围绝经期综合症治疗进展

女性一生中大约有1／3的时间是在绝经后度过的,围绝经期症状使得女性的日常生活及工作受到了很大的影响。传统的治疗方法为激素替代治疗,但因可能会增加乳癌和子宫内膜癌等的发病风险,其应用还存在很大的争议,非激素类药物包括中枢肾上腺素受体激动剂,选择性的5-HT重摄取抑制剂,Y-氨基丁酸类似物,黑升麻类药物等。黑升麻类药物缓解围绝经期症状的疗效是肯定的,黑升麻没有雌激素样作用,可能是通过5-羟色胺受体来发挥作用的。     

围绝经期综合症治疗进展

女性一生中大约有l/3的时间是在绝经后度过的,围绝经期症状使得女性的日常生活及工作受到了很大的影响。传统的治疗方法为激素替代治疗,但因可能会增加乳癌和子宫内膜癌等的发病风险,其应用还存在很大的争议,非激素类药物包括中枢肾上腺素受体激动剂,选择性的5-HT重摄取抑制剂,γ-氨基丁酸类似物,黑升麻类药物等。黑升麻类药物缓解围绝经期症状的疗效是肯定的,黑升麻没有雌激素样作用,可能是通过5-羟色胺受体来发挥作用的。     

黑升麻提取物对去势大鼠体温的影响

目的:观察黑升麻提取物对去势大鼠体温的影响。方法:雌性Sprague-Dawley(SD)大鼠30只,随机分为假手术(Sham)组、去势(OVX)组及去势后黑升麻提取物治疗(OVX+BC)组,每组10只。使用相应药物分别治疗并监测体温8周。结果:1与Sham组比较,OVX组及OVX+BC组大鼠的平均体温明显升高(P0.05);2与OVX组比较,OVX+BC组大鼠的平均体温明显减低(P0.05)。结论:大鼠去势后会出现体温升高。黑升麻提取物可以使去卵巢大鼠体温下降,达到缓解围绝经期潮热症状的目的。     

在人体胸腺细胞和血液单核细胞发现雌激素受体

为了进一步阐明性甾体激素对免疫功能调节作用的机制,荷兰学者 Weusten 等用~(125)Ⅰ标记的雌二醇对人体胸腺细胞和血液单核细胞上是否存在雌激素受体进行了示踪观察,结果发现,在胸腺细胞和单核细胞上均存在低容量和高亲和力的雌二醇结合位点。用未标记的雌二醇可以抑制~(125)Ⅰ-雌二醇对该受体的结合,而雌酮、二氢睾酮、皮质醇和孕激素都无竞争作用。因此,作者认为,该受体与其它靶组织中的雌激素受     

升麻化学成分及现代药理作用研究进展

升麻为毛茛科升麻属植物，在我国分布广泛、品种繁多，其药用历史已有两千余年。升麻化学成分复杂，其特征活性成分为Cycloartane型三萜。现代药理研究表明，升麻具有缓解围绝经期综合征、抗肿瘤、抗炎、抗病毒等作用，不同品种的升麻药材存在品质差异。对升麻化学成分、药理活性及药材品质进行文献归纳，分析升麻开发研究中存在的问题，旨在为升麻资源的深度开发提供参考。     

益坤宁对围绝经期大鼠下丘脑雌激素受体表达的影响

目的检测益坤宁对围绝经期大鼠下丘脑雌激素受体（estrogen receptor,ER）表达的影响,探讨益坤宁治疗围绝经期综合征的作用机制。方法采用自然衰老的围绝经期大鼠,随机分为围绝经期对照组、西药对照组和中药实验组;另取5月龄青年雌性大鼠做青年对照组。各组大鼠分别连续灌胃给予生理盐水、利维爱、中药益坤宁和生理盐水4周。通过免疫组化观察大鼠下丘脑ER蛋白的表达部位;Western blot定量检测大鼠下丘脑ERα和ERβ蛋白表达。结果ERα、ERβ蛋白主要表达于细胞胞质中。围绝经期对照组与青年组相比,ERa、E邓蛋白表达量明显下降（P〈0．05,P〈0．01）;中药实验组与围绝经期对照组比较,ERα、ERB蛋白表达量均明显增多（P〈0．05,P〈0．01）;西药对照组与围绝经期对照组相比,ERα、ERβ蛋白表达量增多（P〈0．05）。结论益坤宁通过提高围绝经期大鼠下丘脑组织中ERα、ERβ蛋白表达水平,使ER的合成增加,从而提高雌激素靶组织中ER的含量以增强雌激素的生物活性而发挥治疗作用。     

雌激素β受体的基因多态性可能与帕金森病的发病年龄有关

雌激素通过拮抗细胞凋亡、氧化应激和神经营养等方式对中脑多巴胺能神经元产生影响 ,从而能预防或延迟帕金森病 (PD)的发生、缓解PD的症状 ,其机制至今尚不清楚。研究发现 ,黑质纹状体的多巴胺能神经元主要表达雌激素 β受体 (ER β) ,而雌激素α受体的表达很低甚至缺如 ,提示E     

雌激素在肠易激综合征内脏高敏感性机制中作用的研究进展

肠易激综合征(irritable bowel syndrome,IBS)是一种以慢性腹部疼痛和排便习惯改变为特征的功能性胃肠病,女性多发,发病率随年龄增加逐渐降低,绝经期雌激素替代治疗又加重了肠易激综合征的发病率,提示这种性别差异与雌激素水平有关。目前内脏高敏感性机制被认为是IBS的特征性病理生理学基础,雌激素影响内脏高敏感性的机制还不清楚。研究表明,雌激素可以通过脊髓-中枢途径和自主神经途径影响内脏感觉,雌激素影响迷走神经功能可能是内脏高敏感性的机制之一。本文综述近年来有关雌激素与内脏高敏感性之关系的研究。     

软体动物基因改写性激素进化史

进化生物学家已发现加利福尼亚海兔,一种科学名字为Aplysiacalifornia的软体动物,含有一种蛋白质相似于人体中对雌激素以及其他甾体激素有反应的蛋白质.这一令人惊喜的发现提示,雌激素是这类激素中第一个发生进化的激素,而雌激素信号系统开始发生的年代可追溯到6亿年前.与过去概念相反的是,雌激素系统显然是在无脊椎动物(例如软体动物与昆虫)与脊椎动物(例如鱼类与哺乳动物)进化路程分叉之前开始产生的.该激素结合蛋白称为甾体激素受体,它以未在脊椎动物之外的动物中发现过.大家都认为,甾体激素受体是在脊椎动物谱系深层的某处出现的.雌激…     

益坤宁对围绝经期大鼠卵巢bcl-2和bax表达的影响

目的:研究中药益坤宁(Yikunning,YKN)对围绝经期大鼠卵巢bcl-2和bax基因表达的影响,探讨益坤宁治疗围绝经期综合征的作用机制。方法:选用自然衰老的围绝经期雌性大鼠,随机分为3组(n=10):围绝经期对照组、利维爱(Livial)对照组和益坤宁组,另选10只青年雌性大鼠作为青年对照组。连续灌胃处理4周后,采用逆转录-聚合酶链反应(RT-PCR)检测大鼠卵巢中凋亡相关基因bcl-2和baxmRNA表达,采用蛋白印迹(Westernblot)检测大鼠卵巢中Bcl-2和Bax蛋白表达。结果:益坤宁组大鼠卵巢中Bcl-2、BaxmRNA及其蛋白表达高于围绝经期对照组,差异有统计学意义(P0.01);益坤宁组大鼠卵巢中Bcl-2/BaxmRNA比值和蛋白比值高于围绝经期对照组,差异有统计学意义(P0.05或P0.01)。结论:中药益坤宁通过上调围绝经期大鼠卵巢中凋亡相关基因bcl-2和bax的表达,上调Bcl-2/BaxmRNA比值和蛋白比值,从而延缓卵巢衰老,这可能是其治疗围绝经期综合征的分子机制之一。     

Comparison of hormonal activity (estrogen,androgen and progestin) of standardized plant extracts for large scale use in hormone replacement therapy

Extracts from red clover (Trifolium pratense), soybean (Glycine max.) and black cohosh (Cimicifuga racemosa) are frequently used as alternative compounds for hormone replacement therapy (HRT) to treat menopausal disorders. Fifteen commercially available products made either from red clover, soybean or black cohosh were tested in in vitro assays in this study. The main polycyclic phenolic compounds of soy and red clover products were biochanin A, genistein, daidzein, formononetin, and glycitein. In red clover products glycitein was not abundant. All the compounds showed clear estrogenic activity through estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta) and affinity to progesterone receptor (PR) and androgen receptor (AR), whereas the compounds from black cohosh did not. This was corroborated by synthetic isoflavones such as biochanin A, daidzein, genistein and formononetin. They exerted affinity to PR and AR in the range of 0.39-110 mM. Statistical analysis applying principal component analysis (PCA) revealed that all red clover and soy products are grouped in different clusters. Red clover products showed a higher affinity to AR and PR than soy products, which is explained by the higher amount of isoflavones present. In vitro assays and chemical analysis showed that theoretical estrogenic activity expressed as equivalent E2 concentration is in the same range as recommended for synthetic estrogens. Broader spectrum of action and hypothesized lower side effects by action through ERbeta make them suitable for alternative hormone replacement therapy.     

Muscle damage induced by black cohosh (Cimicifuga racemosa)

Extracts of black cohosh (Cimicifuga racemosa) are commonly used for the treatment of symptoms associated with menopause. Adverse events with black cohosh are rare, mild and reversible. A few number of serious adverse events, including hepatic and circulatory conditions, have been also reported, but without a clear causality relationship. We report the case of a woman with severe asthenia and very high blood levels of creatine phosphokinase and lactate dehydrogenase. The patient referred to take a dietary supplement derived from black cohosh for ameliorating menopause vasomotor symptoms. To exclude a possible involvement of this product, the patient was suggested to discontinue this therapy. After suspicion the patient showed a progressive normalization of biochemical parameters and improvement of clinical symptoms. We can hypothesise a causative role for black cohosh in the muscle damage observed in this patient. Factors suggesting an association between black cohosh and the observed myopathy included the temporal relationship between use of herbal product and asthenia and the absence of other identified causative factors. Rechallenge with the suspected agent was inadvisable for ethic reasons because of the risk of a serious relapse. This is the first time that asthenia associated with high muscle enzymes serum levels by black cohosh has been reported. In our opinion, this report is of interest because of the widespread diffusion of use of black cohosh as an alternative medicine for relief from menopausal symptoms.     

Analysis of thirteen populations of black cohosh for formononetin.

Black cohosh (Actaea racemosa L. syn. Cimicifuga racemosa (L.) Nutt.), a North American perennial plant, is a promising natural alternative to hormone replacement therapy for treating menopausal symptoms, but the mechanism of action is not understood. The clinical actions of this plant have been attributed to the isoflavonone formononetin since 1985, when its presence was reported in a black cohosh extract. Others have since looked for formononetin, but have not detected it. We looked for formononetin in extracts of black cohosh roots and rhizomes collected in thirteen locations in the eastern United States, including Maryland, New Jersey, New York, North Carolina, Pennsylvania, Virginia, and Tennessee. The rhizome samples were extracted using 80% methanol, and the extracts were partially purified using solid-phase extraction to concentrate any isoflavonoids that might be present. We tested for formononetin in these partially purified samples using thin-layer chromatography and high-performance liquid chromatography with a photodiode array detector and a mass spectrometer. Formononetin was not detected in any of the thirteen plant populations examined. Remifemin, a German product now on the United States market, and CimiPure, a commercially available black cohosh rhizome extract, were also analyzed. We did not detect formononetin, or ononin (formononetin-7-glucoside), in any sample tested by the above-mentioned chemical analyses. Therefore, the clinically observed estrogen-like actions of black cohosh, such as reduction of hot flashes, are likely due to a compound, or combination of compounds, other than formononetin.     

Phytochemical fingerprinting to thwart black cohosh adulteration: a 15 Actaea species analysis

Introduction – The popular use of black cohosh products (Actaea racemosa L., syn. Cimicifuga racemosa L.) is growing as the demand for alternatives to estrogen therapy has increased. Critical to safe use is the assurance of unadulterated, high‐quality products. Questions have been raised about the safety of black cohosh due to cases of liver toxicity in patients who reported taking it; subsequent evaluation found some products to be adulterated with other related herbal species. Correct plant species identification is a key first step for good manufacturing practices of safe black cohosh products. Objectives – To develop analytical methods which distinguish black cohosh from other species (American and Asian) of Actaea increasingly found as adulterants in commercially available black cohosh products. Material and methods – Fifteen species of Actaea were collected from North America and Asia, and the phytochemical fingerprints of these samples were established using HPLC‐PDA and LC‐MS techniques. Results – The HPLC and LC‐MS fingerprints for polyphenols and triterpene glycosides revealed distinct patterns that make black cohosh clearly distinguishable from most other species of Actaea. Two marker compounds, cimifugin and cimiracemoside F, were found to be important to distinguish black cohosh from most Asian species of Actaea. Formononetin was not found from either Asian or American species of Actaea. Conclusions – Phytochemical fingerprinting is a practical, reliable method for authenticating black cohosh and distinguishing it from other species of Actaea increasingly found as adulterants in commercially available black cohosh products. This should facilitate the continued development of high‐quality, unadulterated black cohosh products. Copyright © 2011 John Wiley & Sons, Ltd.     

Analysis of formononetin from black cohosh (Actaea racemosa)

Black cohosh has been widely used as an herbal medicine for the treatment of symptoms related to menopause in America and Europe during the past several decades, but the bioactive constituents are still unknown. Formononetin is an isoflavone with known estrogen-like activity. This compound was first reported to be isolated from black cohosh in 1985, but subsequent research in 2002 using HPLC-PDA and LC-MS revealed no evidence to show the presence of formononetin in 13 populations of American black cohosh. A more recent report published in 2004 claimed to detect formononetin in an extract of black cohosh rhizomes using a TLC-fluorescent densitometry method. To further resolve these conflicting reports, we analyzed black cohosh roots and rhizomes for the presence of formononetin, using a combined TLC, HPLC-PDA and LC-MS method. We examined both methanolic and aqueous methanolic black cohosh extracts by HPLC-PDA and LC-MS methods, and did not detect formononetin in any extracts. We further determined the limits of detection of formononetin by HPLC-PDA and LC-MS. Our experimental results indicated that the sensitivity and accuracy of the HPLC-PDA and LC-MS methods for the analysis of formononetin were slightly higher than those of the reported fluorescent method, suggesting that the HPLC-PDA and LC-MS methods were reliable for the analysis of formononetin from black cohosh. We also repeated the reported TLC method to concentrate two fractions from a modern black cohosh sample and an 86-year-old black cohosh sample, respectively, and then analyzed these two fractions for formononetin using the HPLC-PDA and LC-MS method instead of the fluorescent method. Formononetin was not detected by HPLC-PDA or LC-MS. From the results of the present study it is not reasonable to attribute the estrogen-like activity of black cohosh extracts to formononetin.     

Actaea racemosa L. extract inhibits steroid sulfation in human breast cancer cells: Effects on androgen formation

BackgroundActaea racemosa L., also known as black cohosh, is a popular herb commonly used for the treatment of menopausal symptoms. Because of its purported estrogenic activity, black cohosh root extract (BCE) may trigger breast cancer growth.Study design/methodsThe potential effects of standardized BCE and its main constituent actein on cellular growth rates and steroid hormone metabolism were investigated in estrogen receptor alpha positive (ERα+) MCF-7 and -negative (ERα-) MDA-MB-231 human breast cancer cells. Cell numbers were determined following incubation of both cell lines with the steroid hormone precursors dehydroepiandrosterone (DHEA) and estrone (E1) for 48 h, in the presence and absence of BCE or actein. Using a validated liquid chromatography-high resolution mass spectrometry assay, cell culture supernatants were simultaneously analyzed for the ten main steroids of the estrogen pathway.ResultsInhibition of MCF-7 and MDA-MB-231 cell growth (up to 36.9%) was observed following treatment with BCE (1-25 µg/ml) or actein (1-50 µM). Incubation of MCF-7, but not of MDA-MB-231 cells, with DHEA and BCE caused a 20.9% reduction in DHEA-3-O-sulfate (DHEA-S) formation, leading to a concomitant increase in the androgens 4-androstene-3,17-dione (AD) and testosterone (T). Actein was shown to exert an even stronger inhibitory effect on DHEA-S formation in MCF-7 cells (up to 89.6%) and consequently resulted in 12- to 15-fold higher androgen levels compared with BCE. The formation of 17β-estradiol (E2) and its glucuronidated and sulfated metabolites was not affected by BCE or actein after incubation with the estrogen precursor estrone (E1) in either cell line.ConclusionsThe results of the present study demonstrated that actein and BCE do not promote breast cancer cell growth or influence estrogen levels. However, androgen formation was strongly stimulated by BCE and actein, which may contribute to their ameliorating effects on menopausal symptoms in women. Future studies monitoring the levels of AD and T upon BCE supplementation of patients are warranted to verify an association between BCE and endogenous androgen metabolism.     

哈尔滨地区围绝经期女性健康现状及保健需求分析

目的:了解哈尔滨地区围绝经期女性健康现状及对相关保健知识认知现状。方法:采用分层整群抽样,于2011年从哈尔滨18个区、县随机抽取40～65岁围绝经期女性进行调查。结果:①2520例被调查女性平均年龄49.90岁,其中自然绝经者占37.4%,平均绝经年龄49.49岁。②13项症状的发病率从18.5%～59.1%不等,最常见的前五位症状依次为心悸(59.1%)、疲乏无力(53.4%)、骨关节肌肉痛(50.1%)、性交痛及阴道发干(49.0%)、易激动(48.8%)。Kupperman评分总分≥17分653例,占25.9%。围绝经期综合征随年龄增长逐渐加重,经Logistic回归分析其患病率与教育程度、绝经分期有相关性。③30.3%女性表示"听说过性激素替代治疗",且郊区明显低于城区;使用率仅为1.3%。结论:哈尔滨地区女性围绝经期症状患病率较高,其保健知识有待提高。应依托社区和媒体,加大宣传力度,提高围绝经期女性生活质量。     

Effect of Cynomorium total flavone on depression model of perimenopausal rat

PurposeTo observe the effect of cynomorium total flavone on the depression model of perimenopausal rat and to analyze the action characteristics of cynomorium total flavone on depression of rat with perimenopausal syndrome.MethodDuplicate the model of rat with perimenopausal depression based on the combined method of incomplete castration and chronic stimulation, and keep drug administration for 35d. And then measure related behavior indicators and the change of biochemical index level in serum and brains; measure the estrogen/androgen receptor (ER/AR) in related tissues and the ERmRNA expression in hypothalamus.ResultIt can be seen that cynomorium total flavone can significantly improve the behavior indicators of rat with perimenopausal depression; obviously or significantly change the level of related biomedical indexes in serum and brains of perimenopausal depressed rat; obviously or significantly increase the expression of ER/AR in related tissues of perimenopausal depressed rat; obviously or significantly increase the ERmRNA expression in hypothalamus.ConclusionCynomorium total flavone can adjust hypothalamic-pituitary-gonadal axis by increasing E2, and make related biomedical indexes and hormone receptors tend to be normal, so as to relieve perimenopausal syndrome and perimenopausal syndrome with depression.     

Role of estrogen receptor-alpha in pharmacogenetics of estrogen action

PURPOSE OF REVIEW: To summarize recent data regarding the role of estrogen receptor-alpha polymorphisms in determining the response to estrogen therapy or the risk of clinical cardiovascular events. RECENT FINDINGS: Recent clinical trials of hormone replacement therapy for cardiovascular disease have yielded surprisingly negative results, shifting clinical opinions from a position of presumed cardiovascular benefit to one of confirmed harm. Understanding why hormone replacement therapy has beneficial effects on intermediate risk markers for cardiovascular disease, but produces an increase in cardiovascular events, is an important public health question with the potential to elucidate fundamentally important aspects on atherogenesis, cardiovascular disease, and the biology of estrogen action. One question concerning the cardiovascular effects of hormone replacement therapy is whether genetic factors can substantially modify individual responses to estrogen treatment. New clinical trial evidence is emerging that links the presence of particular variants in the estrogen receptor to the response of HDL and other intermediate endpoints to hormone replacement therapy. SUMMARY: One or more common variants in estrogen receptor-alpha are associated with a differential response to hormone replacement therapy in several domains of estrogen action. However, the effect of these variants on the risk of clinical cardiovascular events in the setting of hormone replacement therapy is not yet known. Additional research focusing on the clinical impact of common variants in estrogen receptor-alpha, estrogen receptor-beta and the progesterone receptor promise to improve clinical decision-making concerning the use of hormone replacement therapy and other novel estrogen agonists.