journal of steroid biochemistry and molecular biology. 2018 Mar:177:15-20.
226. Thyer L et al. A novel role for a major component of the vitamin D axis: vitamin D binding protein-derived macrophage activating factor induces human breast cancer cell apoptosis through stimulation of macrophages. Nutrients. Jul 08 2013;5(7):2577-2589.
227. Fleet JC et al. Vitamin D and cancer: a review of molecular mechanisms. The Biochemical journal. Jan 01 2012;441(1):61-76.
228. Marconett CN et al. Indole-3-carbinol disrupts estrogen receptor-alpha dependent expression of insulin-like growth factor-1 receptor and insulin receptor substrate-1 and proliferation of human breast cancer cells. Molecular and cellular endocrinology. Nov 05 2012;363(1-2):74-84.
229. Lampe JW. Interindividual differences in response to plant-based diets: implications for cancer risk. Am J Clin Nutr. 2009 May;89(5):1553S-1557S.
230. Ambrosone CB et al. Breast cancer risk in premenopausal women is inversely associated with consumption of broccoli, a source of isothiocyanates, but is not modified by GST genotype. J Nutr. 2004;134(5): 1134-1138.
231. Acharya A et al. Chemopreventive properties of indole-3-carbinol, diindolylmethane and other constituents of cardamom against carcinogenesis. Recent Pat Food Nutr Agric. 2010 Jun;2(2):166-77.
232. Weng JR et al. Indole-3-carbinol as a chemopreventive and anti-cancer agent. Cancer Lett. 2008 Apr 18;262(2):153-63.
233. Muti P et al. Estrogen metabolism and risk of breast cancer: a prospective study of the 2:16alpha-hydroxyestrone ratio in premenopausal and postmenopausal women. Epidemiology. 2000;11(6):635–640.
234. Saoudi M et al. Protective effects of oil of Sardinella pilchardis against subacute chlorpyrifos-induced oxidative stress in female rats. Archives of environmental & occupational health. 03 May 2017, 73(2):128-135
235. Kansal S et al. Evaluation of the role of oxidative stress in chemopreventive action of fish oil and celecoxib in the initiation phase of 7,12-dimethyl benz(alpha)anthracene-induced mammary carcinogenesis. Tumour Biol. 2011;32(1):167-77.
236. Bougnoux P et al. Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial. Br J Cancer. 2009;101(12): 1978-1985.
237. Mandal CC et al. Fish oil prevents breast cancer cell metastasis to bone. Biochem Biophys Res Commun. 2010 Nov 26;402(4):602-7.
238. Thangapazham RL et al. Green tea polyphenol and epigallocatechin gallate induce apoptosis and inhibit invasion in human breast cancer cells. Cancer Biol Ther. 2007;6(12): 1938-1943.
239. Thangapazham RL et al. Green tea polyphenols and its constituent epigallocatechin gallate inhibits proliferation of human breast cancer cells in vitro and in vivo. Cancer Lett. 2007;245(1-2): 232-241.
240. Leong H et al. Inhibition of mammary tumorigenesis in the C3(1)/SV40 mouse model by green tea. Breast Cancer Res Treat. 2008;107(3): 359-369.
241. Masuda M et al. Epigallocatechin-3-gallate decreases VEGF production in head and neck and breast carcinoma cells by inhibiting EGFR-related pathways of signal transduction. J Exp Ther Oncol. 2002;2(6): 350-359.
242. Farabegoli F et al. (-)-Epigallocatechin-3-gallate downregulates estrogen receptor alpha function in MCF-7 breast carcinoma cells. Cancer Detect Prev. 2007;31(6): 499-504.
243. Hsuuw YD et al. Epigallocatechin gallate dose-dependently induces apoptosis or necrosis in human MCF-7 cells. Ann N Y Acad Sci. 2007;1095: 428-440.
244. Taheri Rouhi SZ et al. The effect of pomegranate fresh juice versus pomegranate seed powder on metabolic indices, lipid profile, inflammatory biomarkers, and the histopathology of pancreatic islets of Langerhans in streptozotocin-nicotinamide induced type 2 diabetic Sprague-Dawley rats. BMC complementary and alternative medicine. Mar 14 2017;17(1):156.
245. Li Y et al. Dietary Natural Products for Prevention and Treatment of Breast Cancer. Nutrients. 2017 Jul 8;9(7):728.
246. Panth N et al. Anticancer Activity of Punica granatum (Pomegranate): A Review. Phytotherapy research: PTR. Apr 2017;31(4):568-578.
247. Toi M et al. Preliminary studies on the anti-angiogenic potential of pomegranate fractions in vitro and in vivo. Angiogenesis. 2003;6(2):121-8.
248. Sturgeon SR et al. Pomegranate and breast cancer: possible mechanisms of prevention. Nutr Rev. 2010 Feb;68(2):122-8.
参考来源:
http://www.womenshealth.gov
美国更年期学会
http://www.menopause.org
美国FDA官网
https://www.fda.gov/
加拿大女性健康网站
http://www.womenshealthmatters.ca
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