多囊卵巢综合征胰岛素抵抗新进展

多囊卵巢综合征(PCOS)是一种常见的影响育龄期女性生殖和内分泌功能的特殊疾病,其临床表现异质性,以慢性无排卵、卵巢多囊样改变、高雄激素血症为主要临床表现.胰岛素抵抗是其发生、发展的重要病理生理机制之一,也是导致高雄激素血症和卵巢功能改变的重要原因.近年来,PCOS患者胰岛素抵抗的分子机制得到深入研究,为临床治疗提供了...     

多囊卵巢综合征高雄激素血症的治疗与研究进展

多囊卵巢综合征(PCOS)是一种高度异质性的临床内分泌疾病,以持续无排卵、高雄激素血症、卵巢多囊样改变为典型特征,常伴有胰岛素抵抗。体内过高水平的雄激素可导致卵泡的发育成熟过程受限,从而影响排卵。高雄激素血症形成原因复杂,其机制目前尚未完全阐明。本文主要从胰岛素、神经、体液调节与高雄激素血症形成的关系,肾上腺、脂肪等组织与高雄激素血症形成的关系,及基因多态性与高雄激素血症形成的关系等进行综述。同时介绍了目前针对PCOS高雄激素血症的治疗方法,包括西药治疗、中药治疗和中西医联合治疗等进展。     

雄激素过多在多囊卵巢综合征发生发展中的作用

目前多囊卵巢综合征(PCOS)的病因仍不十分明确,尚未发现其确切致病基因,不少研究表明雄激素过多与PCOS的发生密切相关,可能是促进其发生发展的重要因素。现普遍认为高雄激素血症是PCOS发病的根本原因之一,表现为特异性症状和并发症。然而,卵巢多小卵泡、不排卵和胰岛素抵抗的生育期妇女雄激素水平较高,使症状与并发症恶化,这就导致高雄激素血症的恶性循环。就高雄激素血症导致PCOS进行综述。     

体重超重对多囊卵巢综合征患者内分泌改变的影响

目的:探讨体重超重对多囊卵巢综合征患者的内分泌改变的影响。方法:检测31例体重超重和102例非超重多囊卵巢综合征患者的内分泌激素和胰岛素敏感性。结果:超重组的雄激素和空腹胰岛素水平显著升高(P<0.05,P<0.01),GIR显著下降(P<0.01),HOMAIR明显升高(P<0.01),超重组胰岛素抵抗的发生率明显高于非超重组,BMI与胰岛素敏感性呈负相关。结论:体重超重的PCOS患者高雄激素血症和胰岛素抵抗都更为严重,对超重PCOS患者的治疗应注重于纠正高雄激素血症和胰岛素抵抗状态。     

多囊卵巢综合征患者胰岛素抵抗/高胰岛素血症与子宫内膜癌

多囊卵巢综合征(polycystic ovarian syndrome,PCOS)是以排卵稀发、无排卵,高雄激素血症及胰岛素抵抗为特征的内分泌、代谢紊乱症候群。胰岛素抵抗及其伴随的高胰岛素血症是PCOS患者重要的病理生理改变。由于胰岛素具有促进内膜细胞增殖,抑制内膜细胞凋亡,促进胰岛素样生长因子及血管内皮生长因子生成,促进黄体生成素释放激素及促黄体生成素生成及降低体内脂联素水平等作用,可能是PCOS患者罹患内膜癌的危险因素,故对PCOS患者胰岛素抵抗/高胰岛素血症与子宫内膜癌的关系进行探讨。     

ENPP1基因在多囊卵巢综合征发病机制中的研究进展

多囊卵巢综合征（polyeystic ovary syndrome，PCOS）基本的病理生理改变为慢性持续的无排卵和高雄激素血症，其发生发展机制至今尚不清楚。据统计，育龄妇女发病率高达5％～10％。大量的研究证实胰岛素抵抗与PCOS间存在密切关系，且近50％～60％PCOS患者存在胰岛素抵抗，而在普通人群中仅为10％～25％。在PCOS患者中，无论肥胖与否均有不同程度的胰岛素抵抗及高胰岛素血症，胰岛素抵抗可能是PCOS发病的始动因素和中心环节。     

PCOS是卵巢对胰岛素超敏的综合征

多囊卵巢综合征(PCOS)以胰岛素抵抗或高胰岛素血症导致高雄激素血症为主要发病机制。卵巢内胰岛素调节雄激素合成的信号传导途径亢进,即卵巢局部组织对胰岛素作用的敏感性升高。胰岛素可以刺激正常妇女和PCOS妇女卵巢产生雄激素,但在体外PCOS妇女卵巢细胞对胰岛素刺激雄激素合成的反应性更高。多囊卵巢对促性腺激素的刺激敏感性也升高,即卵巢的反应性增强。部分发展为PCOS的妇女是由于卵巢内雄激素合成通路选择性的和特异性地对胰岛素敏感性增强引起的。因此,卵巢内部雄激素合成对胰岛素信号通路的过度敏感是一部分多囊卵巢妇女发展为PCOS的病因。     

多囊卵巢综合征病理生理的一些新认识

多囊卵巢综合征（PCOS）是以长期无排卵及高雄激素为特征的内分泌综合征,以不孕、多毛、无排卵、月经不调等为主要临床表现。PCOS超声下卵巢呈明显多囊性改变,并伴促性腺激素分泌异常。雄激素过多合成在PCOS发病中起关键性作用,膜细胞对颗粒细胞反应性增高、垂体分泌促黄体激素增多以及高胰岛素血症可能是卵巢雄激素合成过多的机制。胰岛素抵抗和肥胖的出现则可能使PCOS临床症状加剧。雄激素、胰岛素、促性腺激素和肥胖间的相互作用促成PCOS患者的生殖表型。     

多囊卵巢综合征病理生理的一些新认识

多囊卵巢综合征（PCOS）是以长期无排卵及高雄激素为特征的内分泌综合征,以不孕、多毛、无排卵、月经不调等为主要临床表现。PCOS超声下卵巢呈明显多囊性改变,并伴促性腺激素分泌异常。雄激素过多合成在PCOS发病中起关键性作用,膜细胞对颗粒细胞反应性增高、垂体分泌促黄体激素增多以及高胰岛素血症可能是卵巢雄激素合成过多的机制。胰岛素抵抗和肥胖的出现则可能使PCOS临床症状加剧。雄激素、胰岛素、促性腺激素和肥胖间的相互作用促成PCOS患者的生殖表型。     

二甲双胍对多囊卵巢综合征患者子宫内膜葡萄糖转运蛋白4表达的影响

多囊卵巢综合征（PCOS）是育龄期妇女最常见的内分泌紊乱性疾病，临床以高雄激素血症、持续无排卵和卵巢多囊样改变为特征，可伴有胰岛素抵抗。高胰岛素血症和胰岛素抵抗被认为是导致PCOS患者糖代谢异常和生殖功能障碍的原因之一。许多研究已发现，在PCOS患者中，胰岛素抵抗在脂肪、肌肉、皮肤、肾上腺与卵巢等组织和靶器官中存在。葡萄糖转运蛋白（GLUT）4作为存在胰岛素依赖的组织中的一种最重要的GLUT，逐渐受到研究者们的重视。Mioni等及Mozzanega等首次证实了GLUT4在PCOS患者子宫内膜的表达，提出子宫内膜局部存在胰岛素抵抗现象。本研究前瞻性地观察了胰岛素增敏剂二甲双胍对PCOS患者子宫内膜GLUT4表达情况的影响，旨在探讨PCOS的发病机制，为寻找合理的药物治疗提供理论依据。     

Altered autophosphorylation of the insulin receptor in the ovary of a woman with polycystic ovary syndrome

OBJECTIVE: To determine whether the tyrosine autophosphorylation of the insulin receptor (IR) in the ovary of a woman with polycystic ovary syndrome (PCOS) was reduced compared to normal. DESIGN: Experimental study. SETTING: Tertiary care medical center. PATIENT(S): One woman with PCOS and one healthy control, both of whom underwent a hysterectomy and bilateral salpingo-oophorectomy. INTERVENTION(S): Plasma membrane fraction of ovarian tissue was isolated, and the IR was purified and concentrated. MAIN OUTCOME MEASURE(S): Western blots of the IR, which had been incubated with and without insulin, were prepared. Colorimetric and chemiluminescent methods were used to detect the presence of the IR beta-subunit and IR tyrosine autophosphorylation, respectively. RESULT(S): The presence of the beta-subunit of the IR was identified in both ovarian samples. The degree of insulin-stimulated IR tyrosine autophosphorylation, reflected by the mean (+/-SD) relative optical density of the 95 kd band, was 4.3-fold higher in the normal ovary compared to the PCOS ovary (0.56 +/- 0.18 optical density vs. 0.13 +/- 0.10 optical density, respectively). CONCLUSION(S): Tyrosine autophosphorylation of the IR may be decreased in the ovaries of women with PCOS, similar to the findings in other tissues. The mechanisms through which insulin acts to produce an excess in ovarian androgen production in the face of a decrease in ovarian IR autophosphorylation remain to be determined.     

Platelet-derived microparticles in overweight/obese women with the polycystic ovary syndrome

A substantial proportion of women with the polycystic ovary syndrome (PCOS) are obese and obesity is considered as a prothrombotic state. Platelet-derived microparticles (PMPs) might be implicated in the activation of the coagulation cascade. We aimed to assess plasma PMPs in overweight/obese women with PCOS. We measured plasma PMPs and determined anthropometric, metabolic, hormonal and ultrasonographic features of PCOS in 67 overweight/obese women with PCOS (with body mass index [BMI] >25.0 kg/m²) and in 21 BMI-matched healthy women. Circulating androgens and markers of insulin resistance (IR) were higher in women with PCOS than in controls. Plasma PMPs were also higher in women with PCOS than in controls (p = 0.046). In women with PCOS, plasma PMPs correlated with the mean number of follicles in the ovaries (r = 0.343; p = 0.006). In controls, plasma PMPs did not correlate with any of the studied parameters. In conclusion, plasma PMPs are elevated in overweight/obese women with PCOS compared with BMI-matched controls. The cause of this increase is unclear but both IR and hyperandrogenemia might be implicated. More studies are required to elucidate the pathogenesis of the elevation of PMPs in PCOS and to assess its implications on the cardiovascular risk of these patients.     

多囊卵巢综合征胰岛素抵抗的新进展

多囊卵巢综合征（PCOS）是青春期及育龄妇女最常见的内分泌和代谢紊乱性疾病,其发病率占育龄妇女的5%～10%。PCOS的基本特征为长期不排卵或稀发排卵、卵巢多囊性增大和高雄激素血症等,此外还表现有胰岛素抵抗（IR）及胰岛β细胞功能失调。PCOS患者妊娠率降低,妊娠期自然流产、妊娠期糖尿病的患病率亦较普通人群高,同时子宫内膜癌发病风险增高。PCOS患者代谢综合征的发病率升高,后者与心血管疾病风险紧密相连,并与IR有密切关系。目前许多学者对PCOS患者的IR做了大量的研究,提示改善PCOS的IR可改善内分泌及生殖功能,而改善生活方式是改善患者IR的有效手段。口服降糖药已成为治疗PCOS的IR的有效方法之一。     

Electro-acupuncture reverses nerve growth factor abundance in experimental polycystic ovaries in the rat

Polycystic ovary syndrome (PCOS) remains one of the most common causes of anovulation in women of reproductive age. There is some evidence that nerve growth factor (NGF) is involved in the pathogenesis of PCOS. Therefore, seeking the pathogenesis of PCOS is important for controlling fertility. In traditional Oriental Medicine, acupuncture has been used for the function of ovaries. The present study was designed to determine whether electro-acupuncture (EA) could affect experimentally induced polycystic ovary (PCO) in the rat. The two acupoints Sp-6 and E-128 were stimulated to test for efficacy in the protein expression of NGF. Polycystic ovaries were induced by a single injection of estradiol valerate (4 mg i.m.). During the experimental period of 8 weeks, some of the rats were treated with EA twice weekly; this group was compared with a vehicle-treated control group and an estradiol-injected group not subjected to EA. At day 60, the protein expression of NGF was examined by immunohistochemistry in the ovaries, the adrenal glands and some parts of the brain. The estradiol treatment induced a clear PCO appearance, and was associated with a robust increase in NGF expression in the ovaries, the adrenal glands and the brain. EA treatment partly reversed the NGF abundance, particularly in the ovaries, but not in the brain. Our data show that EA affects the NGF involvement in ovarian dysfunction.     

Polycystic ovary syndrome in adolescence and early adulthood

Polycystic ovaries and the associated syndrome are recognized as the most common cause of endocrine disturbances in adult women, but much less research has been performed to examine how polycystic ovary syndrome (PCOS) presents in girls and young women. Polycystic ovaries have been demonstrated in childhood, and there is evidence to show that even very young women may show symptoms and signs of the associated syndrome. Closer examination of younger populations (less-than-or-eq, slant 25 years of age), and in particular, studies of girls during the transition from puberty into early adulthood (adolescence), may provide new insights into the pathogenesis and natural history of polycystic ovaries and PCOS, and may indicate whether polycystic ovaries could potentially be considered as a marker for health screening. Consideration should be given to the management of girls and young women with polycystic ovaries and PCOS as this group may have different needs and health risks compared with older women.     

Polycystic ovary syndrome in adolescence and early adulthood

Polycystic ovaries and the associated syndrome are recognized as the most common cause of endocrine disturbances in adult women, but much less research has been performed to examine how polycystic ovary syndrome (PCOS) presents in girls and young women. Polycystic ovaries have been demonstrated in childhood, and there is evidence to show that even very young women may show symptoms and signs of the associated syndrome. Closer examination of younger populations (ˇ- 25 years of age), and in particular, studies of girls during the transition from puberty into early adulthood (adolescence), may provide new insights into the pathogenesis and natural history of polycystic ovaries and PCOS, and may indicate whether polycystic ovaries could potentially be considered as a marker for health screening. Consideration should be given to the management of girls and young women with polycystic ovaries and PCOS as this group may have different needs and health risks compared with older women.     

How common is polycystic ovary syndrome in recurrent miscarriage?

The association between polycystic ovary syndrome (PCOS) and recurrent miscarriage (RM) has been long established, but the relative importance of this condition as a cause of RM is far from clear. Previous studies on the prevalence of PCOS in RM have been hampered by a lack of objective and universally accepted criteria for the diagnosis of PCOS, resulting in considerable controversy. However, the Rotterdam criteria have since been accepted as the gold standard for diagnosis of PCOS, and therefore these criteria have been used to produce a much clearer and more objective assessment of the prevalence of PCOS in RM. Three hundred women with recurrent miscarriage were studied. A diagnosis of PCOS was established via measurement of cycle length and day 21 serum progesterone, determination of the free androgen index and pelvic ultrasonography. All ultrasound reports prior to publication of the Rotterdam criteria were reviewed, ensuring consistency in the diagnosis of a polycystic ovary. Ultrasound scans of 27 patients confirmed polycystic ovaries with a further 10 scans suggestive of polycystic ovaries, but with insufficient information for the Rotterdam criteria to be applied. Hence, 27–37 (9.0–12%) patients presented with ultrasonographic polycystic ovaries. Using the Rotterdam criteria, 25–30 (8.3–10%) patients had PCOS. It is concluded that the prevalence of PCOS in RM is considerably lower than has previously been accepted.     

热休克蛋白10、27和47在多囊卵巢综合征患者卵巢中的表达

目的:探索热休克蛋白(heat shock protein,HSP)10、27和47在多囊卵巢综合征(PCOS)患者卵巢组织中的表达及其意义。方法:采用荧光实时定量PCR(SYBR GREEN Iassay)、Western blot和免疫组织化学技术分别对3例正常妇女(对照组)、3例无排卵PCOS患者(PCOS组)卵巢组织的HSP10、HSP27和HSP47的mRNA及蛋白进行测定。结果:①HSP10 mRNA在PCOS患者卵巢组织的表达与对照组相比,差异无显著性(P>0.05);HSP10蛋白在PCOS患者卵巢组织的表达与对照组相比,表达降低,差异有显著性(P<0.05);免疫组化结果显示HSP10表达于对照组卵巢的所有细胞,而在PCOS组仅在卵泡膜细胞表达水平较高。②HSP27 mRNA和蛋白在PCOS患者卵巢组织的表达降低与对照组相比,差异有显著性(P<0.05);免疫组化结果显示HSP27高表达于对照组卵巢原始卵泡的卵母细胞。③HSP47 mRNA和蛋白在PCOS患者卵巢组织的表达高于对照组,PCOS组卵巢,差异有显著性(P<0.05);免疫组化结果显示HSP47高表达于PCOS组卵巢的卵母细胞、颗粒细胞和间质细胞。结论:HSP10、HSP27和HSP47在PCOS患者卵巢和正常人卵巢中存在差异表达。     

Immunohistochemical detection of plasminogen activator inhibitor-1 in polycystic ovaries.

Anovulation in women with polycystic ovary syndrome (PCOS) is incompletely understood. The concentration of the glycoprotein plasminogen activator inhibitor-1 (PAI-1) is raised in insulin resistance. This has been described in the granulosa and theca cell layers of the animal but not the human ovary. This study was performed to investigate the location of PAI-1 in the human ovary and investigate whether it may contribute to anovulation in PCOS. PAI-1 was localized immunohistochemically and quantitated using computer image analysis in 17 ovarian follicles from five women with a diagnosis of PCOS and compared with 15 follicles from six normal ovaries. PAI-1 was predominantly found in the granulosa and theca cells in both polycystic and normal ovaries. Image analysis did not reveal a difference in the PAI-1 signal from polycystic compared with normal ovaries. This study shows that PAI-1 plays a role in human ovulation, but its role in PCOS requires further research.     

多囊卵巢综合征患者胰岛素抵抗和高胰岛素血症的诊治

胰岛素抵抗(IR)是多囊卵巢综合征(PCOS)的重要病理生理改变。IR及高胰岛素血症是PCOS患者代谢异常的基本特征,也是PCOS患者内分泌代谢紊乱的主要特征之一。肥胖型PCOS患者高胰岛素血症发生率高达75％,非肥胖型PCOS患者约为30％ 。流行病学调查显示PCOS患者发生2型糖尿病、高血压、冠心病等疾病的风险明显增加,胰岛素抵抗可能在PCOS的发生 中起着重要作用。生活方式改变和胰岛素增敏剂是治疗的有效方法。