Regensburg, Univ., Diss., 2009

Regensburg, Univ., Diss., 2008.

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ciências da Saúde, Programa de Pós-Graduação em Ciências da Saúde, 2011. / Submitted by Alaíde Gonçalves dos Santos (alaide@unb.br) on 2012-06-06T13:50:59Z No. of bitstreams: 1 2011_MarianiCarlaPrudenteBatista.pdf: 2376937 bytes, checksum: 7fb074f870b25dd1772145cb9a2403b8 (MD5) / Approved for entry into archive by Jaqueline Ferreira de Souza(jaquefs.braz@gmail.com) on 2012-06-14T14:36:13Z (GMT) No. of bitstreams: 1 2011_MarianiCarlaPrudenteBatista.pdf: 2376937 bytes, checksum: 7fb074f870b25dd1772145cb9a2403b8 (MD5) / Made available in DSpace on 2012-06-14T14:36:13Z (GMT). No. of bitstreams: 1 2011_MarianiCarlaPrudenteBatista.pdf: 2376937 bytes, checksum: 7fb074f870b25dd1772145cb9a2403b8 (MD5) / Síndrome dos Ovários Policísticos (SOP) é um distúrbio endócrino complexo, de etiologia multifatorial, comum nas mulheres em fase reprodutiva, considerada a principal causa de infertilidade anovulatória, distúrbios menstruais e hiperandrogenismo nessa população. Dados atuais suportam que a SOP pode aumentar o risco para o desenvolvimento de diabetes mellitus tipo 2, dislipidemia, doenças cardiovasculares e carcinoma endometrial, enfatizando a necessidade de diagnóstico precoce da síndrome. Embora ainda não completamente elucidados, seus mecanismos moleculares e celulares envolvem anormalidades intrínsecas na esteroidogênese ovariana e adrenal, sugerindo um defeito esteroidogênico primário. Anormalidades neuroendócrinas parecem estar envolvidas na sua etiopatogenia, representadas principalmente pela pulsatilidade excessiva do LH, com aumento na amplitude dos seus pulsos, resultado de um aumento da sensibilidade da hipófise à estimulação GnRH. A base genética da SOP é desconhecida. Reporta-se significativa agregação familiar, entretanto, a determinação do seu modo de herança é difícil, uma vez que a apresentação clínica é muito heterogênea. Vários genes candidatos já foram avaliados com foco, recentemente, naqueles que codificam as enzimas esteroidogênicas na via de biossíntese de andrógenos e os envolvidos na secreção e ação da insulina. Considerando a repercussão funcional de variantes da subunidade beta específica do LH na fisiopatogenia de disfunções reprodutivas, o estudo ampliado da freqüência dos polimorfismos do gene LHB deve ajudar a esclarecer a heterogeneidade de suas manifestações clínicas, particularmente aquelas relacionadas à hiperandrogenemia. Estudamos assim a prevalência desses polimorfismos em controles (n=85) e casos de SOP (n=130) e sua associação com parâmetros clínicos e laboratoriais da síndrome. Através de seqüenciamento genético detectamos 11 polimorfismos na região codante do LHB, sendo 1 deles (233C>A/Thr78Asn) ainda não descrito na literatura. Na análise de associação entre a detecção destes polimorfismos e a presença de SOP, o poder estatístico consequente ao tamanho de nossas amostras não permitiu a observação de associações estatisticamente significativas, mas o nível de associação entre a presença do novo polimorfismo descoberto (233C>A/Thr78Asn) com a presença de SOP revelou um OR= 3,96 (95% IC= 0,43-189,12), sugerindo uma ligação a ser mais explorada em amostras maiores. A distribuição dos parâmetros clínicos estudados ficaram dentro dos níveis reportados na literatura. Observamos, entretanto, que dois polimorfismos, que segregam em desequilíbrio de ligação, são significativamente mais prevalentes na presença da hiperandrogenemia: rs1800447/rs34349826 (Trp28Arg/Ile35Thr) (p=0,015) e outros 2 parecem proteger contra hirsutismo severo embora estas associações não tenham apresentado resultados estatisticamente significativos em nível de p<0,05, mas de p<0,01: rs6521 (Val38=) (p=0,094) e 233C>A (p=0,063). Os resultados do nosso estudo corroboram outros recentemente publicados na literatura em que não foi possível demonstrar um papel causal para os polimorfismos conhecidos do gene LHB no desenvolvimento da SOP. Revelamos, no entanto, que o novo polimorfismo detectado (233C>A) deve ser objeto de mais investigações. ______________________________________________________________________________ ABSTRACT / Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder, of multifactorial a etiology, common in women of reproductive age and considered the leading cause of anovulatory infertility, menstrual disorders, and hyperandrogenism in this population. PCOS is also a risk factor for the development of type 2 diabetes mellitus, dyslipidemia, cardiovascular disease, and endometrial carcinoma, which emphasizes the need for early diagnosis of the syndrome. Although not yet fully understood, its molecular and cellular mechanisms involve intrinsic ovarian and adrenal steroidogenesis abnormalities, suggesting these to be a primary defect. It appears that there are also accompanying neuroendocrine abnormalities along the natural history of PCOS, represented mainly by excessive luteinizing hormone (LH) pulsatility, with the amplified pulse amplitude resulting from increased sensitivity of the pituitary gland to GnRH stimulation. The genetic basis of PCOS is still largely unknown despite significant family clustering; determining its mode of inheritance is particularly difficult given the wide variability in clinical presentation. Several candidate genes have been evaluated with focus switching recently to genes that encode steroidogenic enzymes that regulate androgen biosynthesis and those involved in insulin secretion and action. The crucial functional role played by specific LH beta (LHB) subunits in various reproductive disorders makes these units natural candidates for elucidating the causal pathway and the many clinical manifestations of PCOS, particularly those related to hyperandrogenemia. The present project is a study of the prevalence of these polymorphisms in 85 controls and 130 PCOS cases and their association with clinical and laboratory parameters of the syndrome. Through genetic sequencing 11 polymorphisms were detected in the coding region of LHB, one of them, 233C>A/Thr78Asn, not yet described in the literature. No statistically significant associations were found between polymorphisms and the presence of PCOS, probably due to small sample size and consequent lack of statistical power, however, the level of association between detection of the newly discovered polymorphism (233C>A) and PCOS revealed an OR=3.96 (95% CI = 0.43-189.12), suggesting a possible connection to be further explored in larger samples. The distribution of the clinical parameters studied matched those already reported in the literature. Notable exceptions included two polymorphisms that secrete in link imbalance and were found to be significantly more prevalent in the presence of hyperandrogenemia: rs1800447/rs34349826 (Trp28Arg/Ile35Thr) (p=0.015) and two other which seemed to be protective against severe hirsutism. The latter however, were not found to be statistically significant at the level of p<0,05, but instead, at the level of p<0,01: rs6521 (Val38=) (p=0,094) e 233C>A (p=0,063). The results of this study corroborate other recently published in the literature in that it was not possible to demonstrate a causal role for the known LHB gene polymorphisms in PCOS. However, a newly detected polymorphism (233C>A) should probably be the object of further investigation.

Ulm, Univ., Diss., 2008.

Das Syndrom der polyzystischen Ovarien (PCO-Syndrom) gehört zu den häufigsten endokrinen Erkrankungen junger erwachsener Frauen. Es ist in erster Linie durch eine Hyperandrogenämie charakterisiert. Eine der wichtigsten Quellen für die weibliche Androgenproduktion ist das Nebennierenrindensteroid Dehydroepiandrosteron (DHEA). DHEA kann durch das Enzym Hydroxysteroid-Sulfotransferase (SULT2A1) insbesondere in der Leber rasch zu Dehydroepiandrosteronsulfat (DHEAS) inaktiviert werden, jedoch findet die Rückaktivierung von DHEAS zu biologisch aktivem DHEA in den meisten Geweben nur in einem vernachlässigbaren Umfang statt. Somit spielt das Enzym SULT2A1 die entscheidende Rolle in der Regulation des Verhältnisses von biologisch aktivem DHEA und inaktivem DHEAS. In dieser Arbeit wurde untersucht, ob das Verhältnis von DHEA zu DHEAS bei Patientinnen mit PCO-Syndrom gestört ist. Hierzu wurden Patientinnen mit PCO-Syndrom (n=89) und ein korrespondierendes gesundes Kollektiv untersucht. Die Serumkonzentrationen von DHEA, DHEAS und der periphere Androgenmetabolit Androstandiolglukuronid (ADG) wurden untersucht. Die mittleren Serumkonzentrationen von DHEAS und ADG unterschieden sich nicht signifikant zwischen den Patientinnen mit PCO-Syndrom und dem Kontrollkollektiv. Dagegen war die mittlere Serumkonzentration des aktiven DHEA und somit auch der DHEA/DHEAS-Quotient bei PCOS-Patientinnen gegenüber dem Kontrollkollektiv signifikant erhöht. Es konnte eine Subkohorte an PCOS-Patientinnen identifiziert werden, die knapp ein Drittel des PCOS-Gesamtkollektives ausmachte, bei denen der DHEA/DHEAS-Quotient über der 90. Perzentile des Kontrollkollektivs lag. Auch die mittlere ADG Serumkonzentration war in dieser Subkohorte gegenüber dem Kontrollkollektiv signifikant erhöht. Klinisch (BMI, Taillenumfang, Serumlipide, Blutzucker) unterschieden sich die Patientinnen der neu identifizierten Kohorte nicht von den übrigen Patientinnen. Aus den Analysen kann geschlussfolgert werden, dass eine reduzierte Aktivität des Enzyms SULT2A1 ein bedeutsamer Mechanismus in der Pathogenese des Androgenexzesses bei einem Teil der PCOS-Patientinnen sein könnte. Es bleibt zu klären, worauf die verminderte Aktivität der SULT2A1 zurückzuführen ist. / Polycystic ovary syndrome is one of the most common endocrine disorders of women in reproductive age. It is predominantly characterized by hyperandrogenemia. One of the most important sources for female androgen production is the adrenal steroid dehydroepiandrosterone (DHEA). DHEA can be rapidly inactivated to dehydroepiandrosterone sulfate (DHEAS) particularly in the liver by the enzyme hydroxysteroid-sulfotransferase (SULT2A1). Conversion from inactive DHEAS to active DHEA occurs in the most tissues to a negligible degree. The enzyme SULT2A1 plays the crucial role in the regulation of the ratio of active DHEA and inactive DHEAS. In this study we examined, if the ratio between DHEA and DHEAS is disturbed in patients with polycystic ovary syndrome. We examined patients with polycystic ovary syndrome (n=89) and a correspondent healthy cohort. We measured the serum concentrations of DHEA, DHEAS and of androstanediolglucoronide (ADG). There was no significant difference in the serum concentrations of DHEAS and ADG between both cohorts. The serum concentration of DHEA and the DHEA/DHEAS ratio was significant elevated in patients with polycystic ovary syndrome. We identified a subcohort of patients with polycystic ovary syndrome, where the DHEA/DHEAS ratio was over the 90. percentile of the control cohort. In this subcohort, the serum concentration of ADG was significant elevated. There were no clinical differences in both groups. We suggest, that a reduced activity of the enzyme SULT2A1 is responsible for the androgen excess in some of the patients with polycystic ovary syndrome. Further studies have to show, what is the cause for the reduced activity of the enzyme SULT2A1.

Orientador: Anaglória Pontes / Resumo: Resistência Insulínica (IR) e Hiperandrogenismo (HA) na Síndrome dos Ovários Policísticos (SOP), acompanhada de Acantose Nigricans (AN), denomina-se síndrome de HAIR-AN. Tem sido relacionada com risco aumentado para diabetes mellitus e doença cardiovascular. Estudam-se agentes que melhoram a resistência insulínica na SOP. OBJETIVO: Avaliar a eficácia da metformina em mulheres obesas com síndrome de HAIR-AN. PACIENTES/MÉTODOS: 16 mulheres receberam metformina (850mg/duas vezes ao dia/seis meses). Avaliaram-se: padrão do ciclo menstrual, Índice de Massa Corpórea (IMC), Relação Cintura Quadril, Índice de Ferriman e Gallwey (IFG), acantose nigricans, Teste de Tolerância à Glicose Oral, Área Sob a Curva de Glicemia (ASCG) e Insulina (ASCI), Glicemia/Insulina, Índice de Sensibilidade à Insulina (ISI), Testosterona total e livre, Globulina Carreadora dos Hormônios Sexuais (SHBG), Índice de Androgênios Livres (IAL), Androstenediona, Sulfato de Deidroepiandrosterona, Hormônio Luteinizante/Folículo Estimulante, Prolactina, Estradiol, Estrona, Perfil lipídico e Ultra-sonografia transvaginal. RESULTADOS: Houve melhora dos ciclos menstruais, redução significativa do IMC, IFG, glicemia (jejum e 120min), ASCI, testosterona livre e colesterol total.Os níveis de testosterona total, androstenediona e IAL diminuíram significativamente aos quatro meses de tratamento mas retornaram aos valores basais com seis meses. Aumentou (p<0,05) o ISI e a relação glicemia/insulina. CONCLUSÃO: A metformina é eficaz na síndrome de HAIR-AN: reduz o peso, a resistência insulínica, melhora a intolerância à glicose, os ciclos menstruais e o hiperandrogenismo. / Abstract: Insulin Resistance (GO) and Hyperandrogenism (HA) in Polycystic Ovary Syndrome (PCOS), accompanied of Acanthosis Nigricans (A), it denominates HAIR-AN syndrome. It has been related with risk increased for diabetes mellitus and cardiovascular disease. They study agents that improve insuline resistance in PCOS. OBJECTIVE: Evaluate metformin effectiveness in obese women with HAIR-AN syndrome. PATIENTS/METHODS: 16 women received metformin (850mg/two times a day/6 months). They evaluated: menstrual cycle standard, Corporal Mass Index (CMI), Waist Hip Ratio, Ferriman's Index and Gallwey (FIG), acanthosis nigricans, Oral Glucose Tolerance Test, Area under the curves for Glycemia (ASCG) and Insulin (ASCI), Glycemia/Insulin, Insulin Sensitivity Index (ISI), Total and free Testosterone, sex hormone-binding globulin (SHBG), Free Androgens Index (FAI), Androstenedione, Deidroepiandrosterona's Sulfate, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), Prolactine, Estradiol, Estrone, lipidic profile and transvaginal Ultrasonographic. RESULTS: There was menstrual cycles improvement, significant reduction of IMC and IFG, of glycemia of fast and at 120 min, of ASCI, of free testosterone, androstenedione and total cholesterol. The levels of total testosterona, IAL decreased significantly at four treatment months but they returned to the basal values with six months. It increased (p<0,05) ISI and glycemia/insulin. CONCLUSION: Metformin is effective in HAIR-AN syndrome: it reduces the weight, the insulin resistance, improvement the intolerance to the glucose, the menstrual cycles and hyperandrogenism. / Mestre

Context : The expression of androgen receptors ( AR ) in follicular granulosa cells ( GC ) of mammals suggests a role for direct AR - mediated androgen activity in the regulation of folliculogenesis, however this role and the mechanistic pathways involved have not been fully characterised. In women, excess androgen is a characteristic feature of polycystic ovary syndrome ( PCOS ), but AR - mediated activity has not been widely investigated in relation to the pathophysiology of this disorder. Hypotheses : The current thesis tested two general hypotheses related to AR activity in PCOS : 1 ) The polymorphic ( CAG ) n repeat region in the AR gene, which has functional implications for receptor activity, influences the manifestation of PCOS and 2 ) AR signalling is disrupted in GC from women with PCOS. Results : In a cross - sectional population analysis, this thesis reports an association between PCOS and long CAG repeat tracts in the AR gene, which functionally represent reduced androgen sensitivity. The association was further enhanced by compensating for the influence of X chromosome inactivation ( XCI ) on expression of specific AR alleles. Preferential expression of long CAG repeat tracts positively correlated with serum testosterone levels in PCOS patients. In an analysis of sister pairs with the same CAG repeat genotype at the AR locus, different patterns of XCI were evident when sisters had a different clinical manifestation of PCOS. Collectively, these results provide evidence that supports the hypothesis that the ( CAG ) n polymorphism in the AR influences the manifestation of PCOS, the effects of which are modulated by variable allele expression via a mechanism involving XCI. These findings accord with the concept that both genetic and environmental factors are determinants of this disorder. At the level of the ovary, AR - mediated signalling in follicular GC was influenced by proximity to the oocyte in both pigs and humans. In particular, the ability of androgen to directly induce porcine GC proliferation in vitro was dependent upon presence of the oocyte or the oocyte mitogen, growth differentiation 9 ( GDF9 ). This finding provides a potential mechanism to explain how androgens may enhance early follicle growth. Granulosa cells from women with PCOS had normal mRNA expression for AR signalling molecules, but GC surrounding the oocyte in vivo had reduced AR protein content and diminished responses to androgen in culture as compared to those from normal ovaries. GC from women with PCOS also expressed mRNA for an androgen - regulated serine protease ( hKLK3 ), which did not occur in normal GC. Therefore, follicular GC from women with PCOS have evidence of perturbed AR - mediated signalling which is likely to contribute to the pathophysiology of this disorder. As AR - mediated signalling is influenced by the oocyte, the differences in AR - mediated signalling in GC from women with PCOS may be indicative of dysregulated signals emanating from the oocyte. Conclusion : The results of this thesis indicate that abnormal AR action occurs in PCOS, but further investigation is required to determine whether this phenomenon represents a primary disruption or a secondary consequence of another primary disruption in the sequence of events that leads to aberrant folliculogenesis in this disorder. / Thesis (Ph.D.)--School of Paediatrics and Reproductive Health, 2006.

Sex differences have been established in a number of behaviours, including aspects of cognition, aggression, and sexuality. Although there has been a considerable amount of research concerning the influence of estrogen on sexually dimorphic behaviours, there has been a dearth of investigations on the role of testosterone (T) in these behaviours in women. The studies presented here were undertaken to elucidate the role of T in sexually-dimorphic aspects of psychological functioning in women. In Study 1, users and non-users of oral contraceptives were tested with a battery of neuropsychological tests and questionnaires at two different phases of the menstrual cycle. Results showed that women with chronic low levels of free T induced by oral contraceptives demonstrated better verbal fluency and visuospatial memory performance and reported lower levels of verbal aggression than naturally-cycling women whose free T levels were within the normal female range. Furthermore, although self-ratings of hostility fluctuated across test sessions concomitant with changes in free T levels, performance on cognitive tests did not appear to be influenced by the fluctuations in T levels across the menstrual cycle. In Study 2, women with elevated free T levels due to polycystic ovary syndrome (PCOS) demonstrated worse verbal fluency, verbal memory, manual dexterity, and visuospatial working memory performance, but reported higher levels of anger than healthy, matched control women. Women with PCOS also reported lower levels of sexual cognition and arousal than healthy controls. In Study 3, women with PCOS were randomly assigned to receive 3 months of treatment with an anti-androgen or placebo. Anti-androgen treatment resulted in significant reductions in free T levels and in improvements in verbal fluency performance. Taken together, the results of these three studies suggest that T has a detrimental effect on aspects of cognitive functioning in women, particu

Made available in DSpace on 2014-06-11T19:26:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2001Bitstream added on 2014-06-13T18:29:58Z : No. of bitstreams: 1 ferraz_mfm_me_botfm.pdf: 1034837 bytes, checksum: 3d3a05a0e4702bf9aa71fa831523d395 (MD5) / Resistência Insulínica (IR) e Hiperandrogenismo (HA) na Síndrome dos Ovários Policísticos (SOP), acompanhada de Acantose Nigricans (AN), denomina-se síndrome de HAIR-AN. Tem sido relacionada com risco aumentado para diabetes mellitus e doença cardiovascular. Estudam-se agentes que melhoram a resistência insulínica na SOP. OBJETIVO: Avaliar a eficácia da metformina em mulheres obesas com síndrome de HAIR-AN. PACIENTES/MÉTODOS: 16 mulheres receberam metformina (850mg/duas vezes ao dia/seis meses). Avaliaram-se: padrão do ciclo menstrual, Índice de Massa Corpórea (IMC), Relação Cintura Quadril, Índice de Ferriman e Gallwey (IFG), acantose nigricans, Teste de Tolerância à Glicose Oral, Área Sob a Curva de Glicemia (ASCG) e Insulina (ASCI), Glicemia/Insulina, Índice de Sensibilidade à Insulina (ISI), Testosterona total e livre, Globulina Carreadora dos Hormônios Sexuais (SHBG), Índice de Androgênios Livres (IAL), Androstenediona, Sulfato de Deidroepiandrosterona, Hormônio Luteinizante/Folículo Estimulante, Prolactina, Estradiol, Estrona, Perfil lipídico e Ultra-sonografia transvaginal. RESULTADOS: Houve melhora dos ciclos menstruais, redução significativa do IMC, IFG, glicemia (jejum e 120min), ASCI, testosterona livre e colesterol total.Os níveis de testosterona total, androstenediona e IAL diminuíram significativamente aos quatro meses de tratamento mas retornaram aos valores basais com seis meses. Aumentou (p<0,05) o ISI e a relação glicemia/insulina. CONCLUSÃO: A metformina é eficaz na síndrome de HAIR-AN: reduz o peso, a resistência insulínica, melhora a intolerância à glicose, os ciclos menstruais e o hiperandrogenismo. / Insulin Resistance (GO) and Hyperandrogenism (HA) in Polycystic Ovary Syndrome (PCOS), accompanied of Acanthosis Nigricans (A), it denominates HAIR-AN syndrome. It has been related with risk increased for diabetes mellitus and cardiovascular disease. They study agents that improve insuline resistance in PCOS. OBJECTIVE: Evaluate metformin effectiveness in obese women with HAIR-AN syndrome. PATIENTS/METHODS: 16 women received metformin (850mg/two times a day/6 months). They evaluated: menstrual cycle standard, Corporal Mass Index (CMI), Waist Hip Ratio, Ferriman's Index and Gallwey (FIG), acanthosis nigricans, Oral Glucose Tolerance Test, Area under the curves for Glycemia (ASCG) and Insulin (ASCI), Glycemia/Insulin, Insulin Sensitivity Index (ISI), Total and free Testosterone, sex hormone-binding globulin (SHBG), Free Androgens Index (FAI), Androstenedione, Deidroepiandrosterona's Sulfate, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), Prolactine, Estradiol, Estrone, lipidic profile and transvaginal Ultrasonographic. RESULTS: There was menstrual cycles improvement, significant reduction of IMC and IFG, of glycemia of fast and at 120 min, of ASCI, of free testosterone, androstenedione and total cholesterol. The levels of total testosterona, IAL decreased significantly at four treatment months but they returned to the basal values with six months. It increased (p<0,05) ISI and glycemia/insulin. CONCLUSION: Metformin is effective in HAIR-AN syndrome: it reduces the weight, the insulin resistance, improvement the intolerance to the glucose, the menstrual cycles and hyperandrogenism.

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ciências da Saúde, 2009. / Submitted by Raquel Viana (tempestade_b@hotmail.com) on 2010-05-04T17:43:14Z No. of bitstreams: 1 2009_MicheleDelarmelinaReisBorba.pdf: 1193252 bytes, checksum: 1b59c632c314c03959f687213dd65eb0 (MD5) / Approved for entry into archive by Lucila Saraiva(lucilasaraiva1@gmail.com) on 2010-05-18T04:13:32Z (GMT) No. of bitstreams: 1 2009_MicheleDelarmelinaReisBorba.pdf: 1193252 bytes, checksum: 1b59c632c314c03959f687213dd65eb0 (MD5) / Made available in DSpace on 2010-05-18T04:13:32Z (GMT). No. of bitstreams: 1 2009_MicheleDelarmelinaReisBorba.pdf: 1193252 bytes, checksum: 1b59c632c314c03959f687213dd65eb0 (MD5) Previous issue date: 2009 / Introdução: A síndrome dos ovários policísticos (SOP) é uma endocrinopatia caracterizada por anovulação crônica, não contínua, e excesso de andrógenos, que se manifestam por oligomenorréia ou amenorréia, hirsutismo, acne e alopécia androgênica. A fisiopatogenia e as manifestações clínicas da doença também se relacionam à síndrome metabólica (SM). Existem várias teorias com o objetivo de elucidar o mecanismo etiopatogênico da SOP. Evidências mais recentes a respeito da fisiopatogenia da SOP têm revelado influência de variantes genéticas do LH. Um estudo da freqüência de polimorfismos do gene LHB (subunidade beta do LH) poderia contribuir para a elucidação da fisiopatogenia da doença, bem como a influência sobre a apresentação clínica da mesma e da SM. Objetivos: Verificar a freqüência de polimorfismos no gene LHB em mulheres acometidas pela SOP. Em seguida, analisar a associação entre os polimorfismos identificados com os parâmetros clínicos da SOP e síndrome metabólica (SM). Métodos: Em estudo tipo transversal, foram avaliadas 50 mulheres com diagnóstico de SOP pelos critérios de Rotterdam. Exames físico e laboratorial definiram a apresentação clínica da SOP e da SM. A análise dos polimorfismos do gene LHB foi realizada por meio de seqüenciamento genético. Em seguida, analisadas as relações dos polimorfismos, perfis de genótipos e haplótipos identificados com caracteres da SOP e SM. Resultados: Os diferentes valores encontrados para a média do índice de Ferriman-Gallwey foram significativos na presença dos alelos variantes dos polimorfismos rs1800447 / rs34349826 (p = 0,001), rs1056914 (p = 0,01), rs2387588 / rs427687 (p = 0,04) e rs1056917 (p = 0,02) e para os haplótipos TTCATACT e CCGAC-CC (OR: 4,2 e 19,1, respectivamente). Em relação aos critérios clínicos de SOP, houve maior graduação de hirsutismo na presença do alelo variante C para o polimorfismo rs1800447 / rs34349826 (p = 0,04) e para o haplótipo TTCATACT (OR: 0,4). O hiperandrogenismo, avaliado pela concentração sérica de testosterona, apresentou OR de 45,5, 2,1 e 19,1 para os haplótipos CCGAC-CC, TTGATACT e TTGCTACC, respectivamente. Entretanto, para os haplótipos TTCCC-CC, TTCATACC e TTCATAAT encontrado resultado oposto (OR: -6,6; -22,5; -22,6, nessa ordem). Identificada uma mutação na base 1430 do éxon 3, com a troca de uma citosina por uma adenina não descrita na literatura, que não se mostrou influente sobre as variáveis de SOP Não foram significativos os resultados encontrados para os parâmetros de SM. Conclusões: A freqüência encontrada dos polimorfismos do gene LHB analisados em 50 mulheres brasileiras portadoras da síndrome dos ovários policísticos foi semelhante à descrita na literatura. O polimorfismo rs1800447 / rs34349826 apresentou associação com uma maior graduação do hirsutismo segundo o índice de Ferriman-Gallwey. Resultado semelhante para o haplótipo TTCATACT. A respeito do hiperandrogenismo laboratorial, a concentração sérica da testosterona foi maior para os haplótipos CCGAC-CC, TTGATACT e TTGCTACC. Entretanto, os haplótipos TTCCC-CC, TTCATACC e TTCATAAT, foram indicativos de proteção para o hiperandrogenismo. Não foram estatisticamente significativos os achados para os critérios clínicos da SM. ____________________________________________________________________________________ ABSTRACT / Introduction: The polycystic ovary syndrome (PCOS) is an endocrinopaty characterized by chronic, discontinuous anovulation and excess of androgens, which leads to oligo or amenorrhea, hirsutism, acne and androgenic alopecia. There are many theories to explain the phisiopatogenics of the PCOS, and it is also related to the metabolic syndrome. Recent findings have pointed to the influence of molecular variants of the LH at the origins of PCOS. Objective: To access the rate of polymorphisms in the LHB (beta-subunit luteinizing hormone) gen in women with PCOS and to analyze the association between such polymorphisms and clinical features of PCOS and metabolic syndrome (MS). Methods: Transversal study. Fifty women previously diagnosed with PCOS by Rotterdam criteria were evaluated. Physical and laboratory exams defined the different PCOS and MS clinical presentations. Genetic sequencing of the LHB gen was performed in order to access the occurrence of polymorphisms. The possible relations between single polymorphisms, genetic profile and haplotypes to the PCOS and MS clinical presentation were then analyzed. Results: The Ferriman Gallwey index revealed statistically different means between polymorphisms rs1800447 / rs34349826 (p = 0,001), rs1056914 (p = 0,01), rs2387588 / rs427687 (p = 0,04) and rs1056917 (p = 0,02) and the haplotypes TTCATACT e CCGAC-CC (odds ratio: 4,2 e 19,1 respectively). As to the clinical criteria for PCOS, there was a higher grade of hirsutism when occurring the allelic variant C with the rs1800447 / rs34349826 polymorphisms (p = 0,04) and also with th haplotype TTCATACT (OR: 0,4). Laboratorial hyperandrogenism, evaluatedby testosterone serum concentration, showed that the haplotypes CCGAC-CC, TTGATACT and TTGCTACC had a positive odds ratio (45,5, 2,1 and 39,1, respectively), and the opposite occurred with TTCCC-CC, TTCATACC and TTCATAAT (odds ratio: -6,6; -22,5; -22,6, in that order). One new mutation, not previously reported, at base 1430, éxon 3, by exchanging a cytosine for an adenine, was found, but it presented with no influence at the PCOS and MS variables. Conclusion: The frequency found for polymorphisms at the LHB gene in 50 Brazilian women with POS was similar to that described at the literature. The rs1800447 / rs34349826 polymorphism presented was associated with higher hirsutism grade by the Ferriman-Gallwey index. Similar results were found for the genetic profiles and also the haplotype TTCATACT. As for laboratorial hyperandrogenism, higher serum testosterone concentration was present with the haplotypes CCGAC-CC, TTGATACT and TTGCTACC. However, a protective effect was found for the haplotypes TTCCC-CC, TTCATACC and TTCATAAT. The findings regarding the MS criteria revealed not to be significant.