O exercício físico é intervenção de primeira linha e parece melhorar os sintomas da síndrome dos ovários policísticos (SOP). Porém, os mecanismos dessas alterações ainda são pouco entendidos. O objetivo desse estudo foi avaliar os efeitos do exercício voluntário sobre os aspectos metabólicos e reprodutivos de modelos murinos de SOP induzida por dihidrotestosterona (DHT) ou letrozol (LET). Péletes de DHT ou LET foram utilizados para a indução de SOP experimental em camundongas pré-puberes. Os camundongos controles receberam péletes sem substância ativa. Cinco semanas após a exposição aos compostos teve início o exercício voluntário em rodas de corrida. Foram avaliados peso, composição corporal, tolerância à insulina e à glicose e o ciclo estral. Os grupos experimentais foram: controle (n=9), DHT (n=10), LET (n=9), DHT+exercício (EX) (n=9) e LET+EX (n=10). Após 4-5 semanas de exercício, os animais foram eutanasiados e os tecidos adiposos inguinal e mesentérico foram utilizados para análises morfológicas e moleculares. O grupo DHT apresentou aumento do peso corporal, aumento da proporção de grandes adipócitos mesentéricos e ciclo estral anormal. O grupo LET apresentou aumento do peso corporal e massa gorda, diminuição da sensibilidade à insulina, aumento da população de adipócitos pequenos, aumento da expressão de genes relacionados à lipólise na gordura mesentérica e ciclo estral anormal. O exercício reduziu a massa gorda e a expressão de genes da via NOTCH no tecido adiposo inguinal e mesentérico, e restaurou a morfologia alterada dos adipócitos mesentéricos, e a expressão de genes da via do NOTCH foi negativamente correlacionada com a expressão de genes da via de browning (transformação da gordura branca em gordura de fenótipo marrom) nos grupos DHT+EX e LET+EX. Em conclusão, o exercício restaurou a morfologia dos adipócitos mesentéricos em modelos animais de SOP induzida por DHT e LET, melhorou a sensibilidade à insulina, aumentou a expressão mesentérica de genes relacionados à lipólise e melhorou o ciclo estral em modelo animal de SOP induzida por LET. Esses benefícios podem ser atribuídos, pelo menos em parte, pela inibição de genes da via do NOTCH e pela modulação das vias de browning e lipólise no tecido adiposo / Exercise is the first line treatment and it seems to improve the symptoms of polycystic ovary syndrome (PCOS), but the mechanisms of these alterations are still poorly understood. The objective of this study was to evaluate the effects of voluntary exercise on metabolic and reproductive aspects of PCOS mouse models induced by dihydrotestosterone (DHT) or letrozole (LET). DHT or LET pellets were used for the induction of experimental PCOS in prepubertal mice. Control mice received placebo pellets. Five weeks after exposure to the substances, voluntary exercise on running wheels began. Body weight, body composition, insulin and glucose tolerance, and estrous cycle were evaluated. The experimental groups were control (n = 9), DHT (n = 10), LET (n = 9), DHT+exercise (EX) (n = 9) and LET+EX (n = 10). After 4-5 weeks of exercise, the animals were euthanized and the inguinal and mesenteric fat depots were collected for morphological and molecular analyzes. The DHT group showed increased body weight, increased proportion of large mesenteric adipocytes and abnormal estrous cycle. The LET group presented increased body weight and fat mass, decreased insulin sensitivity, increased population of small adipocytes, increased expression of genes related to lipolysis in mesenteric fat and abnormal estrous cycle. Exercise reduced fat mass and NOTCH pathway gene expression in inguinal and mesenteric adipose tissue, and restored the altered morphology of mesenteric adipocytes, and NOTCH pathway gene expression was negatively correlated with gene expression of the browning (transformation from white fat to brown-like fat) markers in both DHT+EX and LET+EX groups. In conclusion, the exercise restored the mesenteric adipocyte morphology in the DHT- and LET-induced PCOS mouse models, and the insulin sensitivity, the mesenteric expression of genes related to lipolysis, and improved the estrous cycle in the LET-induced PCOS mouse model. These benefits may be attributed, at least in part, to the inhibition of NOTCH pathway genes and the modulation of browning and lipolysis pathways in the adipose tissue

VIEIRA, TMB. Qualidade de Vida em Mulheres Obesas e com Síndrome dos Ovários Policísticos. 2010. 65 fls. Dissertação (Mestrado) - Faculdade de Medicina de Ribeirão Preto. Universidade de São Paulo. Ribeirão Preto. 2010. A síndrome dos ovários policísticos (SOP) é uma das desordens endócrinas mais comuns na idade reprodutiva, sendo a sua prevalência de 6 a 10% na população feminina. A SOP associada à obesidade pode agravar a saúde física e mental com um impacto negativo no funcionamento bio-psico-social. Os distúrbios metabólicos e as manifestações clínicas do hiperandrogenismo, comuns em mulheres com SOP tem levado ao aumento dos distúrbios psicológicos e redução na qualidade de vida (QV). Alguns estudos têm mostrado uma piora da QV na SOP, mas não fazem distinção sobre os efeitos que a própria obesidade pode acarretar a QV, uma vez que mais de 50% das pacientes SOP apresentam sobrepeso e obesidade. O presente estudo objetivou avaliar se há diferença na QV de pacientes com SOP obesas comparadas a controles obesas com ciclos ovulatórios. Foram incluídas 35 obesas com SOP e 28 obesas com ciclos ovulatórios, com idade entre 20 e 40 anos, IMC 30 e que aceitaram assinar o TCLE. Utilizou-se para a caracterização da população o questionário sócio-demográfico, médico, reprodutivo e somatométrico e para a avaliação da qualidade de vida, o questionário SF-36, que avalia os componentes da saúde física e os componentes da saúde mental. As pacientes com SOP mostraram melhor escore no que diz respeito ao domínio da capacidade funcional (73,43±20,57 vs 59,46±22,08) (p=0,01). Para os demais domínios não houve diferenças significativas entre os grupos. Nossos resultados sugerem que o aumento de androgênios comum em obesas com SOP possa estar associado à melhor capacidade funcional. / VIEIRA, TMB. Quality of Life of Obese Women With Polycystic Ovary Syndrome. 2010. 65 fls. Dissertation (Master). Faculdade de Medicina de Ribeirão Preto. Universidade de São Paulo, Ribeirão Preto, 2010. Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders occurring during reproductive age, with a prevalence of 6 to 10% in the female population. PCOS associated with obesity can affect physical and mental health, with a negative impact on biopsychosocial functioning. The metabolic disorders and clinical manifestations of hyperandrogenism, common among women with PCOS, have led to an increase in psychological disorders and a reduction of quality of life (QL). Some studies have shown a worsening of QL in PCOS but without distinguishing between the effects that obesity itself may have on QL, since more than 50% of patients with PCOS are overweight or obese. The objective of the present study was to determine whether there is a difference in the QL of obese patients with PCOS compared to obese controls with ovulatory cycles. The study was conducted on 35 obese women with PCOS and 28 obese women with ovulatory cycles aged 20 to 40 years, with a BMI 30, who gave written informed consent to participate. A sociodemographic, medical, reproductive and somatometric questionnaire was used to characterize the population and QL was assessed with the SF-36 questionnaire, which evaluates the components of physical and mental health. The patients with PCOS had a better score regarding the functional capacity domain (73,43±20,57 vs 59,46±22,08) (p=0,01), whereas no significant differences were observed beween groups regarding the remaining domains. The present results suggest that the increase in androgens commonly occurring among obese women with PCOS may be associated with their better functional capacity.

A síndrome dos ovários policísticos (SOP) e a obesidade estão associadas ao aumento do risco cardiovascular, mas não está estabelecido se tal aumento é determinado por estas condições propriamente ditas ou pelos fatores de risco cardiometabólicos a elas associados. Objetivo: determinar, em mulheres jovens e sem fatores de risco cardiometabólicos, a influência da SOP e da obesidade sobre parâmetros vasculares relacionados ao processo de aterogênese. Métodos: foram estudadas pacientes com SOP, subdivididas em portadoras de índice de massa corpórea (IMC) normal e obesas, as quais foram comparadas a mulheres sem SOP (grupo controle) pareadas para o IMC. Foram excluídas participantes tabagistas, com distúrbios do metabolismo da glicose, hipertensão arterial, LDL-C 160 mg/dL e triglicérides 250 mg/dL. Foram avaliados parâmetros clínicos, laboratoriais (perfis hormonal e metabólico) e vasculares [espessura íntimamédia da artéria carótida comum (EIM-ACC), complacência da artéria carótida comum (CP-ACC) e função endotelial da artéria braquial (DMF)], os quais foram avaliados de maneira não-invasiva através de imagens ultrasonográficas de alta-resolução. Para determinar a influência da SOP e da obesidade sobre tais parâmetros, foram formados grupos de acordo com a presença ou ausência de tais condições: grupo SOP vs grupo Controle, independentemente do IMC; grupo IMC normal vs grupo Obesidade, independentemente da presença da SOP. Resultados: Foram selecionadas 25 pacientes com SOP, sendo 10 com IMC normal (34,0 ± 3,2 kg/m2) e 15 obesas (22,4 ± 2,1 kg/m2) e 23 mulheres controles (12 com IMC normal e 11 obesas). As médias de testosterona livre das pacientes com SOP foram significativamente superiores às médias das mulheres controles, independentemente do IMC. As médias do HOMA-IR e da área sob a curva de insulina das pacientes obesas com SOP foram significativamente superiores às observadas nas pacientes com SOP portadoras de IMC normal e mulheres controles. A média da EIM-ACC das pacientes obesas com SOP foi significativamente superior à das mulheres controles com IMC normal (50,0 ± 4,0 vs 47,0 ± 3,0 mm.10-2; p<0,05). As médias da CP-ACC e da DMF foram semelhantes entre pacientes com SOP e mulheres controles, independentemente do IMC. Para avaliar a influência da SOP e da obesidade, as comparações foram, respectivamente: grupo SOP (n=25) vs grupo Controle (n=23); grupo IMC normal (n=22) vs grupo Obesidade (n=26). A faixa etária global foi de 26,0 ± 4,7 anos. Tanto a SOP quanto a obesidade influenciaram os parâmetros de resistência insulínica. A média da EIM-ACC foi maior no grupo SOP do que no grupo Controle (49,1 ± 1,0 vs 47,2 ± 1,0 mm.10-2; p<0,05) e semelhante entre os grupos IMC normal e Obesidade (49,1 ± 1,0 vs 47,3 ± 1,0 mm.10-2; NS). Não foi observada influência da SOP ou da obesidade na CP-ACC e na DMF. Os parâmetros vasculares estudados não se correlacionaram com as outras variáveis analisadas entre as pacientes com SOP e entre as mulheres controles. Conclusão: Em mulheres jovens e sem fatores de risco cardiometabólicos, a presença da SOP teve influência no aumento da EIM-ACC. Assim, a EIMACC pode ser o marcador inicial do processo de aterogênese nesse grupo de pacientes / Polycystic ovary syndrome (PCOS) and obesity are related to the increase in cardiovascular risk, but it is still not known if such risk is due to these conditions themselves or to the cardiometabolic risk factors associated with them. Objective: determine, in young women without cardiometabolic risk factors, the influence of PCOS as well as obesity on vascular parameters related to the process of atherogenesis. Methods: We studied patients with PCOS, subdivided in patients with normal body mass index (BMI) and obeses, who were compared with women without PCOS (control group) pairwise matched for BMI. We excluded smoking subjects, subjects with glucose metabolism disturbances, with arterial hypertension, LDC -L 160 mg/dl and with triglycerides 250 mg/dl. We evaluated clinical, laboratory (hormonal and metabolic profiles) and vascular parameters [common carotidy artery intima-media thickness (CCA-IMT), compliance of commom carotid artery (CP-CCA) and endothelium function of the braquial artery (FMD)], through a non-invasive method using high resolution ultrasound imaging. In order to determine the influence of PCOS and obesity on such parameters, groups were formed according to the presence or absence of such conditions: PCOS group vs Control group, independently of BMI; normal BMI group vs obesity group, independently of PCOS presence. Results: Twenty-five patients with PCOS were selected, being 10 with normal BMI (34.0 ± 3.2 kg/m²), 15 obeses (22.4 ± 2.1 kg/m²) and 23 control women (12 with normal BMI and 11 obeses). The mean values of free testosterone in PCOS patients were significantly higher than the means in controls, independently of BMI. The means of HOMA-IR and the area under the insulin curve in obese PCOS patients were significantly higher than the ones observed in PCOS patients with normal BMI and controls. The means of CCA-IMT in obese PCOS patients was significantly higher than in controls with normal BMI (50.0 ± 4.0 vs 47.0 ± 3.0 mm.10-2; p<0.05). The means of CP-CCA and FMD were similar between PCOS patients and controls, independently of BMI. To evaluate the influence of PCOS and obesity, the comparisons were respectively: PCOS group (n=25) vs Control group (n=23); normal BMI group (n=22) vs Obesity group (n=26). Global age range was 26.0 ± 4.7 years. PCOS as well as obesity influenced the insulin resistance parameters. The means of CCA-IMT was higher in PCOS group than in Control group (49.1 ± 1.0 vs 47.2 ± 1.0 mm.10-2; p<0.05) and similar between normal BMI and Obesity groups (49.1 ± 1.0 vs 47.3 ± 1.0 mm 10-2; NS). It was not observed any influence of PCOS or obesity in CP-CCA and in FMD. The vascular parameters studied did not correlate with the other variables analized between PCOS patients and controls. Conclusions: In young women without cardiometabolic risk factors, the presence of PCOS had influence on the increase of CCA-IMT. Thus, CCA-IMT might be the initial marker of the atherogenic process in this group of patients

A síndrome dos ovários policísticos (SOP) é o distúrbio endócrino mais frequente em mulheres em idade reprodutiva. Sua etiologia é desconhecida, mas recentemente, fatores ambientais, como o excesso esteróides sexuais em fases precoces da vida, têm sido implicados na origem da SOP. Em ratas, o excesso de androgênios ou estrogênios na vida neonatal altera a função do eixo hipotálamo-hipófise-gonadal e induz alterações reprodutivas e metabólicas similares às observadas na SOP em humanos. O objetivo deste estudo foi analisar a expressão dos genes relacionados ao controle da secreção de GnRH (Gnrh, Gnrhr, Kiss1, Kiss1r e Ar) no hipotálamo de modelos animais de SOP e avaliar a correlação com a morfologia ovariana, níveis séricos de gonadotrofinas e esteróides sexuais, e a expressão de genes chaves na esteroidogênese ovariana (Cyp17a1 e Lhr). Foram utilizadas 30 ratas alocadas em igual número em três grupos. De acordo com os grupos, os animais receberam por injeção subcutânea, entre 0-3 dias de vida, os seguintes compostos: propionato de testosterona (1,25 mg) (grupo Testosterona); benzoato de estradiol (0,5 mg) (grupo Estradiol); e veículo (0,1 mL) (grupo Controle). Os animais foram pesados semanalmente a partir do nascimento até os 90 dias de vida. Ao completarem 90 dias, os animais foram eutanasiados e tiveram coletados o hipotálamo, os ovários e o sangue. Foi avaliada a expressão dos genes Gnrh, Gnrhr, Kiss1, Kiss1r e Ar no hipotálamo e Cyp17a1 e Lhr no ovário por PCR quantitativo em Tempo Real. O ovário também foi analisado morfológica e morfometricamente após coloração com hematoxilina e eosina (H.E.) e o sangue foi utilizado para a dosagem sérica dos hormônios LH, FSH, estradiol, progesterona e testosterona. A análise estatística foi realizada utilizando a análise de variância (ANOVA) complementada pelo teste de comparações múltiplas de Tukey. Os animais dos grupos Estradiol e Testosterona apresentaram 11 anovulação e maior peso corporal em relação ao grupo Controle. O gene Kiss1 encontrou-se hipoexpresso nos grupos Estradiol e Testosterona em relação ao grupo Controle (p<0,0001). No grupo Estradiol, o gene Kiss1r apresentou expressão aumentada em relação ao grupo Controle (p<0,01). O gene Gnrh não exibiu variações de expressão entre os grupos. A expressão de Gnrhr exibiu aumento no grupo Testosterona em relação ao grupo Estradiol (p<0,004). No grupo Testosterona, o gene do receptor de androgênio (Ar) apresentou expressão aumentada em relação ao grupo Controle (p<0,04). Quanto ao nível sérico de LH, o grupo Testosterona exibiu aumento em relação aos grupos Estradiol e Controle (p<0,001). O grupo Estradiol exibiu maior concentração sérica de estradiol em relação ao grupo Testosterona (p<0,01). Os níveis séricos de FSH, progesterona e testosterona não exibiram diferenças significativas entre os grupos. A expressão do gene Lhr apresentou-se aumentada nos grupos Estradiol e Testosterona em comparação ao Controle (p<0,003). O gene Cyp17a1 apresentou-se hiperexpresso no grupo Estradiol em relação aos grupos Controle e Testosterona (p<0,0001 e p<0,001, respectivamente). A contagem diferencial de folículos pré-antrais e antrais não diferiu significativamente entre os grupos. Os ovários dos grupos Estradiol e Testosterona apresentaram ausência de corpos lúteos e exibiram aumento da área intersticial e diminuição do volume do núcleo das células intersticiais, sendo todas essas alterações estatisticamente significativas (p<0,0001). Conclui-se que o excesso de estradiol ou testosterona na vida neonatal altera a fisiologia do hipotálamo e do ovário e leva a anovulação de ratas na vida adulta / Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women at reproductive age. Its etiology is unknown, but recently, environmental factors, such as excess of sex steroids in early life, have been compared to PCOS origin. In female rats, the excess of androgens or estrogens in neonatal life alters the hypothalamus-pituitary-gonadal axis function and induces to reproductive and metabolic alterations like those observed in human PCOS. The aim of this study is to analyze the expression of genes compared to GnRH secretion control (Gnrh, Gnrhr, Kiss1, Kiss1r e Ar) in the hypothalamus of animal models of PCOS and to evaluate the correlation with ovarian morphology, serum levels of gonadotropins and sex steroids and expression of key genes in ovarian steroidogenesis (Cyp17a1 e Lhr). 30 rats were used and allocated equally into three groups. According to the groups, animals received a subcutaneous injection, between 0-3 days old, of the following compounds: testosterone propionate (1.25 mg) (Testosterone group); estradiol benzoate (0.5 mg) (Estradiol group) and vehicle (0.1 mL) (Control group). Animals were weighed weekly from birth until 90 days of life. At 90 days, the animals were euthanized and were collected the hypothalamus, the ovaries and blood. We evaluated the expression of genes Gnrh, Gnrhr, Kiss1, Kiss1r and Ar in hypothalamus and Lhr and Cyp17a1 in ovary, both by quantitative Real-Time PCR. The ovary was also analyzed morphologically and morphometrically after staining with hematoxylin and eosin (H.E.) and the blood was used for evaluation of serum levels of LH, FSH, estradiol, progesterone and testosterone. Statistical analysis was performed using analysis of variance (ANOVA) complemented by Tukeys multiple comparisons test. The animals of the Testosterone and Estradiol groups had anovulation and had higher body weight compared to the Control group. The Kiss1 gene was downregulated in Estradiol and 13 Testosterone groups in relation to the Control group (p<0.0001). In Estradiol group, Kiss1r gene expression was increased in relation to the control group (p<0.01). The Gnrh gene expression did not show variations between groups. The Gnrhr expression was increased in Testosterone group in relation to Estradiol group (p<0.004). In Testosterone group, the androgen receptor gene (Ar) showed an increased expression compared to the Control group (p<0.04). Testosterone group exhibited increased serum levels of LH in comparison to Control and Estradiol groups (p<0.001). Estradiol group exhibited higher serum levels of estradiol compared to Testosterone group (p<0.01). Serum levels of FSH, progesterone and testosterone exhibited no significant differences between groups. Lhr gene expression was increased in Estradiol and Testosterone groups in comparison to the control (p<0.003). The Cyp17a1 gene was upregulated in Estradiol group compared to Testosterone and Control groups (p<0.0001 and p<0.001, respectively). The differential counting of preantral and antral follicles did not differ significantly between groups. Ovaries of the animals of Estradiol and Testosterone groups showed absence of corpora lutea and exhibited increased interstitial area and reduced interstitial cells nuclear volume, and all of these changes were statistically significant (p<0.0001). It was concluded that excess of estradiol or testosterone in neonatal life alters the hypothalamic and ovarian physiology and leads to anovulation in rats at adulthood

Polycystic ovary syndrome (PCOS) is an endocrine system disorder that affects women of reproductive age. If not treated properly, PCOS can lead to infertility. Lack of proper treatment of PCOS may also result in medical complications such as diabetes or heart disease. The rural clinic where this project took place did not have a mandatory guideline for treatment of PCOS; therefore, no standardized method of diagnosis or treatment of PCOS existed. The purpose of this project, guided by the IOWA evidence-based practice model, was to educate providers on the evidence-based guideline for diagnosis and treatment of PCOS outlined by the Endocrine Society Taskforce. The guideline was selected after a comprehensive literature review and was used to develop an educational program that was provided to 5 nurse practitioners, the medical director and staff. A pre-test post-test design was used to determine if the participants understood the content from the guideline that was presented. Results showed that the researcher-developed test administered to participants yielded scores of 74 on the pre-test and increased after the education program with all participants scoring 100 on the post-test. The guideline used for the education was then presented to the clinic for implementation with the assistance of the medical director's support. The project provided an evidence-based guideline for diagnosing and treating PCOS and raised awareness of PCOS among all staff in a rural clinic where many patients with PCOS are treated. Positive social change may result as providers are better prepared to deliver evidence-based care for PCOS and as infertility and complications of untreated PCOS are reduced.

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Kadın Hastalıkları ve Doğum Anabilim Dalı, 2004. / Bibliyografya var.

Το σύνδρομο πολυκυστικών ωοθηκών (PCOS) αποτελεί την πιο συχνή ενδοκρινολογική διαταραχή των γυναικών αναπαραγωγικής ηλικίας που χαρακτηρίζεται από κεντρικού τύπου παχυσαρκία, ακμή , υπερτρίχωση και διαταραχές των εμμηνορησιακών κύκλων που οφείλονται στην υπερανδρογοναιμία και την χρόνια ανωοθυλακιορρηξία. Οι γυναίκες με PCOS αναπτύσσουν και μεταβολικού τύπου διαταραχές όπως η υπερινσουλιναιμία λόγω αντίστασης στην ινσουλίνη, η υπέρταση, ο σακχαρώδης διαβήτης, η δυσλιπιδαιμία και το μεταβολικό σύνδρομο. Σημαντικό ρόλο στην παθοφυσιολογία της των παραπάνω μεταβολικών διαταραχών ασκεί το σύστημα Ρενίνης-Αγγειοτενσίνης-Αλδοστερόνης (Renin-Angiotensin-Aldosterone System – RAAS) που διακρίνεται σε ενδοκρινές κι ιστικό. Στο ιντρόνιο 16 του γονιδίου του ενζύμου ACE(17q23) έχει βρεθεί ο πολυμορφισμός I/D που προκύπτει από την παρουσία ( Insertion– I) ή την απουσία (Deletion–D) μιας Αlu αλληλουχίας μήκους 287 bp, δημιουργώντας τρείς διακριτούς γονότυπους: II, ID και DD Με δεδομένο το ρόλο του συστήματος RAAS σε σχέση με τους παράγοντες κινδύνου για καρδιαγγειακή νόσο και κυρίως με την αντίσταση στην ινσουλίνη, ο ρόλος του πολυμορφισμού ACE I/D έχει καταστεί αντικείμενο μελέτης ως προς την εκδήλωση καρδιαγγειακών συμβαμάτων. Στην παρούσα μελέτη προσδιορίστηκε ο πολυμορφισμός ACE I/D σε 156 φυσιολογικές γυναίκες και σε 212 γυναίκες με την πιο βαριά μορφή του συνδρόμου πολυκυστικών ωοθηκών που είναι η ύπαρξη βιοχημικής υπερανδρογοναιμίας και χρόνιας ανωοθυλακιορηξίας. Το συμπέρασμα μετά τη στατιστική ανάλυση ήταν ότι ο γονότυπος ΙΙ συνδέεται στατιστικώς σημαντικά με την την αντίσταση στην ινσουλίνη κι ο γονότυπος ΙD με τα επίπεδα της 17-OH προγεστερόνης, πρόδρομης ορμόνης κατά την βιοσύνθεση των ανδρογόνων που ίσως σημαίνει με τοπικά αυξημένη ενεργότητα του RAS. Tα ευρήματα αυτά ανάγουν τον πολυμορφισμό της ACE σε ένα πιθανά πολύτιμο δείκτη αυξημένου καρδιαγγειακού κινδύνου στις γυναίκες με PCOS. / The polycystic ovary syndrome (PCOS) is the most common endocrine disorder of women of reproductive age, characterized by central obesity, acne, hirsutism and disorders menstrual cycles due to hyperandrogonemia and chronic anovulation. Women with PCOS develop type and metabolic disorders such as hyperinsulinemia due to insulin resistance, hypertension, diabetes mellitus, dyslipidemia and metabolic syndrome. Important role in the pathophysiology of these metabolic disorders has the renin-angiotensin-aldosterone system (Renin-Angiotensin-Aldosterone System - RAAS), which is divided into endocrine and tissue. In intron 16 of the gene of the enzyme ACE (17q23) has found a polymorphism I / D resulting from the presence (Insertion-I) or absence (Deletion-D) of an Alu sequence length of 287 bp, creating three distinct genotypes: II,ID,DD. Given the role of the RAAS system in relation to risk factors for cardiovascular disease and especially with insulin resistance, the role of polymorphism ACE I / D has become a subject of study as to the occurrence of cardiovascular events. This study identified a polymorphism ACE I / D in 156 healthy women and 212 women with the most severe form of polycystic ovarian syndrome is the presence of biochemical hyperandrogonemia and chronic anovulation. The conclusion after statistical analysis was that the II genotype is associated statistically significant with insulin resistance and ID genotype with levels of 17-OH progesterone hormone precursor in the biosynthesis of androgens which it might means locally increased activity of RAS. These findings suggest the polymorphism of the ACE in a potentially valuable indicator of increased cardiovascular risk in women with PCOS.

Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder that increases a woman’s risk of developing cardiovascular disease and diabetes. Women with PCOS have extremely high rates of obesity, insulin resistance, cardiovascular morbidity and mortality. Obese women with PCOS also tend to have elevated sympathetic nerve activity and systemic markers of inflammation, which likely contribute to cardiometabolic risk and PCOS pathogenesis. While few medication or lifestyle intervention options for women with PCOS target elevated sympathetic nerve activity, inflammation, and insulin resistance, passive heat exposure shows promise as a novel intervention for improving cardiovascular and metabolic health in this population. Therefore, the purpose of this study was to examine changes in inflammation, cardiovascular, autonomic, and metabolic health in obese women with PCOS following a 30-session, 8-10 week chronic passive heat intervention (termed ‘heat therapy’). Eighteen obese women with PCOS (Age: 27±1y, BMI 41.3±1.1 kg·m2) were matched for age and body mass index (BMI), then divided into heat therapy (HT) or time control (CON). At the beginning (Pre), middle (Mid), and end (Post) of 8-10 weeks, subjects participated in study days to assess vascular, autonomic, and metabolic function, and additionally underwent a subcutaneous fat biopsy in Pre and Post. HT subjects took part in 30 one-hour hot tub sessions over 8-10 weeks (3-4 per week) in 40.5˚C water, while CON subjects completed all other testing but were not exposed to heat. No change in BMI was observed over the study in HT or CON; however; HT subjects exhibited dramatically improved vascular and metabolic function, as well as reduced sympathetic nerve activity and circulating inflammatory markers. In fat biopsies, insulin signaling was improved in HT subjects, while CON subjects remained stable over time. These findings show promise for HT as a treatment option for obese women with PCOS to improve cardiovascular and metabolic risk profiles. This dissertation includes previously published co-authored material.

Made available in DSpace on 2014-06-11T19:26:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-10-30Bitstream added on 2014-06-13T20:33:38Z : No. of bitstreams: 1 cirilo_pdr_me_botib.pdf: 1747486 bytes, checksum: 22391af2b4ceae30db573f0e3646f8d4 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A Síndrome do Ovário Policístico (SOP) é uma doença heterogênea que acomete principalmente mulheres em idade reprodutiva e é caracterizada por alterações clínicas como hiperandrogenismo, anovulação crônica e irregularidades menstruais e metabólicas, como resistência insulínica, obesidade, hiperlipidemia e diabetes mellitus tipo 2. Esta síndrome está associada com o risco aumentado de desenvolvimento de doenças cardiovasculares e tromboembólicas. A síndrome HAIR-AN possui manifestações clínicas semelhantes a SOP, porém por critérios de classificação atuais, compõe diagnóstico diferencial apresentando resistência insulínica severa e hiperandrogenismo. Considerando o fenótipo heterogêneo destas patologias, polimorfismos em genes da via de esteróides e da insulina podem estar associados com hiperandrogenismo e hiperinsulinemia. Foram genotipadas para os polimorfismos nos genes ER-α, ER-β, INSR, IGF2 e PAI-1 41 mulheres com fenótipo SOP, 16 com fenótipo HAIR-AN e 49 controles livres da doença. As regiões polimórficas dos genes ER-α e ER-β foram submetidas a análise automatizada no seqüenciador ABI Prism 377 DNA Sequencer para determinação do número de repetições [TA]n e [CA]n, respectivamente. Os alelos foram classificados em curtos ou longos (ER-α - alelos curtos: <15 e longos ≥15 repetições; ER-β - os alelos curtos: ≤22 e longos >22 repetições). A genotipagem de INSR e IGF2 contendo os polimorfismos C/T e A/G, respectivamente, foi realizada por PCR-RFLP com as enzimas de restrição PmlI e ApaI, respectivamente. Para a observação do polimorfismo 5G/4G do gene PAI-1, utilizou-se a técnica de PCR-SSCP e seqüenciamento direto. Não foram observadas diferenças estatísticas significativas entre os genótipos dos genes ER-α, ER-β, INSR, IGF2 e PAI-1 entre casos e controles... / Polycystic Ovary Syndrome (PCOS) is a heterogeneous disorder which is common in reproductive age women and characterized by reproductive and clinical manifestations as hyperandrogenism, anovulatory infertility, increased ovarian secretion, and hyperinsulinaemia, as insulin resistance, type 2 diabetes mellitus, and obesity. The PCOS have been associated with increased risk for development cardiovascular and thromboembolic events. The syndrome of hyperandrogenism, insulin resistance, and acanthosis nigricans (HAIR-AN syndrome) was included in the PCOS subset. However, actually HAIR-AN syndrome shows a differential diagnosis with severe insulin resistance and hyperandrogenism. Genetic polymorphisms in insulin action and steroid pathways genes can be associated with hyperinsulinaemia and hyperandrogenism in PCOS and HAIR-AN patients. The ER-alfa, ER-ß, INSR, IGF2, and PAI-1 genes polymorphisms were evaluated in 41 women with PCOS, 16 women with HAIR-AN, and 49 disease-free control women. The ER-alfa and ER-ß genes polymorphisms were investigated by automated analysis (ABI Prism 377 DNA Sequencer) to determine the [TA]n and [CA]n repeats number, respectively. The alleles were classified as short and long (ER-alfa: <15 and .15 repeats, respectively; and ER-alfa: .22 and >22 repeats, respectively). The INSR and IGF2 genes polymorphisms (C/T and A/G, respectively) were performed by PCR-RFLP methodology using the PmlI and ApaI restriction enzymes, respectively. The PAI-1 gene polymorphisms (5G/4G) were detected by PCR- SSCP and direct sequencing methodologies. No statistical differences were observed between cases and controls for all genes analyzed. However, the comparison between clinical and laboratorial data with the genotypes showed statistical differences (p<0,05). The grouped polymorphisms analysis performed by NeoGene Analysis software defined genotypic classes that can be associated with pathophysiology of the PCOS.

Made available in DSpace on 2014-06-11T19:35:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-08-20Bitstream added on 2014-06-13T19:24:59Z : No. of bitstreams: 1 rehme_mfb_dr_botfm.pdf: 2280081 bytes, checksum: b44989e75865f4acff4695729feffce0 (MD5) / A síndrome dos ovários policísticos (SOP) afeta 5 a 8% das mulheres no menacme e é caracterizada pela anovulação crônica e hiperandrogenismo. A obesidade central e a resistência insulínica (RI) são freqüentes na SOP e desempenham um papel fundamental na etiopatogenia da síndrome metabólica (SM). O hiperandrogenismo tem sido questionado como um fator importante no desenvolvimento da SM em mulheres com SOP. Verificar se o hiperandrogenismo influencia no desenvolvimento de síndrome metabólica em pacientes com SOP. Foram avaliados retrospectivamente os dados clínicos, bioquímicos e ultrassonográficos de 180 mulheres com SOP diagnosticadas pelos critérios de Rotterdam e de 70 mulheres com obesidade simples. As pacientes com SOP foram classificadas de acordo com o índice de massa corporal (IMC) em SOP não obesas e SOP obesas. As pacientes obesas simples não apresentaram hiperandrogenismo clínico nem bioquímico. O índice de sensibilidade à insulínica (ISI) foi avaliado pelo HOMA-IR e ISI de Matsuda e DeFronzo. A SM foi diagnosticada pelos critérios do NCEP-ATP III com modificações sugeridas pelo consenso de Rotterdam. A média de idade das pacientes foi de 27,3 + 4,7 no grupo das pacientes SOP não obesas; 28,8 + 5,0 nas SOP obesas e 27,4 + 5,2 nas obesas simples (p=0, 0773), e o IMC foi de 25,1+3,0 kg/m2; 37,0+ 5,5 kg/m2 e 36,0+ 4,2 kg/m2 respectivamente (p<0, 001). A prevalência de RI e SM não diferiu entre as pacientes obesas com e sem SOP e foi significativamente maior do que nas SOP não obesas (p<0, 001). Entretanto a prevalência de SM foi maior nas SOP obesas com hiperandrogenismo... / Polycystic ovary syndrome (PCOS) affects 5-8% of women at menacme and is characterized by chronic anovulation and hyperandrogenism. Central obesity and insulin resistance (IR) are frequent in PCOS and play a leading role in the etiopathogeny of metabolic syndrome (MS). Hyperandrogenism has been suggested as an important factor in the development of MS in women with PCOS. To determine whether hyperandrogenism influences the development of metabolic syndrome in patients with PCOS. Clinical, biochemical and ultrasonographic data on 180 women with PCOS, as diagnosed by the Rotterdam criteria, and 70 women with simple obesity were retrospectively analyzed. According to body mass index, PCOS patients were classified as nonobese with PCOS and obese with PCOS. No clinical or biochemical hyperandrogenism was observed in patients with simple obesity. Insulin sensitivity indices (ISI) were assessed as proposed by HOMA-IR and ISI (Matsuda and De Fronzo). MS was diagnosed based on NCEP-ATP III criteria with modifications suggested by the Rotterdam consensus. Mean age was 27.3 + 4.7 among non-obese patients with PCOS, 28.8 + 5.0 in obese patients with POS, and 27.4 + 5.2 in those with simple obesity (p=0.0773), while BMI was 25.1+3.0 kg/m2, 37.0+ 5.5 kg/m2 and 36.0+ 4.2 kg/m2, respectively (p<0.001). The prevalence of IR and MS did not differ between obese patients with and without PCOS, and was significantly higher in these patients than in non-obese women with PCOS (p<0.001). The prevalence of MS, however, was higher... (Complete abstract click electronic access below)