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2.
Life Sci ; 259: 118174, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32745529

RESUMO

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder in females of the reproductive age. PCOS is commonly manifested as ovulatory dysfunction, clinical and biochemical excess androgen level, and polycystic ovaries. Metabolic sequelae associated with PCOS, including insulin resistance (IR), type 2 diabetes (T2DM), obesity and increased cardiometabolic risk. The underlying pathology of PCOS is not fully understood with various genetic and environmental factors have been proposed. MicroRNAs (miRNAs), are endogenously produced, small non-coding, single-stranded RNAs that capable of regulating gene expression at the post-transcriptional level. Altered miRNAs expression has been associated with various disorders, including T2DM, IR, lipid disorder, infertility, atherosclerosis, endometriosis, and cancer. Given that PCOS also present with similar features, there is an increasing interest to investigate the role of miRNAs in the diagnosis and management of PCOS. In recent years, studies have demonstrated that miRNAs are present in various body fluids, including follicular fluid of women with PCOS. Therefore, it may act as a potential biomarker and could serve as a novel therapeutic target for the diagnosis and treatment of PCOS. This review aims to summarise the up to date research on the relation between miRNAs and PCOS and explore its potential role in the diagnosis and the management of PCOS.


Assuntos
Biomarcadores/análise , MicroRNAs/análise , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/tratamento farmacológico , Feminino , Humanos , Síndrome do Ovário Policístico/complicações
3.
BMC Womens Health ; 20(1): 132, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576264

RESUMO

BACKGROUND: The universally adopted 2018 PCOS medical diagnostic and treatment guidelines for Polycystic Ovarian Syndrome (PCOS) cites the need for a brief screening measure that can be easily administered in the clinical care setting. We evaluate a 12-item questionnaire emphasizing the medical symptoms of PCOS with a group of women with PCOS as well as comparison samples of college women not diagnosed with PCOS. METHOD: Of 120 undergraduate psychology women 18 to 41 years of age, 86 screened negative on a 12-item PCOS symptoms inventory. They were compared to a group of PCOS patients diagnosed medically in a manner consistent with the Teede et al. (2018) evidence-based diagnostic guidelines. The screen-positive, screen-negative, and PCOS-confirmed groups were compared on the PCOS Quality-of-Life (QoL) questionnaire, Zung Self-Rating Depression Scale (ZDS), Spielberg State-Trait Anxiety Inventory (STAI), Fatigue Symptom Inventory (FSI), Spiritual well-being and Spiritual Beliefs Inventories, the computerized Automated Neuropsychological Assessment Metric (ANAM) battery, and an experimental tachistoscopic Bilateral Perceptual Asymmetries Letter and Dots Matching Bilateral Field Advantage (BFA) test (to evaluate the effects of early brain androgenization possible from PCOS). For each questionnaire and neuropsychological performance principal outcome, the Linear Mixed Effects (LME) model was employed to evaluate the predictive significance of demographic characteristics and group membership (confirmed cases, screen negative and screen positive cases) for these outcomes. RESULTS: The PCOS-confirmed women scored more poorly than the screen-negative (reference) and screen-positive groups on all the measures of physical, emotional, social, and spiritual well-being measures. On the ANAM neuropsychological battery, PCOS-confirmed women did more poorly on Sternberg Memory and Stimulus Response throughput measures. They also had slower correct response speed for both the unilateral and bilateral dot- and letter-matching tachistoscopic stimulus presentations. However, the bilateral field advantage throughput performance ratio did not differ among groups, which is a global measure of bilateral versus unilateral brain/behavior asymmetries. CONCLUSION: PCOS screening can be a feasible and important part of women's healthcare. PCOS-confirmed women should receive not only the medical standard of care from the 2018 guidelines, but also comprehensive psychosocial and neurocognitive support to enhance their quality of life.


Assuntos
Síndrome do Ovário Policístico/diagnóstico , Qualidade de Vida , Adolescente , Adulto , Ansiedade/etiologia , Ansiedade/psicologia , Depressão/etiologia , Depressão/psicologia , Fadiga/etiologia , Fadiga/psicologia , Feminino , Humanos , Testes Neuropsicológicos/estatística & dados numéricos , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/psicologia , Espiritualidade , Estresse Psicológico/etiologia , Estresse Psicológico/psicologia , Inquéritos e Questionários
4.
Pediatrics ; 145(Suppl 2): S210-S218, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32358213

RESUMO

Polycystic ovary syndrome (PCOS) is a common female reproductive disorder that often manifests during adolescence and is associated with disruptions in health-related quality of life. Prompt evaluation and clinical support after diagnosis may prevent associated complications and optimize overall health management. This article incorporates the most recent evidence and consensus guidelines to provide an updated review of the pathogenesis, clinical presentation, diagnostic evaluation, and management strategies for adolescents with this complex condition. We will review the recent international guidelines on PCOS; because the diagnosis of PCOS remains controversial, management of this condition is inconsistent. In 2019, PCOS remains a common, yet neglected, condition, in part, because of the lack of agreement around both diagnosis and management.


Assuntos
Síndrome do Ovário Policístico/diagnóstico , Qualidade de Vida/psicologia , Adolescente , Androgênios/sangue , Feminino , Seguimentos , Fidelidade a Diretrizes , Humanos , Insulina/sangue , Hormônio Luteinizante/sangue , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/psicologia , Síndrome do Ovário Policístico/terapia , Fatores de Risco
5.
BMC Bioinformatics ; 21(1): 177, 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32366216

RESUMO

BACKGROUND: Feature screening plays a critical role in handling ultrahigh dimensional data analyses when the number of features exponentially exceeds the number of observations. It is increasingly common in biomedical research to have case-control (binary) response and an extremely large-scale categorical features. However, the approach considering such data types is limited in extant literature. In this article, we propose a new feature screening approach based on the iterative trend correlation (ITC-SIS, for short) to detect important susceptibility loci that are associated with the polycystic ovary syndrome (PCOS) affection status by screening 731,442 SNP features that were collected from the genome-wide association studies. RESULTS: We prove that the trend correlation based screening approach satisfies the theoretical strong screening consistency property under a set of reasonable conditions, which provides an appealing theoretical support for its outperformance. We demonstrate that the finite sample performance of ITC-SIS is accurate and fast through various simulation designs. CONCLUSION: ITC-SIS serves as a good alternative method to detect disease susceptibility loci for clinic genomic data.


Assuntos
Predisposição Genética para Doença , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/genética , Estudos de Casos e Controles , Feminino , Genoma , Estudo de Associação Genômica Ampla/métodos , Humanos
6.
Am J Obstet Gynecol ; 223(4): 559.e1-559.e21, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32289280

RESUMO

BACKGROUND: Polycystic ovary syndrome is the most common endocrine disorder affecting women of reproductive age. A number of criteria have been developed for clinical diagnosis of polycystic ovary syndrome, with the Rotterdam criteria being the most inclusive. Evidence suggests that polycystic ovary syndrome is significantly heritable, and previous studies have identified genetic variants associated with polycystic ovary syndrome diagnosed using different criteria. The widely adopted electronic health record system provides an opportunity to identify patients with polycystic ovary syndrome using the Rotterdam criteria for genetic studies. OBJECTIVE: To identify novel associated genetic variants under the same phenotype definition, we extracted polycystic ovary syndrome cases and unaffected controls based on the Rotterdam criteria from the electronic health records and performed a discovery-validation genome-wide association study. STUDY DESIGN: We developed a polycystic ovary syndrome phenotyping algorithm on the basis of the Rotterdam criteria and applied it to 3 electronic health record-linked biobanks to identify cases and controls for genetic study. In the discovery phase, we performed an individual genome-wide association study using the Geisinger MyCode and the Electronic Medical Records and Genomics cohorts, which were then meta-analyzed. We attempted validation of the significant association loci (P<1×10-6) in the BioVU cohort. All association analyses used logistic regression, assuming an additive genetic model, and adjusted for principal components to control for population stratification. An inverse-variance fixed-effect model was adopted for meta-analysis. In addition, we examined the top variants to evaluate their associations with each criterion in the phenotyping algorithm. We used the STRING database to characterize protein-protein interaction network. RESULTS: Using the same algorithm based on the Rotterdam criteria, we identified 2995 patients with polycystic ovary syndrome and 53,599 population controls in total (2742 cases and 51,438 controls from the discovery phase; 253 cases and 2161 controls in the validation phase). We identified 1 novel genome-wide significant variant rs17186366 (odds ratio [OR]=1.37 [1.23, 1.54], P=2.8×10-8) located near SOD2. In addition, 2 loci with suggestive association were also identified: rs113168128 (OR=1.72 [1.42, 2.10], P=5.2×10-8), an intronic variant of ERBB4 that is independent from the previously published variants, and rs144248326 (OR=2.13 [1.52, 2.86], P=8.45×10-7), a novel intronic variant in WWTR1. In the further association tests of the top 3 single-nucleotide polymorphisms with each criterion in the polycystic ovary syndrome algorithm, we found that rs17186366 (SOD2) was associated with polycystic ovaries and hyperandrogenism, whereas rs11316812 (ERBB4) and rs144248326 (WWTR1) were mainly associated with oligomenorrhea or infertility. We also validated the previously reported association with DENND1A1. Using the STRING database to characterize protein-protein interactions, we found both ERBB4 and WWTR1 can interact with YAP1, which has been previously associated with polycystic ovary syndrome. CONCLUSION: Through a discovery-validation genome-wide association study on polycystic ovary syndrome identified from electronic health records using an algorithm based on Rotterdam criteria, we identified and validated a novel genome-wide significant association with a variant near SOD2. We also identified a novel independent variant within ERBB4 and a suggestive association with WWTR1. With previously identified polycystic ovary syndrome gene YAP1, the ERBB4-YAP1-WWTR1 network suggests involvement of the epidermal growth factor receptor and the Hippo pathway in the multifactorial etiology of polycystic ovary syndrome.


Assuntos
Síndrome do Ovário Policístico/genética , Receptor ErbB-4/genética , Transativadores/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Estudos de Casos e Controles , Registros Eletrônicos de Saúde , Feminino , Estudo de Associação Genômica Ampla , Humanos , Hiperandrogenismo/genética , Infertilidade Feminina/genética , Pessoa de Meia-Idade , Oligomenorreia/genética , Cistos Ovarianos/genética , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/fisiopatologia , Polimorfismo de Nucleotídeo Único , Superóxido Dismutase/genética , Fatores de Transcrição/metabolismo
7.
BMC Med ; 18(1): 72, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32204714

RESUMO

BACKGROUND: Diagnosing polycystic ovary syndrome (PCOS) during adolescence is challenging because features of normal pubertal development overlap with adult diagnostic criteria. The international evidence-based PCOS Guideline aimed to promote accurate and timely diagnosis, to optimise consistent care, and to improve health outcomes for adolescents and women with PCOS. METHODS: International healthcare professionals, evidence synthesis teams and consumers informed the priorities, reviewed published data and synthesised the recommendations for the Guideline. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied to appraise the evidence quality and the feasibility, acceptability, cost, implementation and strength of the recommendations. RESULTS: This paper focuses on the specific adolescent PCOS Guideline recommendations. Specific criteria to improve diagnostic accuracy and avoid over diagnosis include: (1) irregular menstrual cycles defined according to years post-menarche; > 90 days for any one cycle (> 1 year post-menarche), cycles< 21 or > 45 days (> 1 to < 3 years post-menarche); cycles < 21 or > 35 days (> 3 years post-menarche) and primary amenorrhea by age 15 or > 3 years post-thelarche. Irregular menstrual cycles (< 1 year post-menarche) represent normal pubertal transition. (2) Hyperandrogenism defined as hirsutism, severe acne and/or biochemical hyperandrogenaemia confirmed using validated high-quality assays. (3) Pelvic ultrasound not recommended for diagnosis of PCOS within 8 years post menarche. (4) Anti-Müllerian hormone levels not recommended for PCOS diagnosis; and (5) exclusion of other disorders that mimic PCOS. For adolescents who have features of PCOS but do not meet diagnostic criteria an 'at risk' label can be considered with appropriate symptomatic treatment and regular re-evaluations. Menstrual cycle re-evaluation can occur over 3 years post menarche and where only menstrual irregularity or hyperandrogenism are present initially, evaluation with ultrasound can occur after 8 years post menarche. Screening for anxiety and depression is required and assessment of eating disorders warrants consideration. Available data endorse the benefits of healthy lifestyle interventions to prevent excess weight gain and should be recommended. For symptom management, the combined oral contraceptive pill and/or metformin may be beneficial. CONCLUSIONS: Extensive international engagement accompanied by rigorous processes honed both diagnostic criteria and treatment recommendations for PCOS during adolescence.


Assuntos
Síndrome do Ovário Policístico/diagnóstico , Adolescente , Criança , Feminino , Guias como Assunto , Humanos
8.
Fertil Steril ; 113(3): 661-669.e2, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32192599

RESUMO

OBJECTIVE: To investigate the clinical diagnostic value and role of micro-RNAs (miRNAs) in the pathogenesis of polycystic ovary syndrome (PCOS). DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Patients were women of reproductive age with PCOS and controls. INTERVENTION(S): Summary odds ratio was calculated using a random effects model. MAIN OUTCOME MEASURE(S): Association of micro-RNAs with PCOS. METHOD(S): An electronic literature search was conducted using PubMed, Scopus, and Google Scholar databases to identify all relevant studies up to May 2019. A random effects model was used to conduct a meta-analysis. Fold change and P values were used to pool effect size. A funnel plot was used to assess publication bias. Quality score was calculated using the QUADAS scale. Subgroup analysis was based on tissue type. Odds ratios, 95% confidence intervals, and P values were estimated using meta-analysis. Metaregression was performed for correlating covariates with effect size. Area under the curve and receiver operating characteristic analysis was done to assess diagnostic performance accuracy of miRNAs in PCOS. RESULT(S): Twenty-one studies with a total of 79 miRNAs were included initially. Only three miRNAs (miR-29a-5p, miR-320, miR-93) are reported in more than three studies as of December 2018, so 12 studies were finally included in the quantitative analysis of meta-analysis and 21 studies were involved in the systematic review. The micro-RNAs miR-29a-5p and miR-320 were found to be significantly associated with PCOS. Funnel plot revealed an absence of publication bias for miR-29a-5p and miR-320. Receiver operating characteristic analysis with an area under the curve value of 0.95 proved miR-29a-5p to be the better diagnostic marker of PCOS. CONCLUSION(S): Aberrant expression of various miRNAs plays an important role in PCOS pathogenesis. Micro-RNAs hold potential diagnostic value for PCOS. These findings may offer new insights for PCOS pathogenesis research. PROSPERO REGISTRATION NUMBER: CRD42018106198.


Assuntos
Biomarcadores/análise , MicroRNAs/análise , MicroRNAs/fisiologia , Síndrome do Ovário Policístico/diagnóstico , Adulto , Estudos de Casos e Controles , Técnicas de Diagnóstico Endócrino , Técnicas de Diagnóstico Obstétrico e Ginecológico , Feminino , Humanos , MicroRNAs/genética , Síndrome do Ovário Policístico/genética
9.
Fertil Steril ; 113(4): 876-884.e2, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32147175

RESUMO

OBJECTIVE: To examine whether accounting for a woman's age and body mass index (BMI) would improve the ability of antimüllerian hormone (AMH) to distinguish between women with (cases) and without (controls) polycystic ovarian syndrome (PCOS). DESIGN: An opportunistic case-control dataset of reproductive age women having evaluations for PCOS as defined by National Institutes of Health criteria. SETTING: Two medical centers in the United States enrolled women. Serum samples were analyzed for relevant analytes. PATIENTS: Women were between 18 and 39 years of age when samples and clinical information were collected. Residual samples had been stored for 2-17 years. AMH was measured via immunoassay. INTERVENTIONS: None; this was an observational study. MAIN OUTCOME MEASURES: Detection and false-positive rates for PCOS were computed for AMH results expressed as multiples of the median (MoM) both before and after adjustment for the woman's age and BMI. RESULTS: Using unadjusted AMH MoM results, 168 cases (78%) cases were at or beyond the 90th centile of controls (2.47 MoM). After accounting for each woman's age and BMI, 188 (87%) of those women were beyond the 90th centile of controls (2.20 MoM), a significant increase (P = .015). The adjusted AMH MoM levels fitted logarithmic normal distributions well (mean, standard deviation for controls and cases of 0.0000, 0.2765 and 0.6884, 0.2874, respectively) and this allowed for computation of patient-specific PCOS risks. CONCLUSIONS: Accounting for the woman's age and BMI resulted in significantly higher AMH-based detection rates for PCOS at a 10% false-positive rate, and patient-specific PCOS risks could be computed.


Assuntos
Hormônio Antimülleriano/sangue , Índice de Massa Corporal , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/diagnóstico , Adolescente , Adulto , Fatores Etários , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Adulto Jovem
10.
Fertil Steril ; 113(2): 435-443, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32106995

RESUMO

OBJECTIVE: To study the associations between maternal polycystic ovary syndrome (PCOS) and hirsutism with offspring attention-deficit/hyperactivity disorder (ADHD), anxiety, conduct disorder, and behavioral problems. DESIGN: Prospective birth cohort study. SETTING: Not applicable. PATIENT(S): A total of 1,915 mother-child dyads. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Maternal report of offspring ADHD, anxiety, or conduct disorder diagnosis at 7 to 8 years; emotional symptoms, behavioral problems (including peer relationship, conduct, hyperactivity/inattention), and prosocial problems measured with the Strengths and Difficulties Questionnaire (SDQ) at 7 years. RESULT(S): Prevalence of PCOS and hirsutism were 12.0% and 3.9%; 84% of women with hirsutism had PCOS. After adjustment for sociodemographic covariates, prepregnancy body mass index, and parental history of affective disorders, children born to mothers with PCOS had higher risk of anxiety (adjusted risk ratio [aRR] 1.62; 95% confidence interval [CI], 1.02-2.57) and borderline emotional symptoms (aRR 1.66; 95% CI, 1.18-2.33) compared with children born to mothers without PCOS. The associations between maternal PCOS and offspring ADHD were positive but imprecise. Maternal hirsutism was related to a higher risk of children's ADHD (aRR 2.33; 95% CI, 1.28-4.24), conduct disorder (aRR 2.54; 95% CI 1.18-5.47), borderline emotional symptoms, peer relationship problems, and conduct problems (aRRs 2.61; 95% CI, 1.69-4.05; 1.92; 95% CI, 1.16-3.17; and 2.22; 95% CI, 1.30-3.79, respectively). CONCLUSION(S): Maternal PCOS was associated with offspring anxiety, and hirsutism was related to other offspring behavioral problems. These findings should be interpreted with caution as replication is needed in prospective cohort studies that assess PCOS and hirsutism diagnoses using medical records.


Assuntos
Ansiedade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtornos do Comportamento Infantil/epidemiologia , Comportamento Infantil , Transtorno da Conduta/epidemiologia , Hirsutismo/epidemiologia , Saúde Materna , Síndrome do Ovário Policístico/epidemiologia , Efeitos Tardios da Exposição Pré-Natal , Adulto , Fatores Etários , Ansiedade/diagnóstico , Ansiedade/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Criança , Transtornos do Comportamento Infantil/diagnóstico , Transtornos do Comportamento Infantil/psicologia , Transtorno da Conduta/diagnóstico , Transtorno da Conduta/fisiopatologia , Emoções , Feminino , Hirsutismo/diagnóstico , Humanos , Masculino , New York/epidemiologia , Síndrome do Ovário Policístico/diagnóstico , Gravidez , Prevalência , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Comportamento Social
11.
Trials ; 21(1): 169, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32046752

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine syndrome with poorly understood mechanisms. To provide patients with PCOS with individualized therapy, it is critical to precisely diagnose the phenotypes of the disease. However, the criteria for diagnosing the different phenotypes are mostly based on symptoms, physical examination and laboratory results. This study aims to compare the accuracy and efficacy of diagnosing PCOS by integrating metabolomic markers with common clinical characteristics. METHODS: This is a prospective, multicenter, analyst-blinded, randomized controlled trial. Participants will be grouped into (1) people without PCOS (healthy control group), (2) patients diagnosed with PCOS based on clinical indices (experimental group 1), and (3) patients diagnosed with PCOS based on metabolomic indices (experimental group 2). A total of 276 participants, including 60 healthy people and 216 patients with PCOS, will be recruited. The 216 patients with PCOS will be randomly assigned to the two experimental groups in a 1:1 ratio, and each group will receive a different 6-month treatment. The primary outcome for the experimental groups will be the effect of PCOS treatment. DISCUSSION: The results of this trial should help to determine whether using metabolomic indices is more accurate and effective than using clinical characteristics in diagnosing the phenotypes of PCOS. The results could provide a solid foundation for the accurate diagnosis of different PCOS subgroups and for future research on individualized PCOS therapy. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR-INR-1800016346. Registered 26 May 2018.


Assuntos
Metabolômica , Síndrome do Ovário Policístico/diagnóstico , Adolescente , Adulto , Biomarcadores/sangue , Biomarcadores/metabolismo , Feminino , Hormônios/metabolismo , Humanos , Metabolismo dos Lipídeos , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Exame Físico , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/terapia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
12.
Int J Gynaecol Obstet ; 149(2): 231-236, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32080845

RESUMO

OBJECTIVE: To estimate the prevalence of polycystic ovary syndrome (PCOS) among women of reproductive age across educational institutions in the Kashmir valley. METHODS: A cross-sectional study was conducted from May 2013 to May 2015. Eligible girls and women aged 15-40 years were included using a multistage random selection process from five out of 12 districts in turn housing 14 educational institutions. They were screened through a brief questionnaire in a staged manner. After obtaining consent, women underwent detailed clinical, biochemical, hormonal, and sonographic evaluation to satisfy Rotterdam 2003 criteria. The participants were also evaluated using NIH and AE-PCOS criteria. RESULTS: Out of a total of 3300 eligible women, 964 women were evaluated using a structured questionnaire. Among these, 446 (46.4%) were identified as "probable PCOS" cases. Out of 171 probable PCOS women who completed all biochemical, hormonal, and sonographic assessment, 35.3% qualified for a diagnosis of PCOS using Rotterdam criteria. The prevalence of PCOS was 28.9% by NIH criteria and 34.3% by AE-PCOS criteria. CONCLUSION: The prevalence of PCOS is high among Kashmiri women and is probably the highest in a published series globally. A countrywide systematic prevalence study is warranted to reconfirm the findings.


Assuntos
Síndrome do Ovário Policístico/epidemiologia , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Índia/epidemiologia , Síndrome do Ovário Policístico/diagnóstico , Prevalência , Inquéritos e Questionários , Adulto Jovem
13.
Trends Cardiovasc Med ; 30(7): 399-404, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-31519403

RESUMO

Although polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting women, its etiology is not entirely understood. Clinical symptoms of PCOS include acne, amenorrhea or oligomenorrhea, hirsutism, infertility, and mood disorders, which tend to be the primary focus of clinical management. However, the impact of PCOS on future cardiovascular disease (CVD) risk should not be overlooked, and opportunities to implement CVD prevention strategies in these women should be given high priority. The pathogenesis of PCOS commonly involves insulin resistance which leads to several cardiometabolic abnormalities (e.g., dyslipidemia, hypertension, glucose intolerance, diabetes, and metabolic syndrome), thereby putting women at an increased risk for CVD. Prior studies have found that subclinical CVD markers such as coronary artery calcium scores, C-reactive protein, carotid intima-media thickness, and endothelial dysfunction are more likely to be increased in women with PCOS. While the associations between PCOS and cardiometabolic abnormalities have been well established, whether PCOS is associated with subclinical and clinical CVD, independently of these CVD risk factors, is not entirely clear. Lifestyle interventions and weight management may mitigate some of these future CVD risks and should be encouraged. This review summarizes the literature on PCOS and CVD risk factors and provides recommendations that would aid clinicians in the management of these risk factors.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Estilo de Vida Saudável , Síndrome Metabólica/terapia , Síndrome do Ovário Policístico/terapia , Serviços Preventivos de Saúde , Comportamento de Redução do Risco , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Feminino , Humanos , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/fisiopatologia , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/epidemiologia , Síndrome do Ovário Policístico/fisiopatologia , Medição de Risco , Fatores de Risco , Resultado do Tratamento
14.
J Clin Endocrinol Metab ; 105(1)2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31586179

RESUMO

CONTEXT: The relationship between reproductive and cardiometabolic aging is unclear. It is unknown if the relationship differs across different clinical populations. OBJECTIVE: To determine whether markers of ovarian reserve are associated with cardiometabolic risk in reproductive aged women with unexplained infertility (UI), polycystic ovary syndrome (PCOS), and regularly cycling women (OVA). DESIGN AND SETTING: Cross-sectional data from 8 US-based academic centers. PARTICIPANTS: Women aged 25-40 from 3 clinical populations: 870 with UI, 640 with PCOS, and 921 community-based OVA. MAIN OUTCOME MEASURES: Multivariable linear regression models were used to relate anti-mullerian hormone (AMH) and antral follicle count with cardiometabolic parameters including body mass index (BMI), waist circumference (WC), fasting glucose and insulin, homeostasis model assessment-insulin resistance (HOMA-IR), lipids, and C-reactive protein. RESULTS: In age and study site-adjusted models, AMH inversely related to BMI in the UI and OVA groups (P = 0.02 and P < 0.001). Among women with PCOS, AMH inversely related to BMI (P < 0.001), and also to WC (P < 0.001), fasting insulin (P < 0.01), HOMA-IR (P < 0.01), triglycerides (P = 0.04), and C-reactive protein (P < 0.001) and directly related to higher total (P = 0.02), low-density lipoprotein (P < 0.01), and high-density lipoprotein cholesterol (P < 0.01). In OVA, AMH also varied inversely with WC (P < 0.001), fasting insulin (P = 0.02), and HOMA-IR (P = 0.02). Adjustment for BMI eliminated associations in the OVA group but in PCOS, the relationship of AMH to total (P = 0.03) and low-density lipoprotein cholesterol (P = 0.003) remained. CONCLUSION: Associations observed between AMH and cardiometabolic indices are largely explained by BMI in women with and without PCOS. (J Clin Endocrinol Metab XX: 0-0, 2019).


Assuntos
Hormônio Antimülleriano/sangue , Biomarcadores/sangue , Índice de Massa Corporal , Doenças Cardiovasculares/sangue , Infertilidade Feminina/sangue , Síndrome do Ovário Policístico/sangue , Adulto , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Seguimentos , Humanos , Incidência , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/epidemiologia , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/epidemiologia , Prognóstico , Estados Unidos/epidemiologia
15.
Arch Physiol Biochem ; 126(2): 183-186, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-30450993

RESUMO

Polycystic Ovary Syndrome is a multifactorial reproductive problem and a leading cause of female infertility worldwide. Evidences have shown that Oxidative Stress and decreased antioxidant status are often linked with PCOS. Insulin Resistance in PCOS patients ranges from 50% to 70% and may encourage OS by production of reactive oxygen species.Objective: Our study determines serum MDA levels along with plasma glucose, serum insulin, and insulin resistance in obese and nonobese PCOS subjects.Materials and methods: A case control study was conducted on diagnosed 100 PCOS patients and 100 controls. Fasting plasma glucose was measured by enzymatic method. Insulin was estimated by chemiluminescent microparticle immunoassay using Abott Architect i 2000 SR analyser. Insulin resistance was calculated by HOMA-IR. Malonaldehyde is determined as Thiobarbituric acid reactive substances.Results: CRP and serum MDA levels were increased in women with PCOS irrespective of obesity compared to their respective controls with a p value of < .001. However, though fasting glucose, serum insulin, and IR were increased in both obese and nonobese women with PCOS compared to their BMI adjusted controls with p value of < .001, the values were within reference range in nonobese women.Conclusion: Our study suggests that women with PCOS have oxidative stress and elevated CRP irrespective of obesity. However, hyperinsulinemia and Insulin resistance are seen only in obese women with PCOS, indicating that these women are at high risk for developing low grade inflammation and cardiovascular diseases.


Assuntos
Proteína C-Reativa/metabolismo , Hiperinsulinismo/sangue , Resistência à Insulina , Malondialdeído/sangue , Obesidade/sangue , Síndrome do Ovário Policístico/sangue , Adolescente , Adulto , Biomarcadores/sangue , Glicemia/metabolismo , Índice de Massa Corporal , Estudos de Casos e Controles , Jejum/sangue , Feminino , Humanos , Hiperinsulinismo/diagnóstico , Hiperinsulinismo/patologia , Insulina/sangue , Obesidade/diagnóstico , Obesidade/patologia , Ovário/metabolismo , Ovário/patologia , Estresse Oxidativo , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/patologia , Fatores de Risco
16.
Clin Chim Acta ; 502: 280-286, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31758934

RESUMO

BACKGROUND: The polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder syndrome of women in reproductive age. Metabolomic studies of the follicular fluid can reveal the potential metabolic pathways related to PCOS. The objection of this study was to explore the changes of metabolites in the follicular fluid of PCOS. METHODS: We collected follicular fluid samples of 35 patients with PCOS and 33 controls without PCOS for metabolomic analysis with UPLC Q-Exactive. The identified metabolites were annotated with KEGG and HMDB to determine the disturbances of metabolic pathways in PCOS. Based on the regression model, we conducted the ROC analysis to find the biomarker of PCOS in the follicular fluid. RESULTS: Metabolomic analysis identified 21 differential metabolites in PCOS, which revealed that the Vitamin B6 metabolism, phenylalanine metabolism and carnitine synthesis were the key changed pathways. We found that 7ß-Hydroxycholesterol was potential biomarker of PCOS based on the ROC analysis. CONCLUSION: We identified metabolic alterations and biomarker in the follicular fluid of PCOS, providing novel ways for the diagnosis and treatment of PCOS.


Assuntos
Líquido Folicular/metabolismo , Metabolômica , Síndrome do Ovário Policístico/metabolismo , Adulto , Biomarcadores/análise , Biomarcadores/metabolismo , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/patologia
17.
Clin Chim Acta ; 502: 214-221, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31733195

RESUMO

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease characterized by clinical or laboratorial hyperandrogenism, oligo-anovulation and metabolic abnormalities, including insulin resistance, excessive weight or obesity, type II diabetes, dyslipidemia and an increased risk of cardiovascular disease. The most significant clinical manifestation of PCOS is hyperandrogenism. Excess androgen profoundly affects granulosa cell function and follicular development via complex mechanisms that lead to obesity and insulin resistance. Most PCOS patients with hyperandrogenism have steroid secretion defects that result in abnormal folliculogenesis and failed dominant follicle selection. Hyperandrogenism induces obesity, hairy, acne, and androgenetic alopecia. These symptoms can bring great psychological stress to women. Drugs such as combined oral contraceptive pills, metformin, pioglitazone and low-dose spironolactone help improve pregnancy rates by decreasing androgen levels in vivo. Notably, PCOS is heterogeneous, and hyperandrogenism is not the only pathogenic factor. Obesity and insulin resistance aggravate the symptoms of hyperandrogenism, forming a vicious cycle that promotes PCOS development. Although numerous studies have been conducted, the definitive pathogenic mechanisms of PCOS remain uncertain. This review summarizes and discusses previous and recent findings regarding the relationship between hyperandrogenism, insulin resistance, obesity and PCOS.


Assuntos
Hiperandrogenismo/metabolismo , Resistência à Insulina , Obesidade/metabolismo , Síndrome do Ovário Policístico/metabolismo , Androgênios/biossíntese , Feminino , Humanos , Hiperandrogenismo/diagnóstico , Hiperandrogenismo/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Obesidade/diagnóstico , Obesidade/tratamento farmacológico , Pioglitazona/uso terapêutico , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/tratamento farmacológico , Espironolactona/uso terapêutico
18.
Fertil Steril ; 112(6): 1172-1179, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31843094

RESUMO

OBJECTIVE: To investigate the effects of body mass index (BMI) on assisted reproductive outcomes with the freeze-all strategy for patients with polycystic ovary syndrome (PCOS). DESIGN: Retrospective cohort study. SETTING: Tertiary care academic medical center. PATIENT(S): A total of 3,079 women with PCOS across different BMIs at our institution from January 2015 to May 2017 were stratified into cohorts. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation rate, clinical pregnancy rate, early miscarriage rate, and live birth rate. RESULT(S): The live birth rate was most favorable in underweight (BMI < 18.5 kg/m2) and normal weight cohorts (18.5 ≤ BMI < 25 kg/m2) and progressively decreased as BMI increased. Moreover, the obese cohort (BMI ≥ 30 kg/m2) of patients with PCOS who had frozen ET cycles had a relatively high early miscarriage rate. CONCLUSION(S): The live birth rates are highest in underweight and normal weight patients with PCOS undergoing IVF with the freeze-all strategy. Furthermore, there is a progressive and statistically significant decrease in the live birth rate and an increase in the miscarriage rate in obese patients with PCOS.


Assuntos
Índice de Massa Corporal , Criopreservação , Infertilidade Feminina/terapia , Obesidade Materna/complicações , Síndrome do Ovário Policístico/complicações , Técnicas de Reprodução Assistida , Aborto Espontâneo/etiologia , Adulto , Implantação do Embrião , Feminino , Fertilidade , Fertilização In Vitro , Humanos , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/etiologia , Infertilidade Feminina/fisiopatologia , Nascimento Vivo , Obesidade Materna/diagnóstico , Obesidade Materna/fisiopatologia , Indução da Ovulação , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/fisiopatologia , Gravidez , Taxa de Gravidez , Técnicas de Reprodução Assistida/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
19.
PLoS One ; 14(12): e0226074, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31877155

RESUMO

OBJECTIVE: To date, little is known about differences in the knowledge, diagnosis making and treatment strategies of health care providers regarding polycystic ovary syndrome (PCOS) across different disciplines in countries with similar health care systems. To inform guideline translation, we aimed to study physician reported awareness, diagnosis and management of PCOS and to explore differences between medical disciplines in the Nordic countries and Estonia. METHODS: This cross-sectional survey was conducted among 382 endocrinologists and obstetrician-gynaecologists in the Nordic countries and Estonia in 2015-2016. Of the participating physicians, 43% resided in Finland, 18% in Denmark, 16% in Norway, 13% in Estonia, and 10% in Sweden or Iceland, and 75% were obstetrician-gynaecologists. Multivariable logistic regression models were run to identify health care provider characteristics for awareness, diagnosis and treatment of PCOS. RESULTS: Clinical features, lifestyle management and comorbidity were commonly recognized in women with PCOS, while impairment in psychosocial wellbeing was not well acknowledged. Over two-thirds of the physicians used the Rotterdam diagnostic criteria for PCOS. Medical endocrinologists more often recommended lifestyle management (OR = 3.6, CI 1.6-8.1) or metformin (OR = 5.0, CI 2.5-10.2), but less frequently OCP (OR = 0.5, CI 0.2-0.9) for non-fertility concerns than general obstetrician-gynaecologists. The physicians aged <35 years were 2.2 times (95% CI 1.1-4.3) more likely than older physicians to recommend lifestyle management for patients with PCOS for fertility concerns. Physicians aged 46-55 years were less likely to recommend oral contraceptive pills (OCP) for patients with PCOS than physicians aged >56 (adjusted odds ratio (OR) = 0.4, 95% CI 0.2-0.8). CONCLUSION: Despite well-organized healthcare, awareness, diagnosis and management of PCOS is suboptimal, especially in relation to psychosocial comorbidities, among physicians in the Nordic countries and Estonia. Physicians need more education on PCOS and evidence-based information on Rotterdam diagnostic criteria, psychosocial features and treatment of PCOS, with the recently published international PCOS guideline well needed and welcomed.


Assuntos
Endocrinologistas/psicologia , Médicos/psicologia , Síndrome do Ovário Policístico/diagnóstico , Adulto , Comorbidade , Anticoncepcionais Orais/uso terapêutico , Estudos Transversais , Europa (Continente) , Feminino , Humanos , Estilo de Vida , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/terapia , Psicoterapia , Análise de Regressão , Inquéritos e Questionários
20.
Nat Med ; 25(12): 1894-1904, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31792459

RESUMO

How obesity and elevated androgen levels in women with polycystic ovary syndrome (PCOS) affect their offspring is unclear. In a Swedish nationwide register-based cohort and a clinical case-control study from Chile, we found that daughters of mothers with PCOS were more likely to be diagnosed with PCOS. Furthermore, female mice (F0) with PCOS-like traits induced by late-gestation injection of dihydrotestosterone, with and without obesity, produced female F1-F3 offspring with PCOS-like reproductive and metabolic phenotypes. Sequencing of single metaphase II oocytes from F1-F3 offspring revealed common and unique altered gene expression across all generations. Notably, four genes were also differentially expressed in serum samples from daughters in the case-control study and unrelated women with PCOS. Our findings provide evidence of transgenerational effects in female offspring of mothers with PCOS and identify possible candidate genes for the prediction of a PCOS phenotype in future generations.


Assuntos
Androgênios/metabolismo , Obesidade Materna/genética , Oócitos/metabolismo , Síndrome do Ovário Policístico/genética , Efeitos Tardios da Exposição Pré-Natal/genética , Animais , Estudos de Coortes , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Camundongos , Núcleo Familiar , Obesidade Materna/sangue , Obesidade Materna/metabolismo , Obesidade Materna/fisiopatologia , Oócitos/imunologia , Fenótipo , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/fisiopatologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Análise de Célula Única
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