同型半胱氨酸在多囊卵巢综合征中的研究进展

多囊卵巢综合征(PCOS)是女性常见的内分泌疾病,主要以排卵障碍、卵巢呈多囊样改变和高雄激素血症为特征。同型半胱氨酸(Hcy)是在蛋氨酸循环期间形成的含硫氨基酸,最新发现高同型半胱氨酸血症(HHcy)与PCOS密切相关,影响着PCOS的卵母细胞质量、高雄激素血症、胰岛素抵抗(IR)和高胰岛素血症,并且是其远期并发症如不良妊娠结局、心血管疾病、妊娠糖尿病的潜在危险因素。本文综述近年Hcy与PCOS的相关研究,旨在为PCOS临床诊断和治疗提供新的依据。     

性激素结合球蛋白在多囊卵巢综合征中的研究进展

多囊卵巢综合征(PCOS)是女性常见的内分泌疾病,主要以排卵障碍,卵巢呈多囊样改变和高雄激素血症为特征。性激素结合球蛋白(SHBG)主要作用是结合睾酮和雌激素,调节性激素在血中的浓度。本文对SHBG基因表达水平与PCOS,SHBG水平和胰岛素抵抗(IR)、高雄激素血症、2型糖尿病、代谢综合征(MS)、妊娠糖尿病、乳腺癌和子宫内膜癌等远期并发症的相关性进行综述,以期为PCOS的诊断提供一定参考,为临床治疗提供指导。     

减重手术治疗多囊卵巢综合征的研究进展

多囊卵巢综合征（ polycystic ovary syndrome , PCOS）是育龄期妇女常见的一种内分泌代谢异常性疾病,以慢性无排卵、高雄激素血症和卵巢多囊样改变为主要特征。 PCOS 患病率为5％～10％［1］。PCOS存在胰岛素抵抗（ homeostatic model assessment for insulin resistance,HOMA-IR）、高雄激素血症、高泌乳素血症、肥胖等代谢异常。虽然目前有针对不同情况的PCOS的内分泌药物治疗方法,但药物治疗对PCOS的肥胖效果不佳［2］,且存在症状反复的可能性。同时肥胖的远期并发症也将严重威胁患者的健康,因此,减轻体重对PCOS患者的治疗十分重要。但实际上很多患者依靠运动、节食等方法减重效果十分有限,因此,探讨手术减重对PCOS具有十分重要的意义。本文对减重手术治疗PCOS的代谢效果及可能机制进行综述。     

多囊卵巢综合征与高同型半胱氨酸血症相关性的研究进展

多囊卵巢综合征(polycystic ovary syndrome,PCOS)是一组以内分泌代谢紊乱为主的综合征,临床表现主要包括月经稀发、排卵障碍、高雄激素血症以及卵巢多囊样改变。PCOS患者发生2型糖尿病、动脉硬化以及心血管疾病的风险增加,这主要和PCOS患者体内各种因素导致的胰岛素代谢紊乱和血管内皮系统损伤有关。同型半胱氨酸(homocysteine,HCY)作为血管内皮损伤的标志之一,是心血管疾病发病的独立危险因素,PCOS患者往往伴有高同型半胱氨酸血症(hyperhomocysteinemia,HHCY),这可能是导致PCOS患者心血管并发症的重要因素之一。目前PCOS患者体内HCY水平升高的机制尚未完全清楚,现就国内外这方面的研究进展做一综述。     

母体多囊卵巢综合征对子代不同生长发育阶段影响的研究进展

多囊卵巢综合征(PCOS)是育龄期妇女最常见的妇科内分泌疾病之一,对她们的内分泌健康及生殖健康产生了诸多不良影响,如高雄激素血症、胰岛素抵抗、排卵减少或无排卵等,这些均使得母体成功受孕困难.即使受孕成功,她们的子代从胎儿期直至成年后都受到母体PCOS状态的持续影响,如宫内高雄激素介导的胎盘病理状态、继发的胎儿生长发育异...     

二甲双胍在多囊卵巢综合征的作用

生殖及代谢异常是多囊卵巢综合征(PCOS)的特征性表现。已证实高胰岛素血症及胰岛素抵抗,导致血中雄激素水平过高,是PCOS的重要发病机制。二甲双胍(metformin)称为胰岛素增敏剂,用于治疗PCOS后,可减轻高雄激素血症,使月经周期规律,改善卵巢对诱导排卵的反应,提高妊娠率,降低早孕流产率,且能减低发展为II型糖尿病及心血管疾病的危险性。本文就国外近年有关metformin运用于PCOS的进展作一综述。     

多囊卵巢综合征

在鹿特丹ESHRE/ASRM主办的多囊卵巢综合征 (PCOS)协调会上 ,专家们同意 ,如果妇女有下列三项中的两项即可诊断PCOS :(1)排卵少或不排卵 ;(2 )有高雄激素血症的临床和生化特征 ;(3)超声检查有多囊性卵巢。PCOS确切的病理生理尚不清楚。常见有促性腺激素紊乱导致不排卵和高雄激素血症。近年来 ,有越来越多的证据显示胰岛素抵抗可能在其中起重要的作用。PCOS可能表现有不同的症状 ,包括月经不规律、闭经、多毛或其他高雄激素血症的多种症状和不育。对PCOS患者的处理取决于存在的症状和对生育的要求。有月经不规律的妇女应采用复合口服避孕药或孕激素治疗。合并不育 ,应考虑诱导排卵。如果肥胖 ,应建议减肥。部分妇女在成功减肥后会有排卵 ,减肥也将使诱导排卵药物更为有效。PCOS中诱导排卵的一线药物为克罗米酚 ;如果克罗米酚不能诱导排卵 ,可试用胰岛素增敏剂如二甲双胍加克罗米酚 ;再不排卵 ,应当使用人促性腺激素。PCOS患者通常对促性腺激素非常敏感 ,卵巢过度刺激综合征和多胎妊娠的危险性高。在对克罗米酚无反应的妇女中 ,腹腔镜下卵巢打孔也是有效的。对主要表现多毛 ,有多种药物可以应用如环丙孕酮和安体舒通。有关PCOS长期患者可能合并内膜癌、糖尿病、高血压和心血管疾病的危险。采用适当的方法和     

AMH在多囊卵巢综合征中的研究进展

多囊卵巢综合征(PCOS)是一种常见的妇科内分泌、代谢紊乱性疾病,同时也是一种生殖障碍性疾病,严重危害女性身心健康,但是其具体发病机制目前仍不明确。越来越多的研究证明,抗苗勒氏管激素(AMH)与卵泡生长发育、卵泡募集与成熟、高雄激素血症、胰岛素抵抗等均具有密切关系,在PCOS的发生发展过程中也具有重要调节作用。因此,本文结合AMH与PCOS的最新研究进行综述,以期探讨二者关系及其潜在发病机制,为PCOS的诊治提供新的思路。     

多囊卵巢综合征与复发性流产的研究进展

复发性流产(RSA)的发生与多种因素相关,包括年龄、遗传、内分泌与代谢障碍、免疫因素、子宫发育异常、血栓形成倾向、感染、精液质量和生活方式等。多囊卵巢综合征(PCOS)是一种以持续性无排卵、多卵泡不成熟、雄激素水平升高和胰岛素抵抗为主要特征的生殖功能障碍与糖代谢异常并存的内分泌紊乱综合征。PCOS患者RSA的发生率明显高于普通人群,30%~40%的PCOS患者存在自然流产史。目前,PCOS患者易发生RSA的具体发病机制尚不明确,可能与高黄体生成素血症、高雄激素血症、胰岛素抵抗、肥胖、高泌乳素血症、黄体功能不全、血栓形成等有关。本文从上述方面对PCOS患者发生RSA的常见原因及其预防进行综述。     

多囊卵巢综合征患者胰岛素受体基因外显子17多态性的研究

目的探讨胰岛素受体（INSR）基因外显子17多态性与多囊卵巢综合征（PCOS）发病的关系。方法应用聚合酶链反应限制性内切酶片段长度多态性分析（PCR—RFLP）法对中国汉族96例PCOS患者和56例对照者INRS基因外显子17第1,058位点的多态性进行检测,分析并比较INRS基因外显子17第1,058位点T、C等位基因频率与PCOS胰岛素抵抗、高雄激素血症之间的关系。结果（1）PCOS患者INSR基因外显子17第1,058位点T等位基因出现频率为41．7％,明显高于正常对照组的14．3％（P〈0.05）。（2）PCOS患者出现T等位基因者的体重指数（BMI）明显低于出现C等位基因患者（P〈0.05）。（3）PCOS胰岛素抵抗组与非胰岛素抵抗组T、C等位基因出现频率无统计学差异（P〉0．05）。（4）PCOS高雄激素组与无高雄激素组INSR基因T、C等位基因频率无统计学差异（P〉0．05）。结论INSR基因17外显子C／T单核酸多态性与PCOS患者肥胖密切相关,与PCOS的高雄激素血症、胰岛素抵抗（IR）无明显关系。认为INSR基因第17外显子C／T单核酸多态性仅系PCOS的一个易感基因,对PCOS的发病无决定性作用。     

雄激素对卵泡发育影响的双重性

卵泡生长发育受到内分泌、旁分泌和自分泌等因素的严格调控,其中雄激素在卵泡的募集和发育中起重要作用.但是雄激素对卵泡发育的影响犹如一把双刃剑,其作用是双重的.低剂量的雄激素可以促进卵泡的启动募集使得更多卵泡从储备池进入生长发育池,并作用于窦前卵泡和小窦卵泡上的雄激素受体促进卵泡膜间质细胞和颗粒细胞增生,减少卵泡的凋亡和闭锁.如果雄激素水平过高则会起相反的作用,在一些高雄激素疾病如多囊卵巢综合征中,过高的雄激素会抑制卵泡的选择性生长,诱导卵泡发生凋亡和闭锁,最终导致排卵功能障碍.     

Reappraisal of the concept of hormone therapy in metastatic prostate cancer and implications for treatment

Almost all prostate cancer patients become resistant to hormonal therapy that blocks androgen-mediated cell proliferation. The key to this resistance may lie in expression of the androgen receptor itself. Alternative methods to block the AR-mediated signaling pathways appear to be critical for tumor survival. These signal transduction pathways that interact with AR may enhance the response to androgen ablation therapy. The identification of signaling pathways may be a major goal in the treatment of prostate cancer. The application of novel therapies must be preceded by the identification of the genetic and molecular tumor profiles for each patient.     

Development of polycystic ovary syndrome: involvement of genetic and environmental factors

We have recently proposed that polycystic ovary syndrome (PCOS) has its origin in fetal life. This hypothesis is based on data from animal models (rhesus monkey or sheep that have been exposed prenatally to high doses of androgen) and is supported by clinical studies. It is suggested that, in human females, exposure to excess androgen, at any stage from fetal development of the ovary to the onset of puberty, leads to many of the characteristic features of PCOS, including abnormalities of luteinizing hormone secretion and insulin resistance. It is likely that, in humans with PCOS, the development of the PCOS phenotype results primarily from a genetic predisposition for the fetal ovary to hypersecrete androgen. At present, it is unclear whether the maternal environment directly influences the development of PCOS in the offspring. Maternal androgen excess is unlikely to affect the fetus, because the placenta presents an effective barrier, but metabolic disturbances during pregnancy could affect development of the syndrome in the fetus. In postnatal life, the natural history of PCOS can be further modified by factors affecting insulin secretion and/or action, most importantly, nutrition. We now have evidence for a disorder of early follicular development in the polycystic ovary that is consistent with an increased population of primordial follicles in the fetal ovary. It remains to be determined whether this phenomenon is the cause or the effect of increased exposure to androgen within the ovary. PCOS is the commonest endocrine disorder in women. It is not only a very prevalent cause of anovulatory infertility, menstrual disturbances and hirsutism, but it is also a major risk factor for the development of type 2 diabetes mellitus in later life. The aetiology of the syndrome remains uncertain but there is increasing evidence for a genetic basis. PCOS very often becomes clinically manifest during adolescence with maturation of the hypothalamic-pituitary-ovarian axis but the genesis of the syndrome may be during very early development - perhaps even in utero. In this review, this hypothesis is explored in the light of clinical, biochemical and genetic research.     

基于超高液相色谱-四级杆飞行时间质谱联用技术筛选多囊卵巢综合征患者卵泡液生物标志物

目的分析多囊卵巢综合征(PCOS)患者卵泡液代谢组差异,找寻相关生物学标志物,探讨相关代谢通路变化。方法利用超高液相色谱-四级杆飞行时间质谱联用技术(UHPLC-QTOFMS)对PCOS患者(n=7)及对照组(n=6)的卵泡液进行代谢组学分析。结果PCOS组和对照组组间代谢物分布具有差异性,共计有60种差异代谢物,其中有20种代谢物水平下降(P<0.05),40种代谢物水平增加(P<0.05),主要有氨基酸类、脂肪酸类、有机化合物、有机氧化合物等。其中24种物质为脂质类物质,9种物质为氨基酸类。此外,血清睾酮水平与脯氨酸及多种脂肪酸(包括5-羟色胺、PS(22∶0/18∶4(6Z,9Z,12Z,15Z)))、PC(P-18∶0/22∶4(7Z,10Z,13Z,16Z))、PC(15∶0/20∶2(11Z,14Z))、24-Epibrassinolide、LysoPI(18:0/0:0)具有相关性(P<0.05)。结论本研究鉴定出了60种差异代谢物,其中有1种氨基酸、5种脂肪酸与睾酮水平呈正相关;分析了在PCOS中可能发挥重要作用的2种代谢通路:性激素合成代谢和嘧啶代谢通路,可为今后PCOS的治疗、诊断提供一定的依据和治疗靶点参考。     

多囊卵巢综合征患者卵巢黄素化颗粒细胞瘦素信号转导分子STAT3磷酸化表达的研究

目的检测多囊卵巢综合征(PCOS)患者卵巢黄素化颗粒细胞瘦素信号转导子和活化子STAT3磷酸化(p-STAT3)水平,并观察瘦素体外对培养卵巢黄素化颗粒细胞p-STAT3水平的影响,探讨瘦素在PCOS发病机制中的作用。方法选择行体外受精-胚胎移植(IVF-ET)治疗的肥胖型PCOS患者(肥胖PCOS组)、非肥胖型PCOS患者(非肥胖PCOS组)、排卵功能正常和单纯输卵管因素不育的肥胖(肥胖对照组)及正常体重妇女(正常对照组)各15例。采用免疫印迹技术检测卵巢黄素化颗粒细胞p-STAT3水平。同时将正常人卵巢黄素化颗粒细胞行体外培养,分别加入不同浓度的瘦素(0、10、100、1,000 ng/ml)培养48 h,观察瘦素体外对人卵巢黄素化颗粒细胞p-STAT3水平的影响。结果(1)肥胖型PCOS组、肥胖对照组、非肥胖PCOS组和正常对照组卵巢黄素化颗粒细胞p-STAT3水平分别为(24.28±0.51)、(21.31±1.32)、(11.69±0.67)、(9.03±0.20),实验组间比较有显著性差异(P<0.05),其中肥胖型PCOS组p-STAT3表达水平最高,其次依次为肥胖对照组、非肥胖PCOS组和正常对照组。各组之间两两比较,均有显著性差异(P<0.05)。(2)加入瘦素培养48 h后,卵巢黄素化颗粒细胞p-STAT3水平随瘦素浓度升高而增高,呈浓度依赖性,至瘦素浓度达到100 ng/ml时,p-STAT3水平达到高峰,随后呈下降趋势。结论瘦素通过介导JAK2/STAT3信号途径可能参与了肥胖型PCOS的发病机制。     

Role of insulin and insulin resistance in androgen excess disorders

Insulin has complex effects on cell growth, metabolism and differentiation, and these effects are mediated by a cell-surface bound receptor and eventually a cascade of intracellular signaling events. Among the several metabolic and growth-promoting effects of insulin, insulin resistance is defined as an attenuated effect of insulin on glucose metabolism, primarily the limited export of blood glucose into skeletal muscle and adipose tissue. On the other hand, not all the signaling pathways and insulin-responsive tissues are equally affected, and some effects other than the metabolic actions of insulin are overexpressed. Ovaries and the adrenal glands are two examples of tissues remaining sensitive to insulin actions where insulin may contribute to increased androgen secretion. Polycystic ovary syndrome (PCOS) is the most common form of androgen excess disorder (AED), and its pathogenesis is closely associated with insulin resistance. Patients with idiopathic hirsutism also exhibit insulin resistance, albeit lower than patients with PCOS. Although it is not as evident as in PCOS, patients with congenital adrenal hyperplasia may have insulin resistance, which may be further exacerbated with glucocorticoid overtreatment and obesity. Among patients with severe insulin resistance syndromes, irrespective of the type of disease, hyperinsulinemia promotes ovarian androgen synthesis independently of gonadotropins. It is highly debated in whom and how insulin resistance should be diagnosed and treated among patients with AEDs, including PCOS. It is not suitable to administer an insulin sensitizer relying on only some mathematical models used for estimating insulin resistance. Instead, the treatment decision should be based on the constellation of the signs, symptoms and presence of obesity; acanthosis nigricans; and some laboratory abnormalities such as impaired glucose tolerance and impaired fasting glucose.     

An investigation of acarbose effects in PCOS women with postprandial hyperglycemia

<正> Objectives:To investigate the effects of insulin resistance on serum androgen leveland ovulation of women with polycystic ovary syndrome (PCOS) and observe clinic roleof acarbose in the treatment of hyperinsulinemia,postprandial hyperglycemia andanovulation.Methods:14 women accompanied by postprandial hyperglycemia with PCOS wereadministrated by acarbose for 12 weeks.14 age-matched individuals who had similarbody mass index and normal menstruation were served as controls.Results:Serum T levels declined significantly from 4.09±1.04 nmol/L to 1.71±0.54 nmol/L(P<0.001),after acarbose treatment for 12 weeks.12 out of 14 cases re-stored ovulation and menstrual cycles after acarbose treatment,among which 4 gotpregnant.Conclusion.Acarbose may play a role on reducing postprandial hyperglycemia andHbAic levels,increase ISI and FSG/FI,indirectly reduce serum androgen levels throughreducing plasma insulin level and recover ovarian ovulation in PCOS women with postprandial hyperglycemia.