Manifestações clínicas, bioquímicas, ultrassonográficas e metabólicas da síndrome dos ovários policísticos em adolescentes

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.

Estudo caso-controle em genes polimórficos das vias esteróide (ER-alfa e ER-beta) e da insulina (INSR, PA-1 e IGF2) na síndrome do ovário policístico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeito da metformina em mulheres obesas com a síndrome de hiperandrogenismo-resistência insulínica-acantose nigricans

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Correlação entre o diâmetro de ruptura folicular e ocorrência de gravidez em pacientes com síndrome dos ovários policísticos estimuladas com citrato de clomifeno

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Prevalência de resistência à insulina, intolerância à glicose e diabetes mellitus tipo 2 em pacientes com síndrome doa ovários policísticos(SOP)

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

O hiperandrogenismo influencia no desenvolvimento de síndrome metabólica em pacientes com síndrome dos ovários policísticos?

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Contribuição do hiperandrogenismo para o desenvolvimento de síndrome metabólica em mulheres obesas com síndrome dos ovários policísticos

OBJETIVO: Avaliar a contribuição do hiperandrogenismo para o desenvolvimento da síndrome metabólica (SM) em mulheres obesas com ou sem Síndrome dos Ovários Policísticos (SOP). MÉTODOS: Estudo transversal retrospectivo no qual foram incluídas 60 mulheres obesas com fenótipo clássico da SOP - Consenso de Rotterdam - e 70 obesas sem SOP. A SM foi diagnosticada pelos critérios do NCEP-ATP III. A obesidade foi definida pelo índice de massa corpórea e o hirsutismo, pelo Índice de Ferriman-Gallwey (IFG). As dosagens realizadas foram: testosterona total, sulfato de dehidroepiandrosterona (SDHEA), insulina e glicose, colesterol total, HDL e triglicerídios. A resistência insulínica (RI) foi avaliada pelo HOMA-IR e pelo índice de sensibilidade à insulina de Matsuda e De Fronzo. A analise estatística foi realizada com o teste t de Student, teste do χ² e análise de regressão logística multivariada (p<0,05). RESULTADOS: As obesas com SOP apresentaram significativamente maiores valores de IFG (15,4±6,1), circunferência da cintura (105,6±11,4 cm), testosterona (135,8±71,4 ng/dL), SDHEA (200,8±109,2 µg/dL), HOMA-IR (8,4±8,5) e menores valores de ISI (2,0±1,8) quando comparadas às obesas não SOP (3,2±2,1; 101,4±9,2 cm; 50,0±18,2 ng/dL; 155,0±92,7 µg/dL; 5,1±4,7; 3,3±2,7, respectivamente) (p<0,05). A frequência de SM foi significativamente maior nas obesas com SOP (75%) do que nas obesas não SOP (52,8%) (p=0,01). A análise multivariada não demonstrou contribuição das variávies IFG, testoterona total e SDHEA para o desenvolvimento da SM (p>0,05). CONCLUSÃO: Mulheres obesas com SOP apresentam maior frequência de SM quando comparadas às obesas não SOP. O hiperandrogenismo não mostrou influência nesse grupo de mulheres estudadas.

Avaliação da exposição ao propionato de testosterona em ratas fêmeas in utero e lactação

It is known that exposure to substances in the environment can contribute to various reproductive disorders, especially if such exposure occurs during critical periods of development such as the intra-uterine and postnatal. The female reproductive system may be the target of androgens, both as a result of exposure to environmental chemicals, or by pathological conditions (polycystic ovary syndrome or congenital adrenal hyperplasia).Usually, little attention is given off in relation to the study of androgenic effects in the female reproductive axis. This study aims to evaluate the effects of exposure to androgens on the development, structure and reproductive function in rats whose mothers were exposed to testosterone propionate from gestational day 12 (DG12) after weaning - postnatal day 21 (DPN21) . For this purpose, pregnancy rats were divided into four groups: a control group that received corn oil (vehicle) and three groups receiving testosterone propionate in doses of 0.05 mg / kg / day, 0.1 mg / kg / day and 0.2 mg / kg / day, all under the same experimental conditions. The possible effects of exposure were assessed using reproductive parameters, such as a measure of anogenital distance, count areolas / nipples, age at vaginal opening and first estrus (puberty indicative installation), weight and histological evaluation of the reproductive organs ( uterus and ovaries), weight of the kidneys, liver and pituitary hormone levels, regularity of the estrous cycle, sexual behavior and fertility. Such analysis is important in understanding the effects of androgen exposure on the female genital system, especially on the reproductive potential, and processes that may involve morphofunctional changes. In these experimental conditions, it is concluded that treatment with PT caused reduction in body weight and initial masculinization in females without cubs, however, commit further sexual development

Risco de Farmingham e evento cardiovascular em mulheres com síndrome dos ovários policísticos

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Zinc supplementation for the prevention of type 2 diabetes mellitus in adults with insulin resistance

BackgroundDiabetes is associated with long-term damage, dysfunction and failure of various organs, especially the eyes, kidneys, nerves, heart and blood vessels. The risk of developing type 2 diabetes increases with age, obesity and lack of physical activity. Insulin resistance is a fundamental aspect of the aetiology of type 2 diabetes. Insulin resistance has been shown to be associated with atherosclerosis, dyslipidaemia, glucose intolerance, hyperuricaemia, hypertension and polycystic ovary syndrome. The mineral zinc plays a key role in the synthesis and action of insulin, both physiologically and in diabetes mellitus. Zinc seems to stimulate insulin action and insulin receptor tyrosine kinase activity.ObjectivesTo assess the effects of zinc supplementation for the prevention of type 2 diabetes mellitus in adults with insulin resistance.Search methodsThis review is an update of a previous Cochrane systematic review published in 2007. We searched the Cochrane Library (2015, Issue 3), MEDLINE, EMBASE, LILACS and the ICTRP trial register (frominception toMarch 2015). There were no language restrictions. We conducted citation searches and screened reference lists of included studies.Selection criteriaWe included studies if they had a randomised or quasi-randomised design and if they investigated zinc supplementation compared with placebo or no intervention in adults with insulin resistance living in the community.Data collection and analysisTwo review authors selected relevant trials, assessed risk of bias and extracted data.Main resultsWe included three trials with a total of 128 participants in this review. The duration of zinc supplementation ranged between four and 12 weeks. Risk of bias was unclear for most studies regarding selection bias (random sequence generation, allocation concealment) and detection bias (blinding of outcome assessment). No study reported on our key outcome measures (incidence of type 2 diabetes mellitus, adverse events, health-related quality of life, all-cause mortality, diabetic complications, socioeconomic effects). Evaluation of insulin resistance as measured by the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) showed neutral effects when comparing zinc supplementation with control (two trials; 114 participants). There were neutral effects for trials comparing zinc supplementation with placebo for total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides (2 studies, 70 participants). The one trial comparing zinc supplementation with exercise also showed neutral effects for total cholesterol, HDL and LDL cholesterol, and a mean difference in triglycerides of -30 mg/dL (95% confidence interval (CI) -49 to -10) in favour of zinc supplementation (53 participants). Various surrogate laboratory parameters were also analysed in the included trials.Authors'conclusionsThere is currently no evidence on which to base the use of zinc supplementation for the prevention of type 2 diabetes mellitus. Future trials should investigate patient-important outcome measures such as incidence of type 2 diabetes mellitus, health-related quality of life, diabetic complications, all-cause mortality and socioeconomic effects.

The association between follicular size at time of spontaneous rupture and pregnancy rates in clomiphene citrate treated PCOS patients in coit cycles

Objective: To investigate the follicular size at spontaneous rupture on pregnancy rate in patientswith polycystic ovary syndrome (PCOS) undergoing clomiphene citrate (CC) ovulation.Design: Cross-sectional study.Patients and methods: One hundred and four women with ovulatory cycles after use of CCfollowed by ultrasound to determine the follicle size at the time of rupture, which wassubsequently correlated with the occurrence of pregnancy or not in coit cycles.Results: In the group of follicular rupture at a mean diameter25 mm (n¼54), pregnancy ratewas 35.1% and when follicular rupture occurred at a mean diameter425 mm (n¼50), it was34% (p40.05). When different diameters at follicular rupture were randomly correlated with thepregnancy rate, there was no significant difference.Conclusion: Our data suggest that the occurrence of pregnancy after ovulation induction withCC in women with PCOS is not associated with follicle size at the time of rupture.

Early onset of obesity induces reproductive deficits in female rats

The incidence of obesity is increasing rapidly all over the world and results in numerous health detriments, including disruptions in reproduction. However, the mechanisms by which excess body fat interferes with reproductive functions are still not fully understood. After weaning, female rats were treated with a cafeteria diet or a chow diet (control group). Biometric and metabolic parameters were evaluated in adulthood. Reproductive parameters, including estradiol, progesterone, LH and prolactin during the proestrus afternoon, sexual behavior, ovulation rates and histological analysis of ovaries were also evaluated. Cafeteria diet was able to induce obesity in female rats by increasing body and fat pad weight, which resulted in increased levels of triglycerides, total cholesterol, LDL and induced insulin resistance. The cafeteria diet also negatively affected female reproduction by reducing the number of oocytes and preantral follicles, as well as the thickness of the follicular layer. Obese females did not show preovulatory progesterone and LH surges, though plasma estradiol and prolactin showed preovulatory surges similar to control rats. Nevertheless, sexual receptiveness was not altered by cafeteria diet. Taken together, our results suggest that the cafeteria diet administered from weaning age was able to induce obesity and reduce the reproductive capability in adult female rats, indicating that this obesity model can be used to better understand the mechanisms underlying reproductive dysfunction in obese subjects. (C) 2012 Elsevier Inc. All rights reserved.

Assessment of micronucleus frequency in the peripheral blood of female rats in persistent estrus treated with selective estrogen receptor modulators

The aim of this study was to evaluate micronucleus (MN) frequency in polychromatic erythrocytes (PCE) of female rats in persistent estrus (a model developed to mimic polycystic ovary syndrome) treated with selective estrogen receptor modulators (SERMs, tamoxifen, and raloxifene). Forty female Wistar-Hannover rats were divided into four groups of 10 animals each: Group I (normally cycling rats) and Group II (persistent estrus) both received only vehicle, while Group III (persistent estrus) was treated with tamoxifen (250 mu g/animal/day) and Group IV (persistent estrus) was treated with raloxifene (750 mu g/animal/day). Tamoxifen and raloxifene were given by oral gavage beginning on postnatal day 90 and continuing for 30 consecutive days. Peripheral blood samples were collected from tails 1 day following the last exposure. Blood smears were made on glass slides and stained with 10% Giemsa solution. ANOVA and a Tukey post-hoc test were used for data analysis. Mean percentages of MN were 1.82 +/- 0.13, 5.20 +/- 0.24, 3.32 +/- 0.13, and 3.04 +/- 0.12 in Groups I, II, III, and IV, respectively. The results indicate that tamoxifen and raloxifene similarly reduced the formation of MNPCE of female rats in persistent estrus (P < 0.0001 for Groups III and IV vs. Group II), using the dosages and time periods applied in the present study. The data suggest possibly antimutagenic effects of SERMs under high levels of estrogens. The findings also suggest that this is an interesting animal model for studying the genotoxicity of estrogens. Environ. Mol. Mutagen. 2012. (C) 2011 Wiley Periodicals, Inc.

Potencial envolvimento da adiponectina e seus receptores na modulação da esteroidogênese em corpo lúteo de cadelas ao longo do diestro

No ciclo estral de cadelas a fase luteínica, denominada diestro, compreende um período que varia de 60 a 100 dias em animais não-prenhes, caracterizado pela elevação plasmática de progesterona nos primeiros 20 dias pós ovulação (p.o). A adiponectina é a mais abundante proteína secretada pelo tecido adiposo, porém sua concentração plasmática diminui significativamente em alterações metabólicas como resistência insulínica e Diabetes mellitus tipo2, alterações descritas como relacionadas em algumas cadelas com o período de diestro. O objetivo do estudo foi determinar a expressão e imunolocalização do sistema adiponectina (adiponectina e seus receptores, adipoR1 e adipoR2) no corpo lúteo de cadelas ao longo do diestro, correlacionando-o ao perfil hormonal de 17β-estradiol e progesterona, assim como à expressão de um dos genes alvo do sistema, o PPAR-γ. Para realização do estudo foram coletados corpos lúteos de 28 cadelas durante ovariosalpingohisterectomia de eleição nos dias 10, 20, 30, 40, 50, 60 e 70 pós ovulação (o dia zero da ovulação foi considerado aquele no qual a concentração plasmática de progesterona atingiu 5ng/mL). Os corpos lúteos foram avaliados por imunohistoquímica para adiponectina e seus receptores e a expressão do RNAm do PPAR-γ por PCR em tempo real. A análise estatística da avaliação gênica foi realizada com o teste ANOVA, seguido por comparação múltipla Newman-Keuls. O sinal da adiponectina apresentou-se mais intenso até os primeiros 20 dias p.o, momento de regência da progesterona; houve queda gradativa após este período, coincidindo com a ascensão do 17β-estradiol, cujo pico foi notado próximo do dia 40 p.o. A queda marcante da adiponectina ocorreu após 50 dias p.o. O sinal do adipoR1 mostrou-se bem evidente até os 40 dias p.o e o do adipoR2 até os 50 dias p. o, decaindo posteriormente. Foi observada maior expressão do gene PPAR-γ aos 10, 30 e 70 dias p.o. Estes resultados mostram que a expressão protéica da adiponectina e de seus receptores se altera ao longo do diestro e que estas alterações podem estar relacionados às alterações hormonais e expressão do PPAR- γ, participando do mecanismo fisiológico de desenvolvimento, manutenção, atividade e regressão luteínica em cadelas.

Effect of Type 2 Diabetes Mellitus on the Pharmacokinetics of Metformin in Obese Pregnant Women

Background and Objective The use of metformin throughout gestation by women with polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus (T2DM) significantly reduces the number of first-trimester spontaneous abortions and the rate of occurrence of gestational diabetes and hypertensive syndromes. Metformin is taken up into renal tubular cells by organic cation transport 2 (OCT2) and eliminated unchanged into the urine. The objective of this study was to analyse the influence of T2DM on the pharmacokinetics of metformin in obese pregnant women and in a control group of non-diabetic obese pregnant women with PCOS. Methods Eight non-diabetic obese pregnant women with PCOS and nine obese pregnant women with T2DM taking oral metformin 850 mg every 12 h were evaluated throughout gestation. Serial blood samples were collected over a 12-h period during the third trimester of pregnancy. Steady-state plasma concentrations of metformin were determined by high-performance liquid chromatography with a UV detector. The pharmacokinetic results of the two groups, reported as median and 25th and 75th percentile, were compared statistically using the Mann Whitney test, with the level of significance set at p < 0.05. Results The pharmacokinetic parameters detected for PCOS versus T2DM patients, reported as median, were, respectively: elimination half-life 3.75 versus 4.00 h; time to maximum concentration 2.00 versus 3.00 h; maximum concentration 1.42 versus 1.21 mu g/mL; mean concentration 0.53 versus 0.56 mu g/mL; area under the plasma concentration time curve from time zero to 12 h 6.42 versus 6.73 mu g.h/mL; apparent total oral clearance 105.39 versus 98.38 L/h; apparent volume of distribution after oral administration 550.51 versus 490.98 L; and fluctuation (maximum minimum concentration variation) of 179.56 versus 181.73%. No significant differences in pharmacokinetic parameters were observed between the groups. Conclusion T2DM in the presence of insulin use does not influence the pharmacokinetics of metformin in pregnant patients, demonstrating the absence of a need to increase the dose, and consequently does not influence the OCT2-mediated transport in pregnant women with PCOS.