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1.
Gene ; 731: 144352, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-31935500

RESUMO

Inflammasome complex mediated interleukin 1ß (IL-1ß) and interleukin 18 (IL-18) production may be involved in immunopathogenesis of polycystic ovary syndrome (PCOS). Therefore, this study was conducted to investigate involved inflammasome pathways in PCOS. Therefore, inflammasome genes expression and serum level of IL-1ß were evaluated in 30 patients with confirmed PCOS and 30 women without PCOS. A remarkable increase in expression of the nucleotide binding and oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NALP3), absent in melanoma 2 (AIM2), IL-18 and associated speck-like protein containing a caspase recruitment domain (CARD); (ASC) genes in PCOS were observed (p < 0.05). In contrast, expression level of NALP1, NALP12, NLR family apoptosis inhibitory proteins (NAIP), NLR family caspase recruitment domain (CARD) domain containing 4 (NLRC4) and IL-1ß genes was not significant. Although the IL-1ß protein level in serum of COS patients with BMI ≥ 25 was significantly higher than PCOS patient with BMI < 25, but there was no significant difference in non-PCOS individuals with BMI < 25 or ≥25. Furthermore, significant correlation between expression of AIM2 (r = 0.83, p = 0.032) and NALP3 (r = 0.59, p = 0.0001) was observed with IL-18, while a positive correlation (r = 0.84, p = 0.0001) was revealed between NAIP and IL-1ß. Based on the obtained results on inflammasome components along with increased expression of IL-1ß especially in overweight patients, it can be concluded that IL-18 expression as well as IL-1ß is probably due to activation of AIM2, NALP3 or NAIP inflammasome, which may play a critical role in immunopathology of PCOS.


Assuntos
Inflamassomos/metabolismo , Interleucina-18/genética , Interleucina-1beta/genética , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Adulto , Estudos de Casos e Controles , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Interleucina-18/sangue , Interleucina-18/metabolismo , Interleucina-1beta/sangue , Interleucina-1beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/imunologia , Adulto Jovem
2.
Nat Med ; 25(12): 1894-1904, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31792459

RESUMO

How obesity and elevated androgen levels in women with polycystic ovary syndrome (PCOS) affect their offspring is unclear. In a Swedish nationwide register-based cohort and a clinical case-control study from Chile, we found that daughters of mothers with PCOS were more likely to be diagnosed with PCOS. Furthermore, female mice (F0) with PCOS-like traits induced by late-gestation injection of dihydrotestosterone, with and without obesity, produced female F1-F3 offspring with PCOS-like reproductive and metabolic phenotypes. Sequencing of single metaphase II oocytes from F1-F3 offspring revealed common and unique altered gene expression across all generations. Notably, four genes were also differentially expressed in serum samples from daughters in the case-control study and unrelated women with PCOS. Our findings provide evidence of transgenerational effects in female offspring of mothers with PCOS and identify possible candidate genes for the prediction of a PCOS phenotype in future generations.


Assuntos
Androgênios/metabolismo , Oócitos/metabolismo , Síndrome do Ovário Policístico/genética , Efeitos Tardios da Exposição Pré-Natal/genética , Animais , Estudos de Coortes , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Camundongos , Núcleo Familiar , /metabolismo , Oócitos/imunologia , Fenótipo , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/fisiopatologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Análise de Célula Única
3.
Niger J Clin Pract ; 22(11): 1463-1466, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31719265

RESUMO

Objective: To identify whether red blood cell distribution width coefficient of variation (RDW-CV) and mean platelet volume (MPV) levels can predict clomiphene citrate resistance (CC-R) in infertile, anovulatory females with polycystic ovarian syndrome (PCOS). Methods: A total of 89 infertile patients who were admitted to a tertiary center diagnosed with non-obese PCOS were included in this study. The patients were divided into two groups: the first group comprised 53 non-obese patients with PCOS and CC-R, and the second group included 36 non-obese patients with PCOS and CC-S. RDW-CV, RDW-SD, and MPV values, along with routine whole blood count parameters were compared between the groups. Results: RDW-CV values were found to be significantly higher in the patients with CC-R compared to those with CC-S (P < 0.05). The sensitivity, specificity, positive, and negative predictive values were found to be 69%, 58.1%, 34.5%, and 12.5%, respectively, at an RDW-CV level of 12.85. The odds ratio was calculated as 3.077 (95% CI 1.245-7.603) in terms of the cut-off point. Conclusion: We think that RDW-CV which is a marker of inflammation is a simple, cheap, and accessible marker for the prediction of CC resistance.


Assuntos
Clomifeno/uso terapêutico , Fármacos para a Fertilidade Feminina/uso terapêutico , Infertilidade Feminina/tratamento farmacológico , Inflamação/sangue , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Biomarcadores/sangue , Clomifeno/administração & dosagem , Contagem de Eritrócitos , Feminino , Humanos , Indução da Ovulação , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Sensibilidade e Especificidade , Resultado do Tratamento , Adulto Jovem
4.
J Ovarian Res ; 12(1): 91, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31585548

RESUMO

BACKGROUND: A retrospective case-control study was performed to evaluate whether PCOS-specific serum markers would change in women with polycystic ovary syndrome (PCOS) during the course of two consecutive cycles of clomiphene citrate (CC)-stimulation, which did not lead to a pregnancy. METHODS: Anovulatory PCOS patients who underwent two consecutive CC-cycles (n = 41) and anovulatory PCOS controls who chose an observational approach for two months (n = 24) were included in the study. The main outcome measures were levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), anti-Mullerian hormone (AMH), total testosterone, androstenedione, and sexual hormone binding globulin (SHBG). RESULTS: In the control group, PCOS-specific serum parameters did not change during two months (p > 0.05). In the CC-group, there were decreases in LH (11.8 ± 4.9 mU/mL vs. 10.9 ± 4.0 mU/mL; p = 0.029), the LH:FSH ratio (2.1 ± 0.8 mU/mL vs. 1.8 ± 0.5 mU/mL; p = 0.007), and AMH (8.08 ± 4.27 ng/mL vs. 7.17 ± 3.37 ng/mL; p = 0.011), as well as an increase in SHBG (46.0 ± 20.2 nmol/L vs. 51.2 ± 21.0 nmol/L; p < 0.001). A higher age and lower baseline total testosterone and AMH levels were predictive of an AMH decline (p < 0.05). CONCLUSION: Two cycles of CC-stimulation that did not lead to a pregnancy were accompanied by mean LH, AMH, and LH:FSH ratio declines and an SHBG increase. The clinical significance seems of minor relevance.


Assuntos
Biomarcadores/sangue , Clomifeno/administração & dosagem , Folículo Ovariano/efeitos dos fármacos , Síndrome do Ovário Policístico/sangue , Adulto , Androstenodiona/sangue , Hormônio Antimülleriano/sangue , Estudos de Casos e Controles , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Folículo Ovariano/patologia , Indução da Ovulação , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/patologia , Gravidez , Estudos Retrospectivos , Globulina de Ligação a Hormônio Sexual/metabolismo , Testosterona/sangue
5.
J Ovarian Res ; 12(1): 94, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615559

RESUMO

PURPOSE: The polycystic ovary syndrome (PCOS) is a reproductive endocrine disorder, clinically characterized by oligo-ovulation/chronic anovulation, menstrual irregularities, hyperandrogenism (such as hirsutism, acne), hyperinsulinemia, and obesity. Prostatic-specific antigen (PSA) has been identified as a potential new marker in PCOS women. Although the precise role of PSA in PCOS patients still remains undetermined, PSA might serve as a useful clinical marker and might even represent a new diagnostic criterion of hyperandrogenemia in females of PCOS. METHODS: A meta-analysis was performed in the study to identify the association between the polycystic ovary syndrome and prostatic-specific antigen. To identify eligible original articles, we searched a range of computerized databases, including Medline via PubMed, EMBASE, CNKI and Web of Science with a systematic searching strategy. The characteristics of each study and standard mean differences (SMD) with corresponding confidence intervals (CIs) were calculated and subgroup analysis was performed to analyze heterogeneity. RESULTS: A total of 532 patients from seven articles were included in the meta-analysis. We identified a significant relationship between polycystic ovary syndrome and prostatic-specific antigen, with a pooled SMD of 0.81 (95% CI: 0.58 to 1.04; P < 0.01). The pooled data were calculated with the random-effects model as a moderate significant heterogeneity was found among the studies. CONCLUSIONS: The meta-analysis suggested that there was a significant association between the polycystic ovary syndrome and prostatic-specific antigen and we should not ignore the role of PSA in the PCOS patients in clinical.


Assuntos
Biomarcadores/sangue , Síndrome do Ovário Policístico/sangue , Antígeno Prostático Específico/sangue , Anovulação/sangue , Anovulação/patologia , Feminino , Humanos , Hiperandrogenismo/sangue , Hiperandrogenismo/patologia , Hiperinsulinismo/sangue , Hiperinsulinismo/patologia , Distúrbios Menstruais/sangue , Distúrbios Menstruais/patologia , Obesidade/sangue , Obesidade/patologia , Síndrome do Ovário Policístico/epidemiologia , Síndrome do Ovário Policístico/patologia
6.
PLoS Med ; 16(10): e1002953, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31652273

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with increased metabolic risk, though data on long-term follow-up of cardiometabolic traits are limited. We postulated that Chinese women with PCOS would have higher risk of incident diabetes and cardiometabolic abnormalities than those without PCOS during long-term follow-up. METHODS AND FINDINGS: One hundred ninety-nine Chinese women with PCOS diagnosed by the Rotterdam criteria and with a mean age of 41.2 years (SD = 6.4) completed a follow-up evaluation after an average of 10.6 ± 1.3 years. Two hundred twenty-five women without PCOS (mean age: 54.1 ± 6.7 years) who underwent baseline and follow-up evaluation over the same period were used for comparison. Progression of glycaemic status of women both with and without PCOS was assessed by using 75-g oral glucose tolerance test (OGTT) screening with the adoption of 2009 American Diabetes Association diagnostic criteria. The frequency of impaired glucose regulation, hypertension, and hyperlipidaemia of women with PCOS at follow-up has increased from 31.7% (95% CI 25.2%-38.1%) to 47.2% (95% CI 40.3%-54.2%), 16.1% (95% CI 11.0%-21.2%) to 34.7% (95% CI 28.1%-41.3%), and 52.3% (95% CI 45.3%-59.2%) to 64.3% (95% CI 57.7%-71.0%), respectively. The cumulative incidence of diabetes mellitus (DM) in follow-up women with PCOS is 26.1% (95% CI 20.0%-32.2%), almost double that in the cohort of women without PCOS (p < 0.001). Age-standardised incidence of diabetes among women with PCOS was 22.12 per 1,000 person-years (95% CI 10.86-33.37) compared with the local female population incidence rate of 8.76 per 1,000 person-years (95% CI 8.72-8.80) and 10.09 per 1,000 person-years (95% CI 4.92-15.26, p < 0.001) for women without PCOS in our study. Incidence rate for women with PCOS aged 30-39 years was 20.56 per 1,000 person-years (95% CI 12.57-31.87), which is approximately 10-fold higher than that of the age-matched general female population in Hong Kong (1.88 per 1,000 person-years, [95% CI 1.85-1.92]). The incidence rate of type 2 DM (T2DM) of both normal-weight and overweight women with PCOS was around double that of corresponding control groups (normal weight: 8.96 [95% CI 3.92-17.72] versus 4.86 per 1,000 person-years [95% CI 2.13-9.62], p > 0.05; overweight/obese: 28.64 [95% CI 19.55-40.60] versus 14.1 per 1,000 person-years [95% CI 8.20-22.76], p < 0.05). Logistic regression analysis identified that baseline waist-to-hip ratio (odds ratio [OR] = 1.71 [95% CI 1.08-2.69], p < 0.05) and elevated triglyceride (OR = 6.63 [95% CI 1.23-35.69], p < 0.05) are associated with the progression to T2DM in PCOS. Limitations of this study include moderate sample size with limited number of incident diabetes during follow-up period and potential selection bias. CONCLUSIONS: High risk of diabetes and increased cardiovascular disease risk factors among Chinese women with PCOS are highlighted in this long-term follow-up study. Diabetes onset was, on average, 10 years earlier among women with PCOS than in women without PCOS.


Assuntos
Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Intolerância à Glucose , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Adulto , Antropometria , Glicemia/análise , Doenças Cardiovasculares/complicações , Estudos de Casos e Controles , China/epidemiologia , Comorbidade , Complicações do Diabetes/terapia , Diabetes Mellitus Tipo 2/complicações , Progressão da Doença , Feminino , Seguimentos , Teste de Tolerância a Glucose , Humanos , Incidência , Pessoa de Meia-Idade , Obesidade/complicações , Sobrepeso/complicações , Síndrome do Ovário Policístico/terapia , Estado Pré-Diabético/diagnóstico , Estudos Prospectivos , Análise de Regressão , Fatores de Risco , Inquéritos e Questionários , Resultado do Tratamento , Triglicerídeos/sangue , Adulto Jovem
7.
Medicine (Baltimore) ; 98(39): e16788, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574794

RESUMO

BACKGROUND: The aim of this study was to observe the effect and safety of Heyan Kuntai Capsule (HYKT) on glucose and lipid metabolism in patients with polycystic ovary syndrome (PCOS). METHODS: Hundred patients with PCOS were randomly divided into HYKT group (n = 50) and placebo groups (n = 50) in which the individuals were treated with HYKT and its placebo continuously for 6 months. Meanwhile, all participants received health education (such as exercise and diet). The primary outcomes were serum sex hormone levels, a series of blood lipid, fasting and postprandial 2 hours blood glucose. Body mass index (BMI), waist-hip ratio (WHR), insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and insulin-sensitive index (ISI) were also observed. In addition, adverse events were recorded to evaluate the drug safety. RESULTS: After treatment, the BMI and WHR of all the patients were decreased. The fasting and postprandial 2 hours blood glucose levels were significantly declined when treated with HYKT, which were not observed in the placebo group. Similarly, serum sex hormones including luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH), and testosterone were lowered after treated with HYKT instead of the placebo. Besides, blood lipids outcomes such as total cholesterol, triglyceride, and low-density lipoprotein cholesterol, as well as insulin and HOMA-IR were decreased with significance in HYKT group when compared with those in the placebo group, whereas high-density lipoprotein cholesterol and ISI increased obviously. CONCLUSION: HYKT showed the effect on ameliorating the glucose and lipid metabolism disorder and improving insulin resistance and increase insulin sensitivity of PCOS patients, which is similar to insulin sensitizing agent.


Assuntos
Glicemia/metabolismo , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Lipídeos/sangue , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/tratamento farmacológico , Adolescente , Adulto , Índice de Massa Corporal , Método Duplo-Cego , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Insulina/sangue , Resistência à Insulina , Hormônio Luteinizante/sangue , Prolactina/sangue , Testosterona/sangue , Relação Cintura-Quadril , Adulto Jovem
8.
Endocr Regul ; 53(3): 146-153, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31517633

RESUMO

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common and multifactorial disease associated with female factor infertility. Ulmus minor bark (UMB) is one of the medicinal plants used in Persian folklore as a fertility enhancer. In the current study, we aimed to elucidate the effect of UMB hydro-alcoholic extract on histological parameters and testosterone condition in an experimental model of PCOS rats. METHODS: Thirty female rats were randomly divided into five groups: (1) control, (2) vehicle, (3) PCOS/50 mg [6 mg/kg dehydroepiandrosterone (DHEA) + 50 mg/kg UMB hydro-alcoholic extract], (4) PCOS/150 mg (6 mg/kg DHEA + 150 mg/kg UMB hydro-alcoholic extract), and (5) PCOS (6 mg/kg DHEA). All interventions were performed for 21 days. Afterwards, stereological analysis was done for determination of ovarian volume and follicle number. The serum level of testosterone was measured by ELISA kit. RESULTS: UMB hydro-alcoholic extract improved the total number of the corpus luteum in the treatment groups when compared to the PCOS group (p<0.05). PCOS/150 mg and PCOS/50 mg groups showed significantly lower total number of the primordial, primary, and secondary follicles as well as testosterone level compared to the PCOS group (p<0.05). The total number of antral follicles and volume of ovary did not differ significantly between groups. CONCLUSION: UMB extract may be an effective and good alternative in improving PCOS histo-logical and testosterone disturbances although further studies are warranted to confirm the safety of UMB plant in human.


Assuntos
Ovário/efeitos dos fármacos , Casca de Planta/química , Extratos Vegetais/farmacologia , Síndrome do Ovário Policístico/patologia , Testosterona/sangue , Ulmus/química , Animais , Modelos Animais de Doenças , Etanol/química , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Infertilidade Feminina/sangue , Infertilidade Feminina/patologia , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/patologia , Ovário/patologia , Fitoterapia , Síndrome do Ovário Policístico/sangue , Ratos , Água/química
9.
J Ovarian Res ; 12(1): 86, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31526389

RESUMO

AIMS: This study was designed to evaluate the protective effects of AMPKα and SIRT1 on insulin resistance in PCOS rats, and to illuminate the underlying mechanisms. METHODS: An in vitro PCOS model was established by DHEA (6 mg/(100 g•d)), and the rats were randomly divided into the metformin group (MF group, n = 11), the exenatide group (EX group, n = 11), the PCOS group (n = 10), and the normal control group (NC group, n = 10). The MF group was administered MF 300 mg/(kg•d) daily. The EX group was subcutaneously injected EX 10µg/(kg•d) daily. After 4 weeks of continuous administration, fasting blood glucose and serum androgen, luteinizing hormone and other biochemical indicators were measured. Western and Real-time PCR were used to determine the expression of AMPKα and SIRT1 in the ovaries of each group. RESULTS: After 4 weeks of drug intervention, compared with untreated PCOS group, EX group and MF group had visibly decreased body weight (222.64 ± 16.57, 218.63 ± 13.18 vs 238.30 ± 12.26 g, P = 0.026), fasting blood glucose (7.71 ± 0.72, 8.17 ± 0.54 vs 8.68 ± 0.47 mmol/L, P < 0.01), HOMA-IR (8.26 ± 2.50, 7.44 ± 1.23 vs 12.66 ± 1.44, P < 0.01) and serum androgen (0.09 ± 0.03, 0.09 ± 0.03 vs 0.53 ± 0.41 ng/ml, P < 0.01) and the expressions of AMPKα and SIRT11 were increased progressively (P < 0.05). CONCLUSIONS: Both metformin and exenatide can improve the reproductive and endocrine functions of rats with PCOS via the AMPKα-SIRT1 pathway, which may be the molecular mechanism for IR in PCOS and could possibly serve as a therapeutic target.


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Exenatida/farmacologia , Metformina/farmacologia , Síndrome do Ovário Policístico/tratamento farmacológico , Sirtuína 1/genética , Androgênios/sangue , Animais , Glicemia/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Resistência à Insulina/genética , Hormônio Luteinizante/genética , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/genética , Ratos
10.
Life Sci ; 235: 116843, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31494172

RESUMO

Polycystic ovary syndrome (PCOS) is a multifactorial disease, which is resulted from the three common features, hyperandrogenism (HA), ovulatory dysfunction (OD), and polycystic ovarian morphology (PCOM). The environmental inducers (like diet, lifestyle, chemicals, drugs, and ageing) and cardiometabolic risk factors (such as insulin resistance, metabolic syndrome, and obesity) are involved in pathogenesis of PCOS. The growing body of evidence has been shown that there exist endothelial cell dysfunction (ECD) in women with PCOS independent of age, weight and metabolic abnormalities. It has been shown that a broad spectrum of cardiovascular risk markers are involved in ECD- induced cardiovascular disease. It is well described that there are no worldwide treatments for PCOS and all of pharmacological treatments are off -label without any approval. MNAM is one of potential therapeutic factor, which produced by nicotinamide N-methyltransferase (NNMT) via consumption of S-adenosyl methionine (SAM) and nicotinamide. Only one study has shown higher expression of its producer enzyme, NNMT, in the cumulus cells of women with PCOS. Therefore, we reviewed beneficial effects of MNAM on modulation of cardiometabolic risk factors, which are associated to PCOS and try to describe possible mode of action of MNAM in the regulation of these markers.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Niacinamida/análogos & derivados , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Sintomas Prodrômicos , Biomarcadores/sangue , Feminino , Humanos , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Fatores de Risco
11.
J Ovarian Res ; 12(1): 78, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31470879

RESUMO

BACKGROUND: Reduction of the body iron stores can improve hyperandrogenemia and insulin resistance. This study aimed to compare clinical and para-clinical responses to the treatment of phlebotomy using oral contraceptive pills (OCs) containing cyproterone acetate in women with PCOS. METHODS: In this randomized clinical trial, 64 patients with PCOS were randomly assigned to the phlebotomy and OCs groups (n = 32 in each group). The intervention group, using a single treatment procedure, underwent venesection of 450 mL of whole blood at the early follicular phase of the spontaneous or progesterone-induced menstrual cycle. The control group received OCs pills for 3 months from the 1th day of spontaneous or progesterone-induced menstrual cycle onwards for 3 weeks, followed by a pill-free interval of 7 days. The women were evaluated after the 3-month intervention. The primary outcome measure was a change in the HOMA-IR and free androgen index (FAI). Secondary outcomes were changes in the Ferriman-Gallwey (FG) score and other clinical, biochemical and hormonal changes from the baseline (pre-treatment) to week 12. RESULTS: In the phlebotomy group, 27 (84.3%) and in the OCs group 30 (93.7%) of the women completed the 3-month follow-up. The median HOMA-IR significantly decreased from 3.5 to 2.7 in the phlebotomy, and from 3.1 to 2.8 in the OCs group, and the changes were comparable between the groups. Median changes in the FAI significantly decreased in both groups, but the differences were not statistically significant between the groups (P = 0.061). With regard to secondary outcomes, mean FG scores in both groups significantly decreased [from 16.8 (6) to 13.3 (7.4), P < 0.028] in the phlebotomy group and [from 14.3 (7) to 9.8 (7.6) in the OCs group, P = 0.001] after 3 months of treatment, but such changes had no statistically significant differences between the groups. During treatment, menstrual cycles became regular in all women in the OCs group and in 12.27 (44.4%) of the women in the phlebotomy group, and the difference was statistically significant (P = 0.001). Despite no statistically significant differences in lipid profiles between the groups at the baseline, triglycerides were significantly higher in the OCs group compared to the phlebotomy at end of follow up (p = 0.019). CONCLUSION: Both treatment modalities had similar beneficial effects on insulin resistance and on androgenic profiles. However, OCs was reported more effective in treating menstrual irregularities and phlebotomy had less adverse effects on triglyceride concentrations. TRIAL REGISTRATION: Code: IRCT2013080514277N1 .


Assuntos
Antagonistas de Androgênios/uso terapêutico , Anticoncepcionais Orais/uso terapêutico , Acetato de Ciproterona/uso terapêutico , Flebotomia , Síndrome do Ovário Policístico/terapia , Adolescente , Adulto , Androgênios/sangue , Androstenodiona/sangue , Colesterol/sangue , Feminino , Humanos , Insulina/sangue , Resistência à Insulina , Síndrome do Ovário Policístico/sangue , Testosterona/sangue , Triglicerídeos/sangue , Adulto Jovem
12.
J Ovarian Res ; 12(1): 74, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399035

RESUMO

BACKGROUND: The mechanism of the pathological change of polycystic ovary syndrome (PCOS) is still unclear. Previous studies have shown that PCOS is a chronic nonspecific low-grade inflammatory condition, and that heat shock protein (HSP)70 has a potent anti-inflammatory property. So the aim of this study is to investigate the correlation between HSP70 and the hormones and inflammatory factors and to find out the role of HSP70 in the pathogenesis of PCOS. METHODS: Twenty female Sprague-Dawley (SD) rats (aged 23 days and weighted 80-90 g) were randomly divided into two groups (n = 10 per group), PCOS group and control group. PCOS group were subcutaneously injected with 6 mg/100 g dehydro-epiandrosterone (DHEA) for 20 consecutive days, the control group were subcutaneously injected with a solvent of equivalent amount. All the samples were collected in the morning fasting state, 12 h after the last administration. Histological examinations of ovarian tissues were analyzed. Hormone levels and inflammatory factors levels were measured by enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Serum concentrations of testosterone (T) and luteinizing hormone (LH) were significantly higher in the PCOS group than the control group (P < 0.001), but the concentrations of estradiol (E2), follicle stimulating hormone (FSH) and insulin didn't show significant difference between these two groups. All the concentrations of inflammatory factors including C-reactive protein (CRP), interleukin (IL)-6, IL-18, and tumor necrosis factor (TNF)-α. were significantly higher in PCOS group than the control group (P < 0.001). The expressions of HSP70 were significantly lower in serum but higher in ovarian tissues in the PCOS group than the control group. Spearman rank correlation analysis showed strong negative correlation of serum HSP70 levels with T, LH and all the detected inflammatory factors. CONCLUSION: The abnormal expression of HSP70 correlated with testosterone and inflammatory factors, which indicates that HSP70 may play an important role in PCOS pathology.


Assuntos
Proteínas de Choque Térmico HSP70/metabolismo , Síndrome do Ovário Policístico/etiologia , Síndrome do Ovário Policístico/metabolismo , Animais , Biomarcadores , Citocinas/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Proteínas de Choque Térmico HSP70/genética , Hormônios/metabolismo , Mediadores da Inflamação/metabolismo , Ovário/metabolismo , Ovário/patologia , Síndrome do Ovário Policístico/sangue , Ratos , Ratos Sprague-Dawley
13.
BMC Res Notes ; 12(1): 513, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31416473

RESUMO

OBJECTIVES: To assess the variability and predictability of adiponectin, leptin, resistin and their ratios in non-obese and obese women with anovulatory polycystic ovary syndrome (aPCOS). RESULTS: A total of 52 ovulatory controls (mean age = 31.63 ± 4.88 years, BMI = 25.33 ± 2.68 kg/m2); 54 non-obese (mean age = 32.11 ± 4.25 years, BMI = 25.72 ± 2.95 kg/m2) and 50 obese women with aPCOS (mean age = 33.64 ± 4.14 years, BMI = 39.19 ± 2.99 kg/m2) were recruited. The aPCOS group had lower adiponectin [13.0 (10.49-16.59) vs 18.42 (15.72-19.92) µg/ml, p < 0.0001], adiponectin: leptin ratio (A:L) [0.60 (0.35-0.88) vs 1.19 (0.92-1.37), p < 0.0001], and adiponectin: resistin ratio (A:R) [0.30 (0.21-0.43) vs 0.42 (0.32-0.62), p < 0.0001] but a higher leptin [20.02 (14.54-26.80) vs 16.17 (14.51-18.36) ng/ml, p < 0.0001] and leptin: resistin ratio (L:R) [0.53 (0.37-0.82) vs 0.40 (0.27-0.48), p < 0.0001] compared to the controls. The obese aPCOS group had lower adiponectin [11.04 (5.66-13.25) vs 14.18 (11.04-18.02), p < 0.0001 and 18.42 (15.72-19.92) µg/ml, p < 0.0001], A:L [0.36 (0.27-0.44) vs 0.78 (0.61-1.16), p < 0.0001 and 1.19 (0.92-1.37), p < 0.0001], and A:R [0.24 (0.17-0.38) vs 0.40 (0.23-0.58), p < 0.0001 and 0.42 (0.32-0.62), p < 0.0001] but a higher leptin [26.80 (14.28-32.09) vs 17.95 (14.86-21.26), p < 0.05 and 16.17 (14.51-18.36) ng/ml, p < 0.0001] and L:R [0.63 (0.46-1.03) vs 0.41 (0.30-0.61), p < 0.0001 and 0.40 (0.27-0.48), p < 0.0001] compared to the non-obese aPCOS and control group, respectively. A:L showed the best discriminatory power in predicting aPCOS (AUC = 0.83), followed by adiponectin alone (AUC = 0.79), L:R and leptin alone (both AUC = 0.69). Resistin alone had the poorest discriminatory power (AUC = 0.48).


Assuntos
Adiponectina/sangue , Leptina/sangue , Obesidade/sangue , Síndrome do Ovário Policístico/sangue , Resistina/sangue , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Síndrome do Ovário Policístico/diagnóstico , Valor Preditivo dos Testes , Curva ROC
14.
Arch Endocrinol Metab ; 63(4): 417-426, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365630

RESUMO

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.


Assuntos
Distribuição da Gordura Corporal , Gordura Intra-Abdominal , Síndrome do Ovário Policístico/sangue , Adolescente , Adulto , Biomarcadores/sangue , Glicemia/análise , Composição Corporal , Proteína C-Reativa/análise , Estudos Transversais , Feminino , Humanos , Mediadores da Inflamação/sangue , Insulina/sangue , Produto da Acumulação Lipídica , Sobrepeso/sangue , Sensibilidade e Especificidade , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue , Adulto Jovem
15.
Ann Endocrinol (Paris) ; 80(4): 225-228, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31402043

RESUMO

OBJECTIVES: The prevalence of ovulation disorder (OD) is 3-fold higher in obese than normal-weight women. Most ODs are associated with concomitant polycystic ovary syndrome (PCOS), but obesity by itself can cause OD, through mechanisms that remain poorly documented. The literature on obese non-PCOS women with OD is sparse. The aim of the present study was to analyze a population of obese non-PCOS women with OD to shed further light on the mechanism of ovulation disorder. MATERIAL AND METHODS: This retrospective observational study of infertile obese women without PCOS compared a control group without OD (n=45) to a study group with OD (n=30) (OD group). Clinical, hormonal, and ultrasound characteristics were collected between cycle days 2 and 5. Women older than 37 years and women with PCOM (polycystic ovarian morphology) or hormonal disorder were excluded. RESULTS: Body mass index (BMI) was significantly higher in the OD group, as were waist circumference and insulin and leptin serum levels. Conversely, serum follicle stimulating hormone (FSH) levels were significantly lower. After adjustment for BMI, only serum FSH level remained significantly different between the 2 groups. Discriminant analysis suggested that FSH may have a much stronger effect on OD than BMI. CONCLUSION: Low serum FSH level may contribute to OD in some obese women, independently of BMI. The pathophysiological mechanism of this finding and its impact on therapeutic strategies must be clarified.


Assuntos
Índice de Massa Corporal , Hormônio Foliculoestimulante/sangue , Distúrbios Menstruais/sangue , Obesidade/sangue , Obesidade/complicações , Ovulação/sangue , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Infertilidade Feminina/sangue , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/etiologia , Distúrbios Menstruais/etiologia , Ovulação/fisiologia , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Estudos Retrospectivos , Adulto Jovem
16.
Diabetes Metab Syndr ; 13(5): 2907-2915, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31425955

RESUMO

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is the most common female endocrinopathy among premenopausal women associated with hyperandrogenism, obesity, dyslipidemia, insulin resistance and inflammation. Oxidative stress is an important component of cardio-metabolic risk seen in PCOS. MATERIAL AND METHODS: A total of 95 women with PCOS and 95 healthy controls were included in this observational study. Serum PON1 activity and stress markers were measured by spectrophotometric methods. Circulating TF level was measured by ELISA. RESULTS: We found decreased PON1 activity and increased TF levels in women with PCOS compared to healthy controls. Fasting insulin, HOMA-IR, testosterone, LDL-C, MDA, PC and SOD activity were significantly increased whereas FGIR, QUICKI, HDLC, CAT and TAC were significantly decreased in PCOS women than controls. We observed a positive association of PON1 activity with FGIR, QUICKI, HDL-C and TAC, and its negative association was observed with LH, testosterone, fasting insulin and HOMA-IR in PCOS women. We further observed a positive association of TF with waist, waist to hip ratio, BMI, glucose 1hr, cholesterol, LDL-C, SGPT, uric acid and SOD activity in PCOS women. CONCLUSIONS: Decreased PON1 activity and raised circulating TF levels are respective indicators of pro-inflammatory and procoagulant status in PCOS women. The imbalanced oxidant/antioxidant status further supports the evidences that PCOS is an oxidant state. Further, the association of PON1 activity and TF levels with the clinical, laboratory findings and stress marker levels suggest that these factors taken together are involved in aggravating the pro-inflammatory status in PCOS women.


Assuntos
Arildialquilfosfatase/sangue , Biomarcadores/sangue , Índice de Massa Corporal , Resistência à Insulina , Estresse Oxidativo , Síndrome do Ovário Policístico/fisiopatologia , Tromboplastina/análise , Adulto , Antioxidantes/metabolismo , Estudos de Casos e Controles , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Seguimentos , Humanos , Síndrome do Ovário Policístico/sangue , Prognóstico , Superóxido Dismutase/sangue , Testosterona/sangue , Adulto Jovem
17.
Georgian Med News ; (290): 25-29, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31322509

RESUMO

There are controversial opinions regarding the impact of hyperhomocysteinemia (HHcy) and insulin resistance in PCOS patients who experience Recurrent Pregnancy Loss (RPL). Nowadays the correlation between levels of anti-müllerian hormone (AMH), homocysteine and insulin resistance (IR) have become the main subject of interest in PCOS patients for predicting RPL. Objective - investigate the relationship between level of homocysteine, anti-müllerian hormone and insulin resistance in PCOS patients with Recurrent Pregnancy Loss. 80 Georgian young women (<30 years) with PCOS were involved in the prospective study. The diagnosis of PCOS was based on the criteria of Rotterdam Consensus 2003. Patients were divided into two groups: group I-50 patients, who experienced RPL, and group II-30 patients with live births in anamnesis (control group). Patients with RPL were divided into two subgroups: subgroup A-with insulin resistance (n=28), and subgroup B-without insulin resistance (n=22). All patients underwent hormonal investigation from day 2 to 3 of menstrual cycle. Plasma levels of anti-müllerian hormone, homocysteine, follicle-stimulating hormone, luteinizing hormone (LH), total testosterone (T), free testosterone (FT), sex hormone binding globulin (SHBG) were determined. Between 2-3 days of the menstrual cycle all participants underwent an ultrasound examination using Voluson E10. This was done to determine ovarian volume and antral follicle count. Average homocysteine (Hcy) level in PCOS patients with RPL (11.5±2.24µmol/l) was significantly higher than in controls (7.55±2.45 µmol/l, p<0.001). Incidence of (HHcy) and IR in patients with RPL was 70% and 56% respectively, which was significantly higher than in controls (HHcy-54.3%; IR- 9.4%; p<0.0001). HOMA-IR in patients with RPL was significantly higher compared with controls (p<0.001). Average AMH level in patients with RPL and live births did not differ significantly. In the group of PCOS with RPL significant positive correlation between Hcy and HOMA-IR, BMI, AMH and FT levels was found (p<0.001). Serum homocysteine level is elevated in PCOS patients with RPL. This elevation is correlated with the degree of obesity, BMI, Insulin Resistance status, AMH and androgen levels. The treatment of hyperhomocysteinemia and insulin resistance in women with PCOS might become the bases for prevention of pregnancy losses and improving reproductive outcomes.


Assuntos
Aborto Habitual/etiologia , Hormônio Antimülleriano/sangue , Homocisteína/sangue , Resistência à Insulina , Síndrome do Ovário Policístico/sangue , Aborto Habitual/sangue , Aborto Habitual/epidemiologia , Adulto , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/metabolismo , Gravidez , Estudos Prospectivos , Testosterona/sangue
18.
BMC Res Notes ; 12(1): 455, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31340838

RESUMO

OBJECTIVE: Study analyzes mutation in mtDNA (Mitochondrial DNA) among diabetic women with PCOS in non-diabetic diabetic women and compared with the healthy control. Women with known case of hyperandrogenism, ovulatory dysfunction and/or polycystic ovaries were selected and anthropometric and demographic variables were collected during their clinical visit. Biochemical estimation of glucose, FSH, LH, estradiol (E2), and insulin levels were analyzed. Mutational analysis of mt-tRNA genes of each individual was compared with the updated consensus Cambridge sequence. The mtDNA content was determined in triplicate using SYBR green PCR mastermix. RESULTS: The clinical and biochemical characteristics of participants showed no statistical difference in age and/or FSH, PRL, E2, PRGE or fasting glucose value between patients of different groups. Women with PCOS-D had significantly higher LH, LH/FSH, TT and fasting insulin levels and HOMA-IR with respect to the control group. Ten different type of mutation were seen in POCS group. Most of these mutations were confined to evolutionarily conserved region. The mtDNA copy numbers were considerably lower PCOS group irrespective of diabetic status. To conclude, the current study inferred that the mutations occur in the mitochondrial genome, mt-tRNA in specific, are the important causal factor in PCOS.


Assuntos
DNA Mitocondrial/genética , Diabetes Mellitus Tipo 2/genética , Hiperandrogenismo/genética , Mitocôndrias/genética , Síndrome do Ovário Policístico/genética , RNA de Transferência/genética , Adulto , Glicemia/metabolismo , Estudos de Casos e Controles , Variações do Número de Cópias de DNA , DNA Mitocondrial/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Foliculoestimulante/genética , Expressão Gênica , Humanos , Hiperandrogenismo/sangue , Hiperandrogenismo/complicações , Hiperandrogenismo/patologia , Insulina/sangue , Resistência à Insulina , Hormônio Luteinizante/sangue , Hormônio Luteinizante/genética , Herança Materna , Mitocôndrias/patologia , Ovário/metabolismo , Ovário/patologia , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/patologia , Estudos Prospectivos , RNA de Transferência/sangue
19.
Mediators Inflamm ; 2019: 6321427, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31346314

RESUMO

Background: ANGPTL8 has been reported to be a regulator of lipid metabolism, and it is associated with insulin resistance (IR) and metabolic syndrome (MetS). We investigated whether ANGPTL8 plays a role in MetS. Methods: ANGPTL8 and adiponectin concentrations were measured in PCOS patients with or without MetS and in their corresponding healthy controls. The association of circulating ANGPTL8 with adiponectin and other parameters was also examined. Results: Circulating ANGPTL8 concentrations were higher in PCOS women with MetS than in those without MetS and in the controls (P < 0.01). ANGPTL8 was positively correlated with age, BMI, FAT%, WHR, SBP, TG, FBG, HbA1c, Fins, and HOMA-IR (all P < 0.01) in the study populations and negatively associated with adiponectin and M-values (P < 0.001). In addition, ANGPTL8 was positively correlated with PRL, LH, TEST, and FAI and negatively correlated with SHBG (all P < 0.01). ROC curve analyses showed that the AUCMetS was 0.87 (P < 0.001), with a sensitivity of 92.4% and specificity of 75.4%, and the AUCIR was 0.82 (P < 0.01), with a sensitivity of 76.4% and specificity of 75.6%. Conclusion: ANGPTL8 levels progressively decrease from PCOS patients with MetS to those without MetS and may be a serum marker associated with the degree of metabolic disorders.


Assuntos
Proteínas Semelhantes a Angiopoietina/sangue , Síndrome Metabólica/sangue , Hormônios Peptídicos/sangue , Síndrome do Ovário Policístico/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Resistência à Insulina/fisiologia , Metabolismo dos Lipídeos/fisiologia , Modelos Logísticos , Adulto Jovem
20.
Curr Med Sci ; 39(4): 609-614, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31346998

RESUMO

The effects of metformin treatment on soluble leptin receptor (sOB-R) levels in women with polycystic ovary syndrome (PCOS) were investigated. This prospective and open-label study was conducted by the Department of Obstetrics & Gynecology at Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, China. Fifty-five women with PCOS and insulin resistance (IR) were treated with metformin for 6 months. According to body mass index (BMI), the patients were divided into two groups: lean PCOS group (BMI <23 kg/m2, n=34) and overweight or obese PCOS group (BMI ≥23 kg/m2, n=21). Before and after treatment, serum luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), insulin and sOB-R levels were determined. Thirty-one BMI-matched ovulatory women served as controls. The results showed: (1) The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), androgen levels and hirsutism scores were higher, and sOB-R levels were lower in PCOS groups than in control group. A subgroup analysis of lean and overweight or obese PCOS patients revealed there was significant difference in sOB-R level between lean PCOS group and overweight or obese PCOS group. There were no significant differences in anthropometric parameters between lean PCOS patients and BMI-matched controls. However, sOB-R level was significantly lower in lean PCOS women than in controls. (2) There was no correlation between sOB-R level and BMI, waist and hip circumference, total testosterone, androstendione, DHEAS, LH or hirsutism scores in PCOS patients, but there was a significant negative correlation between sOB-R and HOMA-IR. (3) After treatment with metformin for 6 months, serum insulin levels decreased, and sOB-R levels increased significantly (P<0.01). It was suggested that considering low sOB-R levels supposedly compensate diminished leptin action, PCOS per se might cause leptin resistance. It is likely that reduction of hyperinsulinemia produced by metformin effectively improves the sOB-R levels in PCOS.


Assuntos
Metformina/administração & dosagem , Síndrome do Ovário Policístico/tratamento farmacológico , Receptores para Leptina/genética , Adulto , Androstenodiona/sangue , Índice de Massa Corporal , Sulfato de Desidroepiandrosterona/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Insulina/sangue , Hormônio Luteinizante/sangue , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/patologia , Testosterona/sangue
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