Syndrom der polyzystischen Ovarien (PCOS)

Polycystic ovary syndrome (PCOS), including chronic anovulation, hyperandrogenism and polycystic ovaries, is the most common endocrine disorder in women of reproductive age, affecting around 5–10% with familial clustering. Although the pathophysiology of PCOS is not fully understood, insulin resistance with consecutive hyperinsulinemia plays a central role. Among obese women the observed insulin resistance is at least partially explained by excess adipose tissue, but lean women are affected as well. The symptoms of PCOS range from the cutaneous stigmata of hyperandrogenism and sterility to metabolic syndrome. Because of the severe health implications of the metabolic syndrome, the diagnosis of PCOS should include all facets, especially disturbed glucose metabolism. An optimal form of treatment that targets all symptoms does not exist. This review sheds light on some important aspects of PCOS with the aim of raising awareness about its complexity and its consequences.     

Polycystic ovary syndrome: clinical perspectives and management.

The polycystic ovary syndrome (PCOS) is a common hyperandrogenic disorder and is characterized by a constellation of signs and symptoms often in association with a family history of hyperandrogenism and/or PCOS. It is often associated with hyperinsulinism and insulin resistance, which puts patients at risk for possible potential complications including type 2 diabetes mellitus and cardiovascular disease. Clinical signs may be subtle, and biochemical markers most often include an elevation of free testosterone (T) and possibly dehydroepiandrosterone sulfate (DHEAS). The diagnosis should be sought in any woman with hyperandrogenic features so that appropriate treatment may be used. There is often a good therapeutic response of the hirsutism, acne, or oligomenorrhea associated with PCOS. The new modalities that increase insulin sensitivity as well as weight reduction in the obese woman with PCOS may potentially be useful in modifying the potential later complications of this common endocrinopathy of young adult women.     

Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome

Since the 1990 National Institutes of Health-sponsored conference on polycystic ovary syndrome (PCOS), it has become appreciated that the syndrome encompasses a broader spectrum of signs and symptoms of ovarian dysfunction than those defined by the original diagnostic criteria. The 2003 Rotterdam consensus workshop concluded that PCOS is a syndrome of ovarian dysfunction along with the cardinal features hyperandrogenism and polycystic ovary (PCO) morphology. PCOS remains a syndrome, and as such no single diagnostic criterion (such as hyperandrogenism or PCO) is sufficient for clinical diagnosis. Its clinical manifestations may include menstrual irregularities, signs of androgen excess, and obesity. Insulin resistance and elevated serum LH levels are also common features in PCOS. PCOS is associated with an increased risk of type 2 diabetes and cardiovascular events.     

Androgene und Insulin in Pathophysiologie und Genetik des PCO-Syndroms

Androgens and insulin are the endocrine key-players in the pathophysiology of polycystic ovary syndrome (PCOS), a heterogenic disorder of unknown etiology and genetic background. Androgens transmit the phenotype of this complex disease and consequently,, all criteria of the recent consensus definition of PCOS are based on androgenic effects. Insulin resistance, followed by hyperinsulinemia, is frequently associated with PCOS, transporting a metabolic risk with possible future complications. Recent findings on the insulin and androgen receptor genes of PCOS patients support the pivotal role of insulin and androgens in the pathophysiology and genetics of PCOS. These results could contribute to a better characterization of this heterogenic syndrome in the future.     

Syndrom polyzystischer Ovarien und Adipositas im Jugendalter

Nearly 20% of the adolescent females in Germany are overweight. A typical comorbidity of overweight is polycystic ovary syndrome (PCOS). The diagnosis of PCOS in adolescents needs to be based on the criteria hyperandrogenemia and/or hirsutism as well as oligomenorrhea or amenorrhea. All other diseases with hyperandrogenism need to be excluded. PCOS is caused, among other things, by insulin resistance, which is increased particularly in central obesity. Therefore, other diseases associated with insulin resistance such as metabolic syndrome, type 2 diabetes mellitus, or fatty liver are frequent in girls with PCOS. The treatment of choice for obesity and PCOS is weight reduction, which is difficult to achieve in clinical practice. Drug treatment for hirsutism or menstrual irregularities depends on the accompanying risk factors.     

Diagnosis of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrine disorders among women in reproductive age, but diagnostic criteria used in clinical practice are still controversial. In 1990 the National Institute of HEALTH (NIH) conference on PCOS recommended that diagnostic criteria should include biochemical evidence of hyperandrogenism and ovarian dysfunction (in the absence of non-classical adrenal hyperplasia) without considering the morphological diagnosis of polycystic ovary by ultrasound as an essential part of the diagnosis. In the Rotterdam PCOS workshop of May 2003, however, PCOS is diagnosed when 2 of the following criteria are recognized: oligomenorrhea and/or anovulation, clinical or biochemical signs of hyperandrogenism, ultrasound findings of polycystic ovary. Further-more, it is underlined that the metabolic study is not necessary for PCOS diagnosis, while it is suggested for "at risk patients" (obesity, diabetes, familiar and obstetrical history) with an oral glucose tolerance test (OGTT). A recent study carried out by our group underlined the role of ultrasound parameter, in particular suggesting a ratio between ovarian stroma area and total area of the ovarian section (S/A), with a cut-off of 0.34, as "gold parameter" for PCOS diagnosis, because it shows high sensitivity and specificity (96.3%, 97.0% for the S/A).     

Hyperinsulinaemia and polycystic ovary syndrome

Over the past 20 years, it has been established that hyperinsulinaemia is a fundamental disturbance in many women with polycystic ovary syndrome (PCOS). A subgroup of women with this syndrome have 'metabolic PCOS' which can be considered to be a pre-diabetic state. Clinically, this subgroup is most easily identified in obese women with a strong family history of diabetes in whom menstrual disturbance is the predominant feature. There is an urgent need to define the more subtle features in young lean women with PCOS, in whom the metabolic syndrome is yet to emerge, which would enable the prediction of future health risks. The molecular mechanisms of insulin resistance leading to hyperinsulinaemia are now being elucidated. Abnormalities of both insulin secretion and intracellular insulin signalling have both been proposed in women with PCOS. Strategies to lower serum insulin concentrations include diet, exercise and possibly, oral insulin sensitizing agents such as metformin. Although the short-term efficacy of reducing hyperinsulinaemia in women with PCOS is clear, the best method to prevent the progression to diabetes later in life has not been defined.     

Hyperinsulinaemia and polycystic ovary syndrome

Over the past 20 years, it has been established that hyperinsulinaemia is a fundamental disturbance in many women with polycystic ovary syndrome (PCOS). A subgroup of women with this syndrome have ‘metabolic PCOS’ which can be considered to be a pre-diabetic state. Clinically, this subgroup is most easily identified in obese women with a strong family history of diabetes in whom menstrual disturbance is the predominant feature. There is an urgent need to define the more subtle features in young lean women with PCOS, in whom the metabolic syndrome is yet to emerge, which would enable the prediction of future health risks. The molecular mechanisms of insulin resistance leading to hyper-insulinaemia are now being elucidated. Abnormalities of both insulin secretion and intracellular insulin signalling have both been proposed in women with PCOS. Strategies to lower serum insulin concentrations include diet, exercise and possibly, oral insulin sensitizing agents such as metformin. Although the short-term efficacy of reducing hyperinsulinaemia in women with PCOS is clear, the best method to prevent the progression to diabetes later in life has not been defined.     

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。     

Polycystic ovary syndrome in adolescents

Polycystic ovary syndrome (PCOS) typically manifests with a combination of menstrual dysfunction and evidence of hyperandrogenism in the adolescent population. No single cause has been identified; however, evidence suggests a complex interplay between genetic and environmental factors. Polycystic ovary syndrome presents a particular diagnostic challenge in adolescents as normal pubertal changes can present with a similar phenotype. Management of PCOS in the adolescent population should focus on a multi-modal approach with lifestyle modification and pharmacologic treatment to address bothersome symptoms. This chapter outlines the pathogenesis of PCOS, including the effects of obesity, insulin resistance, genetic, and environmental factors. The evolution of the diagnostic criteria of PCOS as well as specific challenges of diagnosis in the adolescent population are reviewed. Finally, evidence for lifestyle modification and pharmacologic treatments are discussed.     

Serum leptin levels in normal-weight and overweight women with polycystic ovary syndrome

The aim of this study was to evaluate serum leptin levels in women with polycystic ovary syndrome (PCOS) and in controls with normal or abnormal body mass index (BMI), since the literature data are contradictory. The study population comprised 34 women with PCOS and 30 regularly cycling women, with normal or abnormal BMI. PCOS was defined by clinical, ultrasonographic, and hormonal findings. The women were divided into four groups according to the diagnosis of PCOS and their BMI values. In all women serum levels of FSH, LH, prolactin, testosterone, androstenedione, DHEA-S, 17alpha-OH progesterone, SHBG, insulin, glucose and leptin were determined. It was found that: (a) there was a significant interaction between BMI and PCOS in increasing serum leptin levels; (b) the dominant factor for serum leptin levels in women of all Groups was BMI, followed by insulin; (c) once we corrected for BMI, it was found that there was a significant correlation between serum leptin levels and insulin values, as well as between serum leptin levels and testosterone concentrations; and (d) the QUICKI IR formula presented the most significant correlation with serum leptin levels than the other measures of insulin sensitivity. Our results showed that serum leptin levels in a subgroup of overweight women with PCOS and insulin resistance were higher than those expected for their BMI, and therefore leptin might interfere in the pathogenesis of this syndrome.     

肥胖与青少年多囊卵巢综合征

多囊卵巢综合征（PCOS）是育龄妇女常见生殖内分泌疾病。近年发现,随着儿童肥胖患病率增加,青少年PCOS发病率也逐年提高。肥胖可通过增加外周循环胰岛素水平影响PCOS发病机制,PCOS患者高雄激素血症也会增加内脏脂肪沉积。肥胖会增加与PCOS相关的代谢和心血管方面的并发症的患病风险,如胰岛素抵抗（IR）、高脂血症、高血压以及临床症状不明显的动脉粥样硬化等。早期识别青春期PCOS,有利于及时纠正、阻断其内分泌紊乱,防止近期及远期并发症发生。     

Management of polycystic ovary syndrome in adolescence

Polycystic ovary syndrome (PCOS) in the adolescent is a frequent cause of menstrual irregularity (mostly persistent oligomenorrhea), acne, hirsutism and even premature pubarche. Typical ultrasound findings in the ovary can complete the clinical diagnosis. The obese especially should also be examined for impairment of insulin sensitivity and glucose tolerance as these, if untreated, may compromise long-term health. The androgen excess of PCOS acts on the pilo-sebaceous unit to cause acne and hirsutism which often have a disturbing psychosocial effect on the teenager. Early detection of the syndrome and its treatment with anti-androgens can save much anguish and for the overweight, loss of weight is an integral part of correct management. The long-term use of metformin for adolescents is still hotly debated but preliminary data suggest it may have a role for symptomatic, and maybe also preventative treatment.     

Androgens and insulin--two key players in polycystic ovary syndrome. Recent concepts in the pathophysiology and genetics of polycystic ovary syndrome

Androgens and insulin are endocrine key players in the pathophysiology of polycystic ovary syndrome (PCOS), a heterogenic condition of unexplained etiology and a suspected genetic background. Androgens mediate the clinical phenotype of the disease. Therefore,all criteria of the recent PCOS consensus definition are based on their biological effects. Insulin resistance, followed by compensatory hyperinsulinemia, is frequently found in patients with PCOS. Insulin resistance is correlated with a risk of metabolic complications of PCOS, and recent research has focused on possible long-term health consequences of the syndrome. Newest molecular genetic findings at the receptor level of both androgens and insulin support their pivotal role in PCOS. These results could help to better characterize the heterogenic disorder, enabling a refinement of existing individualized therapeutic strategies.     

肥胖与青少年多囊卵巢综合征

多囊卵巢综合征（PCOS）是育龄妇女常见生殖内分泌疾病。近年发现,随着儿童肥胖患病率增加,青少年PCOS发病率也逐年提高。肥胖可通过增加外周循环胰岛素水平影响PCOS发病机制,PCOS患者高雄激素血症也会增加内脏脂肪沉积。肥胖会增加与PCOS相关的代谢和心血管方面的并发症的患病风险,如胰岛素抵抗（IR）、高脂血症、高血压以及临床症状不明显的动脉粥样硬化等。早期识别青春期PCOS,有利于及时纠正、阻断其内分泌紊乱,防止近期及远期并发症发生。     

The role of miRNAs in polycystic ovary syndrome with insulin resistance

PurposeThis review aims to summarize the key findings of several miRNAs and their roles in polycystic ovary syndrome with insulin resistance, characterize the disease pathogenesis, and establish a new theoretical basis for diagnosing, treating, and preventing polycystic ovary syndrome.MethodsRelevant scientific literature was covered from 1992 to 2020 by searching the PubMed database with search terms: insulin/insulin resistance, polycystic ovary syndrome, microRNAs, and metabolic diseases. References of relevant studies were cross-checked.ResultsThe related miRNAs (including differentially expressed miRNAs) and their roles in pathogenesis, and possible therapeutic targets and pathways, are discussed, highlighting controversies and offering thoughts for future directions.ConclusionWe found abundant evidence on the role of differentially expressed miRNAs with its related phenotypes in PCOS. Considering the essential role of insulin resistance in the pathogenesis of PCOS, the alterations of associated miRNAs need more research attention. We speculate that race/ethnicity or PCOS phenotype and differences in methodological differences might lead to inconsistencies in research findings; thus, several miRNA profiles need to be investigated further to qualify for the potential therapeutic targets for PCOS-IR.     

硫氧还蛋白相互作用蛋白在多囊卵巢综合征中作用的研究进展

多囊卵巢综合征（polycystic ovary syndrome，PCOS）是一种常见于育龄妇女的内分泌代谢性疾病，以月经不规则、高雄激素血症和卵巢多囊样改变为特征，常表现为肥胖、不孕和胰岛素抵抗。硫氧还蛋白相互作用蛋白（thioredoxin-interacting protein，TXNIP）是一种多功能调节剂，不仅参与胰岛素分泌和葡萄糖代谢的调节，还与氧化应激、炎症因子和情绪障碍密切相关。PCOS患者体内的TXNIP水平较健康人群明显增加，表明TXNIP可能参与PCOS及其并发症的发生、发展。近年体内外研究尝试应用中药提取物和西医药物抑制TXNIP的表达，TXNIP特异性抑制剂的发现使TXNIP有望成为抑制PCOS进程的有效靶点。综述TXNIP在PCOS中的作用进展，以期为PCOS发病机制的深入研究及临床诊疗提供新的思路和方向。     

Polycystic ovary syndrome and its differential diagnosis

Polycystic ovary syndrome (PCOS) is a common disorder of reproductive-aged women. It affects between 3.4-6.8% of this population. Common clinical symptoms of PCOS include menstrual irregularities, hirsutism, and often obesity. Long-term sequelae include anovulatory infertility, endometrial carcinoma, and an increased risk for cardiovascular disease due to type II diabetes mellitus, dyslipidemia, and systolic hypertension. The diagnosis of PCOS is one of exclusion and is defined by the Rotterdam criteria which were established in 2004. However, several other endocrine disorders can closely resemble PCOS. It is important for practitioners to recognize and distinguish PCOS from other disorders in its differential. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to summarize the short-term reproductive and long-term metabolic consequences of polycystic ovary syndrome (PCOS), point out the importance of meeting the current criteria for diagnosis, and recall the recommended treatment related to the clinical presentation of the patient.