Introdução: o diagnóstico da Síndrome do Ovário Policístico (SOP) na adolescência é desafiador e vem sendo alvo de intensas discussões. Sua prevalência em mulheres adultas em idade fértil varia de 5-10%. Entretanto, a prevalência em adolescentes obesas ainda não foi descrita na literatura. Somado a isso, ainda não é bem estabelecida a relação da SOP com alterações metabólicas e cardiovasculares nesta população. Dessa maneira, objetivamos avaliar a prevalência e as características da SOP na população de adolescentes obesas acompanhadas em um centro hospitalar quaternário. Métodos: realizamos um estudo transversal com 49 adolescentes obesas pós-menarca, com idade média de 15,6 anos. Foi realizada avaliação antropométrica e revisão de prontuários médicos. O hiperandrogenismo clínico e laboratorial foram quantificados utilizando o índice de Ferriman-Gallwey e as dosagens androgênicas, respectivamente. A morfologia ovariana foi avaliada por ultrassonografia suprapúbica. Todas as pacientes tiveram seus perfis metabólicos analisados. Resultados: ao adotarmos a nova Diretriz para SOP na adolescência da Sociedade de Endocrinologia Pediátrica Americana, encontramos uma prevalência de 18,4% de SOP em nossa população de adolescentes obesas. Quando utilizamos os critérios de Rotterdam, da Sociedade de Excesso Androgênico e SOP e do Instituto Nacional de Saúde Americano, as prevalências foram de 26,4%, 22,4% e 20,4%, respectivamente. A irregularidade menstrual foi constatada em 65,3% das pacientes. O hiperandrogenismo clínico foi observado em 16,3% das meninas, e 18,4% tinham concentrações de testosterona total acima do valor de normalidade. A ultrassonografia revelou que 18,4% das meninas tinham ovários policísticos. Adolescentes obesas com SOP apresentaram maior prevalência de síndrome metabólica. Conclusão: a prevalência de SOP em adolescentes obesas é alta quando comparada àquela observada na literatura / Background: polycystic ovary syndrome (PCOS) in adolescence is a challenging diagnosis and therefore has raised intense discussions. Its prevalence in childbearing age women ranges from 5 to 10%. However, the prevalence in obese adolescents has not yet been reported. Besides, the relationship of PCOS with metabolic and cardiovascular disorders in this specific population has not been established. Thus, we aimed to assess the prevalence and characteristics of PCOS in a population of obese adolescents followed at a quarternary hospital. Methods: we performed a cross-sectional study with 49 postmenarcheal obese adolescents with a mean age of 15.6 years. Anthropometric assessment and review of medical records were performed. Clinical and laboratory hyperandrogenism were evaluated using Ferriman-Gallwey index and serum androgens, respectively. The ovarian morphology was evaluated by supra-pubic ultrasound. All patients had their metabolic profile evaluated. Results: the prevalence of PCOS in obese adolescents, according to the new guideline for PCOS in adolescence of the American Pediatric Endocrinology Society, was 18.4%. When assessed by the Rotterdam, the Androgen Excess and PCOS Society and the National Institute of Health criteria, the prevalence of PCOS was 26.4%, 22.4% and 20.4%, respectively. Menstrual irregularity was found in 65.3% of the patients. Clinical hyperandrogenism was observed in 16.3% while 18.4% had total testosterone concentrations above the normal range. Ultrasonography revealed that 18.4% had polycystic ovaries. Obese adolescents with PCOS had higher prevalence of metabolic syndrome. Conclusion: the prevalence of PCOS in obese adolescents is high compared to that observed in the literature

A síndrome dos ovários policísticos (SOP) é um distúrbio endócrino complexo e heterogêneo, caracterizado por hiperandrogenismo e anovulação crônica. Dentre as manifestações clínicas do hiperandrogenismo, o hirsutismo é o mais frequente e pode estar presente em cerca de 70% das pacientes com SOP. Sabe-se que o crescimento e diferenciação do pelo são regulados por fatores locais, endócrinos, parácrinos e genéticos. No entanto, a fisiopatologia do hirsutismo ainda é pouco conhecida. O gene BMP4 (que codifica a Proteína Morfogenética Óssea-4) relaciona-se ao controle do crescimento e diferenciação do pelo, porém não há estudos sobre seu papel no hirsutismo em mulheres com síndrome dos ovários policísticos. Foram estudadas 245 mulheres, 142 SOP e 103 controles em que analisaram-se os polimorfismos rs4898820 e 538 T/C, para verificar frequências genotípicas e alélicas. Nas pacientes com SOP foi investigada a existência de associação entre esses polimorfismos e hirsutismo e parâmetros laboratoriais e clínicos. Não houve diferença significante na frequência dos polimorfismos entre os grupos. Não houve associação dos polimorfismos com hirsutismo. Quando analisados os exames laboratoriais das mulheres com SOP, houve associação do genótipo mutado do polimorfismo 538 T/C (CC) com níveis mais altos de SHBG, menores de glicemia e maior sensibilidade à insulina. Houve também associação entre os alelos mutados (CC ou TC), com menores níveis de testosterona livre. Encontrou-se diferença significante para o FSH nas portadoras do genótipo mutado para o polimorfismo rs4898820 (TT). Não houve associação dos polimorfismos com hirsutismo / Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disorder characterized by chronic anovulation and hiperandrogesnism. Among the clinical manifestations of hyperandrogenism, hirsutism is the most frequent and may be present in approximately 70% of patients with PCOS. It is known that the hair growth and differentiation are coordinated by local, endocrine, paracrine and genetic factors. However, the pathophysiology of hirsutism is poorly understood. BMP-4 (Bone Morphogenetic Protein-4) is a gene involved in the hair growth and differentiation, but there are no studies about its action in hirsutism in women with polycystic ovary syndrome. A total of 245 women, 142 with PCOS diagnostic and 103 control women were studied to investigate the the allelic frequency of the single nucleotide polymorfisms rs4898820 and 538 T/C in PCOS in comparison with the control group. In PCOS group, we sought to investigate a possible association between the genetic variations and the hirsutism. There were no differences for the polymorphisms between groups. There was no association between the genotypes and the presence of hirsutism in PCOS women. When the polymorphisms were analyzed in the PCOS group, those who had homozygous genotype for 538 T/C (CC) had lower levels of SHBG, lower levels of glucose and better insulin sensitivity. Mutated allele (CC or TC), were associated with lower levels of free testosterone. Those who had the mutated genotype for the polymorphism rs4898820 (TT) had higher levels of FSH

Objetivos: Avaliar o fuso meiótico e a distribuição cromossômica de oócitos maturados in vitro obtidos de ciclos estimulados de mulheres inférteis com Síndrome dos Ovários Policísticos (SOP) e fatores masculino e/ou tubário de infertilidade. Métodos: Vinte e seis pacientes inférteis com SOP e 48 pacientes com fator tubário e/ou masculino de infertilidade, submetidas a ciclos estimulados para captação oocitária para injeção intracitoplasmática de espermatozóide, foram selecionadas prospectiva e consecutivamente e divididas em grupos de estudo e controle, respectivamente. Oócitos imaturos (34 e 56 oócitos) foram obtidos de 13 e 27 pacientes, respectivamente, dos grupos SOP e controle, sendo submetidos à maturação in vitro (MIV), respectivamente, por 19 horas ± 1 hora (VG) e 4 horas ± 30 minutos (MI), conforme curva de MIV previamente realizada no presente serviço. Oócitos em metáfase II (MII) após MIV, foram fixados, submetidos a imunocoloração e microscopia de fluorescência para avaliação morfológica do fuso e da distribuição cromossômica. Resultados: Não observamos diferença significativa nas taxas de MIV entre os dois grupos avaliados (50% e 42,8%, respectivamente, para os grupos SOP e controle). Na análise por microscopia de imunofluorescência, detectaram-se 3 e 2 oócitos, respectivamente, no grupo de estudo e no grupo controle, em estágio de Telófase I e 3 oócitos ativados partenogeneticamente no grupo controle. Ocorreu a impossibilidade de análise de 4 oócitos do grupo controle em virtude de dificuldades técnicas durante o processo de imunocoloração. Não houve diferença significativa nas proporções de anomalias meióticas entre os grupos SOP e controle (57,1 e 46,7%, respectivamente). Conclusões: Os dados preliminares do presente estudo, apesar de não demonstrarem aumento significativo na incidência de anomalias meióticas nas portadoras de SOP, sugerem uma tendência a maior ocorrência de anomalias meióticas nos oócitos deste grupo de pacientes, quando comparados aos de portadoras de fator masculino e/ou tubário de infertilidade, o que deverá ser mais bem avaliado em estudos com maiores casuísticas. Estes achados têm potencial clínico para apontar uma possível explicação para as controversas menores taxas de fertilização observadas em pacientes com SOP submetidas às Técnicas de Reprodução Assistida. / Objectives: To evaluate the meiotic spindle and the chromosome distribution of in vitro matured oocytes obtained during stimulated cycles from infertile women with Polycystic Ovary Syndrome (PCOS) and with male factor and/or tubal infertility. Methods: Twenty six infertile patients with PCOS and 48 patients with infertility due to tubal and/or male factor, submitted to stimulated cycles for oocyte retrieval for intracytoplasmic sperm injection, were selected prospectively and consecutively and respectively assigned to the study group and the control group. Imature oocytes (34 and 56 oocytes) were obtained from 13 and 27 patients, respectively, of PCOS and control groups, and submitted to in vitro maturation (IVM) for 19 hours ± 1 hour (GV) and 4 hours ± 30 minutes (MI) according to the IVM curve previously constructed in the present service. After IVM, oocytes in metaphase II (MII) were fixed and submitted to immunostaining and fluorescence microscopy for morphological evaluation of the spindle and of chromosome distribution. Results: IVM rates were similar between the two analyzed groups (50% e 42.8%, respectively, in PCOS e control groups). By immunofluorescence analysis, there were 3 and 2 oocytes, respectively, in PCOS e control groups, in telophase I stage, and 3 parthenogenetic activated oocytes in control group. Because of technical difficulties during the execution of the immunofluorescence protocol, 4 oocytes from the control group could not be analyzed. The difference in the proportions of meiotic anomalies between the two groups was not statistically significant (57.1 e 46.7%, respectively, in PCOS e control groups). Conclusions: The present preliminary data, although not showing a significant increase in the incidence of meiotic anomalies in women with PCOS, suggest a tendency to a higher occurrence of meiotic anomalies in the oocytes of this group of patients compared to women with male and/or tubal infertility, a fact to be better evaluated in studies on larger patient series. The present findings have the clinical potential to provide a possible explanation for the controversial lower fertilization rates observed in patients with PCOS submitted to Assisted Reproduction Techniques

A síndrome dos ovários policísticos (SOP) é um distúrbio endócrino complexo, associado a resistência insulínica, hiperinsulinemia, obesidade, acúmulo de gordura visceral e dislipidemia. Essas alterações podem levar a aumento de risco de doenças como \"diabetes mellitus\", doenças cardiovasculares, esteatose hepática ou até mesmo esteato-hepatite. Em ratas, o excesso de androgênios ou estrogênios no período neonatal induz a alterações metabólicas e reprodutivas similares às observadas na SOP em humanos. O objetivo deste estudo é analisar os efeitos da exposição neonatal à testosterona e ao estrogênio no fígado de ratas adultas. Para isso foram utilizadas 30 ratas, divididas em três grupos de 10 animais cada. Foi administrada por via subcutânea, entre 1 e 3 dias de vida, uma única dose dos seguintes compostos: 0,1 mL de óleo de oliva (veículo) - grupo Controle (n=10); propionato de testosterona (1,25 mg/0,1mL de veículo) - grupo Testosterona (n=10); benzoato de estradiol (0,5 mg/0,1mL de veículo) - grupo Estradiol (n=10), de acordo com o grupo a que pertenciam. Após cerca de 90 dias, os animais foram sacrificados, sendo retirados fragmentos do fígado que foram preparados para análise da metabolômica e da histomorfologia. Histologicamente, o fígado dos animais do grupo testosterona apresentaram maior infiltração gordurosa e infiltrado inflamatório; e do grupo estradiol apresentou hepatócitos binucleados, além do aumento do volume nuclear. Houve, no grupo testosterona modificações no perfil metabolômico ligadas a maior resistência à insulia e maior risco para diabete. O grupo exposto ao estrogênio apresentou alterações relacionadas ao metabolismo e síntese de lipídeos. Nossos resultados sugerem que os riscos metabólicos associados à SOP podem ter origem e mecanismos diferentes / Polycystic ovary syndrome (PCOS) is a complex endocrine disorder associated with insulin resistance, hyperinsulinemia, central obesity, accumulation of visceral fat and dyslipidemia. Those changes can lead to increased risk of diseases such as diabetes mellitus, cardiovascular disease, nonalcoholic fat liver disease or even nonalcoholic steatohepatitis. In rats, the excess of androgens or estrogens in the neonatal period leads to metabolic and reproductive alterations similar to those observed in SOP in humans. The objective of this study is to analyze the effects of exposure to neonatal testosterone and estrogen in the liver of adult rats. For this we used 30 female rats, sorted into three groups of 10 animals each. It was administered subcutaneously between 1 and 3 days of age a single dose of the following compounds: 0.1 mL olive oil (vehicle) - Control Group (n = 10); testosterone propionate (1.25 mg / 0.1 mL vehicle) - Testosterone (n = 10); estradiol benzoate (0.5 mg / 0.1 mL vehicle) - Estradiol group (n = 10). After 90 days, the animals were sacrificed, and the liver removed fragments were prepared for analysis of metabolomics and histomorphometry. Histologically, the testosterone group displayed greater fat deposition and higher degree of inflammatory infiltration. The estradiol group had binucleate hepatocytes and increased nuclear volume. Testosterone group showed changes in the metabolomic profile linked to increased insulin resistance and increased risk for diabetes mellitus. The group exposed to estrogen showed changes related to metabolism and synthesis of lipids. Our results indicate that the metabolic risks associated with PCOS may have origin and different mechanisms

Made available in DSpace on 2016-08-19T18:16:05Z (GMT). No. of bitstreams: 1 dissertacao Debora.pdf: 708623 bytes, checksum: e13258642ac00185a278de8f61921fca (MD5) Previous issue date: 2012-10-30 / BACKGROUND: Polycystic ovary syndrome (PCOS) has been correlated with metabolic syndrome (MS), both with common characteristics regarding the altered lipid profile, obesity, hypertension and the occurrence of cardiovascular diseases. OBJECTIVES: Identify the prevalence of Metabolic Syndrome in women with PCOS and its association with cardiovascular risk markers. METHODS: Cross-sectional, prospective. 191 women between 18 and 42 years were evaluated in the Clinic of Gynecology, University Hospital Maternal-Child Unit of the Federal University of Maranhão, leaving 82 patients with PCOS. The patients underwent a clinical evaluation and screening with detailed history, conducting biochemical and ultrasonographic examinations. To collect data, we used two sheets of protocol, with questionnaires containing identification, weight, height, among other measures, in addition to personal, family, and gynecological history. RESULTS: In women with PCOS, the presence of metabolic syndrome was observed in 21%. In this group, the significant clinical variables were age group from 26 to 32 years (59%), obesity (82%) and acanthosis nigricans (87%). Among the diagnostic criteria for MS, the most common were HDL and waist circumference change (65% and 39%, respectively). Regarding inflammatory markers, only elevated CRP was significant (p value = 0.0030). CONCLUSION: The present study showed a high prevalence of women with MS, mostly young and obese women. Their risk of cardiovascular disease was associated with increased CRP level. / Introdução: A síndrome dos ovários policísticos tem sido correlacionada com a Síndrome Metabólica, ambas com características comuns quanto à alteração do perfil lipídico, obesidade, hipertensão e a ocorrência de doenças cardiovasculares. Objetivo: Identificar a prevalência de Síndrome Metabólica em mulheres com síndrome dos ovários policísticos e sua associação com marcadores de risco cardiovascular. Metodologia: Transversal. Foram avaliadas 191 mulheres entre 18 e 42 anos atendidas no Ambulatório de Ginecologia do Hospital Universitário Unidade Materno-Infantil da Universidade Federal do Maranhão, restando 82 pacientes com síndrome dos ovários policísticos. As pacientes foram submetidas a uma triagem com avaliação clínica e anamnese detalhada, realização de exames bioquímicos e ultrassonográficos. Para a coleta de dados, foram utilizadas duas fichas de protocolo, com questionários sobre identificação, peso, altura, dentre outras medidas, além de antecedentes pessoais, familiares e ginecológicos. Resultados: Nas portadoras de síndrome dos ovários policísticos, a presença de síndrome metabólica foi constatada em 21%. Neste grupo, as variáveis clínicas significativas foram a faixa etária de 26 a 32 anos (59%), obesidade (82%) e acantose nigricans (87%). Dentre os critérios diagnósticos para síndrome metabólica, os mais freqüentes foram HDL e circunferência da cintura alterados (65% e 39%, respectivamente). Em relação aos marcadores inflamatórios, somente a PCR-US elevada foi significante (p valor = 0,0030). Conclusão: O presente estudo evidenciou alta prevalência de mulheres com SM, em sua maioria jovens e obesas. O risco das mesmas para doença cardiovascular associou-se à PCR-US aumentada.

Made available in DSpace on 2016-08-19T18:16:05Z (GMT). No. of bitstreams: 1 Dissertacao Joelma.pdf: 599807 bytes, checksum: 496d32d46e118e53ae391f662bfa6dbd (MD5) Previous issue date: 2012-10-29 / FUNDAÇÃO DE AMPARO À PESQUISA E AO DESENVOLVIMENTO CIENTIFICO E TECNOLÓGICO DO MARANHÃO / The polycystic ovary syndrome (PCOS) is considered the most common endocrine disease during the woman's reproductive life, with prevalence ranging from 5 to 10% of women of reproductive age and is characterized by chronic anovulation and hyperandrogenism, showing complex multifactorial pathogenesis. Objective: To determine the cutoff the lipid accumulation product in women with polycystic ovary syndrome. Methods: Cross-sectional study with 78 women between 18 and 42 years diagnosed with polycystic ovary syndrome according to the Rotterdam criteria directed to nutritional evaluation at the Maternal and Child Unit of the University Hospital UFMA. The interest variables were recorded in protocol form: socio-demographic, behavioral, gynecological history, personal and family history of diseases, anthropometric data (weight, height, body mass index and waist circumference), laboratory tests, imaging exams and blood pressure values. The product of lipid accumulation was calculated by the formula described by Kahn. Regarding the analysis of data normality of quantitative variables was analyzed by the Shapiro Wilk; to compare the means of the variables we used the t Student test. To check the correlation between the lipid product accumulation and cardiovascular risk markers was applied Linear Correlation coefficient (r) test. The lipid product accumulation was analyzed according to the Receiver Operating Characteristic Curve, being discriminated values of high sensitivity and specificity simultaneously. The significance level for all tests was 5%. Results: Using the Receiver Operating Characteristic curve to determine the best cutoff of predicted LAP index risk for cardiovascular disease, it was noted that the value above 39.32 cm.mmol/L representing the area under the 0.8845 of the curve. Every women who had lipid product accumulation product value above the cutoff defined also showed the highest changes in mean of risk markers analyzed of cardiovascular diseases, a statistically significant difference. Regarding the analysis of correlation between the product of lipid accumulation above the cutoff defined and risk markers for cardiovascular diseases, there was a significant correlation. Conclusion: These results demonstrate that cutoff values ≥ 39.32 cm.mmol/L of LAP index seems to indicate the increased risk for CVD and should be used as a screening tool and research for its ease of measurement and interpretation, as well as its low cost and may even have its applicability in primary health care. / A síndrome dos ovários policísticos (SOP) é considerada a endocrinopatia mais comum durante a vida reprodutiva da mulher, com prevalência que varia entre 5 a 10% das mulheres em idade fértil sendo caracterizada por anovulação crônica e hiperandrogenismo, apresentando fisiopatogenia complexa de caráter multifatorial. Objetivo: Determinar o ponto de corte do produto da acumulação lipídica em mulheres com síndrome dos ovários policísticos. Metodologia: Estudo transversal realizado com 78 mulheres entre 18 e 42 anos atendidas no Hospital Universitário Unidade Materno-Infantil da Universidade Federal do Maranhão com o diagnóstico de síndrome dos ovários policísticos de acordo com os critérios de Rotterdam. As variáveis de interesse foram registradas em ficha-protocolo com: dados sócio-demográficos, comportamentais, história ginecológica, antecedentes pessoais e familiares de patologias, dados antropométricos (peso, altura, índice de massa corporal e circunferência da cintura), exames laboratoriais, exame de imagem e valores de pressão arterial. O produto da acumulação lipídica foi calculado pela fórmula descrita por Kahn. Com relação à análise de dados a normalidade das variáveis quantitativas foi analisada pelo teste Shapiro Wilk, para comparação das médias das variáveis utilizou-se o Teste t de Student. Na verificação de Correlação entre o produto da acumulação lipídica e os marcadores de risco cardiovascular foi aplicado o teste de Correlação Linear de Pearson (r). O produto da acumulação lipídica foi submetido à análise segundo a Curva Receiver Operating Characteristic, sendo discriminados os valores de maior sensibilidade e especificidade, simultaneamente. O nível de significância para todos os testes foi de 5%. Resultados: Utilizando-se a Curva Receiver Operating Characteristic para determinar o melhor ponto de corte do produto da acumulação lipídica preditivo de risco para doença cardiovascular, notou-se que o valor acima de 39,32 cm.mmol/L, representou a área sob a curva de 0,8845. Todas as mulheres que apresentaram o valor do produto da acumulação lipídica acima do ponto de corte definido, também apresentaram as maiores alterações nas médias dos marcadores de risco de doença cardiovascular analisados, diferença estatisticamente significativa. No que concerne à análise de correlação entre o produto da acumulação lipídica acima do ponto de corte definido e os marcadores de risco para doenças cardiovasculares, houve uma correlação significativa. Conclusão: Estes resultados demonstram que valores de ponto de corte ≥ 39,32 cm.mmol/L do produto da acumulação lipídica parecem apontar risco aumentado à doença cardiovascular e pode ser utilizado como ferramenta de triagem e investigação pela sua facilidade de mensuração e interpretação, além do baixo custo, podendo ter, inclusive, sua aplicabilidade na atenção primária em saúde.

Το σύνδρομο των πολυκυστικών ωοθηκών (PCOS) είναι ίσως η συχνότερη διαταραχή των γυναικών αναπαραγωγικής ηλικίας. Οι κύριες κλινικές εκδηλώσεις του συνδρόμου είναι η υπερανδρογοναιμία και η χρόνια ανωοθυλακιορρηξία, ενώ σχετίζεται σε μεγάλο βαθμό με την παχυσαρκία και την αντίσταση στην ινσουλίνη. Η αντίσταση στην ινσουλίνη έχει ένα σημαντικό ρόλο τόσο ως αίτιο όσο και ως αποτέλεσμα του συνδρόμου. Στις γυναίκες τόσο η υπερινσουλιναιμία όσο και η υπερανδρογοναιμία σχετίζεται με αυξημένο καρδιοαγγειακό κίνδυνο. Το PCOS σχετίζεται με αυξημένο καρδιοαγγειακό κίνδυνο, ενώ τόσο η αλλαγή τρόπου ζωής και η φαρμακολογική παρέμβαση έχει δειχθεί ότι βελτιώνει την υπερανδρογοναιμία και την υπογονιμότητα και ελαττώνει τον καρδιοαγγειακό κίνδυνο. Μαζί με τους κλασικούς καρδιοαγγειακούς παράγοντες κινδύνου, αιμοδυναμικές και αιματολογικές μεταβλητές παίζουν σημαντικό ρόλο στην παθογένεση της αθηρωσκλήρυνσης. Η γλοιότητα του πλάσματος είναι σημαντική αιματολογική μεταβλητή και εξαρτάται απο μακρομόρια όπως το ινωδογόνο, οι ανοσοσφαιρίνες και οι λιποπρωτεϊνες. Ο σκοπός της παρούσης μελέτης ήταν να ερευνήσει τις μεταβολές της γλοιότητας του πλάσματος σε γυναίκες με PCOS και την συσχέτιση τους με την υπερανδρογοναιμία, την παχυσαρκία και την αντίσταση στην ινσουλίνη. Η μελέτη συμπεριέλαβε 96 ασθενείς με PCOS και 72 γυναίκες με φυσιολογική έμμηνο ρύση ως ομάδα ελέγχου. Η γλοιότητα πλάσματος ήταν 1.243±0.670 mm2/s στην ομάδα ελέγχου (n=72), και 1.250±0.079 στιν γυναίκες με PCOS (n=96) (p=0.524). Η γλοιότητα του πλάσματος εμφάνισε σημαντική συσχέτιση με BMI (b=0.315, p=0.013), Ολικές Πρωτείνες (b=0.348, p=0.005), AUCIns (b=0.320, p=0.011). Στις γυναίκες με PCOS με αντίσταση στην ινσουλίνη (PCOS-IR) η γλοιότητα του πλάσματος ήταν 1.300 ± 0.055 mm2/s, ενώ στις γυναίκες με PCOS χωρίς αντίσταση στην ινσουλίνη (PCOS-ΝIR) η γλοιότητα του πλάσματος ήταν 1.231± 0.49 mm2/s (p=0.004). Στη συνέχεια χωρίσαμε όλες τις γυναίκες με PCOS σε 2 υποομάδες: αυτές με BMI<25 και αυτές με BMI>25. Η γλοιότητα πλάσματος ήταν 1.235±0.786mm2/s στις γυναίκες με PCOS και BMI<25, και 1.273±0.756mm2/s στις γυναίκες με PCOS και BMI>25 (p=0.024). Σε νέες γυναίκες με PCOS η αύξηση της γλοιότητας του πλάσματος συσχετίσθηκε με την παχυσαρκία και την αντίσταση στην ινσουλίνη. Συμπερασματικά στις νέες γυναίκες με PCOS η γλοιότητα του πλάσματος επιδεινώθηκε από την αντίσταση στην ινσουλίνη. Καθώς η αυξημένη γλοιότητα του πλάσματος είναι ένας πρώιμος παράγοντας κινδύνου για καρδιοαγγειακή νόσο, ο κλινικός χειρισμός των νέων υπέρβαρων γυναικών με PCOS θα πρέπει πάντα να περιλαμβάνει μία μείωση του σωματικού τους βάρους και τη λελογισμένη και με προσοχή χρήση των αντισυλληπτικών δισκίων ως θεραπευτική προσέγγιση. / Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility in women. PCOS is characterized by hirsutism, anovulation, hyperandrogenemia and is also highly associated with obesity and insulin resistance. Insulin resistance plays a significant role, both as a cause and as a result of the syndrome. Both hyperinsulinemia and androgen excess in women is associated with increased cardiovascular risk. PCOS is linked to cardiovascular disease, while, altering lifestyle or pharmacological intervention has been shown to improve hyperandrogenism and infertility and reduce cardiovascular risk. Along with classic cardiovascular risk factors, hemodynamic and hemorheologic variables play an important role in the pathogenesis of atherosclerosis. Plasma viscosity is an important hemorheologic variable and is mainly determined by several macromolecules, including fibrinogen, immunoglobulins, and large lipoproteins. Our objective was to investigate plasma viscosity in women with PCOS. The acquired data were tested for association with hyperandrogenemia, obesity and insulin resistance in PCOS patients. The study included 96 young PCOS women and 72 healthy controls. Plasma viscosity was 1.243±0.670 mm2/s in the control group and 1.250±0.079 in PCOS women (p=0.524). Total protein (B=0.348, p=0.005), AUC for Insulin (B=0.320, p=0.011) and BMI (B=0.315, p=0.013) were proven to be significantly correlated to plasma viscosity. Plasma viscosity was significantly increased in PCOS women with Insulin Resistance (IR) compared to matched for age and BMI PCOS women without IR (1.300±0.055 mm2/s versus 1.231±0.049 mm2/s) (p=0.004). Then we divided all PCOS women in two separate groups, lean PCOS with BMI<25 and obese PCOS with BMI>25. Plasma viscosity was 1.235±0.786mm2/s in PCOS women with BMI<25, in the group of women was and 1.273±0.756mm2/s in PCOS women with BMI>25 (p=0.024). Young PCOS women presented a plasma viscosity which was increased by obesity and IR. In conclusion, young PCOS women presented a plasma viscosity which was deteriorated by IR. As increased plasma viscosity is an early risk factor for cardiovascular disease, clinical management of young overweight PCOS women with IR should always include a serious reduction in body weight and the use of oral contraceptive treatment with cautious.

Disease-specific compounds (biomarkers) are analyzed in clinical laboratories to assist with diagnosing diseases. This thesis describes development and validation of liquid chromatography tandem mass spectrometry (LC-MS/MS) based tests for diagnosing a diverse group of endocrine and metabolic diseases. The analytical methods used on-line and off-line sample extraction and analytical derivatization as means of enhancing the analytical sensitivity, specificity and clinical utility. All developed methods were extensively validated and reference intervals for the biomarker concentrations were established in blood samples of healthy adults and children. Advantages of the LC-MS/MS as an analytical technique include possibility of simultaneous measurement of multiple analytes and ability of confirming their identity. In this thesis we proposed and evaluated approaches for the assessment of the specificity of analysis in the methods that use tandem mass spectrometry detection. To enhance throughput of the LC-MS/MS tests for the biomarkers that have endogenous or exogenous isomers an approach was developed for quantitation of isomers from unresolved chromatographic peaks. Using methods developed in this thesis we performed a study of the steroidogenesis in ovarian follicles of healthy women and women with polycystic ovary syndrome (PCOS). Obtained data on the steroid concentrations and associations between the steroid metabolites in the pathway would be helpful for better understanding of the ovarian pathophysiology. Potential biomarkers of PCOS were identified in the thesis; further studies will be necessary to confirm their clinical utility.

Diss. (sammanfattning) Stockholm : Karolinska institutet 2006. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2005. / Härtill 4 uppsatser.