SUBSCRIBE

荷尔蒙健康heermengjiankang

DHEA恢复疗法

时间:2021-02-25 20:15 阅读:1437 来源:朴诺健康研究院

目  录

一、概况

二、引言

三、DHEA:背景和生物学

四、DHEA的作用

五、参考文献


一、概况

概要速览

  1. 衰老破坏了激素平衡,与年轻时相比,几种关键激素水平显著降低。DHEA也不例外。到了80岁,DHEA水平比年轻时下降了80%-90%。

  2. 本文提供了有关DHEA及其对人体的多种益处的信息。DHEA作为雄激素(雄性激素)和雌激素(雌性激素)的前体,在维持激素平衡和青春活力方面起着重要作用。

  3. 恢复年轻的DHEA水平提供了一个独特的机会来减轻激素减少的后果。与直接给予雄激素(如睾酮替代疗法)或雌激素(如雌激素替代疗法)不同,提高DHEA水平提供了这种激素前体的储备,各种组织可以将其转化为雄激素和雌激素。

什么是DHEA恢复疗法

脱氢表雄酮(DHEA)是一种具有多种生物学功能的甾体激素。DHEA是性激素(雄激素和雌激素)的前体,具有许多独立于性激素的功能。DHEA水平随着年龄的增长而下降,青春激素平衡的丧失,尤其是DHEA与许多年龄相关疾病有关。恢复年轻的DHEA水平可能有助于预防或改善一些疾病的结果。

DHEA水平(通常通过测量代谢物DHEA-S获得)应该作为男性和女性健康老龄化策略的一部分进行监测。DHEA可以是一个综合激素替代疗法的主要部分。

DHEA偏低的风险是什么

  1. 认知衰退

  2. 心血管疾病

  3. 骨丢失

  4. 癌症

  5. 抑郁

  6. 性功能障碍

  7. 炎症和炎症性疾病

恢复DHEA的潜在好处是什么?

  1. 改善认知功能和情绪

  2. 增加骨密度

  3. 增强心血管健康

  4. 提高胰岛素敏感性

  5. 增强免疫功能

  6. 恢复年轻的皮肤

  7. 改善男性和女性的性功能

  8. 炎症标志物水平降低

  9. 延长寿命

  10. DHEA的一种代谢物7-酮-DHEA,与代谢的改善有关

注:已有人对DHEA的补充和激素敏感型癌症表示担忧。迄今为止,还没有研究能令人信服地表明,补充DHEA的人患激素依赖性癌症的风险增加。像往常一样,任何有疾病的人在开始使用新的补充剂或药物治疗前都应该咨询他们的医生。


二、引言

40年前,医学界基本上不知道支持天然甾体激素脱氢表雄酮(DHEA)这种激素的多方面益处的科学数据。而时至今日,已有超过3700篇论文评估了DHEA对人体许多不同细胞和组织的科学作用。这种多功能激素及其代谢物硫酸脱氢表雄酮(DHEA-S)对男性和女性都有重要的激素的益处(Traish 2011;Savineau 2013)。DHEA作为雄激素(雄性激素)和雌激素(雌性激素)的前体,在维持激素平衡和青春活力方面起着重要作用。它还通过独立于雄激素和雌激素前体作用的直接作用,调节全身涉及健康和疾病各个方面的各种通路(Samaras 2013;Traish 2011;Savineau 2013)。

衰老破坏了激素平衡,与年轻时相比,一些关键激素的水平显著降低,DHEA也不例外。到了80岁,DHEA的水平比年轻时下降了80%-90%(Samaras 2013)。在理解DHEA在通过多个身体系统支持健康、年轻的生理机能中的作用后,这一点的重要性就很清楚了。研究表明,DHEA-S水平降低与许多年龄相关的疾病状态的病理生理学相关,包括认知能力下降、心血管疾病、骨质流失、癌症、抑郁症、性功能障碍和各种炎症性疾病(Samaras 2013;Traish 2011;Savineau 2013;Dong 2012;Zaluska 2009;Labrie)2009年;Straub 2000年;Krysiak 2008年;Lopez Marure 2011年)。

恢复年轻时的DHEA水平提供了一个独特的机会来减轻激素减少的后果。与直接给予雄激素(即睾酮替代疗法)或雌激素(即雌激素替代疗法)不同,提高DHEA水平提供了这种激素前体的“蓄水池”,各种组织可以将其转化为雄激素和雌激素(Traish 2011;Arlt 1998;Morales 1994;Aldred 2010;Samaras 2013;Panjari 2007)。然而,DHEA治疗不能取代测量和恢复其他激素的需要,因为其转化为雄激素和雌激素的效率因个体和性别而异(Samaras 2013;Arlt 1999;Schulze 2013;Fitzpatrick 2001;Miller 2004)。因此,恢复DHEA水平应被视为一个完整的激素恢复方案的一个重要部分,而不是替代男性睾酮替代疗法和女性雌激素替代疗法的方案。

除了作为激素前体的作用外,DHEA还能调节炎症,炎症是许多疾病的驱动力。这种多功能激素还通过激活一种名为内皮型一氧化氮合酶(eNOS)的酶,促进细胞信号分子一氧化氮(nitricoxide)在纤细的血管内膜的生成。因为其刺激血管扩张的能力,一氧化氮是血流的关键调节器。因此,在医学文献中,DHEA水平低与心血管疾病相关并不奇怪(Samaras 2013;Traish 2011)。

口服给药后,DHEA大部分被转化为DHEA-S,DHEA-S在血液中的循环时间远长于DHEA。循环中的DHEA-S是组织可以吸收的储备物。一旦被组织吸收,DHEA-S就会转化回DHEA,然后可以局部地转化为雄激素和雌激素或发挥直接作用(Samaras 2013;Traish 2011)。

由于DHEA-S在血液中的含量比DHEA更为丰富(Traish 2011;Savineau 2013),因此测量DHEA-S浓度的简单血液测试可以纳入任何男性和女性的健康老龄化策略中。通过定期监测血液中DHEA-S和其他激素的水平,可以向个体提供有关其激素环境状态的具体反馈(Traish 2011)。可以依此制定、实施和优化个体化治疗方案,以帮助成熟的个体过上充实、积极、健康的生活(Samaras 2013)。

生物同源性激素替代疗法是一种使用结构与人体产生的相同的激素的疗法。用生物同源性的DHEA治疗,是所有综合激素恢复方案的一个重要部分。另一方面,一些传统的激素替代疗法使用的激素与人类产生的激素不完全相同,它们要么来自动物,要么是人工合成的。有证据表明,与传统的激素替代疗法相比,生物相同的激素替代疗法可能更安全,患者满意度更高(Holtorf 2009)。关于雄激素恢复和雌激素恢复的文章提供了生物同源性激素替代疗法的全面概述,应与本文一起参阅。


三、DHEA:背景和生物学

人体通过两种酶反应从胆固醇中获得DHEA。首先,胆固醇被转化为孕烯醇酮,有时被称为“主激素”,因为它是激素级联的前体,最终产生主要的性激素睾酮和雌激素。接下来,孕烯醇酮转化为DHEA(Traish 2011;Samaras 2013;Savineau 2013)。

DHEA产生的主要部位是肾上腺的外层,称为肾上腺皮质;一些其他组织,如男性的睾丸和绝经前女性的卵巢也产生DHEA,但产出要小得多。DHEA的产量在生命的第二至第三个十年达到高峰。此后,水平随着年龄的增长而稳步下降(Traish 2011;Samaras 2013)。

到本世纪初,对DHEA的研究主要集中在它作为雄激素和雌激素前体的作用上。然而,最近的研究揭示了DHEA直接介导的几种生物学行为。研究表明,血管内膜(内皮)、心脏、肾脏和肝脏细胞膜上的特殊受体与DHEA直接相互作用(Samaras 2013;Traish 2011)。例如,DHEA的一个显著的非雄激素和非雌激素依赖性作用是激活血管中一种称为内皮型一氧化氮合酶(eNOS)的酶,这能产生对健康的血管功能非常重要的有效血管舒张剂一氧化氮(NO)(Samaras 2013;Traish 2011;Liu 2002;Liu 2004;Simoncini 2003)。


四、DHEA的作用

DHEA在情绪与脑健康中的作用

尽管大部分的DHEA由肾上腺产生,它也可以由大脑产生(Lazaridis 2011)。此外,中枢神经系统(CNS)中的DHEA水平是血液中的6-8倍(Traish 2011)。这导致一些研究人员将DHEA归类为“神经甾体”(Lazaridis 2011;Baulieu 1998)。DHEA已被证明能调节大脑不同区域神经递质的释放和信号传递。因此,人们对DHEA在某些涉及大脑的健康状况(如抑郁和焦虑)中的作用产生兴趣也就不足为奇了(Traish 2011;Samaras 2013;Dong 2012)。

随着人类年龄的增长,认知功能和记忆通常会受损。这与年龄相关的脑神经甾体水平降低相对应。同样,一些神经退行性疾病如阿尔茨海默症也与神经甾体水平下降有关(Aldred 2010;Charalampopoulos 2008)。年龄相关的DHEA下降被认为可能损害神经元的功能和完整性(Charalampopoulos 2008)。

一些研究已经揭示了DHEA和认知功能之间的关系。一项对755名老年人进行了3年跟踪调查的研究发现,DHEA-S水平随着认知功能的下降而下降,这是通过一项标准化的认知评估——简易智力状态检查量表(MMSE)检测得出的结论。此外,与基线得分较低的受试者相比,基线MMSE得分较高的受试者DHEA-S水平更高,同时基线较低的DHEA-S水平预测了研究期间认知功能的较大下降(Valenti 2009)。在另一项针对24名健康年轻男性的研究中,持续7天每天两次服用150毫克DHEA改善了受试者的情绪和记忆力。这项研究还发现补充DHEA可以降低晚上皮质醇的水平,皮质醇是一种因压力释放的激素(Alhaj 2006)。另一项双盲、安慰剂对照的研究招募了24名绝经后妇女,通过多项标准化测试发现,每天50毫克DHEA可以改善视觉-空间表现。研究人员还发现,DHEA及其代谢物水平越高,视觉-空间任务的表现越好(Stangl 2011)。一项对居住在日本的辅助医疗机构的27名65-90岁女性进行的研究发现,6个月内每天补充25毫克DHEA可以改善被分配进行积极治疗的受试者的认知评分,而接受安慰剂的受试者的认知功能恶化(Yamada 2010)。

DHEA在某些人群中调节认知功能的一种方式是保留一些神经保护因子的产生,如IGF-1(胰岛素样生长因子-1)、VEGF(血管内皮生长因子)和TGF-β(转化生长因子β)。一项实验室研究测量了从轻度到中度的阿尔茨海默症患者身上提取的细胞产生的这些神经保护因子的水平,并将结果与从健康的、年龄匹配的对照组中提取的样本进行了比较。科学家们发现,与健康细胞相比,阿尔茨海默症患者的细胞产生的这些神经保护生长因子的数量明显减少。然而,当阿尔茨海默氏症患者的细胞与DHEA-s一起培养时,生长因子的产生恢复到与健康对照细胞相似的水平。作者评论说:“这些数据表明DHEA-S能够增加……神经保护性生长因子的产生……这表面了一种治疗痴呆症的新方法”(Luppi 2009)。

此外,DHEA可能通过对抗糖皮质激素(如皮质醇)对神经元的有害作用发挥神经保护作用。在情绪障碍的情况下,这是一个重要的考虑事项,因为糖皮质激素升高与社交焦虑和抑郁等精神疾病有关(Herbert 1998)。事实上,研究已经将抑郁症与成人、老年人和青少年人群的低血清DHEA浓度联系起来(Wong 2011;Herbert 1998;Yaffe 2008;Zaluska 2009)。补充DHEA还可以降低精神分裂症患者的焦虑,改善其对抗精神病药物的反应(Ritsner 2011;Strous 2005)。在中年人中,DHEA(每天90毫克,持续3周,然后每天450毫克,持续3周)改善了精神抑郁(一种慢性、低度抑郁情绪)(Bloch 1999)。老年男性和女性持续6个月每天补充50毫克DHEA,可改善心理健康(Morales 1994)。另一项研究发现,DHEA,持续8周每天100-400毫克,可以缓解HIV/AIDS患者的非重度持续性抑郁(Rabkin 2006)。当垂体功能欠佳时,DHEA水平的恢复也可能可以支持情绪。每日50mg DHEA替代治疗可使在进行生长激素替代治疗的垂体功能低下的男性和女性患者的心理健康状况得到长期改善(Brooke 2006)。

DHEA与骨健康

尽管人们通常认为骨质疏松症只影响女性,但它也影响男性的生活。美国有数百万男性受骨质疏松症或低骨量的影响,而且这个数字可能会随着人口老龄化而增长(Cawthon 2011;Kawate 2010;Nuti 2010)。此外,有证据表明,与DHEA-S水平正常的绝经后妇女相比,骨密度低的绝经后妇女DHEA-S水平较低。事实上,捷克的一项研究发现,86%的DHEA-S水平下降的妇女骨密度较低,而健康的绝经后妇女中这一比例预计为30%(Fingerova 1998)。骨密度在很大程度上受两种细胞类型的调节:塑造骨的成骨细胞;分解或再吸收骨的破骨细胞。DHEA促进成骨细胞活性,抑制破骨细胞介导的骨破坏。这似乎是它通过转化为雌激素(刺激成骨细胞活性)和通过非雄激素和非雌激素依赖性机制实现的(Adachi 2006;Wang 2012)。

骨组织对激素调节特别敏感。因此,与年龄相关的激素水平下降,包括DHEA,对男性和女性的骨骼健康都有相当大的影响(Corina 2012;Weiss 2009)。DHEA和其他雄激素在骨骼形成过程中起着关键作用;因此,DHEA水平下降可能会损害骨代谢并促进骨质疏松症(Adachi 2006;Samaras 2013)。DHEA已被证明能有效地治疗骨质疏松症,在一年的时间里,每天50毫克的剂量通过增加腰椎的骨密度有效治疗了除患骨质疏松以外健康的老年妇女。DHEA也被证明能降低血清中1型胶原的C末端肽,这是骨转换的标志物(Okuno 2005;von Mühlen 2008)。在另一项研究中,65-75岁的女性每天服用50毫克DHEA,同时服用650 IU的维生素D和700毫克的钙,经过2年的治疗后,脊柱骨密度增加了3.6%(Weiss,2009年)。

有关支持骨骼健康的策略的全面概述,请参阅骨质疏松症的有关文章。

DHEA与心血管健康

与衰老相关的DHEA-S下降可能导致血管疾病和增加心脏事件的风险,尤其是在绝经后的妇女中(Shufelt 2010)。对男性,DHEA-S水平降低似乎与糖尿病和冠心病的高风险相关(Ponholzer 2009)。观察性研究也表明,随着DHEA-S水平的下降,心血管疾病的发病率上升(Mitchell 1994)。

DHEA补充剂已被证明能改善心血管健康。健康老年受试者短期服用DHEA似乎可以增加NO的生成,降低低密度脂蛋白(LDL)胆固醇,并增加睾酮水平(Martina 2006)。DHEA也被发现能抑制血管最内层细胞层(内皮)的炎症过程(Li 2009)。在3个月内服用100毫克DHEA-S的肥胖妇女脂肪酸平衡发生变化,血液中的饱和脂肪减少,从而表明代谢状况更健康(Gómez Santos 2012;Gómez Santos 2011)。

此外,DHEA可能支持损伤后血管组织的健康重塑(Ii 2006)。接受心血管手术(即冠状动脉造影)的女性,在6年的随访时间内,DHEA-S水平处于分布的下三分之一的女性比DHEA-S水平处于分布的上三分之二的女性更可能因任何原因死亡。具体来说,在随访期间,21%的DHEA-S水平处于最低1/3分布的妇女死亡,而DHEA-S水平处于最高2/3分布的妇女只有10%死亡。这一证据表明DHEA在心脏病中具有进一步的保护作用(Schufelt,2010)。动物研究进一步表明,DHEA对血管重塑有良好的作用(Dumas de la Roque 2010)。

DHEA与血糖调节

DHEA似乎可以增加胰岛素敏感性和对抗胰岛素抵抗。胰岛素抵抗是2型糖尿病的早期指标,与肥胖密切相关,两者都是心脏病的主要危险因素(Basat 2006;Steinberger 2003)。DHEA已被证明在对抗糖尿病中具有保护作用(Heurta Garcia 2011)。事实上,一项研究表明,口服葡萄糖耐量试验显示,服用50毫克DHEA 一年可改善胰岛素反应,研究开始时糖耐量受损的参与者两年后胰岛素反应进一步改善(Weiss 2011)。另一项研究表明,6个月内每天服用50毫克DHEA会导致胰岛素抵抗降低(Talaei 2010)。这些研究的综合结果可能表明,可能需要长期服用以看到胰岛素抵抗的显著变化。

另一组研究人员发现,存在潜在肾上腺功能受损的女性在12周内每天补充50毫克DHEA后,胰岛素敏感性有所提高(Dhatariya 2005)。另一项研究发现77%的2型糖尿病冠心病患者体内DHEA-S水平较低。当低DHEA-S与其他三个危险因素(睾酮缺乏、高敏C反应蛋白[hs-CRP]升高以及血浆N-末端B型利钠肽前体[NTproB]升高)相结合时,心血管死亡的风险比健康对照组高出惊人的63倍(Ponikowska 2009)。其他证据表明DHEA可以防止高浓度葡萄糖引起的血管损伤(Huerta Garcia,2011)。升高的血糖可以通过一个叫做糖基化的过程来驱动氧化应激和形成功能失调的蛋白质,从而导致损伤。一项针对20名2型糖尿病患者的研究表明,连续12周每天补充50毫克DHEA,可改善由高血糖水平引起的氧化失衡,防止晚期糖基化终产物(AGE)的形成。这些发现表明DHEA可能对2型糖尿病患者慢性并发症的发生和/或进展产生有益的影响(Brignardello 2007)。

进一步讨论请参见减肥有关文章。

DHEA与免疫功能

DHEA的另一个重要作用是对抗皮质醇(“应激激素”)在免疫系统中的作用。DHEA增强免疫力,皮质醇抑制免疫力(Butcher 2005;Buford 2008)。这对于老年人来说尤其重要,因为年龄的增长与DHEA:皮质醇比率的下降相关(Buford,2008年)。换句话说,与年轻人相比,老年人暴露于更多的皮质醇的非对抗性免疫抑制,这可能增加他们感染的风险(Butcher 2005)。

事实上,人们认为,与年龄相关的DHEA缺乏,会导致DHEA和皮质醇之间的失衡,这也可能是导致老年人普遍免疫功能下降的部分原因(Butcher 2005;Bufford 2008;Roxas 2007)。一般来说,随着年龄的增长,免疫系统的功能会下降。这就是所谓的免疫衰老。同样,由于多个腺体(包括肾上腺皮质)功能丧失而导致的激素分泌下降被称为内分泌衰老(Buford 2008)。在老年人中,每天50毫克DHEA可以增强免疫系统,并可能预防一些常见的感染(Roxas 2007)。

DHEA与皮肤

DHEA已被证明在皮肤中具有抗氧化和抗炎作用(Puizina Ivic 2010;Chan 2013),DHEA的减少与皮肤萎缩和皮肤老化增加有关(El-Alfy 2010;Labrie 2010)。局部施用DHEA可通过刺激胶原蛋白生物合成和改善真皮(皮肤表面下的组织层)的结构组织,在皮肤中发挥抗衰老作用(El-Alfy 2010;Calvo 2008)。通过对绝经后妇女局部施用1%DHEA配方超过4个月,发现研究参与者的皮脂分泌增加,这有助于皮肤的柔顺(Noveau 2008)。

DHEA与男女性功能的关系

大量的研究调查了DHEA与性健康之间的关系,特别是在女性中。随着女性年龄的增长,除了骨质疏松症和心脏病的风险增加外,性功能和性兴趣也趋于下降(Yasui,2012年)。DHEA已经被证明可以改善性功能的几乎所有方面,包括欲望、唤醒、活动、兴趣和驱动力(Traish 2011)。一项研究发现,对绝经后有中度至重度阴道萎缩症状的妇女阴道给予DHEA,对性功能的几个重要方面,包括性唤起/感觉、润滑和性高潮,都会产生有益的影响(Labrie,2009年)。另一项研究发现,在健康的绝经后妇女中,每日口服10毫克剂量的DHEA治疗可显著改善性功能和性交频率(Genazzani,2011年)。DHEA也被证明对男性的性健康有益(Traish 2011)。阳痿男性每天服用50毫克DHEA 6个月,性功能得到改善,但PSA、睾酮、催乳素或前列腺体积没有增加(Reiter 1999)。

DHEA和减肥–关注7-Keto DHEA

7-Keto DHEA是DHEA的代谢物,不转化为睾酮或雌激素,但具有激素原特性(Worrel 2011;Amato 2012)。7-Keto DHEA似乎增加了基础代谢率和产热(即,将体内储存的能量转化为热量)(Bobyleva 1997;Ihler 2003;Hampl,Starka 2006)。更大的基础代谢率和产热导致能量储存(即身体脂肪)减少。在一项研究中,使用含有50 mg 7-Keto DHEA以及柠檬酸钙、绿茶提取物、维生素C、铬和维生素D3的组合配方,超重成年人的静息代谢率增加了3.4%(Zenk 2007)。此外,DHEA及其代谢物会抵消皮质醇的作用,皮质醇是一种分解代谢应激激素,与脂肪堆积有关(Moyer 1994;Abraham 2013;Muller 2006;Hennebert 2007;Marin 1992;Buoso 2011)。在健康男性中,7-Keto DHEA已被证明在4周内高达200毫克/天的剂量是安全的(Davidson 2000)。

DHEA在炎症和自身免疫中的作用

随着人类年龄的增长,免疫系统会减弱。免疫系统逐渐老化的可能后果之一是某些癌症的发病率和感染倾向增加(Ramos Casals 2003)。DHEA调节免疫系统的几个方面。在老年男性中,细胞因子的产生以及T细胞、B细胞、NK细胞和单核细胞的功能似乎可以被DHEA改善(Khorram 1997)。炎症标志物白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)在慢性炎症或炎症性疾病患者中均升高,DHEA似乎对其产生积极影响(James 1997;Straub 1998;Straub 2002;Leowattana 2001)。在一项实验研究中,从哮喘患者身上提取免疫细胞并用DHEA治疗。科学家们发现DHEA抑制了这些细胞释放炎症介质,降低了它们的高反应性(Choi,2008)。

此外,研究表明,在某些情况下,恢复最佳DHEA水平可能起到免疫调节剂的作用(Hazeldine 2010)。一项研究显示,在患有自身免疫性甲状腺功能减退症的女性受试者中,DHEA和某些代谢物会减少(Drbalová2008)。另一项研究发现,一组女性1型糖尿病患者的DHEA-S降低(Simunkova 2010)。在系统性红斑狼疮,脱氢表雄酮导致临床显着改善生活质量根据几项研究(克罗斯比2007年)的综合审查。在成年女性中,用DHEA治疗狼疮(每天200毫克)可减少16%的耀斑患者,每天50-200毫克DHEA的剂量在临床上是有益的(van Vollenhoven 1998;Chang 2002)。

DHEA与预防虚弱

一些研究将老年人DHEA的下降作为衰老的主要标志。其中一项研究发现DHEA的下降与生活质量指标(比如女性的步态速度、精神状态和神经心理学分数的下降)是一致的。基本上,DHEA-S水平最高的老年妇女在这些测试中表现最好。因此,测量DHEA-S的血液水平可能是一种简单的帮助确定一个人的衰老率的方法(Sanders 2010)。

跌倒和骨折是老龄化人口的一个重要问题。DHEA在这方面也能提供可能的帮助。在一项为期6个月的试验中,低DHEA-S、低骨密度和虚弱的妇女每天服用50毫克DHEA(以及维生素D和钙),同时每周进行2次温和的锻炼。在试验结束时,下肢肌肉力量和功能得到改善(Kenny 2010)。2010年3月,医学博士William Davis发表了一篇题为《不要成为衰弱的受害者:老年人长寿的循证策略》的文章。在这篇文章中,Davis博士揭示了一些证据,其中包括DHEA在改善身体机能和健康方面的应用(Davis 2010;Morales 1994)。

DHEA与长寿

许多科学研究发现,DHEA水平下降与多种原因导致的死亡的可能性增加有关:

  1. 在一项对270名被怀疑心肌血流量减少的女性进行的研究中,DHEA-S水平在分布的下三分之一范围内的受试者在9年的随访期内死于任何原因的可能性比DHEA水平在分布的上三分之二范围内的女性高11%(Shufelt,2010年)。

  2. 在另一项研究中,242名年龄在50至79岁之间的男性被随访12年,DHEA-S水平低于140微克/分升的心血管疾病死亡的风险是较高水平的3.3倍。此外,DHEA-S中100微克/分升的增加与任何原因导致的死亡风险降低36%相关,即使在对一些混杂因素进行调整后也是如此(Barrett-Connor 1986)。

  3. 剑桥大学的研究人员对963名男性进行了长达9年的跟踪调查,发现循环中DHEA-S水平高于分布的下1/4时,任何原因导致的死亡风险降低了约30%(Trivedi,2001年)。

  4. 在一项针对因慢性肾病接受透析的男性的研究中,与校正潜在混杂因素后的较高水平相比,血浆DHEA-S水平较低与任何原因导致的死亡风险增加约2.9倍有关(Hsu 2012)。

  5. 对313名接受透析的男性进行的类似研究证实,DHEA-S水平较低预示该人群的死亡率增加(Kakiya,2012年)。

  6. 在一项对2644名来自瑞典的男性进行平均4.5年跟踪调查的研究中,DHEA-S水平在较低1/4分布范围内的男性与DHEA-S水平较高的男性相比,在跟踪调查期间死亡的可能性高出54%,即使在研究调整了调查结果以考虑进可能影响结果的变量的情况下也是如此(Ohlsson 2010)。

  7. 对4255名越战时期的美国退伍军人进行的分析显示,DHEA-S水平升高与15年随访期内死亡可能性降低49%相关(Phillips 2010)。

  8. 一项跟踪940名受试者27年的长期研究发现,DHEA-S水平高于200微克/分升的男性在研究期间死亡的可能性明显低于DHEA-S水平较低的男性(Enomoto 2008)。

  9. 在963名台湾老年人中进行的一项为期3年的研究显示,DHEA-S水平低于54.5微克/分升在研究期间的死亡风险高出64%(Glei 2006)。

  10. 法国研究人员对290名受试者进行了为期10年的研究,发现DHEA-S水平低的男性的死亡风险比DHEA-S水平高的男性增加了1.9倍;这在65-69岁的男性中尤其如此,其风险程度是6.5倍(Mazat 2001)。

  11. 在另一项研究中,123名心脏病发作幸存者进行了长达10年的随访,发现低DHEA-S水平预示着心血管疾病导致的死亡(Jansson 1998)。

  12. 在参与法国社区研究的622名年龄在65岁以上的人中,DHEA-S水平低与男性2年和4年以上的更大死亡风险密切相关(Berr 1996)。

  13. 在另一项研究中,当低DHEA-S与其他三个危险因素(睾酮缺乏、高敏C反应蛋白[hs-CRP]升高和血浆N末端B型利钠肽前体[NTproB]升高)相结合时,心血管死亡的风险比健康对照组高出惊人的63倍(Ponikowska,2009年)。

有趣的是,除了DHEA-S的总体水平外,一些证据表明,DHEA-S随年龄增长而下降的速度可能独立地影响寿命。在一项对950名65岁或65岁以上的人进行的研究中,那些DHEA-S水平下降更快的人在研究期间死亡的可能性比DHEA-S水平下降较慢的人高75%。尽管在这项研究中,基线DHEA-S与死亡率无关,但这些发现仍然存在(Cappola 2009)。

DHEA与癌症风险

由于DHEA可能会增加性激素水平,人们对DHEA在患有或患过激素相关癌症的人群中的应用表示担忧。迄今为止,还没有研究令人信服地表明,补充DHEA或孕烯醇酮会增加人类激素依赖性癌症的风险(Trevano 2011;Krysiak 2008;Traish 2011)。2011年7月,有一篇文章“加利福尼亚州颁布法令,在DHEA和孕烯醇酮上贴上强烈警告标签”提到了这一问题,如下所述。

孕烯醇酮和DHEA都是性激素雌激素、孕酮和睾酮的“母体”激素。因此,服用孕烯醇酮或DHEA补充剂可能确实会提高这些性激素的水平;事实上,这被认为是理想的效果之一。然而,主流医生仍对晚年性激素水平的升高表示担忧,他们引用了激素依赖性恶性肿瘤的风险理论(Trevano 2011),例如乳腺癌和前列腺癌等。

真相一如既往地微妙。哈佛大学泌尿科医生Abraham Morgentaler等人的重要研究表明,低睾酮水平可能增加前列腺癌的风险,尽管这是一个有争议的概念。 Morgentaler本人已经成为老年男性补充睾酮的强烈支持者。他还是一项研究的首席研究员,该研究证明,在大鼠中补充DHEA可提高总睾酮水平,而不会对前列腺组织产生任何有害的变化(Trevano 2011;Rhoden 2003)。

类似的理论风险也适用于乳腺癌。但是在对天然雌二醇和孕酮(DHEA和/或孕烯醇酮的天然产物)联合应用的大量研究中,没有发现乳腺癌风险的增加。此外,单独使用天然孕酮可能会降低癌症风险,这再次表明使用DHEA和孕烯醇酮等前体物质提高性激素水平是安全的。最近的一项动物研究表明DHEA对肥胖大鼠有直接的抗癌作用(Trevano 2011;Hakkak 2010)。

任何已知患有任何类型癌症的个人在使用任何新的补充剂或药物时应咨询其医生(Trevano 2011)。


本文提出了许多问题,这些问题可能会随着新数据的出现而发生变化。 我们建议的营养或治疗方案均不用于确保治愈或预防任何疾病。Piping Rock健康研究院没有对参考资料中包含的数据进行独立验证,并明确声明对文献中的任何错误不承担任何责任。


五、参考文献

  1. Abraham SB, Rubino D, Sinaii N, Ramsey S, Nieman LK. Cortisol, obesity, and the metabolic syndrome: a cross-sectional study of obese subjects and review of the literature.Obesity (Silver Spring, Md.).Jan 2013;21(1):E105-117.

  2. Adachi M, Takayanagi R. Role of androgens and DHEA in bone metabolism, Clin Calcium 2006 Jan; 16(1):61-6.

  3. Ahmed LA, Schirmer H, Bjornerem A, Emaus N, Jorgensen L, Stormer J, Joakimsen RM. The gender- and age-specific 10-year and lifetime absolute fracture risk in Tromso, Norway. Eur J Epidemiol. 2009;24(8):441-8.

  4. Aldred S, Mecocci P. Decreased dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) concentrations in plasma of Alzheimer's disease (AD) patients. Arch Gerontol Geriatr. 2010 Jul-Aug;51(1):e16-8.

  5. Alhaj HA, Massey AE, McAllister-Williams RH. Effects of DHEA administration on episodic memory, cortisol and mood in healthy young men: a double-blind, placebo-controlled study. Psychopharmacology (Berl). 2006 Nov; 188(4):541-51.

  6. Amato RJ, Hulin MW, Winsauer PJ. A comparison of dehydroepiandrosterone and 7-keto dehydroepiandrosterone with other drugs that modulate ethanol intake in rats responding under a multiple schedule.Behavioural pharmacology.Jun 2012;23(3):250-261.

  7. Arlt W, Haas J, Callies F, Reincke M, Hubler D, Oettel M, . . . Allolio B. Biotransformation of oral dehydroepiandrosterone in elderly men: significant increase in circulating estrogens. The Journal of clinical endocrinology and metabolism. Jun 1999;84(6):2170-2176.

  8. Arlt W, Justl HG, Callies F, Reincke M, Hubler D, Oettel M, . . . Allolio B. Oral dehydroepiandrosterone for adrenal androgen replacement: pharmacokinetics and peripheral conversion to androgens and estrogens in young healthy females after dexamethasone suppression. The Journal of clinical endocrinology and metabolism. Jun 1998;83(6):1928-1934.

  9. Arlt W. Androgen therapy in women. Eur J Endocrinol. 2006 Jan; 154(1):1-11.

  10. Barrett-Connor E, Khaw KT, Yen SS. A prospective study of dehydroepiandrosterone sulfate, mortality, and cardiovascular disease.The New England journal of medicine.Dec 11 1986;315(24):1519-1524.

  11. Basat O, Ucak S, Ozkurt H, Basak M, Seber S, Altuntas Y. Visceral adipose tissue and an indicator of insulin resistance in nonobese patients with new onset type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes. 2006;114(2):58-62.

  12. Baulieu EE, Robel P. Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) as neuroactive neurosteroids.Proceedings of the National Academy of Sciences of the United States of America.Apr 14 1998;95(8):4089-4091.

  13. Belanger A, Candas B, et al. Changes in serum concentrations of conjugated and unconjugated steroids in 40- to 80-year-old men. J CLin Endocrinol Metab . 1994;79:1086-1090.

  14. Berr C, Lafont S, Debuire B, Dartigues JF, Baulieu EE. Relationships of dehydroepiandrosterone sulfate in the elderly with functional, psychological, and mental status, and short-term mortality: a French community-based study.Proceedings of the National Academy of Sciences of the United States of America.Nov 12 1996;93(23):13410-13415.

  15. Bloch M, Schmidt PJ, Danaceau MA, Adams LF, Rubinow DR. Dehydroepiandrosterone treatment of midlife dysthymia. Biol Psychiatry. 1999 Jun 15;45(12):1533-41.

  16. Bobyleva V, Bellei M, Kneer N, Lardy H. The effects of the ergosteroid 7-oxo-dehydroepiandrosterone on mitochondrial membrane potential: possible relationship to thermogenesis.Archives of biochemistry and biophysics.May 1 1997;341(1):122-128.

  17. Bradley M, McElhiney M, Rabkin J. DHEA and Cognition in HIV-Positive Patients with Non-Major Depression. Psychosomatics 2012 53 (3):244–249

  18. Brazo V, Santello FH, Caetano LC, Del Vecchio Filipin M, Paula Alonso Toldo M, do Prado JC, Jr. Immunomodulatory effects of zinc and DHEA on the Th-1 immune response in rats infected with Trypanosoma cruzi. Immunobiology. 2010 May;215(5):427-34.

  19. Brignardello E, Runzo C, Aragno M, et al. Dehydroepiandrosterone administration counteracts oxidative imbalance and advanced glycation end product formation in type 2 diabetic patients. Diabetes Care. 2007 Nov; 30(11):2922-7.

  20. Brooke AM, Kalingag LA, Miraki-Moud F, et al. Dehydroepiandrosterone improves psychological well-being in male and female hypopituitary patients on maintenance growth hormone replacement. J Clin Endocrinol Metab. 2006 Oct; 91(10):3773-9.

  21. Buford TW, Willoughby DS. Impact of DHEA(S) and cortisol on immune function in aging: a brief review. Appl Physiol Nutr Metab. 2008 Jun;33(3):429-33.

  22. Buoso E, Lanni C, Molteni E, Rousset F, Corsini E, Racchi M. Opposing effects of cortisol and dehydroepiandrosterone on the expression of the receptor for Activated C Kinase 1: implications in immunosenescence.Experimental gerontology.Nov 2011;46(11):877-883.

  23. Butcher SK, Killampalli V, Lascelles D, Wang K, Alpar EK, Lord JM. Raised cortisol:DHEAS ratios in the elderly after injury: potential impact upon neutrophil function and immunity. Aging cell. Dec 2005;4(6):319-324.

  24. Caetano LC, Santello FH, Del Vecchio Filipin M, et al. Trypanosoma cruzi: dehydroepiandrosterone (DHEA) and immune response during the chronic phase of the experimental Chagas’ disease. Vet Parasitol. 2009 Jul 7;163(1-2):27-32.

  25. Calvo E, Luu-The V, Morissette J, et al. Pangenomic changes induced by DHEA in the skin of postmenopausal women. J Steroid Biochem Mol Biol. 2008 Dec; 112(4-5):186-93.

  26. Cameron DR , Braunstein GD. The use of dehydroepiandrosterone therapy in clinical practice. Treat Endocrinol . 2005;4(2):95-114.

  27. Cappola AR, O'Meara ES, Guo W, Bartz TM, Fried LP, Newman AB. Trajectories of dehydroepiandrosterone sulfate predict mortality in older adults: the cardiovascular health study.The journals of gerontology. Series A, Biological sciences and medical sciences.Dec 2009;64(12):1268-1274.

  28. Cawthon PM. Gender Differences in Osteoporosis and Fractures. Clin Orthop Relat Res. 2011 Jul;469(7):1900-5

  29. Chan CC, Liou CJ, Xu PY, Shen JJ, Kuo ML, Len WB, . . . Huang WC. Effect of dehydroepiandrosterone on atopic dermatitis-like skin lesions induced by 1-chloro-2,4-dinitrobenzene in mouse.Journal of dermatological science.Jul 9 2013.

  30. Chang DM, Lan JL. et al. Dehydroepiandrosterone treatment of women with mild-to-moderate systemic lupus erythematosus: a multicenter randomized, double-blind, placebo-controlled trial. Arthritis Rheum . 2002 Nov;46(11):2924-7.

  31. Charalampopoulos I, Remboutsika E, Margioris AN, Gravanis A. Neurosteroids as modulators of neurogenesis and neuronal survival. Trends Endocrinol Metab. 2008 Oct; 19(8):300-7.

  32. Chlebowski RT, Anderson GL, Gass M, et al. WHI Investigators. Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. JAMA. 2010 Oct 20;304(15):1684-92.

  33. Choi IS, Cui Y, Koh YA, Lee HC, Cho YB, Won YH, Effects of dehydroepiandrosterone on Th2 cytokine production in peripheral blood mononuclear cells from asthmatics. Korean J Intern Med. 2008 Dec; 23(4):176-81.

  34. Corina M, Vulpoi C, Branisteanu D. Relationship between bone mineral density, weight, and estrogen levels in pre- and postmenopausal women. Rev Med Chir Soc Med Nat Iasi. 2012 Oct-Dec;116(4):946-50.

  35. Crosbie D, Black C, McIntyre L, Royle PL, Thomas S. Dehydroepiandrosterone for systemic lupus erythematosus. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005114.

  36. Davidson M, Marwah A, Sawchuk RJ, Maki K, Marwah P, Weeks C, Lardy H. Safety and pharmacokinetic study with escalating doses of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy male volunteers. Clin Invest Med. 2000 Oct;23(5):300-10.

  37. Davis W. Don’t Fall Victim to Frailty. Life Extension Magazine March 2010. http://www.lifeextension.com/magazine/mag2010/mar2010_Dont-Fall-Victim-to-Frailty_01.htm

  38. Dhatariya K, Bigelow ML, Nair KS. Effect of dehydroepiandrosterone replacement on insulin sensitivity and lipids in hypoadrenal women. Diabetes. 2005 Mar;54(3):765-9.

  39. Dong Y, Zheng P. Dehydroepiandrosterone sulphate: action and mechanism in the brain. J Neuroendocrinol. 2012 Jan;24(1):215-24.

  40. Dong Y, Zheng P. Dehydroepiandrosterone sulphate: action and mechanism in the brain. Journal of neuroendocrinology. Jan 2012;24(1):215-224.

  41. Drbalová K, Matucha P, Matejková-Behanová M, Bílek R, Kríz L, Kazihnitková H, Hampl R. Immunoprotective steroids and SHBG in non-treated hypothyroidism and their relationship to autoimmune thyroid disorders. Physiol Res. 2008;57 Suppl 1:S119-25.

  42. Dumas de la Roque E, Savineau JP, Bonnet S. Dehydroepiandrosterone: A new treatment for vascular remodeling diseases including pulmonary arterial hypertension.Pharmacology & therapeutics.May 2010;126(2):186-199.

  43. Duskova M, Simunkova K, Hill M, Starka L. 7-hydroxylated derivatives of dehydroepiandrosterone as possibly related to menstrual mood change in healthy women. Endocr Regul. 2011 Jul; 45(3):131-7

  44. El-Alfy M, Deloche C, Azzi L, Bernard BA, Bernerd F, Coutet J, Chaussade V, Martel C, Leclaire J, Labrie F. Skin responses to topical dehydroepiandrosterone: implications in antiageing treatment Br J Dermatol. 2010 Nov;163(5):968-76.

  45. Enomoto M, Adachi H, Fukami A, Furuki K, Satoh A, Otsuka M, . . . Imaizumi T. Serum dehydroepiandrosterone sulfate levels predict longevity in men: 27-year follow-up study in a community-based cohort (Tanushimaru study).Journal of the American Geriatrics Society.Jun 2008;56(6):994-998.

  46. Fingerova H, Matlochova J. [Reduced serum dehydroepiandrosterone levels in postmenopausal osteoporosis].Ceska gynekologie / Ceska lekarska spolecnost J. Ev. Purkyne.Apr 1998;63(2):110-113.

  47. Fitzpatrick JL, Ripp SL, Smith NB, Pierce WM, Jr., Prough RA. Metabolism of DHEA by cytochromes P450 in rat and human liver microsomal fractions.Archives of biochemistry and biophysics.May 15 2001;389(2):278-287.

  48. Ganong WF, 'Review of Medical Physiology', 22nd Ed, McGraw Hill, 2005, page 362

  49. Genazzani AR, Stomati M, Valentino V, Pluchino N, Pot E, Casarosa E, Merlini S, Giannini A, Luisi M. Effect of 1-year, low-dose DHEA therapy on climacteric symptoms and female sexuality. Climacteric. 2011 Dec;14(6):661-8.

  50. Glei DA, Goldman N. Dehydroepiandrosterone sulfate (DHEAS) and risk for mortality among older Taiwanese.Annals of epidemiology.Jul 2006;16(7):510-515.

  51. Gómez-Santos C, Hernández-Morante JJ, Tébar FJ, Granero E, Garaulet M. Differential effect of oral dehydroepiandrosterone-sulphate on metabolic syndrome features in pre- and postmenopausal obese women. Clin Endocrinol (Oxf). 2012 Oct;77(4):548-54.

  52. Gómez-Santos C, Larque E, Granero E, Hernandez-Morante JJ, Garaulet M. Dehydroepiandrosterone-sulphate replacement improves the human plasma fatty acid profile in plasma of obese women. Steroids. Dec 11 2011;76(13):1425-1432.

  53. Hakkak R, Shaaf S, Jo CH, MacLeod S, Korourian S. Dehydroepiandrosterone intake protects against 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in the obese Zucker rat model.Oncology reports.Aug 2010;24(2):357-362.

  54. Hampl R, Stárka L, Jansky L. Steroids and thermogenesis. Physiol Res. 2006; 55(2):123-31.

  55. Hampl R, Sulcová J, Bílek R, Hill M. How short-term transdermal treatment of men with 7-oxo-dehydroepiandrosterone influence thyroid function. Physiol Res. 2006; 55(1):49-54.

  56. Hauffa BP, Kaplan SL, et al. Dissociation between plasma adrenal androgens and cortisol in Cushing's disease and ectopic ACTH-producing tumour: relation to adrenarche. Lancet . 1984 Jun 23;1(8391):1373-6.

  57. Hazeldine J, Arlt W, Lord JM. Dehydroepiandrosterone as a regulator of immune cell function. J Steroid Biochem Mol Biol. 2010 May 31;120(2-3):127-36.

  58. Hennebert O, Chalbot S, Alran S, Morfin R. Dehydroepiandrosterone 7alpha-hydroxylation in human tissues: possible interference with type 1 11beta-hydroxysteroid dehydrogenase-mediated processes. J Steroid Biochem Mol Biol. 2007 May;104(3-5):326-33.

  59. Herbert, J. Neurosteroids, brain damage, and mental illness. Exp Gerontol. 1998 Nov-Dec;33(7-8):713-27.

  60. Hinson JP, Raven PW. DHEA deficiency syndrome: a new term for old ageThe Journal of endocrinology.Oct 1999;163(1):1-5.

  61. 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.

  62. 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 Postgraduate medicine. Jan 2009;121(1):73-85.

  63. Hsu HJ, Yen CH, Chen CK, Hsu KH, Hsiao CC, Lee CC, . . . Wu MS. Low plasma DHEA-S increases mortality risk among male hemodialysis patients.Experimental gerontology.Dec 2012;47(12):950-957.

  64. Huerta-García E, Ventura-Gallegos JL, Victoriano ME, Montiél-Dávalos A, Tinoco-Jaramillo G, López-Marure R. Dehydroepiandrosterone inhibits the activation and dysfunction of endothelial cells induced by high glucose concentration. Steroids. 2012 Feb;77(3):233-40.

  65. Ihler G, Chami-Stemmann H. 7-oxo-DHEA and Raynaud's phenomenon.Medical hypotheses.Mar 2003;60(3):391-397.

  66. Ii M, Hoshiga M, Negoro N, et al. Adrenal androgen dehydroepiandrosterone sulfate inhibits vascular remodeling following arterial injury. Atherosclerosis. 2009 Sep;206(1):77-85.

  67. James K, Premchand N, et al. IL-6, DHEA and the ageing process. Mech Ageing Dev . 1997 Feb;93(1-3):15-24.

  68. Jansson JH, Nilsson TK, Johnson O. von Willebrand factor, tissue plasminogen activator, and dehydroepiandrosterone sulphate predict cardiovascular death in a 10 year follow up of survivors of acute myocardial infarction.Heart (British Cardiac Society).Oct 1998;80(4):334-337.

  69. Kakiya R, Shoji T, Hayashi T, Tatsumi-Shimomura N, Tsujimoto Y, Tabata T, . . . Inaba M. Decreased serum adrenal androgen dehydroepiandrosterone sulfate and mortality in hemodialysis patients.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.Oct 2012;27(10):3915-3922.

  70. Kawate H, Takayanagi R. [Secondary osteoporosis UPDATE. Treatment of male osteoporosis. Testosterone replacement therapy etc]. Clin Calcium. 2010 May;20(5):744-51.

  71. Kenny AM, Boxer RS, Kleppinger A, Brindisi J, Feinn R, Burleson JA. Dehydroepiandrosterone combined with exercise improves muscle strength and physical function in frail older women. J Am Geriatr Soc. 2010 Sep;58(9):1707-14.

  72. Khorram O, Vu L, et al. Activation of immune function by dehydroepiandrosterone (DHEA) in age-advanced men. J Gerontol A Biol Sci Med Sci . 1997 Jan;52(1):M1-M7.

  73. Krysiak R, Frysz-Naglak D, Okopien B. [Current views on the role of dehydroepiandrosterone in physiology, pathology and therapy]. Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego. Jan 2008;24(139):66-71.

  74. Krysiak R, Frysz-Naglak D, Okopień B. Current views on the role of dehydroepiandrosterone in physiology, pathology and therapy. Pol Merkur Lekarski. 2008 Jan;24(139):66-71.

  75. Kurita H, Maeshima H, Kida S, Matsuzaka H, Shimano T, Nakano Y, Baba H, Suzuki T, Arai H. Serum dehydroepiandrosterone (DHEA) and DHEA-Sulfate (S) levels in medicated patients with major depressive disorder compared with controls. J Affect Disord. 2012 Oct 25. pii: S0165-0327(12)00623-4.

  76. LabCorp. Dehydroepiandrosterone (DHEA) Sulfate. Available at: https://www.labcorp.com/wps/portal/!ut/p/c1/ hY1LDoIwFADP4gFMHwUqbDXlI1CsRflsCAFDMPwxGDi9XEDNLCeTQQnaaLO5KrNX1bVZjSKUkJ RrhHHMMGgeNgDL5AjqiUpgks3H3z3An5pZXfNAMUoO6Y0qQrJ1GXxTYLCF7CsMM0I0QAGKQEn FE3rPnVpv1f2LS1Xm0tHPnRGCAaZ10R3ghXO-FnU98LAM74FX20ERz1K-yI7BrXQQR9he8c9X30Rvac93H5v96_Y!/ dl2/d1/L0lJS2FZQSEhL3dMRUJGcUFFQWpNQy9ZSTV5bHchIS83X1VFNFMxSTkzME9HUzIwSVMzTzROMk42 NjgwL3ZpZXdUZXN0/testId=408381 Accessed 8/29/2013.

  77. Labrie F, Archer D, Bouchard C, Fortier M, Cusan L, Gomez JL, Girard G, Baron M, Ayotte N, Moreau M, Dubé R, Cté I, Labrie C, Lavoie L, Berger L, Gilbert L, Martel C, Balser J. Effect of intravaginal dehydroepiandrosterone (Prasterone) on libido and sexual dysfunction in postmenopausal women. Menopause. 2009 Sep-Oct; 16(5):923-31

  78. Labrie F. DHEA, important source of sex steroids in men and even more in women. Prog Brain Res. 2010;182:97-148.

  79. Lazaridis I, Charalampopoulos I, Alexaki VI, Avlonitis N, Pediaditakis I, Efstathopoulos P, . . . Gravanis A. Neurosteroid dehydroepiandrosterone interacts with nerve growth factor (NGF) receptors, preventing neuronal apoptosis.PLoS biology.Apr 2011;9(4):e1001051.

  80. Leowattana W. DHEA(S): the fountain of youth. J Med Assoc Thai . 2001 Oct;84(Suppl 2):S605-S612.

  81. Li Y, Xia Z, Wang M. Dehydroepiandrosterone inhibits CD40/CD40L expression on human umbilical vein endothelial cells induced by interferon gamma. Int Immunopharmacol. 2009 Feb; 9(2):168-72

  82. Liu D, Dillon JS. Dehydroepiandrosterone activates endothelial cell nitric-oxide synthase by a specific plasma membrane receptor coupled to Galpha(i2,3). The Journal of biological chemistry. Jun 14 2002;277(24):21379-21388.

  83. Liu D, Dillon JS. Dehydroepiandrosterone stimulates nitric oxide release in vascular endothelial cells: evidence for a cell surface receptor. Steroids. Apr 2004;69(4):279-289.

  84. Lopez-Marure R, Contreras PG, Dillon JS. Effects of dehydroepiandrosterone on proliferation, migration, and death of breast cancer cells.European journal of pharmacology.Jun 25 2011;660(2-3):268-274.

  85. Luppi C, Fioravanti M, Bertolini B, Inguscio M, Grugnetti A, Guerriero F, Rovelli C, Cantoni F, Guagnano P, Marazzi E, Rolfo E, Ghianda D, Levante D, Guerrini C, Bonacasa R, Solerte SB. Growth factors decrease in subjects with mild to moderate Alzheimer's disease (AD): potential correction with dehydroepiandrosterone-sulphate (DHEAS). Arch Gerontol Geriatr. 2009;49 Suppl 1:173-84.

  86. Lutsenko MT, Andrievskaia IA, Dovzhikova IV. [DHEA-S synthesis during pregnancy with cytomegalovirus infection]. Arkh Patol. 2012 Jan-Feb;74(1):46-7.

  87. Manabe A, et al. Nitric oxide synthesis is increased after dehydroepiandrosterone sulphate administration in term human pregnancy. Human Reproduction 1999 14(8): 2116-2119.

  88. Marder W, Somers EC, Kaplan MJ, Anderson MR, Lewis EE, McCune WJ. Effects of prasterone (dehydroepiandrosterone) on markers of cardiovascular risk and bone turnover in premenopausal women with systemic lupus erythematosus: a pilot study. Lupus. 2010 Sep;19(10):1229-36.

  89. Marin P, Darin N, Amemiya T, Andersson B, Jern S, Bjorntorp P. Cortisol secretion in relation to body fat distribution in obese premenopausal women.Metabolism: clinical and experimental.Aug 1992;41(8):882-886.

  90. Martina V, Benso A, Gigliardi VR, Masha A, Origlia C, Granata R, Ghigo E. Short-term dehydroepiandrosterone treatment increases platelet cGMP production in elderly male subjects. Clin Endocrinol (Oxf). 2006 Mar; 64(3):260-4.

  91. Mayo Clinic. DHEA. Available at: http://www.mayoclinic.com/health/dhea/NS_patient-dhea. 2012.

  92. Mazat L, Lafont S, Berr C, Debuire B, Tessier JF, Dartigues JF, Baulieu EE. Prospective measurements of dehydroepiandrosterone sulfate in a cohort of elderly subjects: relationship to gender, subjective health, smoking habits, and 10-year mortality.Proceedings of the National Academy of Sciences of the United States of America.Jul 3 2001;98(14):8145-8150.

  93. Miller KK, Cai J, Ripp SL, Pierce WM, Jr., Rushmore TH, Prough RA. Stereo- and regioselectivity account for the diversity of dehydroepiandrosterone (DHEA) metabolites produced by liver microsomal cytochromes P450.Drug metabolism and disposition: the biological fate of chemicals.Mar 2004;32(3):305-313.

  94. Mitchell LE, Sprecher DL, Borecki IB, Rice T, Laskarzewski PM, Rao DC. Evidence for an association between dehydroepiandrosterone sulfate and nonfatal, premature myocardial infarction in males. Circulation. 1994 Jan; 89(1):89-93.

  95. Morales AJ, Nolan JJ, Nelson JC, Yen SS. Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. J Clin Endocrinol Metab. 1994 Jun;78(6):1360-7.

  96. Morales AJ, Nolan JJ, Nelson JC, Yen SS. Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. The Journal of clinical endocrinology and metabolism. Jun 1994;78(6):1360-1367.

  97. Morgentaler A, Lipshultz LI, Bennett R, Sweeney M, Avila D, Jr., Khera M. Testosterone therapy in men with untreated prostate cancer.The Journal of urology.Apr 2011;185(4):1256-1260.

  98. Morgentaler A. Turning conventional wisdom upside-down: low serum testosterone and high-risk prostate cancer.Cancer.Sep 1 2011;117(17):3885-3888.

  99. Moyer AE, Rodin J, Grilo CM, Cummings N, Larson LM, Rebuffe-Scrive M. Stress-induced cortisol response and fat distribution in women.Obesity research.May 1994;2(3):255-262.

  100. Mueck AO, Seeger H, Buhling KJ. Use of dydrogesterone in hormone replacement therapy. Maturitas. 2009 Dec;65 Suppl 1:S51-60.

  101. Muller C, Hennebert O, Morfin R. The native anti-glucocorticoid paradigm. J Steroid Biochem Mol Biol. 2006 Jul; 100(1-3):95-105.

  102. Nouveau S, Bastien P, Baldo F, de Lacharriere O. Effects of topical DHEA on aging skin: a pilot study. Maturitas. 2008 Feb 20;59(2):174-81.

  103. Nuti R, Merlotti D, Francucci CM, Gennari L. Bone fragility in men: where are we J Endocrinol Invest. 2010;33(7 Suppl):33-8.

  104. Ohlsson C, Labrie F, Barrett-Connor E, Karlsson MK, Ljunggren O, Vandenput L, . . . Tivesten A. Low serum levels of dehydroepiandrosterone sulfate predict all-cause and cardiovascular mortality in elderly Swedish men.The Journal of clinical endocrinology and metabolism.Sep 2010;95(9):4406-4414.

  105. Okuno S, Inaba M, Kitatani K, Ishimura E, Yamakawa T, Nishizawa Y. Serum levels of C-terminal telopeptide of type I collagen: a useful new marker of cortical bone loss in hemodialysis patients. Osteoporos Int. 2005 May;16(5):501-9. Epub 2004 Aug 11.

  106. Orentreich N, Brind JL, et al. Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. J Clin Endocrinol Metab . 1984 Sep;59(3):551-5.

  107. Panjari M, Davis SR. DHEA therapy for women: effect on sexual function and wellbeing.Human reproduction update.May-Jun 2007;13(3):239-248.

  108. Phillips AC, Carroll D, Gale CR, Lord JM, Arlt W, Batty GD. Cortisol, DHEA sulphate, their ratio, and all-cause and cause-specific mortality in the Vietnam Experience Study.European journal of endocrinology / European Federation of Endocrine Societies.Aug 2010;163(2):285-292.

  109. Ponholzer A, Madersbacher S, Rauchenwald M, Jungwirth S, Fischer P, Tragl KH. Vascular risk factors and their association to serum androgen levels in a population-based cohort of 75-year-old men over 5 years: results of the VITA study. World J Urol. 2009 Apr;28(2):209-14.

  110. Ponikowska B, Jankowska EA, Maj J, et al. Gonadal and adrenal androgen deficiencies as independent predictors of increased cardiovascular mortality in men with type II diabetes mellitus and stable coronary artery disease. Int J Cardiol. 2010 Sep 3;143(3):343-8.

  111. Puizina-Ivi N, Miri L, Carija A, Karlica D, Marasovi D. Modern approach to topical treatment of aging skin. Coll Antropol. 2010 Sep;34(3):1145-53.

  112. Rabkin JG, McElhiney MC, Rabkin R, McGrath PJ, Ferrando SJ. Placebo-controlled trial of dehydroepiandrosterone (DHEA) for treatment of nonmajor depression in patients with HIV/AIDS. Am J Psychiatry. 2006 Jan; 163(1):59-66.

  113. Ramos-Casals M, García-Carrasco M, Brito MP, López-Soto A, Font J. Autoimmunity and geriatrics: clinical significance of autoimmune manifestations in the elderly. Lupus. 2003;12(5):341-55.

  114. Reiter WJ, Pycha A, Schatzl G, Pokorny A, Gruber DM, Huber JC, Marberger M. Dehydroepiandrosterone in the treatment of erectile dysfunction: a prospective, double-blind, randomized, placebo-controlled study. Urology. 1999 Mar;53(3):590-4; discussion 594-5.

  115. Rhoden EL, Gobbi D, Rhoden CR, et al. Effects of chronic administration of dehydroepiandrosterone on serum testosterone levels and prostatic tissue in rats. J Urol. 2003 Nov;170(5):2101-3.

  116. Rhoden EL, Gobbi D, Rhoden CR, Menti E, Roehe AN, Hartmann A, Morgentaler A. Effects of chronic administration of dehydroepiandrosterone on serum testosterone levels and prostatic tissue in rats.The Journal of urology.Nov 2003;170(5):2101-2103.

  117. Ritsner, MS. The clinical and therapeutic potentials of dehydroepiandrosterone and pregnenolone in schizophrenia. Neuroscience. 2011 Sep 15; 191:91-100.

  118. Roxas M, Jurenka J. Colds and influenza: a review of diagnosis and conventional, botanical, and nutritional considerations. Altern Med Rev. 2007 Mar;12(1):25-48.

  119. Samaras N, Samaras D, Frangos Lordos E, Forster A, Philippe J. A review of age related dehydroepiandrosterone (DHEA) decline and its association with well-known geriatric syndromes. Is treatment beneficial Rejuvenation research. May 7 2013.

  120. Sanders JL, Cappola AR, Arnold AM, Boudreau RM, Chaves PH, Robbins J, . . . Newman AB. Concurrent change in dehydroepiandrosterone sulfate and functional performance in the oldest old: results from the Cardiovascular Health Study All Stars study. The journals of gerontology. Series A, Biological sciences and medical sciences. Sep 2010;65(9):976-981.

  121. Santos CD, Toldo MP, Santello FH, Filipin Mdel V, Brazo V, do Prado Júnior JC. Dehydroepiandrosterone increases resistance to experimental infection by Trypanosoma cruzi. Vet Parasitol. 2008 May 31;153(3-4):238-43.

  122. Savineau JP, Marthan R, Dumas de la Roque E. Role of DHEA in cardiovascular diseases. Biochemical pharmacology. Mar 15 2013;85(6):718-726.

  123. Schulze J, Johansson M, Thorngren JO, Garle M, Rane A, Ekstrom L. SULT2A1 Gene Copy Number Variation is Associated with Urinary Excretion Rate of Steroid Sulfates.Frontiers in endocrinology.2013;4:88.

  124. Shufelt C, Bretsky P, Almeida CM, Johnson BD, Shaw LJ, Azziz R, Braunstein GD, Pepine CJ, Bittner V, Vido DA, Stanczyk FZ, Bairey Merz CN. DHEA-S levels and cardiovascular disease mortality in postmenopausal women: results from the National Institutes of Health--National Heart, Lung, and Blood Institute (NHLBI)-sponsored Women's Ischemia Syndrome Evaluation (WISE). J Clin Endocrinol Metab. 2010 Nov;95(11):4985-92.

  125. Simoncini T, Mannella P, Fornari L, Varone G, Caruso A, Genazzani AR. Dehydroepiandrosterone modulates endothelial nitric oxide synthesis via direct genomic and nongenomic mechanisms. Endocrinology. Aug 2003;144(8):3449-3455.

  126. Simunkova K, Hampl R, Hill M, Kriz L, Hrda P, Janickova-Zdarska D, Zamrazil V, Vrbikova J, Vondra K. Adrenocortical function in young adults with diabetes mellitus type 1. J Steroid Biochem Mol Biol. 2010 Oct;122(1-3):35-41.

  127. Sorwell KG, Urbanski HF. Dehydroepiandrosterone and age-related cognitive decline. Age (Dordr). 2010 Mar;32(1):61-7.

  128. Srinivasan M, Irving BA, Dhatariya K, et al. Effect of dehydroepiandrosterone replacement on lipoprotein profile in hypoadrenal women. J Clin Endocrinol Metab. 2009 Mar;94(3):761-4.

  129. Stangl B, Hirshman E, Verbalis J. Administration of dehydroepiandrosterone (DHEA) enhances visual-spatial performance in postmenopausal women. Behav Neurosci. 2011 Oct;125(5):742-52.

  130. Steinberger J, Daniels S. Obesity, Insulin Resistance, Diabetes, and Cardiovascular Risk in Children. Circulation. 2003;107:1448-53.

  131. Straub RH, Konecna L, et al. Serum dehydroepiandrosterone (DHEA) and DHEA sulfate are negatively correlated with serum interleukin-6 (IL-6), and DHEA inhibits IL-6 secretion from mononuclear cells in man in vitro: possible link between endocrinosenescence and immunosenescence. J Clin Endocrinol Metab . 1998 Jun;83(6):2012-7.

  132. Straub RH, Lehle K, et al. Dehydroepiandrosterone in relation to other adrenal hormones during an acute inflammatory stressful disease state compared with chronic inflammatory disease: role of interleukin-6 and tumour necrosis factor. Eur J Endocrinol . 2002a Mar;146(3):365-74.

  133. Straub RH, Scholmerich J, Zietz B. Replacement therapy with DHEA plus corticosteroids in patients with chronic inflammatory diseases--substitutes of adrenal and sex hormones. Zeitschrift fur Rheumatologie. 2000;59 Suppl 2:Ii/108-118.

  134. Strous RD, Maayan R, Kotler M, Weizman A. Hormonal profile effects following dehydroepiandrosterone (DHEA) administration to schizophrenic patients. Clin Neuropharmacol. 2005 Nov-Dec;28(6):265-9.

  135. Talaei A, Amini M, Siavash M, Zare M. The effect of dehydroepiandrosterone on insulin resistance in patients with impaired glucose tolerance. Hormones (Athens). 2010 Oct-Dec;9(4):326-31.

  136. Traish AM, Kang HP, Saad F, Guay AT. Dehydroepiandrosterone (DHEA)--a precursor steroid or an active hormone in human physiology. The journal of sexual medicine. Nov 2011;8(11):2960-2982; quiz 2983.

  137. Trevano J. State of California Decrees Strong Warning Labels on DHEA and Pregnenolone. Life Extension. July. 2011.

  138. Trivedi DP, Khaw KT. Dehydroepiandrosterone sulfate and mortality in elderly men and women.The Journal of clinical endocrinology and metabolism.Sep 2001;86(9):4171-4177.

  139. Turgeon JL, Carr MC, Maki PM, Mendelsohn ME, Wise PM. Complex actions of sex steroids in adipose tissue, the cardiovascular system, and brain: Insights from basic science and clinical studies. Endocr Rev. 2006 Oct;27(6):575-605.

  140. UMMC. University of Maryland Medical Center (UMMC). Dehydroepiandrosterone. Available at: http://umm.edu/health/medical/altmed/supplement/dehydroepiandrosterone 2013.

  141. Valenti G, Ferrucci L, Lauretani F, et al. Dehydroepiandrosterone and cognitive function in the elderly: The InCHIANTI Study. J Endocrinol Invest. 2009 Oct; 32(9):766-72.

  142. van Broekhoven F, Verkes RJ. Neurosteroids in depression: a review. Psychopharmacology (Berl). 2003 Jan;165(2):97-110. Epub 2002 Nov 6.

  143. van Vollenhoven RF, Morabito LM, et al. Treatment of systemic lupus erythematosus with dehydroepiandrosterone: 50 patients treated up to 12 months. J Rheumatol . 1998 Feb;25(2):285-9.

  144. von Mühlen D, Laughlin GA, Kritz-Silverstein D, Bergstrom J, Bettencourt R. Effect of dehydroepiandrosterone supplementation on bone mineral density, bone markers, and body composition in older adults: the DAWN trial. Osteoporos Int. 2008 May;19(5):699-707.

  145. Wang YD, Tao MF, Cheng WW, Liu XH, Wan XP, Cui K. Dehydroepiandrosterone indirectly inhibits human osteoclastic resorption via activating osteoblastic viability by the MAPK pathway. Chin Med J (Engl). 2012 Apr; 125(7):1230-5.

  146. Wang YD, Wang L, Li DJ, Wang WJ. Dehydroepiandrosterone inhibited the bone resorption through the upregulation of OPG/RANKL. Cell Mol Immunol. 2006 Feb; 3(1):41-5.

  147. Weiss EP, et al. Dehydroepiandrosterone (DHEA) replacement decreases insulin resistance and lowers inflammatory cytokines in aging humans. Aging (Albany NY). 2011 May; 3(5): 533–542.

  148. 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): 1459–1467.

  149. Whetzel CA, Klein LC. Measuring DHEA-S in saliva: time of day differences and positive correlations between two different types of collection methods. BMC Research Notes 2010, 3:204

  150. Wong SY, Leung JC, Kwok T, Ohlsson C, Vandenput L, Leung PC, Woo J. Low DHEAS levels are associated with depressive symptoms in elderly Chinese men: results from a large study. Asian J Androl. 2011 Nov;13(6):898-902.

  151. Worrel ME, Gurkovskaya OV, Leonard ST, Lewis PB, Winsauer PJ. Effects of 7-keto dehydroepiandrosterone on voluntary ethanol intake in male rats.Alcohol (Fayetteville, N.Y.).Jun 2011;45(4):349-354.

  152. Yaffe K, Ettinger B, Pressman A, Seeley D, Whooley M, Schaefer C, Cummings S. Neuropsychiatric function and dehydroepiandrosterone sulfate in elderly women: a prospective study. Biol Psychiatry. 1998 May 1;43(9):694-700.

  153. Yamada S, Akishita M, Fukai S, Ogawa S, Yamaguchi K, Matsuyama J, Kozaki K, Toba K, Ouchi Y. Effects of dehydroepiandrosterone supplementation on cognitive function and activities of daily living in older women with mild to moderate cognitive impairment. Geriatr Gerontol Int. 2010 Oct;10(4):280-7.

  154. Yasui T, Matsui S, Tani A, Kunimi K, Yamamoto S, Irahara M. Androgen in postmenopausal women. J Med Invest. 2012;59(1-2):12-27.

  155. Zauska M, Janota B. [Dehydroepiandrosteron (DHEA) in the mechanisms of stress and depression]. Psychiatr Pol. 2009 May-Jun;43(3):263-74.

  156. Zenk JL, Frestedt JL, Kuskowski MA. HUM5007, a novel combination of thermogenic compounds, and 3-acetyl-7-oxo-dehydroepiandrosterone: each increases the resting metabolic rate of overweight adults. J Nutr Biochem. 2007 Sep; 18(9):629-34.