hyperandrogenism

雄激素过多症
  • 文章类型: Journal Article
    多囊卵巢综合征(PCOS)是最常见的内分泌疾病,影响约5%至18%的育龄妇女和3%至11%的青少年。成人患者使用的诊断标准不适合青少年患者的诊断,因为某些特征可能是青春期的生理特征,因此,研究仍在进行中,以改善诊断青少年PCOS的标准。多囊卵巢综合征与激素和代谢变化有关,并可能易患许多其他疾病的发生,比如肥胖,代谢综合征,高血压,2型糖尿病和非酒精性脂肪性肝病(NAFLD)。由于PCOS的高患病率及其带来的各种健康问题,有必要从风险群体中选择青春期女孩,做出有效的诊断,开始适当的治疗,并尽快引导病人改变生活方式。研究人员的注意力越来越集中在已经在青少年时期出现PCOS的患者身上。在我们的工作中,我们想看看关于患病率的最新报告,青春期女孩PCOS的病理生理学和诊断。
    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting approximately 5 to 18% of women of reproductive age and 3 to 11% of teenagers. The diagnostic criteria used in adult patients are not suitable for the diagnosis of adolescent patients, because some of the features may be physiological for puberty, so research is still ongoing to improve the criteria for diagnosing PCOS in teenagers. Polycystic ovary syndrome is associated with hormonal and metabolic changes and may predispose to the occurrence of many other diseases, such as obesity, metabolic syndrome, hypertension, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Due to the high prevalence of PCOS and the various health problems it brings, it is necessary to select adolescent girls from the risk group, make an efficient diagnosis, start appropriate treatment, and lead the patient through a lifestyle change as soon as possible. Researchers\' attention is increasingly focused on patients presenting with PCOS already in their teenage years. In our work, we want to look at the latest reports regarding the prevalence, pathophysiology and diagnosis of PCOS in adolescent girls.
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  • 文章类型: Journal Article
    多囊卵巢综合征(PCOS)是育龄期妇女的一种内分泌代谢紊乱。本研究旨在探讨育龄期PCOS女性不同表型的代谢特征。
    这项横断面研究共招募了442名PCOS患者。根据不同的表型,将所有女性分为三组:慢性排卵功能障碍和高雄激素血症组(OD-HA组,n=138),慢性排卵功能障碍和多囊卵巢形态学组(OD-PCOM组,n=161),和高雄激素血症和多囊卵巢形态学组(HA-PCOM组,n=143)。比较3组患者的代谢危险因素和代谢紊乱患病率。
    体重指数(BMI),腰围,OD-HA组和HA-PCOM组的女性的腰臀比(WHR)明显高于OD-PCOM组的女性(p<0.05)。OD-HA组和HA-PCOM组女性口服葡萄糖粉后2h和3h的血清胰岛素浓度和胰岛素抵抗稳态模型评估(HOMAIR)均明显高于OD-PCOM组(p<0.05)。血清总胆固醇(TC),甘油三酯(TG),OD-HA组和HA-PCOM组女性的低密度脂蛋白胆固醇(LDL-C)明显高于OD-PCOM组女性(p<0.05)。糖耐量受损(IGT)的患病率2型糖尿病(T2DM),胰岛素抵抗(IR),代谢综合征(MS),非酒精性脂肪性肝病(NAFLD),PCOS女性的血脂异常占17.9%,3.6%,58.4%,29.4%,46.6%,和43.4%,分别。IGT的患病率,IR,MS,NAFLD,OD-HA组和HA-PCOM组妇女血脂异常明显高于OD-PCOM组妇女(p<0.05)。T浓度(>1.67nmol/L)和Ferriman-Gallwey(F-G)评分(>3)显著增加PCOS患者代谢紊乱的风险(p<0.05)。
    与OD-PCOM相比,患有PCOS的女性中OD-HA和HA-PCOM的表型易受代谢紊乱的影响。因此,PCOS女性尤其是HA表型女性的代谢紊乱应引起更多关注,以减少长期并发症.
    UNASSIGNED: Polycystic ovary syndrome (PCOS) is an endocrine metabolic disorder in reproductive-aged women. The study was designed to investigate the metabolic characteristics of different phenotypes in women with PCOS of reproductive age.
    UNASSIGNED: A total of 442 women with PCOS were recruited in this cross-sectional study. According to different phenotypes, all women were divided into three groups: the chronic ovulatory dysfunction and hyperandrogenism group (OD-HA group, n = 138), the chronic ovulatory dysfunction and polycystic ovarian morphology group (OD-PCOM group, n = 161), and the hyperandrogenism and polycystic ovarian morphology group (HA-PCOM group, n = 143). The metabolic risk factors and prevalence rates of metabolic disorders among the three groups were compared.
    UNASSIGNED: The body mass index (BMI), waist circumference, and waist-to-hip ratio (WHR) of women from the OD-HA group and HA-PCOM group were significantly higher than those of women from the OD-PCOM group (p < 0.05). The serum insulin concentration and homeostasis model assessment of insulin resistance (HOMA IR) at 2 h and 3 h after oral glucose powder in women from the OD-HA group and HA-PCOM group were significantly higher than those from the OD-PCOM group (p < 0.05). The serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in women from the OD-HA group and HA-PCOM group were significantly higher than those in women from the OD-PCOM group (p < 0.05). The prevalence rates of impaired glucose tolerance (IGT), type 2 diabetes mellitus (T2DM), insulin resistance (IR), metabolic syndrome (MS), nonalcoholic fatty liver disease (NAFLD), and dyslipidemia of women with PCOS were 17.9%, 3.6%, 58.4%, 29.4%, 46.6%, and 43.4%, respectively. The prevalence rates of IGT, IR, MS, NAFLD, and dyslipidemia of women in the OD-HA group and HA-PCOM group were significantly higher than those of women in the OD-PCOM group (p < 0.05). T concentration (>1.67 nmol/L) and Ferriman-Gallwey (F-G) score (>3) significantly increased the risk of metabolic disorders in women with PCOS (p < 0.05).
    UNASSIGNED: The phenotypes of OD-HA and HA-PCOM in women with PCOS were vulnerable to metabolic disorders compared to OD-PCOM. Thus, the metabolic disorders in women with PCOS especially those with the HA phenotype should be paid more attention in order to reduce long-term complications.
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  • 文章类型: Journal Article
    特发性多毛症(IH)是一种常见的临床疾病,具有多种诊断和治疗不确定性。没有明确的诊断和治疗建议。此实践更新旨在指导初级保健医生和专家更好,更系统地管理IH,特别是在印度背景下。十二名经验丰富的成员由杰出的内分泌学家组成,医师,皮肤科医生,糖尿病和内分泌综合学院(IDEA)邀请了一名妇科医生和一名精神科医生.使用PubMed的在线数据库进行了文献检索,科克伦图书馆和谷歌学者。发表来自同行评审索引期刊的文章,偏爱荟萃分析和随机对照试验,被选中。举行了一次会议,所有12名成员分别就预定的感兴趣的问题发表意见。在IDEACON2023的初次会议之后,又举行了两次会议,并在投票后制定了惯例更新。在重要领域进行了实践更新,例如印度人口修改后的Ferriman-Gallwey评分的截止日期,诊断IH前要排除的条件,当提到专家时,对疑似IH病例的调查及其治疗方法的选择。
    Idiopathic hirsutism (IH) is a common clinical condition with multiple diagnostic and therapeutic uncertainties. There are no clear recommendations for the diagnosis and management of the condition. This practice update was developed to guide the primary care physicians and the specialists in better and more systematic management of IH particularly in the Indian context. Twelve experienced members consisting of eminent endocrinologists, physicians, a dermatologist, a gynaecologist and a psychiatrist were invited by the Integrated Diabetes and Endocrine Academy (IDEA). A literature search was performed using online databases from PubMed, Cochrane Library and Google Scholar. Published articles from peer-reviewed indexed journals, with a preference for meta-analyses and randomized controlled trials, were selected. A meeting took place with all the 12 members individually giving their opinions on predetermined questions of interest. After the initial meeting during IDEACON 2023, two more meetings were held and the practice update was formulated after voting. Practice updates were made on important areas such as the cut-off for modified Ferriman-Gallwey Score for the Indian population, conditions to be excluded before diagnosing IH, when to refer to specialists, investigations in a suspected case of IH and choice of therapies for its management.
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  • 文章类型: Journal Article
    多囊卵巢综合征(PCOS)是一种影响许多育龄妇女的内分泌妇科疾病。
    评估葡萄糖样肽-1受体激动剂对PCOS肥胖女性的疗效和安全性。
    我们搜索了PubMed,Embase,WOS,和截至2023年6月的CochraneLibarary数据库。如果是将GLP-1RA与PCOS患者的任何其他治疗方法进行比较的随机对照试验(RCT),则这些研究符合资格。
    总的来说,本综述共纳入8项RCT,7项RCT比较了GLP-1RA与二甲双胍,1个RCT比较了GLP-1Ras与达格列净。与对照组相比,GLP-1RA在改善胰岛素敏感性方面更有效,降低BMI,并导致较小的腰围。
    GLP-1RA对于患有PCOS的肥胖女性可能是一个不错的选择,尤其是那些有胰岛素抵抗的人。然而,未来还需要高质量的研究来评估GLP-1RAs在PCOS女性患者中的疗效.
    UNASSIGNED: Polycystic ovary syndrome (PCOS) is an endocrine gynaecological disorder that affects many women of childbearing age.
    UNASSIGNED: To evaluate the efficacy and safety of glucose-like peptide-1 receptor agonists for obese women with PCOS.
    UNASSIGNED: We searched the PubMed, Embase, WOS, and Cochrane Libarary databases up to June 2023. Studies were eligible if they were randomised controlled trials (RCTs) comparing GLP-1RAs against any other treatments for patients with PCOS.
    UNASSIGNED: Overall, a total of 8 RCTs were included in this review, 7 of the RCTs compared GLP-1RAs with metformin, and 1 RCT compared GLP-1Ras with dapagliflozin. Compared with control group, GLP-1RAs were more effective at improving insulin sensitivity, reducing BMI, and resulting in a smaller waist circumference.
    UNASSIGNED: GLP-1RAs may be a good option for obese women with PCOS, especially those with insulin resistance. However, high-quality studies are also needed in the future to assess the efficacy of GLP-1RAs in women with PCOS.
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  • 文章类型: Journal Article
    多囊卵巢综合征(PCOS)是一种复杂的常见内分泌疾病,影响育龄妇女。排卵功能障碍被认为是主要的不育因素,然而,即使是药物诱导和恢复排卵,PCOS患者继续经历降低的累积妊娠率和更高的自发流产率。雄激素过多症,PCOS的标志性特征,影响卵巢卵泡发育,子宫内膜容受性,以及怀孕的建立和维持。蜕膜化是指子宫内膜基质部分必须经历的转化,以适应妊娠,受孕酮水平上升和当地cAMP产量的驱动。然而,关于高雄激素血症对蜕膜化影响的研究有限。在这项研究中,我们观察到,PCOS女性患者的原代子宫内膜基质细胞在体外蜕膜化过程中表现出对孕酮的异常反应.高浓度的睾酮抑制人子宫内膜基质细胞(HESC)蜕膜化。RNA-Seq分析表明,与没有高雄激素血症的PCOS患者相比,丙酮酸脱氢酶激酶4(PDK4)在高雄激素血症患者子宫内膜中的表达显着降低。我们还表征了在分泌中期子宫内膜基质中PDK4的表达升高。人工蜕膜化能增强PDK4的表达,而PDK4的下调导致体内和体外的异常蜕膜化。机械上,睾酮过量抑制IGFBP1和PRL表达,然后磷酸化刺激PDK4表达的AMPK。基于免疫共沉淀分析,我们观察到SIRT1和PDK4之间的相互作用,促进糖酵解以促进蜕膜化.AR激活的抑制恢复了睾酮过量抑制的AMPK/SIRT1/PDK4途径,表明睾酮主要通过AR刺激作用于蜕膜化。子宫内膜雄激素过量通过破坏AMPK/SIRT1/PDK4信号通路抑制蜕膜化这些数据证明了子宫内膜PDK4在调节蜕膜化中的关键作用,并为了解蜕膜化过程中的潜在机制提供了有价值的信息。
    Polycystic ovary syndrome (PCOS) is a complex common endocrine disorder affecting women of reproductive age. Ovulatory dysfunction is recognized as a primary infertile factor, however, even when ovulation is medically induced and restored, PCOS patients continue to experience reduced cumulative pregnancy rates and a higher spontaneous miscarriage rate. Hyperandrogenism, a hallmark feature of PCOS, affects ovarian folliculogenesis, endometrial receptivity, and the establishment and maintenance of pregnancy. Decidualization denotes the transformation that the stromal compart of the endometrium must undergo to accommodate pregnancy, driven by the rising progesterone levels and local cAMP production. However, studies on the impact of hyperandrogenism on decidualization are limited. In this study, we observed that primary endometrial stromal cells from women with PCOS exhibit abnormal responses to progesterone during in vitro decidualization. A high concentration of testosterone inhibits human endometrial stromal cells (HESCs) decidualization. RNA-Seq analysis demonstrated that pyruvate dehydrogenase kinase 4 (PDK4) expression was significantly lower in the endometrium of PCOS patients with hyperandrogenism compared to those without hyperandrogenism. We also characterized that the expression of PDK4 is elevated in the endometrium stroma at the mid-secretory phase. Artificial decidualization could enhance PDK4 expression, while downregulation of PDK4 leads to abnormal decidualization both in vivo and in vitro. Mechanistically, testosterone excess inhibits IGFBP1 and PRL expression, followed by phosphorylating of AMPK that stimulates PDK4 expression. Based on co-immunoprecipitation analysis, we observed an interaction between SIRT1 and PDK4, promoting glycolysis to facilitate decidualization. Restrain of AR activation resumes the AMPK/SIRT1/PDK4 pathway suppressed by testosterone excess, indicating that testosterone primarily acts on decidualization through AR stimulation. Androgen excess in the endometrium inhibits decidualization by disrupting the AMPK/SIRT1/PDK4 signaling pathway. These data demonstrate the critical roles of endometrial PDK4 in regulating decidualization and provide valuable information for understanding the underlying mechanism during decidualization.
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  • 文章类型: Journal Article
    背景:多囊卵巢综合征(PCOS)是一种常见的女性心脏代谢生殖疾病。目前尚不清楚全球肥胖流行是否正在影响PCOS的高患病率。
    目的:确定肥胖对全球PCOS发展的影响程度。
    方法:进行了系统评价,以确定全球PCOS患病率的人群研究,到2023年7月。线性回归和随机效应模型用于检查平均体重指数(BMI)或肥胖患病率与1990年美国国立卫生研究院(NIH)诊断的PCOS患病率之间的关系。2003鹿特丹(鹿特丹),和2006雄激素过量-PCOS(AE-PCOS)标准。还对招募方法和研究质量进行了亚组分析。
    结果:纳入了来自24个国家的85,956名成年人的58项研究。考虑到所有可用的数据,当使用AE-PCOS时,观察到PCOS和肥胖患病率之间的边界关联,但不是NIH或鹿特丹标准。或者,采用较好招募方法的亚组研究分析显示,使用鹿特丹或AE-PCOS标准时,人群平均BMI或肥胖患病率与PCOS患病率呈显著正相关,而仅使用高质量的研究揭示了使用NIH以及鹿特丹和AE-PCOS标准的相关性。总的来说,我们观察到,按照鹿特丹标准,肥胖患病率增加1%导致PCOS患病率增加约0.4%.
    结论:这些数据表明肥胖增加了PCOS的发展,虽然效果不大。我们的数据还强调了在评估PCOS流行病学时只需要进行高质量的研究。
    BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a common female cardio-metabolic-reproductive disorder. It is unclear whether the global obesity epidemic is impacting the high PCOS prevalence.
    OBJECTIVE: To determine the extent to which obesity contributes to the PCOS development globally.
    METHODS: A systematic review was conducted to identify population studies on PCOS prevalence globally, through July 2023. Linear regression and random-effect models were applied to examine the association of mean body mass index (BMI) or obesity prevalence with the prevalence of PCOS diagnosed by 1990 National Institute of Health (NIH), 2003 Rotterdam (Rotterdam), and 2006 Androgen Excess-PCOS (AE-PCOS) criteria. Subgroup analyses were also conducted for recruitment methods and study quality.
    RESULTS: Fifty-eight studies with 85,956 adults from 24 countries were included. Considering all available data, a borderline association was observed between PCOS and obesity prevalence when using the AE-PCOS, but not the NIH or Rotterdam criteria. Alternatively, subgroup analysis of studies with better recruitment methods demonstrated a significant positive association of population mean BMI or obesity prevalence with PCOS prevalence when using the Rotterdam or AE-PCOS criteria, while using only high-quality studies revealed an association using NIH as well as Rotterdam and AE-PCOS criteria. Overall, we observed that a 1% increase in obesity prevalence resulted in an approximately 0.4% increase in PCOS prevalence by the Rotterdam criteria.
    CONCLUSIONS: These data indicate that obesity increases the development of PCOS, although the effect is modest. Our data also emphasizes the need to undertake only high-quality studies in assessing PCOS epidemiology.
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  • 文章类型: Case Reports
    目标:卵巢增生病(OHT)是青少年年龄组中严重高雄激素血症的罕见原因。我们描述了两个病例报告,并在文献综述的基础上提出了这个年龄段的管理方法。
    方法:患者A在13岁时出现,有2年的安隆病和多毛症病史。她的睾酮水平升高到8.3nmol/L,她的卵巢两侧明显增大。影像学上没有发现局灶性肾上腺或卵巢病变。她接受了促性腺激素释放激素(GnRH)激动剂和螺内酯治疗,生化和临床改善。患者B在14岁时出现继发性闭经,并有2年的安罗汉病病史,多毛症和雄激素性脱发。她的睾酮水平是12nmol/L,盆腔超声显示每个卵巢中有许多大小正常的卵泡。她最初是用GnRH激动剂治疗的,现在继续服用联合口服避孕药。
    结论:在出现严重高雄激素血症的绝经前妇女中,需要考虑卵巢增生。排除产生雄激素的肾上腺和卵巢肿瘤后。该年龄组的治疗原则是促性腺激素抑制和激素替代。
    OBJECTIVE: Ovarian hyperthecosis (OHT) is a rare cause of severe hyperandrogenism in the adolescent age group. We describe two case reports, and present an approach to management in this age group based on a review of the literature.
    METHODS: Patient A presented at age 13 years with a 2 year history of androphonia and hirsuitism. Her testosterone level was elevated at 8.3 nmol/L, and there was marked enlargement of her ovaries bilaterally. There were no focal adrenal or ovarian lesions identified on imaging. She was treated with a gonadotropin releasing hormone (GnRH) agonist and spironolactone with biochemical and clinical improvement. Patient B presented at age 14 years with secondary amenorrhoea, and a 2 year history of androphonia, hirsutism and androgenetic alopecia. Her testosterone level was 12 nmol/L, and a pelvic ultrasound revealed numerous follicles in each ovary which were otherwise normal in size. She was managed with GnRH agonist initially, and now continues on a combined oral contraceptive pill.
    CONCLUSIONS: Ovarian hyperthecosis needs to be considered in pre-menopausal women presenting with severe hyperandrogenism, after exclusion of androgen-producing adrenal and ovarian tumours. The principles of management in this age group are gonadotropin suppression and hormone replacement.
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  • 文章类型: Journal Article
    多囊卵巢综合征(PCOS)是不孕的主要原因,估计全球患病率在5%至15%之间。我们对121名PCOS患者和155名对照进行了病例对照研究,以评估穆尔西亚女性咖啡摄入量与PCOS诊断之间的关系。西班牙。根据鹿特丹标准确定PCOS诊断(存在以下三种情况中的两种:高雄激素血症,低聚无排卵,和/或多囊卵巢形态)。使用经过验证的食物频率问卷评估咖啡消耗。使用多元逻辑回归估计调整后的比值比(ORs)和95%置信区间(CIs)。咖啡消费被归类为从不,每天不到一杯,每天一杯,每天两杯或更多杯。我们发现了一个显著的反线性趋势:咖啡消费量越高,多变量分析中PCOS的概率越低(p趋势=0.034).与从未喝咖啡的女性相比,患有PCOS的女性喝一杯咖啡的可能性较小(OR=0.313,95%CI:0.141-0.69)。每天至少一杯咖啡的消耗可能与PCOS症状的减少有关。
    Polycystic ovary syndrome (PCOS) is a leading cause of infertility, with an estimated worldwide prevalence between 5% and 15%. We conducted a case-control study with 121 PCOS patients and 155 controls to assess the association between coffee intake and the presence of having a diagnosis of PCOS in women in Murcia, Spain. The PCOS diagnosis was determined following Rotterdam criteria (the presence of two of the following three conditions: hyperandrogenism, oligo-anovulation, and/or polycystic ovarian morphology). Coffee consumption was assessed using a validated food frequency questionnaire. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multiple logistic regression. Coffee consumption was categorized into never, less than one cup per day, one cup per day, and two or more cups per day. We found a significant inverse linear trend: the higher the coffee consumption, the lower the probability of having PCOS in multivariable analysis (p-trend = 0.034). Women who presented with PCOS were less likely to drink one cup of coffee compared to those who had never drunk coffee (OR = 0.313, 95% CI: 0.141-0.69). The consumption of at least one cup of coffee per day may be associated with a decrease in PCOS symptoms.
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  • 文章类型: Journal Article
    背景:多囊卵巢综合征(PCOS)是一种普遍存在的内分泌疾病,具有重要的代谢意义,包括心血管疾病和糖尿病的风险增加。Kallistatin,一种具有抗炎和抗氧化特性的丝氨酸蛋白酶抑制剂,由于其在调节炎症和氧化应激中的作用,已被确定为PCOS的潜在生物标志物。
    方法:这项前瞻性队列研究在一所大学医院的妇科诊所进行。它包括220名诊断为PCOS的女性和220名年龄和体重指数相匹配的健康对照。使用酶联免疫吸附测定(ELISA)技术定量评估Kallistatin水平。Kallistatin水平与PCOS临床表现之间的关系,包括高雄激素血症和代谢谱,进行了检查。
    结果:PCOS患者的Kallistatin水平(2.65±1.84ng/mL)明显低于对照组(6.12±4.17ng/mL;p<0.001)。钾盐抑制素水平与雄激素浓度之间存在强烈的负相关(r=-0.782,p=0.035)。在kallistatin水平与胰岛素抵抗或血脂谱之间没有发现显着关联。
    结论:研究结果表明,降低的激肽素水平与PCOS密切相关,可以作为诊断PCOS的有希望的生物标志物。与高雄激素血症的特定相关性表明,kallistatin对于鉴定以雄激素水平升高为特征的PCOS亚型可能特别有效。这项研究支持了kallistatin在改善PCOS诊断方案方面的潜力,促进更早和更准确的检测,这对于有效的管理和治疗至关重要。
    BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder with significant metabolic implications, including an increased risk of cardiovascular diseases and diabetes. Kallistatin, a serine proteinase inhibitor with anti-inflammatory and antioxidative properties, has been identified as a potential biomarker for PCOS due to its role in modulating inflammation and oxidative stress.
    METHODS: This prospective cohort study was conducted at a university hospital\'s gynecology clinic. It included 220 women diagnosed with PCOS and 220 healthy controls matched for age and body mass index. Kallistatin levels were quantitatively assessed using enzyme-linked immunosorbent assay (ELISA) techniques. Associations between kallistatin levels and clinical manifestations of PCOS, including hyperandrogenism and metabolic profiles, were examined.
    RESULTS: Kallistatin levels were significantly lower in patients with PCOS (2.65 ± 1.84 ng/mL) compared to controls (6.12 ± 4.17 ng/mL; p < 0.001). A strong negative correlation existed between kallistatin levels and androgen concentrations (r = -0.782, p = 0.035). No significant associations were found between kallistatin levels and insulin resistance or lipid profiles.
    CONCLUSIONS: The findings indicate that reduced kallistatin levels are closely associated with PCOS and could serve as a promising biomarker for its diagnosis. The specific correlation with hyperandrogenism suggests that kallistatin could be particularly effective for identifying PCOS subtypes characterized by elevated androgen levels. This study supports the potential of kallistatin in improving diagnostic protocols for PCOS, facilitating earlier and more accurate detection, which is crucial for effective management and treatment.
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  • 文章类型: Journal Article
    目的:高雄激素血症是否通过激活铁凋亡影响卵巢颗粒细胞的功能,
    方法:在接受试管婴儿的多囊卵巢综合征(PCOS)患者中检测到颗粒细胞的铁细胞凋亡和内质网应激水平。在对照小鼠和PCOS样小鼠模型中检测卵巢组织和卵泡发育的铁凋亡和内质网应激水平,脱氢表雄酮诱导。用睾酮和铁凋亡抑制剂Fer-1构建KGN细胞的体外PCOS模型。内质网应激抑制剂,牛磺熊去氧胆酸盐(TUDCA),确定与PCOS相关的颗粒细胞过度诱导铁凋亡的潜在机制,并检测铁性凋亡和内质网应激水平。
    结果:在PCOS女性和不同的PCOS样小鼠的颗粒细胞中发生铁细胞凋亡和内质网应激的激活。在KGN细胞中的发现表明,睾酮治疗导致氧化应激水平升高,特别是脂质过氧化,和颗粒细胞内的铁积累。铁死亡相关因子相关基因和蛋白的表达,线粒体膜电位和超微结构显示睾酮激活铁凋亡,而Fer-1逆转了这些改变。在体外实验中,在颗粒细胞中检测到睾酮处理诱导的内质网应激的激活。在颗粒细胞中,TUDCA,内质网应激的抑制剂,显著减轻睾酮诱导的铁凋亡。
    结论:Ferroptosis在PCOS相关的高雄激素介导的生殖损伤中起作用,并且可能受内质网应激的调节。
    OBJECTIVE: Does hyperandrogenaemia affect the function of ovarian granulosa cells by activating ferroptosis, and could this process be regulated by endoplasmic reticulum stress?
    METHODS: Levels of ferroptosis and endoplasmic reticulum stress in granulosa cells were detected in women with and without polycystic ovary syndrome (PCOS) undergoing IVF. Ferroptosis and endoplasmic reticulum stress levels of ovarian tissue and follicle development were detected in control mice and PCOS-like mice models, induced by dehydroepiandrosterone. An in-vitro PCOS model of KGN cells was constructed with testosterone and ferroptosis inhibitor Fer-1. Endoplasmic reticulum stress inhibitor, tauroursodeoxycholate (TUDCA), determined the potential mechanism associated with excessive induction of ferroptosis in granulosa cells related to PCOS, and levels of ferroptosis and endoplasmic reticulum stress were detected.
    RESULTS: Activation of ferroptosis and endoplasmic reticulum stress occurred in granulosa cells of women with PCOS and the varies of PCOS-like mice. The findings in KGN cells demonstrated that testosterone treatment results in elevation of oxidative stress levels, particularly lipid peroxidation, and intracellular iron accumulation in granulosa cells. The expression of genes and proteins associated with factors related to ferroptosis, mitochondrial membrane potential and ultrastructure showed that testosterone activated ferroptosis, whereas Fer-1 reversed these alterations. During in-vitro experiments, activation of endoplasmic reticulum stress induced by testosterone treatment was detected in granulosa cells. In granulosa cells, TUDCA, an inhibitor of endoplasmic reticulum stress, significantly mitigated testosterone-induced ferroptosis.
    CONCLUSIONS: Ferroptosis plays a part in reproductive injury mediated by hyperandrogens associated with PCOS, and may be regulated by endoplasmic reticulum stress.
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