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.     

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).     

Polycystic ovary syndrome. A diagnostic challenge

Polycystic ovary syndrome remains a diagnostic challenge because there is no single defining test. The clinical presentation must dictate the extent of the work-up. The typical PCOS patient has a history of irregular menses and appears hirsute. Demonstration of ovulatory dysfunction and hyperandrogenism can also be made by appropriate hormonal measurements. An ultrasound showing multiple small ovarian follicles can support a diagnosis of PCOS in the patient for whom the clinical diagnosis has been made. Other causes of hyperandrogenism and ovulatory dysfunction should be excluded.     

Rotterdam consensus in adolescent girls: which investigations and how to interpret them to make the diagnosis of PCOS?

The polycystic ovary syndrome (PCOS) is the most frequent cause of hyperandrogenism and anovulation in adult women as well as in adolescent girls. Since 2003 the diagnosis of PCOS has been based on the association of hyperandrogenism, oligoanovulation and polycystic ovary (PCO) morphology at ultrasound (at least 2 items out of 3). In adolescents however, PCOS features may be difficult to distinguish from the symptoms of the end of puberty. Moreover, transvaginal ultrasound examination is seldom possible, and it is difficult to get precise imaging of the ovaries by abdominal route. However, the diagnosis of PCOS in a hyperandrogenic and/or oligomenorrheic adolescent requires on the strict application of the Rotterdam criteria, as in adult women. Priority should be given to clinical features whereas pelvic ultrasound must be considered as optional. Few hormonal assays will serve mainly to make the differential diagnosis, in addition to clinical findings. Once established, the diagnosis of PCOS in an adolescent girl must lead to the detection of the metabolic syndrome by means of simple investigations. This will allow early prevention of its complications.     

单侧多囊卵巢与多囊卵巢综合征的比较研究

目的:探讨单侧多囊卵巢的临床病理特点及病因。方法:收集单侧多囊卵巢12例,与8例典型多囊卵巢综合征对照比较,分析其临床表现、生化参数、卵泡液中相关激素水平以及卵巢间质细胞超微结构。结果:单侧PCO患者临床表现多样,和典型PCOS比较,单侧PCO出现月经改变和不孕显著减少。单侧PCO组血清PRL和T水平显著高于正常对照组,P<0.05;LH水平显著低于PCOS组,P<0.01。单侧PCO卵泡液中T和INS的水平比正常侧卵巢组显著升高,P<0.01;LH水平显著低于PCOS组,P<0.05。单侧PCO间质细胞粗面内质网、光面内质网不同程度出现扩张,部分粗面内质网有脱粒现象;线粒体出现扩张。结论:单侧PCO是一种不同于PCOS的特殊疾病类型,其临床表现多样,对卵巢生殖和内分泌功能的损害比PCOS轻。单侧PCO与PRL和卵巢局部T异常分泌均有关。单侧PCO间质细胞超微结构改变介乎正常卵巢和典型PC0S之间。     

Definitions, prevalence and symptoms of polycystic ovaries and polycystic ovary syndrome

Polycystic ovarian morphology is seen on ultrasound in approximately 22% of women. Polycystic ovary syndrome (PCOS) is a common and perplexing endocrine disorder of women in their reproductive years, with a prevalence of up to 10%. Clinical expression of the syndrome varies but commonly includes menstrual cycle disturbance, hyperandrogenism, insulin resistance and obesity. Recently, the European Society for Human Reproduction and Embryology and the American Society for Reproductive Medicine (ESHRE/ASRM) achieved a new consensus regarding the definition of PCOS. This is now defined as the presence of any two of the following three criteria: (i) polycystic ovaries; (ii) oligo-/anovulation; and/or (iii) clinical or biochemical evidence of hyperandrogenism. This revised definition provides an international framework for the clinical assessment of PCOS and for future research and collaboration.     

三维及彩色多普勒超声对多囊卵巢综合征的辅助诊断价值

目的探讨三维及彩色多普勒超声对多囊卵巢综合征(PCOS)的辅助诊断价值。方法对中国医科大学附属盛京医院2005年2月至2007年6月收治的60例PCOS患者和60例健康育龄女性进行三维及彩色多普勒超声检查,检测卵泡数目、三维容积和血流动力学指标,并进行对比分析。结果PCOS组的卵泡数目、卵巢容积、卵巢间质容积、卵泡容积大于对照组[分别为(16.91±4.34)个、(12.56±3.96)cm3、(11.49±3.50)cm3、(1.07±0.61)cm3对(5.48±2.10)个、(4.76±1.78)cm3、(4.43±1.74)cm3、(0.32±0.21)cm3],差异均有统计学意义(P<0.01);卵巢间质内动脉阻力指数低于对照组(0.53±0.06对0.65±0.09),收缩期峰值血流速度高于对照组[(12.68±3.10)cm/s对(9.30±1.64)cm/s],差异具有统计学意义(分别P<0.01,P<0.05)。结论三维超声和彩色多普勒超声增加了鉴别PCOS的客观定量指标,对多囊卵巢综合征有较高的辅助诊断价值。     

Ultrasonography in polycystic ovary syndrome: an update

Polycystic ovary syndrome (PCOS) is a convergence of multisystem endocrine derangements. During the last decade, the role of ultrasonography in the diagnosis and monitoring of this endocrinopathy underwent significant changes. However, there remain many concerns about whether these changes should be more widely introduced in clinical practice. Current concepts include the use of high-resolution, 3-dimensional ultrasound instead of conventional 2-dimensional ultrasound; formulaic methods of measuring ovarian volume; and correlation between ultrasonographic features, biochemical indices and ovarian stromal changes, such as enhanced echogenicity and increased blood flow. These issues, together with the new Rotterdam 2003 European Society of Human Reproduction and Embryology (ESHRE)/American Society for Reproductive Medicine (ASRM)-sponsored consensus criteria for the diagnosis of PCOS, are discussed in this review article.     

血清黄体生成素与卵泡刺激素比值对卵巢多囊样改变患者确诊多囊卵巢综合征的价值

目的 探讨血清黄体生成素(LH)与卵泡刺激素(FSH)的比值对卵巢呈多囊样改变(PCO)患者确诊多囊卵巢综合征(PCOS)的价值,比较欧洲人类生殖与胚胎学会及美国生殖学会的诊断标准(鹿特丹标准)与日本妇产科学会的诊断标准(日本标准)间的差异.方法 对195例就诊于南方医科大学南方医院生殖医学中心、阴道B超示PCO的患者,分别按照鹿特丹标准和日本标准进行判别,比较两种标准诊断的PCOS与非PCOS患者之间各项指标间的差异,并通过受试者工作特征(ROC)曲线下面积分析LH、LH/FSH、睾酮等指标在PCOS诊断中的意义;另选择119例非PCO且月经周期正常者作为对照组.结果 195例PCO者中,鹿特丹标准确诊PCOS患者144例,非PCOS患者51;日本标准确诊PCOS患者111例,非PCOS患者84例.鹿特丹标准确诊PCOS患者与非PCOS患者的LH/FSH分别为1.59±0.84和0.85±0.47,日本标准确诊PCOS患者与非PCOS患者的LH/FSH分别为1.87±0.76和0.78±0.39,LH/FSH对鹿特丹标准和日本标准诊断为PCOS进行判别时,ROC曲线下面积分别为0.786和0.942.结论 LH/FSH≥1对PCO者确诊PCOS有重要的参考价值,且日本标准更适合我国PCOS的诊断.

Abstract：

Objective To investigate the value of ratio of luteinizing hormone (LH) to folliclestimulating hormone (FSH) in diagnosis of polycystic ovarian syndrome (PCOS) among women with ploycystic ovary (PCO) and to compare the difference of the diagnostic criteria between the Rotterdam Consensus and the Committee for Reproductive and Endocrine in Japan Society of Obstetrics and Gynecology.Methods By means of transvaginal Doppler ultrasound, 195 women with PCO were diagnosed in Nanfang Hospital of Reproductive Medicine Center and compare difference of multiple clinical indexes according to Rotterdam consensus and Japan consensus respectively. In the mean time, the ratio of LH/FSH, the level of LH, testosterone (T) and recevier operating characteristic (ROC) curve were explored to on the value of diagnosis of PCOS. Results By Rotterdam consensus, 144 women were diagnosed with PCOS and 51 women were non-PCOS, while 111 were identified as PCOS and 84 were non-PCOS according to Japan consensus. LH/FSH in PCOS and non-PCOS were 1.59 ±0. 84 and 0. 85 ±0. 47 respectively when based on Rotterdam consensus, and this ratio were 1.87 ± 0. 76 in PCOS and 0. 78 ± 0. 39 in non-PCOS based on Japan consensus. When using LH/FSH to diagnosis PCOS by Rotterdam consensus and Japan consensus,areas under ROC curve are 0. 786 and 0. 942, respectively. Conclusions The ratio of LH/FSH ≥ 1 provide the significant value in the diagnosis of PCOS. The criteria of the Committee for Reproductive and Endocrine in Japan Society of Obstetrics and Gynecology is more suitable for Chinese patients.     

Definition of polycystic ovary syndrome

This article aims to answer two questions in defining polycystic ovary syndrome (PCOS): what is PCOS and how should the syndrome be recognized in clinical practice? Whether PCOS is a primary or a secondary ovarian disease remains controversial. It has been suggested for many years that the main pathophysiological factor in PCOS is dysregulation of the relationship between the hypothalamus, the pituitary and the ovary. However, PCOS also involves intraovarian morphological and functional abnormalities. With respect to clinical practice, many reports have questioned the sensitivity as well as the specificity of a high LH concentration. Similarly, the biological hyperandrogenism of PCOS cannot define the syndrome. GnRH agonist or hCG tests are not convenient for the diagnosis of PCOS in practice. Stromal hyperplasia is considered to be indicative of PCOS but it is highly dependent on the settings of the ultrasound machine, thus use of the total ovarian area, the upper normal limit of which is 5.5 cm(2), is recommended. The need for diagnostic markers of PCOS depends on the clinical presentation. In the full-blown syndrome (classic PCOS), the clinical symptoms provide the most powerful indication and the association of the three components (hyperandrogenism, anovulatory dysfunction and metabolic abnormalities) has a strong diagnostic potency. In non-classic PCOS, a cost-effective and safe work-up should be applied, which includes ultrasonography and hormonal assays (basal serum concentrations of testosterone, sex hormone binding globulin, 17-hydroxyprogesterone, LH, FSH and prolactin). Asymptomatic PCOS may be discovered incidentally during ultrasonography, and it is important to take this finding into account when designing an ovulation induction protocol. In most cases of PCOS, the diagnosis may remain presumptive providing other diagnoses have been ruled out and the follow-up does not disclose any atypical development of the condition.     

Are there differences in ultrasound parameters between Chinese women with polycystic ovaries only and with polycystic ovary syndrome?

OBJECTIVE: We aimed to compare antral follicle count (AFC), ovarian volume, ovarian stromal blood flow between Chinese women with polycystic ovary (PCO) only and polycystic ovary syndrome (PCOS) and to evaluate the effect of age on these ultrasound parameters in these women. STUDY DESIGN: In the second to fourth day of the period, they underwent a transvaginal three-dimensional scanning with power Doppler to determine total AFC, total ovarian volume, total ovarian vascularization index (VI), flow index (FI) and vascularization flow index (VFI). Hormonal profile was also measured. RESULTS: A total of 71 Chinese women were recruited in the study: 39 women with PCO only and 32 women with PCOS. Women with PCO only had significantly lower AFC, ovarian volume, ovarian VI, serum LH, testosterone and DHEAS concentrations but higher serum SHBG concentration when compared with PCOS women. When women with PCO only and PCOS were considered together, the rate of decline of AFC over age was 0.905 follicle per year (95% CI=0.008-1.803, p=0.048) and there was no significant decline of ovarian volume and total ovarian VI, FI and VFI over age. CONCLUSION: PCO only represents a milder end of the PCOS spectrum.     

Ovarian pregnancy in polycystic ovary syndrome: a case report.

A case is reported of ectopic pregnancy occurring within an ovary with the morphologic appearance of polycystic ovary syndrome (PCOS). The hyperandrogenism and elevated LH/FSH ratio characteristic of PCOS were noted 2 months after removal of the ovarian gestation. The thickened ovarian cortex of the PCOS ovary and a defect in oocyte-cumulus complex detachment within the follicle are suggested as possible factors contributing to intraovarian fertilization in PCOS.     

济南市汉族育龄妇女PCOS患病状况的初步调查

目的:探讨济南市汉族育龄妇女多囊卵巢综合征(PCOS)患病状况及其临床特点。方法:以2003年ESHRE/ASRM建议诊断标准,按流行病学整群抽样方法调查济南市1027例育龄妇女中PCOS的患病状况。结果:(1)以ESHRE/ASRM 3条指标符合2条的原则检出PCOS 85例,群体患病率为6.46%;(2)检出的PCOS中稀发排卵、多囊样卵巢(PCO)、高睾酮(T)血症、临床高雄(F-G≥6多毛和痤疮)分别占89.4%、72.94%、57.65%、38.8%(1.18%和38.8%);每两项指标组合:稀发排卵+PCO、稀发排卵+高T、PCO+高T分别占60%、45.9%、38.8%;符合3条指标而临床、生化高雄仅有其一者占48.2%,两者均有占11.8%;不孕占7.06%、肥胖占8.23%。按汉族妇女F-G≥2分标准,群体PCOS中多毛率为37.65%。结论:(1)PCOS占济南市汉族育龄妇女的6.46%。(2)ESHRE/ASRM标准总体上是适合济南汉族育龄妇女PCOS检出的标准,多项指标可提高检出的特异度;(3)多毛作为临床高雄指标F-G≥2分更适于汉族人群。     

Polycystic ovary syndrome and pregnancy outcome: red herring or red flag?

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women, associated with a characteristic ovarian appearance at ultrasound scan, hyperandrogenism, and ovulatory disorders. The pathogenesis appears to be mainly related to reduced insulin sensitivity in peripheral tissues, leading to hyperinsulinaemia. There is a wide variation in the severity of PCOS symptoms. Women with PCOS are believed to be predisposed to a variety of complications in pregnancy. We present a summary of the evidence surrounding these claims and discuss the weaknesses of the available to date studies.     

Characteristics of different phenotypes of polycystic ovary syndrome in a Bulgarian population.

AIM: Our aim was to investigate the percentage occurrence of different phenotypes of polycystic ovary syndrome (PCOS) in a Bulgarian population, and their clinical, biochemical and hormonal characteristics. METHODS: The study included 70 women with PCOS, diagnosed according to the European Society of Human Reproduction & Embryology/American Society for Reproductive Medicine criteria. The women were divided into four phenotypes: hyperandrogenism (HA) + oligo-/anovulation (OA) + polycystic ovaries at ultrasound (PCO) (full-blown syndrome, phenotype A); HA + OA (former National Institutes of Health definition, phenotype B); OA + PCO (phenotype C); and HA + PCO (phenotype D). Serum levels of testosterone, immune-reactive insulin, sex hormone-binding globulin, dehydroepiandrosterone sulfate and lipid metabolism parameters were measured. Free androgen index and homeostasis model assessment of insulin resistance were calculated. Body mass index and waist-to-hip ratio were assessed. RESULTS: The percentages of phenotypes A, B, C and D in a Bulgarian population are 58.6%, 11.4%, 10.0% and 20.0%, respectively. The women with the classical form of PCOS (phenotypes A and B) were more obese, had more strongly expressed hyperandrogenemia, and were more insulin-resistant compared with the women of phenotypes C and D. CONCLUSION: There is a significant difference in anthropometric, hormonal and metabolic indices between the classical form and the clinical variants of PCOS in the studied Bulgarian population.     

Influence of oral contraceptive pills on phenotype expression in women with polycystic ovary syndrome

Polycystic ovarian syndrome (PCOS) is characterized by a heterogeneous phenotype including chronic anovulation, hyperandrogenism and polycystic ovaries. The use of oral contraceptive pills (OCP) alters features characteristic for the syndrome. In the present study, PCOS features were compared between women using or not using OCP at the time of the study. One hundred and one women diagnosed with normogonadotrophic anovulatory infertility were included. A total of 81 (80%) women were diagnosed with PCOS (revised 2003 criteria). From these women, a total of 54 did not use OCP, whereas 27 women did. Corrected for age, women taking OCP had increased serum concentrations of sex hormone-binding globulin (P < 0.001). Serum concentrations of testosterone (P = 0.04) and androstenedione (P = 0.01) were decreased. These differences resulted in a decreased free androgen index for women currently taking OCP compared with women without (P < 0.001). The mean ovarian volume/ovary and the mean follicle number/ovary were not different. Use of OCP influences phenotype expression (the observable trait) of individual women known to suffer from PCOS by reducing hyperandrogenism. Despite taking OCP, women still fulfilled the revised 2003 criteria for the syndrome, as PCO morphology was still present. Hence, OCP use does not appreciably affect the PCOS phenotype.     

抗苗勒管激素与不同表型多囊卵巢综合征发病特征的相关性分析

目的探讨不同表型多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者血清抗苗勒管激素(AMH)及性激素指标水平,并评估AMH与这些指标的相关性。方法应用UNION免疫分析仪和Uni Cel Dx I800免疫分析系统检测702例PCOS患者和118例健康女性(对照组)AMH和其他性激素水平,并进行超声下窦卵泡计数(AFC)和卵巢体积测量。应用Pearson分析进行双变量相关分析。结果 PCOS患者的卵泡刺激素(FSH)低于对照组,其中无排卵或稀发排卵(OA)+高雄激素血症(HA)+多囊卵巢(PCO)组与对照组间的差异具有统计学意义(P0.05)。黄体生成素(LH)、L H/F S H、AMH均显著高于对照组。血清睾酮(T)水平在O A+H A组和O A+H A+P C O组显著升高。各组间泌乳素(P R L)、雌二醇(E2)水平无明显差异。A M H与F S H呈负相关,与L H、L H/F S H、T、A F C、左卵巢体积和右卵巢体积呈正相关。结论血清AMH浓度可以反映窦卵泡的数目和血清T的浓度高低,可作为PCOS诊断与监测指标之一,提高PCOS诊断的简便性,在临床上有广泛的应用前景。     

Characteristics of different phenotypes of polycystic ovary syndrome in a Bulgarian population

Aim. Our aim was to investigate the percentage occurrence of different phenotypes of polycystic ovary syndrome (PCOS) in a Bulgarian population, and their clinical, biochemical and hormonal characteristics.

Methods. The study included 70 women with PCOS, diagnosed according to the European Society of Human Reproduction & Embryology/American Society for Reproductive Medicine criteria. The women were divided into four phenotypes: hyperandrogenism (HA) + oligo-/anovulation (OA) + polycystic ovaries at ultrasound (PCO) (full-blown syndrome, phenotype A); HA + OA (former National Institutes of Health definition, phenotype B); OA + PCO (phenotype C); and HA + PCO (phenotype D). Serum levels of testosterone, immune-reactive insulin, sex hormone-binding globulin, dehydroepiandrosterone sulfate and lipid metabolism parameters were measured. Free androgen index and homeostasis model assessment of insulin resistance were calculated. Body mass index and waist-to-hip ratio were assessed.

Results. The percentages of phenotypes A, B, C and D in a Bulgarian population are 58.6%, 11.4%, 10.0% and 20.0%, respectively. The women with the classical form of PCOS (phenotypes A and B) were more obese, had more strongly expressed hyperandrogenemia, and were more insulin-resistant compared with the women of phenotypes C and D.

Conclusion. There is a significant difference in anthropometric, hormonal and metabolic indices between the classical form and the clinical variants of PCOS in the studied Bulgarian population.     

B超在多囊卵巢综合征诊断中的应用研究

目的 探讨测量卵巢间质等变化的B超参数对多囊卵巢综合征的诊断价值。方法 2001年2月至2002年8月对38例LH/FSH>2的多囊卵巢综合征(PCOS)患者及30例正常育龄妇女志愿者进行卵巢B超观测,参数为卵巢总体积(OV)、卵巢切面总面积(TA)和间质面积(SA)、SA/TA以及间质回声变化,并分析与性激素的相关性。结果 PCOS组OV、SA与SA/TA较对照组明显增高,SA、SA/TA尤其是后者与LH、LH/FSH明显相关,并与雄激素有一定相关性。结论 SA、TA和SA/TA可考虑作为PCOSB超方面的诊断指标。阴道B超(TVUS)和腹部B超(TAUS)联合应用能提高诊断准确性,减少漏诊率。