Is there any association between vitamin D levels and polycystic ovary syndrome (PCOS) phenotypes?

ABSTRACT Objective The aim of this study was to assess the serum vitamin D level in a retrospective study in women with polycystic ovary syndrome (PCOS), according to the different phenotypes of the disease. Subjects and methods In this retrospective study, the records of 351 infertile women who were diagnosed with PCOS were examined, and 200 of them were enrolled in the study randomly in 4 PCOS phenotypes. Fifty normal ovulatory women with the history of male factor were selected as the control group. Parameters, including age, infertility duration, body mass index (BMI), hormone profile, as well as the serum vitamin D level were compared among the 4 phenotypes, with the P-value ≤ 0.05 considered statistically significant. Results The findings showed a higher serum vitamin D level in the control group than in PCOS patients, which was statistically significant (P < 0.001). In addition, there was no significant difference in the serum vitamin D level among the four phenotypes of PCOS. Conclusions No significant difference was found in the serum vitamin D level of the different phenotypes of PCOS. Further studies with larger sample sizes are recommended to be done to establish the role of the serum vitamin D level in PCOS patients.

Increased sympathetic cardiac autonomic modulation after two consecutive tilt tests in women with polycystic ovary syndrome / Aumento da modulação autonômica cardíaca simpática após dois testes de inclinação consecutivos em mulheres com síndrome dos ovários policísticos

Abstract Objective The present study aimed to analyze cardiac autonomic modulation via spectral and symbolic analysis of heart rate variability (HRV) in women with polycystic ovary syndrome (PCOS) who were subjected to two consecutive tilt tests. Methods A total of 64 women were selected and divided into 2 groups: control (without PCOS), and PCOS. Concentrations of follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, homocysteine, sex hormone-binding globulin, thyroid stimulating hormone, fasting insulin, testosterone, androstenedione, and 17-hydroxyprogesterone levels, triglycerides, free androgen index (FAI), and homeostasis assessment model (HOMA-IR) were assessed. Cardiac autonomic modulation was evaluated by spectral and symbolic analyses during two consecutive tilt tests (two moments) and supine moments before, between and after (three moments) the tilt tests. Results Women with PCOS had higher fasting insulin, HOMA-IR indexes, testosterone and FAI. Additionally, we observed that the PCOS group had greater sympathetic autonomic cardiac modulation in supine 2, tilt 1, and supine 3 moments compared with controls. Conclusion Women with PCOS had higher autonomic sympathetic cardiac modulation even after a second tilt test. No adaptation to this provocative test was observed. Spectral analysis was more sensitive for identifying differences between groups than the symbolic analysis.

Resumo Objetivo O presente estudo teve como objetivo analisar a modulação autonômica cardíaca por análise espectral e simbólica da variabilidade da frequência cardíaca (VFC) em mulheres com síndrome dos ovários policísticos (SOP) que foram submetidas a dois testes consecutivos de inclinação. Métodos Um total de 64 mulheres foram selecionadas e divididas em 2 grupos: controle (sem SOP) e SOP. Concentrações de hormônio folículo-estimulante, hormônio luteinizante, prolactina, estradiol, homocisteína, globulina de ligação a hormônios sexuais, hormônio estimulante da tireóide, insulina em jejum, testosterona e androstenediona e níveis de 17-hidroxiprogesterona, triglicerídeos, índice de andrógeno livre (FAI) e homeostase modelo de avaliação (HOMA-IR) foram avaliados. A modulação autonômica cardíaca foi avaliada por análises espectrais e simbólicas durante dois testes de inclinação consecutivos (dois momentos) e momentos supinos antes, entre e após (três momentos) os testes de inclinação. Resultados Mulheres com SOP apresentaram insulina em jejuM, índices HOMA-IR, testosterona e FAI mais altos. Além disso, observamos que o grupo PCOS apresentou maior modulação cardíaca autonômica simpática nos momentos supino 2, inclinado 1 e supino 3 em comparação aos controles. Conclusão Mulheres com SOP apresentaram modulação cardíaca simpática autonômica mais alta mesmo após um segundo teste de inclinação. Nenhuma adaptação a esse teste provocativo foi observada. A análise espectral foi mais sensível para identificar diferenças entre os grupos do que a análise simbólica.

Association of measures of central fat accumulation indices with body fat distribution and metabolic, hormonal, and inflammatory parameters in women with polycystic ovary syndrome

ABSTRACT Objective To investigate the associations among visceral adiposity index (VAI), lipid accumulation product (LAP), body fat percentage (%), and android/gynoid ratio (A/G ratio) in women with polycystic ovary syndrome (PCOS) and verify if the parameters representative of visceral obesity correlate with and exhibit the same frequency as body composition variables; anthropometric indices; and metabolic, hormonal, and inflammatory parameters. Subjects and methods This was a cross-sectional study that included 94 women with PCOS. Hormonal, metabolic, and inflammatory parameters were analyzed in all women. Free androgen index (FAI) and homeostasis model assessment (HOMA-IR), as well as LAP, VAI, and anthropometric indices, were calculated. The regions of interest (ROIs) in body composition and body composition indices were evaluated using a dual X-ray absorptiometry (DXA). Overall, 32 variables were selected as markers of body fat distribution. Results Among the 32 markers evaluated, 29 correlated with LAP, whereas 25 correlated with VAI, 19 with body fat (%), and 30 with A/G ratio. Additionally, some markers correlated with the four adiposity indices evaluated: ROIs, except for total mass and leg fat (%); body composition (body mass index, waist circumference, and hip circumference) indices; fasting insulin; and C-reactive protein. Conclusion LAP and VAI may be sensitive measures for screening and preventing metabolic syndrome and insulin resistance in PCOS, with LAP being more sensitive than VAI, and the A/G ratio may be more sensitive than body fat percentage.

Estudios del laboratorio de diversos parámetros orientados a tratar de dilucidar la fisiopatología del síndrome de ovarios poliquísticos (SOP). Parte 2 / Laboratory studies of several parameters aimed to elucidate the pathophysiology of polycystic ovary syndrome. Second part

RESUMEN Diversos estudios bioquímicos adicionales a la evaluación de Testosterona total (TT), biodisponible (Tbio) y libre (TL) han sido realizados a los efectos que pudieran resultar de mayor utilidad para el diagnóstico de patologías concomitantes en el SOP, entre otros. En la hormona anti Mülleriana, cuando la concentración supera a los 3,0 ng/ml existen evidencias de que el 79% de las mismas pueden ser identificadas correctamente como SOP. El Antígeno Prostático Específico (PSA), marcador de singular importancia en pacientes con cáncer de Próstata, con técnicas ultrasensibles ha podido ser detectado en más del 50% en mujeres. En un grupo de pacientes con SOP, los niveles circulantes de PSA fueron significativamente mayores que en las mujeres sin SOP. El Kiss-1 aislado de la placenta y demostrado en otros tejidos, presenta niveles aumentados que correlacionan con la LH, TT, TL y resistencia a la insulina (RI) en adolescentes con SOP versus adolescentes sin SOP, sugiriendo que el Kiss-1 podría estar involucrado en el desarrollo del SOP en estas pacientes. Algunas pacientes con SOP están asociadas a patologías relevantes, de las cuales han sido comunicadas el aumento del BMI, mayor grado de dislipemia, adiposidad central, RI y Síndrome Metabólico (SMe). En las pacientes con un fenotipo clásico (hiperandrogenismo, alteración del ciclo menstrual y ovarios poliquísticos), estas patologías son de mayor frecuencia y severidad que en los otros fenotipos, particularmente aquellos sin hiperandrogenismo. Otras determinaciones como TNFα, interleuquinas, test de tolerancia a la glucosa, ApoB, partículas pequeñas de LDL e Inhibidor del Activador del Plasminógeno-1 han sido comunicados que podrían ser de utilidad para tener mayor sensibilidad en la definición de patología concomitantes en el SOP. Actualmente se ha comenzado a evaluar otros marcadores como el Fetuin-A; Quemerina, Nesfatina-1, Neopterina y Endocannabinoides, cuyos resultados preliminares parecerían ser un aporte importante para evaluar SMe y RI en paciente con SOP y tratar de definir su prevalencia en los distintos fenotipos de esta patología.

ABSTRACT Several biochemical studies in addition to the evaluation of total Testosterone (TT), bioavailable (bioT) and free (FT) have been performed to the effects that could be of greater use for the diagnosis of concomitant pathologies in the PCOS, among others. The anti-Müllerian hormone whose concentration when exceeds 3.0 ng/ml, there is evidence that 79% of these patients can be correctly identified as PCOS. The Prostate-Specific Antigen (PSA), a marker of singular importance in patients with prostate cancer, with ultra-sensitive techniques, has been detected in more than 50% of women. In a group of patients with PCOS, circulating levels of PSA are significantly higher than in women without PCOS. The Kiss-1 isolated from the placenta and demonstrated in other tissues, has increased levels that correlate with LH, TT, TL and insulin resistance (IR) in adolescents with PCOS respect to adolescents without PCOS, suggesting that Kiss-1 could be involved in the development of the PCOS in these patients. In some patients with PCOS, they are associated with relevant pathologies, of which the increase in BMI, higher degree of dyslipidemia, central adiposity, IR and Metabolic Syndrome (MeS) have been reported. Those that show a classic phenotype (hyperandrogenism, alteration of the menstrual cycle and polycystic ovaries) these characteristics are of greater frequency and severity than in the other phenotypes, particularly those without hyperandrogenism. Other determinations such as TNFα, interleukins, glucose tolerance test, ApoB, small particles of LDL and Plasminogen Activator Inhibitor-1 have been reported that could be useful to have greater sensitivity in the definition of concomitant pathology in the PCOS. Currently, other markers such as Fetuin-A, Chemerin, Nesfatin-1 Neopterin and Endocannabinoids have been evaluated. The preliminary results suggest to be an important contribution to define MeS and IR in patient with PCOS and to try to determine its prevalence in the different phenotypes of this pathology.

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.

Alta frecuencia de trastornos tiroideos en el síndrome de ovario poliquístico / High frequency of thyroid abnormalities in polycystic ovary syndrome

La prevalencia de trastornos tiroideos (TT) no ha sido suficientemente evaluada en mujeres con síndrome de ovario poliquístico (SOP). El propósito de esta investigación fue examinar dicha relación. En este estudio prospectivo de diseño caso-control, se incluyeron 194 mujeres. El grupo SOP consistió en 142 pacientes diagnosticadas por criterios Rotterdam 2003, y el grupo control incluyó a 52 mujeres sanas apareadas por edad. Se extrajeron muestras de sangre en ayuno para dosajes de T4 libre, tirotrofina, anticuerpos antiperoxidasa (ATPO), insulinemia y glucemia y se calculó el índice HOMA. Un total de 52 pacientes con SOP presentó autoinmunidad tiroidea (AIT+) y/o hipotiroidismo subclínico (HSC) (36.6%) (TT+) en comparación con 7 mujeres del grupo de control (13.5%), lo que representa una frecuencia cinco veces mayor de TT en pacientes con SOP en comparación con los controles (odds ratio ajustado: 5.6; IC 95%: 2.1-14.9; p < 0.001). Las pacientes TT+ tuvieron valores de insulinemia y HOMA significativamente más altos que aquellas sin trastornos tiroideos (TT-) (p < 0.05).Este estudio muestra una alta tasa de TT en mujeres con SOP asociada a mayores niveles de insulinemia y HOMA. Teniendo en cuenta que el SOP, el hipotiroidismo y la autoinmunidad tiroidea pueden tener un profundo impacto en la salud reproductiva, nuestros datos sugieren que las pacientes con SOP deberían ser evaluadas para descartar TT.

The prevalence of thyroid abnormalities (TA) has not been sufficiently assessed in polycystic ovary syndrome (PCOS). Our aim was to evaluate this relationship. In this prospective study 194 women were included. The PCOS group consisted of 142 patients (diagnosed by Rotterdam 2003 criteria) and the control group included 52 age-matched healthy women. Fasting blood samples were drawn for free T4, thyrotropin, thyroperoxidase antibodies (TPOAb), fasting insulin, glucose and HOMA-IR were calculated. A total of 52 PCOS patients had either autoimmune thyroiditis (AIT+) and/or subclinical hypothyroidism (HSC) (36.6%) (thyroid abnormalities:TA+) compared with 7 women of the control group (13.5%), accounting for more than a five fold higher prevalence of TA in PCOS patients, compared with the age-matched controls (adjusted odds ratio: 5.6; CI 95%: 2.1 -14.9; p < 0.001). TA+ patients had significantly higher FI and HOMA-IR values than patients without thyroid abnormalities(p < 0.05). These results demonstrate a high rate of TA in young PCOS women, associated with higher levels of FI and HOMA-IR. As PCOS, hypothyroidism and thyroid autoimmunity may have a profound impact on reproductive health, our data indicate that PCOS patients should be screened for TA.

Triglyceride Is a Useful Surrogate Marker for Insulin Resistance in Korean Women with Polycystic Ovary Syndrome

PURPOSE: To evaluate lipid profiles and liver enzymes as surrogate markers used for recognizing insulin resistance in Korean women with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: 458 women with PCOS were divided into two groups: non-obese with a body mass index (BMI) or =25.0 kg/m2. Anthropometric measures and blood sampling for hormone assay, liver enzymes, lipid profiles and 75 g oral glucose tolerance test were performed. Insulin resistance was defined as homeostasis model assessment of insulin resistance (HOMA-IR)> or =2.5. Areas under the receiver operating characteristic (ROC) curves were used to compare the power of serum markers. Multiple linear regression analysis was used to evaluate the contribution of each confounding factor for HOMA-IR. RESULTS: In non-obese and obese groups, the ROC curve analyses demonstrated that the best marker for insulin resistance was triglyceride (TG), with the areas under the ROC curve of 0.617 and 0.837, respectively. Low-density lipoprotein cholesterol (LDL-C) was the significant marker for insulin resistance with areas under the ROC curve of 0.698 in obese group, but not significant in non-obese group. TG and LDL-C were significantly associated with HOMA-IR in both non-obese and obese PCOS women by multiple linear regression analysis. The optimal cut-off points of TG> or =68.5 was a marker for predicting insulin resistance in non-obese PCOS patients and TG> or =100.5 in obese group. CONCLUSION: TG can be used as a useful marker for insulin resistance in Korean women with PCOS, especially for obese patients.

Adipokines, insulin-like growth factor binding protein-3 levels, and insulin sensitivity in women with polycystic ovary syndrome

BACKGROUND/AIMS: Many women with polycystic ovary syndrome (PCOS) exhibit insulin resistance. Adipose tissue plays an important role in insulin resistance, and adipokines including tumor necrosis factor (TNF)-alpha and adiponectin are altered in PCOS. Insulin-like growth factor binding protein-3 (IGFBP-3), alone or in conjunction with other adipokines, is also associated with insulin resistance. We evaluated the effects of TNF-alpha, adiponectin, and IGFBP-3 on insulin sensitivity and the relationships among these proteins in women with PCOS. METHODS: We recruited 40 women with PCOS and 40 age- and body mass index (BMI)-matched regular cycling women (controls). The women were divided into obese (BMI > or = 25 kg/m2) and nonobese (BMI < 25 kg/m2) groups. Anthropometric measurements were performed, and serum levels of TNF-alpha, adiponectin, and IGFBP-3 were determined. Insulin sensitivity was estimated using the metabolic clearance rate (MCR) of glucose calculated from the oral glucose tolerance test. RESULTS: Serum levels of TNF-alpha and IGFBP-3 did not differ between the PCOS and control groups, but adiponectin levels in the PCOS group were lower than those in control women in the nonobese group (p < 0.05). TNF-alpha, adiponectin, and IGFBP-3 levels were not correlated with each other in women with PCOS, but a significant positive correlation was observed between adiponectin levels and MCR (p < 0.05). Multiple regression analysis revealed that adiponectin levels were significantly associated with insulin sensitivity (p < 0.05) in women with PCOS. CONCLUSIONS: IGFBP-3 and TNF-alpha levels were not associated with insulin sensitivity, but adiponectin levels were related to insulin sensitivity in women with PCOS.

Morfologia das células intersticiais de ovários policísticos de ratas: um estudo experimental / Morphology of the interstitial cells of rat polycystic ovaries: an experimental study

OBJETIVOS: Avaliar a histomorfometria das células intersticiais dos ovários, bem como analisar a concentração sanguínea de esteroides sexuais de ratas portadoras de ovários policísticos induzidos pela luz contínua. MÉTODOS: Vinte ratas foram divididas em dois grupos: ratas na fase de estro (GCtrl ) e ratas portadoras de ovários policísticos induzidos pela iluminação contínua (GOP). Os animais do GCtrl permaneceram com período de luz das 7:00 s 19:00 horas, e os animais do GOP, com iluminação contínua (400 Lux), durante um período de 60 dias. Ao final desse período todos os animais foram anestesiados, foi coletado o sangue, para determinação dos níveis séricos de estradiol (E2), progesterona (P4) e testosterona (T), seguido da retirada dos ovários que foram fixados em formol a 10% e processados para inclusão em parafina. Cortes histológicos com 5 µm corados pela hematoxilina e eosina foram utilizados para análise histomorfométrica. As análises morfológicas, contagem de cistos, determinação da concentração e do volume nuclear das células intersticiais foram realizadas com o auxílio de microscópio de luz adaptado a uma câmera de alta resolução (AxioCam), cujas imagens foram transmitidas e analisadas em computador com software AxioVision Rel 4.8 (Carl Zeiss). Os dados obtidos foram submetidos ao teste t de Student (p<0,05). RESULTADOS: A morfologia mostrou a presença de cistos nos ovários pertencentes ao Grupo OP e de corpos lúteos no GCtrl, mostrando ainda evidências da origem das células intersticiais a partir das células da teca interna desses cistos. Com relação aos níveis hormonais o GOP apresentou níveis séricos de estradiol (pg/mL) aumentados em relação ao GCtrl (GOP=124,9±4,2>GCtrl=73,2±6,5; p<0,05), o mesmo ocorrendo com os níveis de testosterona (pg/mL) (GOP=116,9±4,6>GCtrl=80,6±3,9; p<0,05). Entretanto os níveis de progesterona (ng/mL) foram mais elevados no GCtrl em relação ao GOP (GCtrl=16,3±2,0>GOP=4,2±1,5; p<0,05). A morfometria mostrou haver aumento significante do volume nuclear no grupo GOP (GOP=102,1±5,2>GCtrl=63,6±16,5; p<0,05), assim como da área ocupada (%) pelas células intersticiais (GOP=24,4±6,9>GCtrl=6,9±3,2; p<0,05) em relação aos animais do GCtrl. CONCLUSÃO: As células intersticiais do ovário policístico da rata provavelmente provêm dos cistos ovarianos devido degeneração das células da granulosa e diferenciação das células da teca interna. As elevações dos níveis séricos de testosterona e de estradiol provavelmente provêm do aumento significativo da atividade celular e da área ocupada pelas células intersticiais.

PURPOSES: To evaluate the histomorphometry of ovarian interstitial cells, as well as the blood sex steroid concentrations of female rats with polycystic ovaries induced by continuous light. METHODS: Twenty female rats were divided into two groups: Control Group - in the estrous phase (CtrlG), and a group of rats with polycystic ovaries induced by continuous illumination (POG). CtrlG animals were maintained on a light period from 07:00 a.m. to 07:00 p.m., and POG animals with continuous illumination (400 Lux) for 60 days. After this period all animals were anesthetized and blood was collected for the determination of serum estradiol (E2), progesterone (P4), and testosterone (T), followed by removal of the ovaries that were fixed in 10% formalin and processed for paraffin embedding. Five-µm histological sections were stained with hematoxylin and eosin and used for histomorphometric analysis. Morphological analyses, cyst count, determination of concentration and of the nuclear volume of interstitial cells were performed with the aid of a light microscope adapted to a high resolution camera (AxioCam), whose images were transmitted to and analyzed by the computer using AxioVision Rel 4.8 software (Carl Zeiss). Data were analyzed statistically by the Student's t-test (p<0.05). RESULTS: Morphological analysis showed the presence of ovarian cysts in POG animals and corpora lutea in CtrlG animals, as well as evidence of the origin of interstitial cells from the internal theca of these cysts. POG animals presented increased serum estradiol levels (pg/mL) compared to CtrlG animals (POG=124.9±4.2>CtrlG=73.2±6.5, p<0.05), the same occurring with testosterone levels (pg/mL) (POG=116.9±4.6>CtrlG=80.6±3.9, p<0.05). However, progesterone levels (ng/mL) were higher in CtrlG than in POG animals (CtrlG=16.3±2.0>POG=4.2±1.5, p<0.05). Morphometry showed a significant increase in nuclear volume in POG animals (POG=102.1±5.2>CtrlG=63.6±16.5, p<0.05), as well as in the area occupied (%) by interstitial cells (POG=24.4±6.9>CtrlG=6.9±3.2, p<0.05) compared to CtrlG animals. CONCLUSION: The interstitial cells of the rat polycystic ovary probably originate from ovarian cysts due to the degeneration of granulosa cells and differentiation of the internal theca cells. The elevations of serum testosterone and estradiol were probably due to the significant increase in cell activity and in the area occupied by interstitial cells.

Resistência à insulina em mulheres com síndrome dos ovários policísticos: relação com as variáveis antropométricas e bioquímicas / Insulin resistance in women with polycystic ovary syndrome: relationship with anthropometric and biochemical variables

OBJETIVO: Analisar a prevalência de resistência à insulina de acordo com diferentes medidas antropométricas e bioquímicas em mulheres com síndrome dos ovários policísticos. MÉTODOS: Foram analisadas, retrospectivamente, 189 pacientes com síndrome dos ovários policísticos. O diagnóstico de resistência à insulina foi obtido utilizando-se insulinemia, HOMA-IR, QUICKI, índice de sensibilidade à insulina e relação glicemia/insulina. Foram utilizados o índice de massa corpórea e o lipid accumulation product. Para análise dos resultados, aplicou-se a estatística descritiva, a ANOVA, o pós-teste de Tukey e a correlação de Pearson. RESULTADOS: As pacientes apresentaram média de idade de 24,9±5,2 e de índice de massa corpórea de 31,8±7,6. O percentual de pacientes obesas foi de 57,14 por cento. Dentre os métodos de investigação de resistência à insulina, o índice de sensibilidade à insulina foi a técnica que mais detectou (56,4 por cento) a presença de resistência à insulina nas mulheres com síndrome dos ovários policísticos. Em 87 por cento das pacientes obesas, detectou-se a resistência à insulina. A relação glicemia/insulinemia de jejum e o índice de sensibilidade à insulina apresentaram correlação forte com o lipid accumulation product. CONCLUSÃO: A prevalência de resistência à insulina variou de acordo com o método utilizado e foi maior quanto maior o índice de massa corpórea. O lipid accumulation product também está relacionado à resistência à insulina.

PURPOSE: To analyze the prevalence of insulin resistance, according to different biochemical and anthropometric measurements in women with polycystic ovary syndrome. METHODS: A total of 189 patients with polycystic ovary syndrome were retrospectively analyzed. Insulin resistance diagnosis was performed using fasting insulin, HOMA-IR, QUICKI, insulin sensibility index and glucose/fasting insulin ratio. Body mass index and lipid accumulation product were used. Data were analyzed statistically by descriptive statistics, ANOVA, Tukey post-test, and Pearson's correlation. RESULTS: The polycystic ovary syndrome patients had a mean age of 24.9±5.2 and a mean body mass index of 31.8±7.6. The percentage of obese patients was 57.14 percent. Among the methods of insulin resistance investigation, the insulin sensibility index was the technique that most detected (56.4 percent) the presence of insulin resistance in women with polycystic ovary syndrome. The insulin resistance was detected in 87 percent of obese patients. The fasting glucose/fasting insulin ratio and insulin sensibility index were strongly correlated with lipid accumulation product. CONCLUSION: The prevalence of insulin resistance varied according to the method used, and it was greater the higher the body mass index. Lipid accumulation product was also related to insulin resistance.

[ effects of an aerobic exercise program on LH, FSH, TST and DHEA levels in obese women with polycystic ovary syndrome]

Polycystic ovary syndrome [PCOS] is an endocrine disorder, characterized by anovulation, hirsutism, acne, hyperandrogenism, impaired glucose tolerance, insulin resistance and obesity. Life style modifications are recommended to prevent and treat obese and over weight women with PCOS. The purpose of this study was to determine the effects of aerobic exercise program on concentrations of LH, FSH, TST and DHEA in obese women with polycystic ovary syndrome. Seventeen obese female volunteers who were diagnosed with polycystic ovary syndrome [age: 15-30 y and BMI=29.35 +/- 2.88 Kg/m2] were selected. An aerobic exercise program was performed for 12-weeks, three sessions week]. Anthropometric characteristics, metabolic and hormonal profiles were measured at base line and after 12-week exercises or [36th session]. Data were analyzed by Paired-Samples T Test [t-student], P values <0.05 being considered significant. After the 12-week exercise program, subjects showed a significant reduction in body weight, body fat percent, waist circumference, luteinizing hormone and an increase in Vo2-peak[P<0/05]; changes however in body mass index, FSH, TST and DHEA were not significant. These results suggest that aerobic exercise training affects some of anthropometric characteristics and metabolic and hormonal profiles and also improves metabolic status and ovulation disorders, including polycystic ovary syndrome

Participação dos androgênios adrenais na síndrome dos ovários policísticos / Adrenal androgen participation in the polycystic ovary syndrome

OBJETIVO: reavaliar a função adrenal em pacientes com síndrome dos ovários policísticos, após a introdução dos critérios de Roterdã. MÉTODOS: estudo descritivo de corte transversal, incluindo 53 pacientes com média de idade de 26±5,1 anos. Glicose, hemoglobina glicada, lipídios, estradiol, progesterona, 17-OHP4, DHEAS, FSH, LH, TSH, PRL, androstenediona, tiroxina livre, insulina, testosterona total, SHBG e índice de androgênios livres foram estimados. Resistência à insulina, examinada pelo modelo homeostático, foi admitida com índice >2,8. A resposta adrenal à cortrosina foi avaliada pelo incremento hormonal observado após 60 minutos e área sobre a curva. RESULTADOS: entre as 53 pacientes elegíveis, hiperandrogenismo bioquímico foi encontrado em 43 (81,1 por cento). Trinta e três delas, com idade de 25,1±5,0 anos, apresentaram hiperandrogenismo adrenal (62,2 por cento), pesavam 74,9±14,9 kg; tinham IMC de 28,8±6,0 e razão cintura/quadril de 0,8±0,1. DHEAS foi >6,7 nmol/L em 13 (39,4 por cento) e androstenendiona >8,7 nmol/L em 31 (93,9 por cento). Cortisol, 17-OHP4, A e progesterona tiveram incremento de 153 por cento, 163 por cento, 32 por cento e 79 por cento, respectivamente. O modelo usado para avaliar a resistência á insulina foi >2,8 em 14 (42,4 por cento). Não foi encontrada correlação entre as concentrações de insulina ou estradiol com as de cortisol ou androgênios. CONCLUSÕES: a utilização de múltiplos parâmetros hormonais revela alta prevalência de hiperandrogenismo bioquímico na SOP, sendo que as adrenais têm participação em dois terço dos casos. Níveis de estradiol e insulina não influenciam a secreção adrenal de androgênios e cortisol.

PURPOSE: to reassess the adrenal function of patients with PCOS after the introduction of the Rotterdam's criteria. METHODS: descriptive and cross-sectional study including 53 patients 26±5.1 years old. Glucose, glycosylated hemoglobin, lipids, estradiol, progesterone, 17-OHP4, DHEAS, FSH, LH, TSH, PRL, androstenedione, free thyroxine, insulin, total testosterone, SHBG, and free androgen index were measured. Insulin resistance was considered to be present with a homeostatic model assessment index >2.8. The adrenal response to cortrosyn was assessed by the hormonal rise observed at 60 minutes, and by the area under the response curve. RESULTS: biochemical hyperandrogenism was found in 43 of 53 eligible patients (81.1 percent). Thirty-three women had adrenal hyperandrogenism (62.2 percent). The weight of these 33 women, aging 25.1±5.0 years, was 74.9±14.9 kg, BMI was 28.8±6.0 and the waist/hip ratio was 0.8±0.1. DHEAS was >6.7 nmol/L in 13 (39.4 percent) and androstenendione was >8.7 nmol/L in 31 (93.9 percent). The increments in 17-OHP4, cortisol, A, and progesterone were 163 percent, 153 percent, 32 percent, and 79 percent, respectively. The homeostatic insulin resistance model was >2.8 in 14 (42.4 percent). Insulin and estradiol were not correlated with cortisol or androgens. CONCLUSIONS: the use of multiple endocrine parameters showed a high prevalence of biochemical hyperandrogenism in patients with PCOS. Two thirds of the patients had adrenal hyperandrogenism, and estradiol and insulin did not influence adrenal secretion.

Marcadores séricos de estresse oxidativo e resultados dos procedimentos de reprodução assistida em pacientes inférteis com síndrome dos ovários policísticos e controles / Serum markers of oxidative stress and assisted reproduction procedures results in infertile patients with polycystic ovary syndrome and controls

Objetivo: comparar os níveis séricos de cinco marcadores de estresse oxidativo e os resultados de reprodução assistida (RA), entre pacientes com infertilidade por fator tubário e/ou masculino e portadoras de síndrome dos ovários policísticos (SOP). Métodos: foram inclusos 70 pacientes, sendo 58 com infertilidade por fator tubário e/ou masculino e 12 com SOP, que foram submetidas à estimulação ovariana controlada para realização de injeção intracitoplasmática de espermatozoide (ICSI). A coleta de sangue foi realizada entre o terceiro e o quinto dia do ciclo menstrual, no mês anterior à realização da estimulação ovariana. Foram analisados os níveis de malondialdeído, hidroperóxidos, produtos de oxidação proteica, glutationa e vitamina E, pela leitura da absorbância em espectrofotômetro e por cromatografia líquida de alta eficiência (HPLC). Para a análise estatística, utilizou-se o teste t de Student e o teste exato de Fisher. Resultados: entre as pacientes com SOP, foi constatado maior índice de massa corporal, volume ovariano e número de folículos antrais e uma menor dose total utilizada de hormônio folículo estimulante. Não observamos diferença em relação à resposta à estimulação ovariana, aos resultados de RA e aos níveis séricos de malondialdeído, hidroperóxidos, produtos de oxidação proteica, glutationa e vitamina E entre os grupos. Conclusões: no estudo não evidenciamos diferença entre os níveis séricos de marcadores de estresse oxidativo, nem nos resultados de RA, comparando pacientes inférteis não-obesas com SOP e controles. Estes dados sugerem que, neste subgrupo específico de portadoras de SOP, os resultados de RA não estejam comprometidos. Todavia, as interpretações acerca da ação do estresse oxidativo sobre os resultados de RA ainda não estão claras e as implicações reprodutivas do estresse oxidativo precisam ser mais bem avaliadas.

Purpose: to compare the serum levels of five markers of oxidative stress and assisted reproduction (AR) outcomes among infertile patients, with tubal and/or male factor and with polycystic ovary syndrome (PCOS). Methods: 70 patients were included, 58 with tubal and/or male factor infertility and 12 with PCOS, who underwent controlled ovarian stimulation to perform intracytoplasmic sperm injection (ICSI). A blood sample was collected between the third and fifth day of the menstrual cycle in the month prior to ovarian stimulation. We analyzed the levels of malondialdehyde, hydroperoxides, protein oxidation products, glutathione and vitamin E, by reading the absorbance with a spectrophotometer and by high performance liquid chromatography (HPLC). Data were analyzed statistically by the Student's t-test and Fisher's exact test. Results: significant increases in the body mass index, ovarian volume and number of antral follicles were observed in PCOS patients, as well as the use of a lower total dose of follicle stimulating hormone for these patients. There were no differences in the response to ovarian stimulation, in the results of AR or serum levels of malondialdehyde, hydroperoxides, advanced oxidation protein products, glutathione and vitamin E between groups. Conclusions: the present data did not demonstrate a difference in the levels of serum markers of oxidative stress or in AR results when comparing non-obese infertile patients with PCOS and controls. These data suggest that the results of AR may not be compromised in this specific subgroup of patients with PCOS. However, interpretations of the action of oxidative stress on the results of AR are still not clear and the reproductive implications of oxidative stress need to be better evaluated.

Homocisteinemia em mulheres com síndrome dos ovários policísticos / Homocysteinemia in polycystic ovary syndrome women

Objetivos: comparar os níveis sanguíneos de homocisteína em mulheres com e sem a síndrome dos ovários policísticos (SOP) e correlacioná-los com os parâmetros clínicos, hormonais e metabólicos. Métodos: estudo tipo corte transversal com 110 mulheres: 56 com SOP e 54 controles normais. As pacientes foram submetidas à anamnese, exame físico e ultrassonografia pélvica, dosagens de homocisteína, da proteína C reativa (PCR), glicose, insulina, hormônio folículo-estimulante (FSH), hormônio luteinizante (LH), hormônio tireoide-estimulante (TSH), tiroxina livre (T4L), prolactina e testosterona.. Para análise estatística, foram usados os testes t de Student, χ2 e a correlação de Pearson. A realização da análise multivariada, pelo método "enter", foi utilizada para verificar a associação independente entre as variáveis. Resultados: encontrou-se um aumento significativo na média dos níveis plasmáticos de homocisteína nas pacientes com SOP quando comparadas ao Grupo Controle (5,9±2,9 versus 5,1±1,3 µmol/L; p=0,01). Como era esperado, por fazerem parte do quadro clínico da SOP, o índice de massa corpórea, circunferência abdominal, colesterol total, colesterol HDL, triglicerídeos, insulina e HOMA também se mostraram com diferenças significativas entre os dois grupos. Houve correlação da SOP e do IMC com os níveis de homocisteína. A análise multivariada mostrou que a SOP por si só não se correlaciona com altos níveis de homocisteína. Conclusões: pacientes com SOP estão expostas a níveis significativamente altos de homocisteína, porém outros fatores intrínsecos à síndrome, e não identificados neste estudo, seriam os responsáveis por esta alteração.

Purpose: to compare serum homocysteine levels in polycystic ovary syndrome (PCOS) and non-PCOS women and correlate them with clinical, hormonal and metabolic parameters. Methods: transverse study with carried out on 110 women, including 56 with PCOS and 54 normal controls. Patients were submitted to anamnesis, physical examination and pelvic sonograms and to the determination of homocysteine, C-reactive protein (CRP), glucose insulin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), free thyroxin (Free T4), prolactin, and testosterone. For the statistical analysis, we used the Student's t test, Pearson's product-moment correlation coefficient and the χ2 test. The "enter" method was used to determine independent association between variables. Results: there was a significant increase in the average serum homocysteine levels in the group of patients with PCOS compared to controls (5.97±2.95 versus 5,17±1.33 µmol/L; p=0,015). As expected, since they are affected by PCOS, values of body mass index (BMI), waist circumference, total cholesterol, HDL cholesterol, triglycerides, insulin and HOMA were significantly different between groups. Serum homocysteine levels, BMI and PCOS were correlated. Multivariate analysis showed that PCOS, by itself, does not correlate with high serum homocysteine levels. Conclusions: PCOS women have significantly higher serum levels of homocysteine that may increase their risk for cardiovascular disease. However, other intrinsic PCOS-related factors, not identified in this study, may be responsible for this alteration.

Association of polycystic ovary syndrome and a non-dipping blood pressure pattern in young women

OBJECTIVE: The association between polycystic ovarian syndrome and increased cardiovascular disease risk is still a controversial issue. In light of data documenting some common pathways or common end-points, the present study was undertaken to determine whether there is a relationship between sleep blood pressure pattern disturbances and polycystic ovarian syndrome in young women. METHOD: The daytime and nighttime ambulatory blood pressures (BPs) were determined for each subject, according to the actual waking and sleeping times recorded in their individual diaries, in this cross-sectional study. RESULTS: The study group comprised 168 women (mean age: 25.7±5.5) diagnosed with polycystic ovarian syndrome, while the control group included 52 age- and BMI-matched healthy subjects (mean age: 26.1±5.4). When nocturnal BP declines very little or not at all, with the BP falling less than 10 percent during sleep compared with waking values, this pattern is classified as a non-dipping BP pattern. However, the non-dipping pattern of BP changes was significantly more common in polycystic ovarian syndrome patients compared to the control group (p<0.01). The prevalence of a non-dipping BP pattern was 43.4 percent (73 patients) in polycystic ovarian syndrome patients and 3.9 percent (2 patients) in the control group. CONCLUSION: Our cross-sectional study revealed that a non-dipping BP pattern is highly prevalent in polycystic ovarian syndrome patients, even if they are young and non-obese.

Prostate specific antigen in polycystic ovary syndrome

Polycystic ovary syndrome [PCOS] is the most common cause of hyperandrogenism, and anovulatory infertility; its affects 5-10% of females at their reproductive age. Prostate specific antigen is a glycoprotein that is secreted from the prostate in males and from paraurethral glands and breast in female. To evaluate the total and free prostate specific antigen levels in female with PCOS, and find out its relation with FSH, LH, Prolactin and testosterone [F,T]. Eight patients with PCOS diagnosed based on three criteria. High LH: FSH ratio; LH luteinizing hormone to FSH follicle stimulating hormone is 2:1 or more particularly in the early phase of menstrual cycle [3-6] day. Ultrasound reveals polycystic ovaries. Biomedical hyperandrogenism. Elevated androgens particularly free testosterone. Forty normal fertile females servced as a control group in this study. Blood samples were taken from all individuals from 3-6 days of menstrual cycle to measure total and free prostate specific antigen, total and free testosterone [by enzyme linked immunosorbent assay] and FSH, LH, Prolactin [by Immunoadiometric assay]. Patients with PCOS and controls differed significantly in all parameters studied, except FSH [P] > 0.05]. LH and LH: FSH ration were significantly elevated in PCOS group compared to normal control group [11.9 +/- 5.4 vs. 7.0 +/- 0.6] an d[2.3 +/- 1.1 vs. 1.2 +/- 0.01] respectively. Total and free testosterone were significantly elevated in patient with PCOS compared to non control group [50 +/- 9.6 vs. 24 +/- 3.4] and [8.9 +/- 1.0 vs. 1.9 +/- 0.4] respectively. Total and free PSA significantly elevated in patient with PCOS compared to normal control group [1.2 +/- 0.4 vs. 0.1 +/- 0.02] and [0.04 +/- 0.01 vs. 0.01 +/- 0.003] respectively. Positive correlation between T-PSA, F-PSA and T-testo, F-testo. Total and free serum prostate specific antigen levels are higher in patient with PCOS. Serum PSA measurement might be marker of hyperandrogenism in females suffering from PCOS

Adiponectina: elo entre obesidade, resistência à insulina e síndrome do ovário policístico? / Adiponectin: the link between obesity, insulin resistance and polycystic ovary syndrome?

A síndrome do ovário policístico é a endocrinopatia ginecológica mais frequente das mulheres em idade reprodutiva, clinicamente caracterizada pela presença de anovulação crônica hiperandrogênica, hirsutismo e infertilidade. Além das alterações reprodutivas, uma proporção considerável das portadoras da síndrome apresenta anormalidades metabólicas como: resistência à insulina e obesidade, com aumento significativo do risco para o desenvolvimento de intolerância à glicose; diabetes mellitus e doença cardiovascular. No entanto, os mecanismos fisiopatológicos que vinculam a obesidade, a resistência à insulina e os demais distúrbios metabólicos presentes na síndrome do ovário policístico ainda não estão completamente esclarecidos. Estudos recentes sugerem que a adiponectina, uma proteína secretada especificamente pelo tecido adiposo, que apresenta propriedades antiaterogênicas, anti-inflamatórias e sensibilizadora à ação da insulina, poderia apresentar um importante papel integrador na patogênese desses distúrbios metabólicos.

Polycystic ovary syndrome is the most common gynecologic endocrinopathy of reproductive age women. It is clinically characterized by hyperandrogenic chronic anovulation, hisrutism and infertility. In addition to reproductive alterations, a significant proportion of polycystic ovary syndrome women display metabolic abnormalities such as insulin resistance and adiposity, predisposing to greater risk of developing glucose intolerance; diabetes mellitus and cardiovascular disease. However, the physiopathologic mechanisms linking obesity, insulin resistance and the other polycystic ovary syndrome metabolic disturbances are not completely understood. Recent studies suggest that adiponectin, a protein specifically secreted by adipose tissue and which has antiatherogenic, anti-inflammatory and insulin-sensitizing properties, could play an important and integrative role in the pathogenesis of these metabolic disturbances.

Serum C-Reactive Protein Levels in Normal-Weight Polycystic Ovary Syndrome

BACKGROUND/AIMS: Serum levels of highly sensitive C-reactive protein (hsCRP), a vascular inflammatory marker, may predict the development of cardiovascular disease (CVD) and type 2 diabetes. Women with polycystic ovary syndrome (PCOS) are at greater risk for type 2 diabetes and CVD. The aim of this study was to compare hsCRP levels between normal weight women with PCOS and controls with a normal menstrual cycle and to determine the factors associated with serum hsCRP levels. METHODS: Thirty-nine lean PCOS patients and 24 healthy, regular cycling women were enrolled in this study. We performed anthropometric measurements, fat computed tomography (CT), and blood sampling to determine blood chemistry and levels of hsCRP, gonadotropins, testosterone, and sex-hormone binding globulin. We also conducted 75-g oral glucose-tolerance test and euglycemic hyperinsulinemic clamp to assess insulin sensitivity. RESULTS: Serum hsCRP concentrations were higher in women with PCOS than in women with regular mensturation. However, this difference was no longer significant after adjusting for body mass index (BMI). hsCRP levels were correlated with waist circumference (r=0.46, p<0.01), BMI (r=0.46, p<0.01), visceral fat area (r=0.45, p<0.01), and systolic (r=0.42, p<0.05) and diastolic blood pressure (r=0.39, p<0.05). hsCRP also tended to be negatively associated with insulin-mediated glucose uptake (IMGU) (r=-0.31, p=0.07). A multiple regression analysis revealed that BMI (beta=0.29, p<0.05), systolic blood pressure (beta=0.39, p<0.01), and IMGU (beta=-0.31, p<0.05) predicted serum hsCRP levels in women with PCOS. CONCLUSIONS: PCOS by itself does not seem to be associated with increased hsCRP levels, whereas known CVD risk factors affect serum hsCRP levels in PCOS.

Alteraciones neuroendocrinas del síndrome de poliquistosis ovárica en la adolescencia / Neuroendrocrine anormalities in adolescents with polycystiz ovary sindrome

El síndrome de poliquistosis ovárica (SPCO) es una de las endocrinopatías más comunes que afecta a las mujeres en edad reproductiva, su expresión clínica comienza en edad perimenárquica y si bien fue descripto hace más de 70 años, hasta el presente, el(los) mecanismo(s) fisiopatológico(s) que lo origina(n) no se conoce(n) con certeza. Debido a la gran heterogeneidad en la expresión clínica y bioquímica que caracteriza al SPCO es probable que existan subgrupos de pacientes en las que sea posible identificar alguno de los mecanismos implicados en la patogenia como el responsable de los principales signos y síntomas observados. La presente revisión propone conocer en profundidad las anormalidades neuroendocrinas como uno de los principales componentes del síndrome. En nuestra experiencia, las adolescentes con SPCO presentan hipersecreción de LH (aumento de la masa de LH secretada por pulso, de la frecuencia de pulsos y de la tasa de producción), y un patrón desordenado de secreción de LH (mayores valores de ApEn) en relación a adolescentes eumenorreicas. Varias líneas de evidencia sugieren que uno de los mecanismos responsables de estos defectos es el aumento de frecuencia de secreción del GnRH. Las adolescentes con SPCO secretan moléculas de LH con mayor actividad biológica y mayor proporción de isoformas con punto isoeléctrico más alcalino que las adolescentes eumenorreicas. La preponderancia de isoformas más básicas y más bioactivas en estas pacientes se relaciona con elevados niveles séricos de 17-hidroxiprogesterona, androstenodiona (A) y testosterona (T). El aumento de la frecuencia de pulsos de GnRH y un microambiente hormonal caracterizado por exceso de andrógenos podrían conjuntamente promover la predominante secreción de este tipo de isoformas de LH. En ausencia de obesidad, las pacientes con SPCO presentan un incremento de la tasa de producción de GH y un patrón de secreción más ordenado (menores valores de ApEn, similar al patrón de secreción de GH observado en el varón adulto). La mayor secreción de GH podría potenciar la acción gonadotrófica sobre la esteroideogénesis ovárica. Analizando la sincronía entre pares de hormonas relacionadas mediante dos técnicas complementarias (cross ApEn y cross correlación) se demuestra que las adolescentes con SPCO presentan un deterioro en las asociaciones entre LH-andrógenos comparadas con las adolescentes eumenorreicas. El desacople de la secreción bihormonal (LH-A y LH-T) en adolescentes con SPCO es consistente con defectos en el control de la secreción ovárica de andrógenos dependiente de LH y con una alteración en el control negativo que ejercen los andrógenos sobre la secreción GnRH/LH. Estas alteraciones neuroendocrinas en la unidad GnRH/LH y andrógenos ováricos podrían promover el hiperandrogenismo y alterar la maduración folicular.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women in reproductive age, frequently begins during adolescence causing menstrual irregularity and hirsutism. Although described up more than seventy years ago, the primary pathophysiologic mechanisms underlying this disorder remain unknown.There is not a single etiologic factor that fully accounts for the spectrum of abnormalities in the PCOS. This review addresses current knowledge about the neuroendocrine abnormalities as a major component of the syndrome. From this perspective, adolescents with PCOS exhibit an accelerated frequency and/or higher amplitude of LH pulses, augmentation of secretory burst mass, and a more disorderly LH release (higher ApEn) than eumenorrheic adolescents. Several lines of evidence suggest that the mechanisms underlying the defects in LH secretion in PCOS include an increased frequency of GnRH secretion. These patients also show elevated in vitro LH bioactivity and a preponderance of basic LH isoforms, which correlate positively with elevated serum of 17-hydroxyprogesterone, androstenedione (A), and testosterone (T) concentrations. Heightened GnRH drive of gonadotropin secretion and steroid-permissive milieu appear to jointly promote elevated secretion of basic LH isoforms. Non obese adolescents with PCOS secrete GH at a higher rate and with more orderly patterns (resembling a male profile) than controls. Indeed, GH appears to act as a co-gonadotropin. When synchronicity of paired hormone profiles was appraised by two independent, but complementary, statistical tools (cross-entropy and cross correlation), concomitant uncoupling of the pairwise synchrony of LH - androgens was demonstrated in girls with PCOS. Asynchrony of LH-A and LH-T pairs further localizes a pathway defect to LH-dependent feedforward control of ovarian androgen secretion. These abnormalities are also consistent with altered androgen negative feed-back regulation of GnRH/LH output. These data suggest that in PCOS there are anomalies of signaling between GnRH/LH and ovarian androgens that promote hiperandrogenism and impaired follicle maturation.