Particularidades de la resistencia a la insulina en el síndrome de ovario poliquístico / Particularities of insulin resistance in polycystic ovary syndrome

Introducción: La resistencia a la insulina e hiperinsulinemia son frecuentes en las mujeres con síndrome de ovario poliquístico. Una condición que resulta relevante como factor patogénico principal de las alteraciones metabólicas que acompañan al síndrome y porque condiciona fenotipos con mayor riesgo metabólico y reproductivo. Objetivo: Realizar una revisión bibliográfica sobre la resistencia a la insulina en el síndrome de ovario poliquístico. Métodos: Se realizó una revisión bibliográfica tipo estado del arte. Se consultaron 229 artículos obtenidos de las bases PubMed, Medline, SciELO y Google Académico. Conclusiones: La resistencia a la insulina tiene importancia capital en el síndrome de ovario poliquístico, no sólo por su frecuencia, sino también por el amplio espectro de alteraciones metabólicas y reproductivas que se le asocian. Como en otros trastornos que caracterizan al síndrome, los mecanismos fisiopatogénicos específicos no están del todo claros, pero existe la posibilidad de diagnosticarla y tratarla oportunamente, con lo que pueden prevenirse complicaciones, algunas de importancia vital. Por esto, la educación para la salud desde edades tempranas, que propicie estilos de vida saludable, prevención del sobrepeso corporal y control de otros factores que agravan la resistencia a la insulina, así como la evaluación temprana de la resistencia a la insulina, deben entenderse como cruciales en el manejo de las mujeres con síndrome de ovario poliquístico, con independencia de su peso corporal(AU)

Introduction: Insulin resistance and hyperinsulinemia are frequent in women with polycystic ovary syndrome. This condition is relevant as the main pathogenic factor of the metabolic alterations that accompany the syndrome and because it conditions phenotypes with higher metabolic and reproductive risk. Objective: To perform a literature review on insulin resistance in polycystic ovary syndrome. Methods: A state-of-the-art literature review was performed. The particularities of insulin resistance associated with the syndrome and its clinical expression are described. Conclusions: Insulin resistance is of paramount importance in polycystic ovary syndrome, not only because of its frequency, but also because of the wide spectrum of metabolic and reproductive alterations associated with it. As in other disorders that characterize the syndrome, the specific pathophysiological mechanisms are not entirely clear. However, it is possible to diagnose and treat it in a timely manner, thus preventing complications, some of which are of vital importance. Therefore, and regardless of their body weight, health education from an early age to promote healthy lifestyles, prevention of body overweight and control of other factors that aggravate insulin resistance, including early evaluation of insulin resistance, should be understood as crucial in the management of women with polycystic ovary syndrome(AU)

Repercussões metabólicas: quais, como e por que investigar? / Metabolic repercussions: which ones, how and why investigate?

A síndrome dos ovários policísticos (SOP) é frequentemente acompanhada de distúrbio metabólico, principalmente dos carboidratos e dos lipídeos, aumentando o risco de síndrome metabólica. Por essa razão, alguns investigadores ainda denominam a SOP de síndrome metabólica-reprodutiva. O objetivo deste capítulo é descrever as principais repercussões metabólicas, bem como como investigá-las e saber como suas consequências podem ser deletérias para a saúde da mulher. Esta é uma revisão narrativa mostrando a implicação do metabolismo dos carboidratos e dos lipídeos nas dislipidemias, bem como da síndrome metabólica sobre o sistema reprodutor, e o risco cardiovascular da mulher com SOP. Conclui-se que o manejo adequado dos distúrbios metabólicos na SOP é benéfico a curto e a longo prazo tanto para o sistema reprodutor quanto para o cardiovascular.(AU)

Can the genetic polymorphisms of the folate metabolism have an influence in the polycystic ovary syndrome?

ABSTRACT Objective To investigate the association of the genetic variants of the folate metabolism genes (MTHFR C677T; MTHFR A1298C; MTR A2756G; MTRR A66G and RFC-1 A80G) with the development of polycystic ovary syndrome (PCOS). Subjects and methods This study included 203 women (99 women with PCOS and 104 controls). The genotyping was performed by PCR-RFLP. Chi-squared test and multiple logistic regression were used in the statistical analysis. Haplotype analysis was conducted using the SNPstat program. The results were presented in odds ratio (OR) and confidence interval of 95% (CI-95%), with a significance level of 5% (p ≤ 0.05). Results The genotypic distribution of the RFC-1 A80G polymorphism showed significant difference between the two groups, showing that the heterozygous genotype (AG genotype) was most frequent in controls. The polymorphic homozygous (GG genotype) of MTRR A66G polymorphism were most frequent in controls. The T-C haplotype MTHFR C677T and A1298C polymorphisms were more frequent in the control group (OR = 0.19; CI 95% — 0.04 to 0.93 e p = 0.042). The multivariate analysis evidenced that family history of PCOS was more frequent in the PCOS group (OR = 3.29; CI 95% — 1.48 to 7.31; p = 0.003). Conclusion In our casuistry, the polymorphic homozygous of MTRR A66G polymorphism gene and heterozygous of RFC-1 A80G polymorphism gene, the haplotype T-C C677T and A1298C polymorphisms of MTHFR gene, can be associated with protective factors for the disease.

Repercussões metabólicas e uso dos medicamentos sensibilizadores da insulina em mulheres com síndrome dos ovários policísticos / Metabolic repercussions and use of insulin-sensitizing drugs in women with polycystic ovary syndrome

A síndrome dos ovários policísticos (SOP) é um distúrbio endócrino-metabólico muito frequente no período reprodutivo. Quando associado ao distúrbio metabólico, as mulheres com SOP podem ter ainda risco acrescido para doença cardiovascular. O objetivo deste manuscrito é descrever as repercussões metabólicas, incluindo quais as principais, como investigar e as consequências desse distúrbio sobre a saúde da mulher. É uma revisão narrativa mostrando a implicação da resistência insulínica, das dislipidemias e da síndrome metabólica sobre o sistema reprodutor e sobre o risco cardiovascular da mulher com SOP, bem como do uso de sensibilizadores de insulina no seu tratamento. Conclui-se que a correção dos distúrbios metabólicos na SOP é benéfica tanto para o sistema reprodutor quanto para o cardiovascular. A primeira linha de tratamento é a mudança de estilo de vida e a perda de peso. Na resposta inadequada, o tratamento medicamentoso está recomendado. Nas mulheres com obesidade mórbida que não tiveram bons resultados com o tratamento clínico, a cirurgia bariátrica é uma opção.(AU)

Efeitos da suplementação de ômega 3 na resistência à insulina em mulheres com síndrome do ovário policístico: revisão sistemática / Effects of omega 3 supplementation on insulin resistance in women with polycystic ovary syndrome: systematic review

Introdução: A síndrome do ovário policístico (SOP) é uma disfunção hormonal que acomete mulheres em idade reprodutiva podendo causar infertilidade, alterações no ciclo menstrual, hirsutismo, presença de cistos nos ovários, amenorreia e distúrbios metabólicos. Dentre as alterações metabólicas, resistência à insulina (RI) está presente em 70,5% das brasileiras com SOP. Objetivo: Revisar sistematicamente a literatura para descrever os efeitos da suplementação de ômega-3 na RI em mulheres com SOP. Materiais e métodos: As buscas pela informação foram realizadas na base de dados PubMed e LILACS utilizando os descritores "síndrome do ovário policístico"; "ácidos graxos ômega-3" e "resistência à insulina", em português e inglês. Resultados: Foram encontrados sessenta estudos e após o crivo metodológico seis foram selecionados para compor esta revisão. Ao total dos ensaios clínicos incluídos nesta revisão, 326 mulheres com faixa etária correspondente a 18-45 anos foram avaliadas com variações de índice de massa corporal entre 25 e 45 kg/m2. A variação de tempo de acompanhamento entre os estudos foi de 2 a 6 meses. Discussão: Em todos os estudos incluídos nesta revisão, a homeostase da glicose sérica foi avaliada pelo índice HOMA. Apenas 1 estudo avaliou o índice quantitativo de verificação da sensibilidade à insulina (QUICK1); 2 estudos avaliaram hemoglobina glicada e índice de sensibilidade à insulina (ISI de Matsuda). A avaliação da insulinemia de jejum foi realizada em 4 estudos. Metade dos estudos incluídos suplementou os pacientes com 1.000 mg de ômega-3 ao dia, enquanto 25% dos estudos utilizou a dosagem de 2000 mg/dia 25% utilizou 4000 mg/dia. A maioria das pesquisas encontradas (67%) descreveu efeito positivo entre a suplementação de ômega-3 e melhora da RI de mulheres com SOP, utilizando os diferentes métodos de dosagem da homeostase da glicose sérica. Conclusão: Conclui-se que o consumo de ômega-3 pode ter efeito positivo sobre a RI.

Introduction: Polycystic ovarian syndrome (PCOS) is a hormonal dysfunction that affects women of childbearing age and can cause infertility, changes in the menstrual cycle, hirsutism, ovarian cysts, amenorrhea, and metabolic disorders. Among the metabolic changes insulin resistance (IR) is present in 70.5% of Brazilians with PCOS. Objective:To systematically review the literature to describe the effects of omega-3 supplementation on IR in women with PCOS. Materials and methods: Information searches were performed in the PubMed and LILACS database using the descriptors "polycystic ovarian syndrome"; "fatty acids omega-3" and "insulin resistance", in Portuguese and English. Results: Sixty studies were found and six were selected to compose this review. In the total of the clinical trials included in this review, 326 women aged 18-45 years were evaluated with variations in body mass index between 25 and 45 kg/m2. The variation in follow-up time between the studies was from 2 to 6 months. Discussion: In all studies included in this review, serum glucose homeostasis was assessed by the HOMA index. Only 1 study evaluated the quantitative index of insulin sensitivity (QUICK1); 2 studies evaluated glycated hemoglobin and insulin sensitivity index (Matsuda ISI). The evaluation of fasting insulinemia was performed in 4 studies. Half of the included studies supplemented patients with 1000 mg omega-3 daily, while 25% of the studies used the dosage of 2000 mg / day 25% used 4000 mg / day. Most of the researches (67%) described a positive effect between omega-3 supplementation and improvement of IR in women with PCOS, using the different dosing methods for serum glucose homeostasis. Conclusion: It is concluded that omega-3 consumption may have a positive effect on IR.

Association between insulin resistance and cardiovascular risk factors in polycystic ovary syndrome patients / Associação entre resistência à insulina e fatores de risco cardiovascular em pacientes com síndrome dos ovários policísticos

Abstract Objective To analyze the association between the indirect methods of evaluating insulin resistance (IR) and blood pressure, anthropometric and biochemical parameters in a population of polycystic ovary syndrome (PCOS) patients. Methods Cross-sectional study performed at the Hospital Universitário de Brasília (HUB, in the Portuguese acronym) involving PCOS patients diagnosed from January 2011 to January 2013. Four indirect methods, namely, fasting blood insulin level, fasting glucose/insulin ratio (G/I), homeostatic model-assessment-insulin resistance (HOMA-IR), and the quantitative insulin sensitivity check index (QUICKI), were used to obtain the IR diagnosis. The data were analyzed using the test of proportions, the Chisquare test, and Fisher exact test, when indicated. Results Out of the 83 patients assessed, aged 28.79 ± 5.85, IR was found in 51.81- 66.2% of them using the G/I ratio and the QUICKI, respectively. The test of proportions did not show a significant difference between the methods analyzed. The proportion of IR diagnoses was statistically higher in obese women than in women with normal body mass index (BMI). We observed a statistically significant association between all the methods for diagnosing IR and BMI, waist circumference (WC) and lipid accumulation product (LAP). With regards to arterial hypertension (AH), we observed a significant association according to three methods, with the exception of the ratio G/I. Conclusion Insulin resistance prevalence varied according to the diagnostic method employed,with no statistical difference between them. The proportion of IR diagnoses was statistically higher in obese women than in women with normal BMI.We observed a significant association between IR andWC, BMI, LAP, as well as dyslipidemia and AH in a high proportion of patients.

Resumo Objetivo Analisar a associação entre os métodos indiretos de avaliação de resistência à insulina (RI) e parâmetros pressóricos, antropométricos e bioquímicos em uma população de pacientes com síndrome dos ovários policísticos (SOP). Métodos Estudo transversal realizado no Hospital Universitário de Brasília (HUB), envolvendo pacientes que apresentaram o diagnóstico de SOP no período de janeiro de 2011 a janeiro de 2013. O diagnóstico de RI foi obtido por meio de quatro métodos indiretos: insulinemia de jejum, relação glicemia de jejum/insulinemia de jejum (G/I), avaliação da resistência à insulina através do modelo homeostático (HOMA-IR) e índice quantitativo de sensibilidade à insulina (QUICKI). Os dados foram analisados utilizando o teste de proporções, o teste do Qui-quadrado e o teste exato de Fisher, quando indicado. Resultados Foram avaliadas 83 pacientes com idade média de 28,79 ± 5,85 anos. A RI foi diagnosticada em 51,81-66,27% dos casos pela relação G/I e QUICKI, respectivamente, e o teste de proporções não evidenciou diferença significativa entre osmétodos analisados. A proporção de diagnósticos de RI foi estatisticamente maior em mulheres obesas em comparação à proporção de mulheres com índice de massa corporal (IMC) normal. Foi observada uma associação estatisticamente significativa entre todos os métodos diagnósticos de RI e IMC, circunferência da cintura (CC) e produto de acumulação lipídica (LAP). Quanto à hipertensão arterial (HA), foi observada associação significativa de acordo com três métodos, com exceção da relação G/I. Conclusão A prevalência de RI variou conforme o método diagnóstico utilizado, mas não houve diferença estatística entre eles. A proporção de diagnósticos de IR foi maior nas mulheres obesas do que naquelas com peso normal. Foi observada associação significativa entre RI e CC, IMC e LAP, assim como com dislipidemia e HA em uma proporção elevada de pacientes.

Hypothalamic transcriptional expression of the kisspeptin system and sex steroid receptors differs among polycystic ovary syndrome rat models with different endocrine phenotypes

OBJECTIVES: Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects reproductive-age women. The mechanisms underlying the endocrine heterogeneity and neuroendocrinology of polycystic ovary syndrome are still unclear. In this study, we investigated the expression of the kisspeptin system and gonadotropin-releasing hormone pulse regulators in the hypothalamus as well as factors related to luteinizing hormone secretion in the pituitary of polycystic ovary syndrome rat models induced by testosterone or estradiol. METHODS: A single injection of testosterone propionate (1.25 mg) (n=10) or estradiol benzoate (0.5 mg) (n=10) was administered to female rats at 2 days of age to induce experimental polycystic ovary syndrome. Controls were injected with a vehicle (n=10). Animals were euthanized at 90-94 days of age, and the hypothalamus and pituitary gland were used for gene expression analysis. RESULTS: Rats exposed to testosterone exhibited increased transcriptional expression of the androgen receptor and estrogen receptor-β and reduced expression of kisspeptin in the hypothalamus. However, rats exposed to estradiol did not show any significant changes in hormone levels relative to controls but exhibited hypothalamic downregulation of kisspeptin, tachykinin 3 and estrogen receptor-α genes and upregulation of the gene that encodes the kisspeptin receptor. CONCLUSIONS: Testosterone- and estradiol-exposed rats with different endocrine phenotypes showed differential transcriptional expression of members of the kisspeptin system and sex steroid receptors in the hypothalamus. These differences might account for the different endocrine phenotypes found in testosterone- and estradiol-induced polycystic ovary syndrome rats.

Anti-inflammatory effect of silymarin on ovarian immunohistochemical localization of TNF-alpha associated with systemic inflammation in polycystic ovarian syndrome / Efecto antiinflamatorio de la silimarina en la localización inmunohistoquímica ovárica del TNF-alfa asociado con la inflamación sistémica en el síndrome de ovario poliquístico

Tumor necrosis factor alpha (TNF-a) and interleukin (IL)-6, are prominent mediators of inflammation and have been confirmed to be elevated in at least a subgroup of women with polycystic ovary syndrome (PCOS). In this study, the effects of Silymarin (SLM) on the expression TNF-a, IL-6, CRP and symptoms of PCOS were studied. In this research, PCOS was induced by injection of Estradiol Valerate. PCOS rats were divided into control and experimental groups received intraperitoneal injection SLM extract daily. After syndrome induction, ovaries were collected for histological and immunohistochemical evaluations. Serum IL-6 was detected by the ELISA kit. The results indicated the significant reduction in inflammatory markers and significant changes follicular layers thickness in the treatment group as compared with control. It can be concluded that having anti-inflammatory substances, Silymarin is effective in symptoms of this syndrome and metabolic syndrome.

El factor de necrosis tumoral alfa (TNF-a) y la interleucina (IL) -6 son mediadores prominentes de la inflamación y se ha confirmado que están elevados en al menos un subgrupo de mujeres con síndrome de ovario poliquístico (SOP). En este estudio se estudiaron los efectos de Silymarin (SLM) en la expresión TNF-a, IL-6, PCR y síntomas de SOP. El SOP fue inducido por inyección de valerato de estradiol. Las ratas SOP se dividieron en grupos control y los grupos experimentales recibieron diariamente un extracto de SLM por inyección intraperitoneal. Después de la inducción del síndrome, los ovarios se analizaron mediante histología e inmunohistoquímica. Se detectó IL-6 en suero mediante el kit ELISA. Los resultados indicaron una reducción significativa en los marcadores inflamatorios y cambios significativos en el espesor de las capas foliculares en el grupo de tratamiento en comparación con el control. Se puede concluir que con sustancias anti-inflamatorias, Silymarin es eficaz en los síntomas de este síndrome y el síndrome metabólico.

Thyroid-stimulating Hormone and Insulin Resistance: Their Association with Polycystic Ovary Syndrome without Overt Hypothyroidism / Hormônio tireoestimulante e resistência insulínica: sua associação com a síndrome do ovário policístico sem hipotireoidismo clínico

Abstract Objective This study analyzed the effectiveness of the thyroid-stimulating hormone (TSH) as a predictor of insulin resistance (IR) and its association with the clinical and metabolic parameters of women with polycystic ovary syndrome (PCOS) without overt hypothyroidism. Study Design A cross-sectional study was performed. Women with PCOS and without overt hypothyroidism (n = 168) were included. Methods Receiver operating characteristic (ROC) curve was used to determine the cut-off point for TSH that would maximize sensitivity and specificity for a diagnosis of IR using homeostatic model assessment of insulin resistance (HOMA-IR)≥ 2.71. Clinical and metabolic parameters were compared as a function of the TSH cut-off limit and the presence of IR. Results Thyroid-stimulating hormone ≥ 2.77 mIU/L was associated with a diagnosis of IR, with sensitivity of 47.9% and specificity of 65.3%. There were no differences in clinical, hormonal or metabolic parameters between TSH < 2.77 and TSH of 2.77 - 10 mIU/L. Conclusion In women with PCOS without overt hypothyroidism, TSH ≥2.77 mIU/L is associated with IR; however, with poor sensibility, showing TSH to be a poor predictor of IR in this population. No clinical or metabolic alterations were found that would justify a change in clinical management. Thus, the IR should be investigated in all women with PCOS irrespective of TSH level.

Resumo Objetivo Este estudo analisou a efetividade do hormônio tireoestimulante (TSH) como preditor da resistência insulínica (IR), bem como a associação do TSH com os parâmetros clínicos e metabólicos de mulheres com síndrome do ovário policístico (PCOS) sem hipotireoidismo clínico. Desenho do Estudo Estudo de corte transversal com inclusão de mulheres com PCOS e sem hipotireoidismo clínico (n =168). Métodos Utilizou-se análise através de curva ROC (Receiver operating characteristic) para determinar o valor de corte para o nível sérico de TSH que poderia maximizar a sensibilidade e especificidade para o diagnóstico de IR considerada com avaliação da homeostase de resistência insulínica (HOMA-IR) ≥ 2.71. Parâmetros clínicos e metabólicos foram comparados de acordo com o ponto de corte de TSH determinado e com a presença de IR. Resultados Níveis séricos de TSH ≥2.77 mIU/L estiveram associados com o diagnóstico de IR, com sensibilidade de 47.9% e especificidade de 65.3%. Não foram evidenciadas diferenças nos parâmetros clínicos, hormonais e metabólicos quando TSH < 2.77 ou TSH de 2.77 - 10 mIU/L. Conclusão Em mulheres com PCOS sem hipotireoidismo, TSH ≥2.77 mIU/L está associado a IR, porém com baixa sensibilidade, mostrando que a dosagem de TSH não é um bom preditor de IR nesta população. Também não se evidenciou alteração clínica ou metabólica que justificasse alteração na investigação desta população. Assim, a resistência insulínica deve ser investigada em todas as mulheres com PCOS, independente dos níveis séricos de TSH.

Does insulin resistance increase thyroid volume in patients with polycystic ovary syndrome?

ABSTRACT Objective To investigate the effect of gonadotropin, sex hormone levels and insulin resistance (IR) on thyroid functions and thyroid volume (TV) in polycystic ovary syndrome (PCOS). Subjects and methods 69 new diagnosed PCOS patients (age 24.82 ± 6.17) and 56 healthy control female (age 26.69 ± 5.25) were involved to the study. Fasting plasma glucose, lipid profile, insulin, thyroid stimulating hormone (TSH), free thyroxine (fT4), estradiol (E2), luteinizing hormone (LH), follicle stimulating hormone levels and urine iodine were measured in all participants. Thyroid and pelvic ultrasound were performed in all participants. Results Insulin, HOMA-IR, LH, E2 and TV were higher in PCOS group (p < 0.05). TV was significantly higher in PCOS patients with IR compared to non-IR PCOS patients (p < 0.001), while TSH, fT4, and urine iodine levels were similar between these groups (p > 0.05). There was a negative correlation between E2 and TSH (p < 0.05) and a positive correlation between TSH and TV (p < 0.05). There was a significant positive correlation between TV and LH, insulin, HOMA-IR (p < 0.05). Conclusion This study showed that TV was increased in patients with insulin resistance but differences in TSH and LH levels may affect TV changes as well.

Association of oral contraceptive and metformin did not improve insulin resistance in women with polycystic ovary syndrome / A associação de contraceptivo hormonal oral e metformina não melhora a resistência insulínica em mulheres com síndrome dos ovários policísticos.

Summary Objective: Objective: to compare clinical and laboratory parameters in women with polycystic ovary syndrome (PCOS) using metformin or combined oral contraceptive (COC) after 6 months. Methods: retrospective study analyzing records of patients with PCOS using the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society criteria. The groups were: I-COC (21 tablets, pause of 7 days; n=16); II-metformin (850mg 12/12h, n=16); III-COC plus metformin (n=9). Body mass index (BMI), acne (% of improvement), modified Ferriman-Gallway index and menstrual cycle index (MCI), luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), androstenedione (A) and homeostasis model assessment: insulin resistance (HOMA-IR) index were assessed Results: isolated use of COC compared to metformin was better regarding to acne, Ferriman index, MCI, LH, TT and A levels. On the other hand, metformin was better in the HOMA-IR index (4.44 and 1.67 respectively, p=0.0007). The association COC plus metformin, compared to metformin alone shows the maintenance of improvement of acne, Ferriman index, MCI, and testosterone levels. The HOMA-IR index remained lower in the metformin alone group (4.19 and 1.67, respectively; p=0,046). The comparison between COC plus metformin and COC alone, in turn, shows no difference in the improvement of acne, Ferriman index, MCI, LH, TT and A levels, indicating that the inclusion of metformin did not lead to additional benefits in these parameters. Still, the HOMA-IR index was similar in both groups (4.19 and 4.44 respectively; p=0.75), showing that the use of metformin associated with COC may not improve insulin resistance as much as it does if used alone. Conclusion: our data suggest that the combination of metformin and contraceptive does not improve insulin resistance as observed with metformin alone. .

Resumo Objetivo: comparar parâmetros clínicos e laboratoriais de mulheres com síndrome dos ovários policísticos (SOP) em uso de metformina ou contraceptivo hormonal oral (CHO) após 6 meses. Casuística e métodos: estudo retrospectivo com análise do prontuário de pacientes com SOP (pelos critérios da Androgen Excess and Polycystic Ovary Syndrome Society [AE-PCOS Society]), divididos em 3 grupos: (I) CHO (21 comprimidos e pausa de 7 dias; n=16), (II) metformina (850 mg a cada 12 horas; n=16) e (III) CHO associado com metformina (n=9). Foram avaliados: índice de massa corpórea (IMC), acne (% de melhora), índice de Ferriman-Gallway modificado, índice de ciclos menstruais (ICM), LH, FSH, testosterona total (TT), androstenediona (A) e resistência a insulina (HOMA-IR, do inglês homeostatic model assessment: insulin resistance). Resultados: o uso isolado de CHO comparado ao de metformina foi melhor em relação a acne, índice de Ferriman, ICM, níveis de LH, TT e A. Por outro lado, a metformina foi melhor para HOMA-IR (4,44 e 1,67; p=0,0007). O uso do CHO e metformina, em comparação com o de metformina isolada, manteve a melhora da acne, do índice de Ferriman, do ICM e dos níveis da TT. O índice de HOMA-IR manteve-se menor no grupo metformina isolada (4,19 e 1,67; p=0,046). Por sua vez, a melhora na acne, Ferriman, ICM, LH, TT e A são semelhantes nos grupos CHO associado com metformina e CHO isolado, indicando que a adição de metformina não trouxe benefícios nesses parâmetros. Ainda, o HOMA-IR foi semelhante nos dois grupos (4,19 e 4,44; p=0,75), mostrando que o uso de metformina em associação com o contraceptivo pode não melhorar a resistência insulínica como ocorre no uso isolado. Conclusão: os dados sugerem que a associação de metformina e contraceptivo não melhora a resistência insulínica como ocorre no uso da metformina isolada. .

LAP (produto da acumulação lipídica) e síndrome metabólica em pacientes com síndrome dos ovários policísticos / LAP (lipid accumulation product) and metabolic syndrome in patients with polycystic ovary syndrome

INTRODUÇÃO: A síndrome dos ovários policísticos (SOP) é uma desordem endócrina comum que afeta 5 a 10% das mulheres em idade reprodutiva. A associação entre síndrome metabólica e alterações relacionadas à glicose e insulina é frequente em pacientes com SOP, eleva o risco cardiovascular dessas pacientes. O LAP é um índice de risco cardiovascular emergente que se baseia na combinação da circunferência abdominal (CA) e triglicérides (TGL) em jejum e reflete de forma simples a acumulação lipídica em adultos. OBJETIVOS: O presente estudo avaliou as possíveis correlações entre síndrome metabólica e o LAP nos parâmetros metabólicos e reprodutivos de pacientes com SOP. MATERIAIS E MÉTODOS: O estudo incluiu 299 pacientes portadoras de SOP, definida pelos critérios de Rotterdam, acompanhadas no Ambulatório de Hiperandrogenismo do Hospital das Clínicas da Universidade Federal de Minas Gerais (HC‐UFMG). Foram avaliados: (1) dosagens séricas de triglicérides, testosterona total, glicemia de jejum e duas horas após sobrecarga de 75 gramas de dextrosol (GPD), TSH; (2) cálculo do LAP; (3) cálculo do índice de Ferriman; (4) avaliação do volume dos ovários; (5) medida da circunferência abdominal e (6) presença ou não de síndrome metabólica. RESULTADOS: A média do LAP foi 60,9 e a mediana 51,3. Pacientes com ou sem síndrome metabólica quando comparadas entre si não apresentaram diferenças quanto a volume ovariano, testosterona total, índice de Ferriman, glicemia de jejum e pós‐dextrosol. As mulheres com síndrome metabólica tiveram valores de TSH mais altos do que as mulheres sem síndrome metabólica. Já as mulheres no quartil superior do LAP tiveram TSH, índice de Ferriman e GPD maiores do que as mulheres nos quartis inferiores de LAP...

INTRODUCTION: Polycystic Ovary Syndrome (SOP) is a common endocrine disorder that affects 5-10% of women of reproductive age. The association between metabolic syndrome and changes related to glucose and insulin is frequent in patients with SOP, increasing the cardiovascular risk of these patients. The LAP is an emerging cardiovascular risk based on the combination of waist circumference (WC) and triglycerides (TGL) and fasting simply reflects the lipid accumulation in adults. OBJECTIVES: This study examined the possible correlation between metabolic syndrome or LAP and reproductive and metabolic parameters in patients with SOP. MATERIALS AND METHODS: The study included two hundred ninety-nine patients with SOP, defined by the Rotterdam criteria followed at HC-UFMG who had assessed their levels of triglycerides, total testosterone, fastingand two hours after 75 grams of overload dextrosol (GPD), TSH, LAP, Ferriman index, ovarian volume and abdominal circumference, and the presence or absence of metabolic syndrome. RESULTS: The mean LAP was 60.9 and the median 51.3. Patients with and without metabolic syndrome when compared to each others howed no differences in ovarian volume, total testosterone, Ferriman, fastingand post-dextrosol. Women with metabolic syndrome had higher TSH levels than women without metabolic syndrome. The women in the top quartile of the LAP had TSH, Ferriman and GPD higher than women in the lower quartiles of LAP...

Acantose nigricante: inter-relações metabólicas inerentes à síndrome dos ovários policísticos / Acanthosis nigricans: metabolic interrelations inherent to the polycystic ovary syndrome

OBJETIVO: Estabelecer a prevalência da acantose nigricante (AN) no contexto da síndrome dos ovários policísticos (SOP) e as respectivas associações com a obesidade, a resistência insulínica (RI), a insulinemia e a síndrome metabólica (SM). MÉTODOS: Em um estudo transversal e prospectivo, foram selecionadas cem pacientes acometidas pela SOP, diagnosticadas segundo o Consenso de Rotterdam (2003). O exame cutâneo incluiu, além da verificação da presença da AN, a presença do hirsutismo (escore ≥8) e da acne. Foram investigados os dados clínicos e bioquímicos, os fatores de risco cardiovascular que se fazem presentes na SM, como circunferência abdominal (CA), obesidade, hipertensão e os índices de HDL e triglicérides. O modelo de aferição da resistência insulínica foi realizado por meio do teste homeostatic model assessment of insulin resistance (HOMA-IR). RESULTADOS: A prevalência da AN (53%) mostrou correspondência significativa com o hirsutismo (p=0,02), o índice de massa corpórea (IMC) (p<0,01), a insulinemia basal (p<0,01), o HOMA-IR (p<0,01) e a SM (p<0,05). A SM alcançou a prevalência de 36% e associou-se significativamente apenas com a AN (p<0,01). Conquanto ausente o diabetes mellitus, sobressaem as conotações do HOMA-IR alterado (p=0,01) com a SM (p<5%) e a AN (p<0,01). CONCLUSÕES: A AN integra o quadro fenotípico grave da SOP como mais um signo previsível dos riscos da doença cardiovascular. .

PURPOSE: To establish the prevalence of acanthosis nigricans (AN) within the context of polycystic ovary syndrome (PCOS) and its associations with obesity, insulin resistance, insulinemia, and metabolic syndrome (MS). METHODS: A cross-sectional prospective study was conducted on 100 patients with PCOS diagnosed according to the Rotterdam Consensus (2003). The skin test included, in addition to the detection of the presence of AN, the presence of hirsutism (score ≥8) and acne. In addition to clinical and biochemical data, we investigated cardiovascular risk factors present in MS such as abdominal circumference, obesity, hypertension and HDL and triglyceride levels. Insulin resistance was determined by the HOMA-IR test. RESULTS: The prevalence of AN (53%) was significantly correlated with hirsutism (p=0.02), body mass index (p<0.01), basal insulinemia (p<0.01), (HOMA-IR) (p<0.01), and MS (p<0.01). The prevalence of MS reached 36% and was significantly associated only with AN (p<0.01). Although diabetes mellitus was absent, there was a significant association of altered HOMA-IR (p<0.01) with MS (p<5%) and AN (p<0.01). CONCLUSION: AN is part of the severe phenotypic profile of PCOS as an additional predictable sign of the risks of cardiovascular disease. .

Características clínicas y metabólicas de síndrome de ovario poliquístico en la ciudad de Temuco / Clinical and metabolic characteristics of polycystic ovary syndrome in the city of Temuco

Polycystic Ovarian Syndrome (PCOS) is the most common endocrine disorder, its etiologyis multifactorial. It is associated with multiple metabolic abnormalities. Objective: To evaluate statistical association between the clinical characteristics of patients diagnosed with PCOS. Patients and Methods: Descriptive study, 121 patients between 13 and 44 years with PCOS were included, and their clinical characteristics, blood glucose, insulin, lipid profile and calculated HOMA were evaluated. Data was analyzed with Chi2, considering p < 0.05 as statistically significant. Results: Mean age 25,5 years, 12,5 years menarche. 22 percent with a history of abortion. Mean BMI 31,4. Acanthosis nigricans was presented in 58,6 percent. Average Glucose 96,5 mg/dl. Insulin resistance (IR) was found in 79.3 percent. Average HOMA 4,5. 64 percent of patients with IR presented Acanthosis nigricans (p = 0.002).It showed direct relationship between BMI and RI (p 0.000). 38,8 percent had dysglycemia. RI was found in 78,7 percent of patients with dysglycemia (p 0.8). Lipid profile was measured in 78 patients, of whom 40 percent had total cholesterol above 200 mg/dl, 49 percent hypertriglyceridemia and high LDL in 13 percent of cases. Conclusions: The data reported are similar to those reported in the international literature. Ourpopulation has obesity and dyslipidemia figures higher than those reported in national studies. The menarche occurs at a younger age while the prevalence of dyslipidemia and RI is greater than the general population, forming a higher risk group...

Polycystic ovary syndrome: implications of metabolic dysfunction / Síndrome dos ovários policísticos: implicações da disfunção metabólica

OBJECTIVE: To determine the prevalence of metabolic syndrome (MS) and its clinical interrelations in polycystic ovary syndrome (PCOS). METHODS: This was a cross-sectional, prospective study with 100 patients with diagnosed PCOS based on the consensus of Rotterdam (2003). We investigated the interrelationships of MS, with intrinsic PCOS data. Dermatological profile was analyzed, in addition to acanthosis nigricans (AN) in the presence of hirsutism and acne. The use of HOMA-IR (homeostatic model assessment of insulin resistance) aimed at the correlation with MS in order to establish the metabolic dysfunction with the state of insulin resistance. RESULTS: The mean and standard deviations corresponding figures for age, body mass index and waist circumference were, respectively, 25.72 (± 4.87), 30.63 (± 9.31) and 92.09 (± 18.73). The prevalence of MS was 36% and significantly correlated with BMI, AN, and in 51% of patients the state of insulin resistance (HOMA-IR). Regarding skin profile, only AN significant correlation with MS. CONCLUSION: We propose the routine inspection of metabolic components related to severe PCOS. These parameters configure the cardiovascular risk and such conduct is of undoubted importance to public health. .

OBJETIVO: estabelecer a prevalência da síndrome metabólica (SM) e as respectivas inter-relações clínicas no contexto da síndrome dos ovários policísticos (SOP). MÉTODO: estudo transversal, prospectivo, em 100 pacientes portadoras de SOP diagnosticada com base no consenso de Rotterdam (2003). Investigam-se, principalmente, as interrelações da SM, com os dados intrínsecos à SOP. O perfil dermatológico analisado consiste, além da acantose nigricante (AN), na presença de hirsutismo e da acne. O emprego do HOMA-IR (homeostatic model assessment of insulin resistance - modelo matemático de aferição da resistência insulínica) objetivou a correlação com a SM a fim de legitimar a disfunção metabólica com o estado de RI. RESULTADOS: Os valores médios e respectivos desvios-padrões relativos à idade, ao índice de massa corporal e a circunferência abdominal foram respectivamente 25,72 (±4,87), 30,63 (±9,31) e 92,09 (±18,73). A prevalência da SM, 36%, mostrou correlação significativa com o IMC, prevalecido pela constituição do sobrepeso e obesidade, a AN e, em 51% das pacientes, o estado de resistência à insulina (HOMA-IR). No que concerne ao perfil dérmico, apenas a AN evidenciou correlação significativa com a SM. CONCLUSÃO: propõe-se a inspeção rotineira dos componentes metabólicos relacionados ao quadro grave da SOP. Tais parâmetros configuram o risco cardiovascular e tal conduta se constitui de indubitável importância no que tange à saúde pública. .

Association of glucocorticoid receptor polymorphisms with clinical and metabolic profiles in polycystic ovary syndrome

OBJECTIVES: We aimed to investigate whether glucocorticoid receptor gene polymorphisms are associated with clinical and metabolic profiles in patients with polycystic ovary syndrome. Polycystic ovary syndrome is a complex endocrine disease that affects 5-8% of women and may be associated with metabolic syndrome, which is a risk factor for cardiovascular disease. Cortisol action and dysregulation account for metabolic syndrome development in the general population. As glucocorticoid receptor gene (NR3C1) polymorphisms regulate cortisol sensitivity, we hypothesized that variants of this gene may be involved in the adverse metabolic profiles of patients with polycystic ovary syndrome. METHOD: Clinical, metabolic and hormonal profiles were evaluated in 97 patients with polycystic ovary syndrome who were diagnosed according to the Rotterdam criteria. The alleles of the glucocorticoid gene were genotyped. Association analyses were performed using the appropriate statistical tests. RESULTS: Obesity and metabolic syndrome were observed in 42.3% and 26.8% of patients, respectively. Body mass index was positively correlated with blood pressure, triglyceride, LDL-c, total cholesterol, glucose and insulin levels as well as HOMA-IR values and inversely correlated with HDL-c and SHBG levels. The BclI and A3669G variants were found in 24.7% and 13.4% of alleles, respectively. BclI carriers presented a lower frequency of insulin resistance compared with wild-type subjects. CONCLUSION: The BclI variant is associated with a lower frequency of insulin resistance in women with polycystic ovary syndrome. Glucocorticoid gene polymorphism screening during treatment of the syndrome may be useful for identifying subgroups of at-risk patients who would benefit the most from personalized treatment. .

Perfil metabólico em mulheres de diferentes índices de massa corporal com síndrome dos ovários policísticos / Metabolic profile in women of different body mass indices with polycystic ovary syndrome

OBJETIVO: Caracterizar e comparar variáveis clínicas, antropométricas e bioquímico-metabólicas de pacientes com síndrome dos ovários policísticos (SOP), estratificadas segundo o índice de massa corpórea (IMC). MÉTODOS: Estudo transversal com 78 mulheres entre 18 e 45 anos com diagnóstico de SOP, pelos Critérios de Rotterdam. As pacientes foram estratificadas segundo o IMC. As variáveis analisadas foram: idade, estado civil, sedentarismo, irregularidade menstrual, pressão arterial (PA), medidas antropométricas, perfil lipídico, glicemia em jejum e dosagens hormonais. Para comparar as variáveis analisadas entre os diferentes IMC, usou-se a Análise de Variância e o Teste de Kruskal-Wallis. O nível de significância para todos os testes foi de 5%. RESULTADOS: As pacientes apresentaram média de idade de 26,3 anos, sendo 79,5% classificadas como sedentárias e 68% com hiperandrogenismo. A circunferência da cintura, a Razão cintura/quadril, a Razão cintura/estatura e a porcentagem de gordura corporal foram maiores no grupo de obesas. A presença de marcadores de risco cardiovascular (RCV - glicemia de jejum, PA sistólica e diastólica e LDL-colesterol) foi diretamente proporcional ao IMC, enquanto que os níveis de HDL-colesterol e SHBG foram inversamente proporcionais ao IMC. CONCLUSÃO: A presença de marcadores de RCV aumentou proporcionalmente ao IMC, evidenciando que o perfil metabólico das mulheres obesas com SOP é mais desfavorável do que n não obesas.

PURPOSE: To characterize and compare clinical, anthropometric and biochemical-metabolic variables in patients with polycystic ovary syndrome (PCOS), stratified according to body mass index (BMI). METHODS: A cross-sectional study conducted on 78 women aged 18 to 45 years with a clinical diagnosis of PCOS by the Rotterdam criteria. Patients were stratified according to BMI. The variables analyzed were: age, marital status, physical inactivity, menstrual irregularity, blood pressure (BP), anthropometric measurements, lipid profile, fasting glucose, and hormone measurements. To compare the variables between the different BMI values we used analysis of variance and the Kruskal-Wallis test. The level of significance was set at 5% for all tests. RESULTS: The patients had a mean age of 26.3 years, 79.5% of them were sedentary and 68% had hyperandrogenism. Waist circumference, waist/hip ratio, waist/height ratio and percentage of body fat were higher in the obese group. The markers of cardiovascular risk (CVR - fasting glucose, systolic and diastolic BP and LDL-cholesterol) were directly proportional to BMI, whereas HDL-cholesterol and SHBG were inversely related to BMI. CONCLUSION: The presence of markers of CVR factors increased proportionally to BMI, indicating that the metabolic profile of obese women with PCOS is more unfavorable than that of non-obese patients.

Manifestações clínicas, bioquímicas, ultrassonográficas e metabólicas da síndrome dos ovários policísticos em adolescentes / Clinical manifestations, biochemical, ultrasonographic and metabolic of polycystic ovary syndrome in adolescents

OBJETIVO: Avaliar os parâmetros clínicos, ultrassonográficos, bioquímicos e as alterações metabólicas em adolescentes com síndrome dos ovários policísticos (SOP). MÉTODOS: Estudo retrospectivo realizado com 44 adolescentes entre 12 e 19 anos, com diagnóstico de SOP pelo Consenso de Rotterdam. As alterações metabólicas foram avaliadas de acordo com as recomendações da Federação Internacional de Diabetes, sendo consideradas: circunferência da cintura (CC) >percentil 90 (10-15 anos de idade) ou >80 cm (idade >16 anos); glicemia de jejum >100 mg/dL; triglicerídios >150 mg/dL; HDL <40 mg/dL, e pressão arterial >Hg 130/85 mm. RESULTADOS: A média de idade foi de 16,7±2,2 anos e da idade da menarca 11,8±1,4 anos. A irregularidade menstrual mais observada foi amenorreia (72,7%) seguida de oligomenorréia (27,3%); hirsutismo foi observado em 86,4% e acne em 56,8%. Ovários policisticos ao ultrassom observados apenas em 27,3%. A média do IMC foi de 30,3±6,6 kg/m². De acordo com o IMC, 52,3% das adolescentes eram obesas, 13,6% estavam com sobrepeso e 6,8% eram eutróficas. O aumento da circunferência da cintura (63,6%, 28/44) e a redução do HDL-C (34,1%, 15/44) foram as alterações metabólicas mais observadas. Triglicerídios aumentados foram observados em 27,3% (12/44), pressão arterial e aumento da glicemia de jejum alterada foram encontrados em 9,1% (4/44) e 4,5% (2/44) dos casos, respectivamente. Acantosis nigricans foi observada em 52,3% das adolescentes com SOP e a resistência insulinica encontrada em 62,8%. A sindrome metabólica foi identificada em seis adolescentes (13,6%), sendo todas obesas ou com sobrepeso. CONCLUSÃO: Entre as adolescentes com SOP do estudo, a irregularidade menstrual e o hirsutismo são as manifestações clínicas mais frequentes, enquanto os achados ultrassonográficos compatíveis com ovários policísticos são os menos prevalentes. A obesidade associada à resistência à insulina predispõe estas adolescentes à maior frequência de alterações metabólicas.

PURPOSE: To evaluate the clinical, ultrasonographic, biochemical and metabolic alterations of adolescents with polycystic ovary syndrome (PCOS). METHODS: Retrospective observational study conducted on 44 adolescents aged 12 to 19 years, diagnosed with PCOS according to the Rotterdam Consensus. Metabolic changes were assessed according to the recommendations of the International Diabetes Federation, considering: waist circumference (WC) >90th percentile (10-15 years of age) or >80 cm (age >16 years), fasting glucose >100 mg/dL, triglycerides >150 mg/dL, HDL <40 mg/dL, and blood pressure >Hg 130/85 mm. RESULTS: Mean age was 16.7±2.2 years and age at menarche was 11.8±1.4 years. The menstrual irregularity most frequently observed was amenorrhea (72.7%) followed by oligomenorrhea (27.3%); hirsutism was observed in 86.4% and acne in 56.8%. Polycystic ovaries were observed by ultrasound only in 27.3%. Mean BMI was 30.3±6.6 kg/m². According to BMI, 52.3% of adolescents were obese, 13.6% were overweight and 6.8% had a healthy weight. Increased waist circumference (63.6%, 28/44) and the reduction of HDL-C (34.1%, 15/44) were the metabolic changes most frequently observed. Increased triglycerides were observed in 27.3% (12/44) and increased blood pressure and impaired fasting glucose were found in 9.1% (4/44) and 4.5% (2/44) of cases, respectively. Acanthosis nigricans was observed in 52.3% and insulin resistance in 62.8% of the adolescents with PCOS. Metabolic syndrome was identified in six children (13.6%), all of them obese or overweight. CONCLUSION: In the adolescents with PCOS studied here, menstrual irregularity and hirsutism were the most common clinical manifestations, while the sonographic findings consistent with polycystic ovaries were less prevalent. Obesity associated with insulin resistance predisposes these adolescents to a higher frequency of metabolic disorders.