RESUMO
AIM: To assess serum chemerin levels and investigate the association of chemerin with the hyperandrogenic and normoandrogenic phenotypes of Polycystic Ovary Syndrome (PCOS) and with the metabolic status of the analyzed population. MATERIAL AND METHODS: A cross-sectional study was conducted on 106 women with PCOS and 60 healthy controls from Argentina. Patients were classified as showing a hyperandrogenic or normoandrogenic phenotype. Participants underwent anthropometric and clinical evaluation and markers of cardiovascular risk, insulin resistance, metabolic syndrome (MS), and serum chemerin levels were assessed. RESULTS: PCOS patients showed increased levels of chemerin. In adjusted models for age and body mass index (BMI), chemerin was associated with markers of metabolic status. The analysis of chemerin levels considering the cutoff values of BMI, homeostatic model of insulin sensitivity (HOMA-IR) and TG/HDL marker showed that PCOS patients always presented higher levels of chemerin than controls. PCOS group showed increased chemerin levels independently of the presence of MS. CONCLUSION: PCOS patients always showed increased levels of chemerin independently of their phenotype and presence of overweight, as well as higher levels of chemerin than controls when considering the cutoff values of HOMA-IR and TG/HDL. Therefore, argentine women with PCOS display increased chemerin levels independently of their metabolic or androgenic status.
Assuntos
Quimiocinas/sangue , Hiperandrogenismo/sangue , Síndrome Metabólica/sangue , Síndrome do Ovário Policístico/sangue , Adulto , Argentina , Índice de Massa Corporal , Estudos de Casos e Controles , HDL-Colesterol/sangue , Feminino , Humanos , Resistência à Insulina , Triglicerídeos/sangue , Circunferência da Cintura , Adulto JovemRESUMO
Polycystic ovary syndrome (PCOS) is an endocrine disorder. PCOS women are at high risk of developing insulin resistance (IR) and cardiovascular disorders since young age. We aimed to study the reliability of lipid accumulation product (LAP) and visceral adiposity index (VAI) as markers of metabolic disturbances (MD) associated with IR in young reproductive aged PCOS patients. We also evaluated the association between LAP and VAI and the presence of hyperandrogenism. In a cross-sectional study, 110 PCOS patients and 88 control women (18-35 years old) were recruited. PCOS patients were divided into 2 groups, as hyperandrogenic and non-hyperandrogenic considering the signs of hyperandrogenism (clinical or biochemical). Anthropometric measurements were taken and blood samples collected. Metabolic and anthropometric characteristics and their association with IR and associated MD were evaluated and LAP and VAI were calculated. LAP and VAI were compared with TC/HDL-c and TG/HDL-c to define the best markers of MD in this population. Independently of the phenotype, young PCOS patients showed high IR and dyslipidemia. Both LAP and VAI showed to be more effective markers to assess MD and IR in these young women than TG/HDL-c or TC/HDL-c [cut-off values: LAP: 18.24 (sensitivity: 81.43% specificity: 73.49%), positive predictive value (PPV): 75.0%, negative predictive value (NPV): 77.27%, VAI: 2.19 (sensitivity: 81.16% specificity: 72.15% PPV: 74.65% NPV: 72.22%)]. LAP and VAI are representative markers to assess MD associated with IR in young PCOS patients. All PCOS patients, independently of their androgenic condition, showed high metabolic risk.
Assuntos
Biomarcadores , Resistência à Insulina , Gordura Intra-Abdominal/patologia , Produto da Acumulação Lipídica , Doenças Metabólicas/complicações , Síndrome do Ovário Policístico/complicações , Adiposidade/fisiologia , Adolescente , Adulto , Argentina , Biomarcadores/metabolismo , Estudos Transversais , Feminino , Humanos , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/etiologia , Doenças Metabólicas/patologia , Obesidade Abdominal/complicações , Obesidade Abdominal/diagnóstico , Obesidade Abdominal/metabolismo , Obesidade Abdominal/patologia , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Diâmetro Abdominal Sagital , Adulto JovemRESUMO
OBJECTIVE: The aim of this study was to explore ß2-adrenoceptor (ADRB2) haplotype associations with phenotypes and quantitative traits related to insulin resistance (IR) and the metabolic syndrome (MS) in a polycystic ovary syndrome (PCOS) population. A secondary purpose was to assess the association between ADRB2 haplotype and PCOS. DESIGN: Genetic polymorphism analysis. Cross-sectional case-control association study. SETTING: Medical University Hospital and research laboratory. PATIENTS: One hundred and sixty-five unrelated women with PCOS and 116 unrelated women without PCOS (control sample). MEASUREMENTS: Clinical and biochemical measurements, and ADRB2 genotyping in PCOS patients and control subjects. METHODS: ADRB2 haplotypes (comprising rs1042711, rs1801704, rs1042713 and rs1042714 in that order), genotyping and statistical analysis to evaluate associations with continuous variables and traits related to IR and MS in a PCOS population. Associations between ADRB2 haplotypes and PCOS were also assessed. RESULTS: We observed an age-adjusted association between ADRB2 haplotype CCGG and lower insulin (P = 0·018) and HOMA (P = 0·008) in the PCOS sample. Interestingly, the expected differences in surrogate measures of IR between cases and controls were not significant in CCGG/CCGG carriers. In the case-control study, genotype CCGG/CCGG was associated with a 14% decrease in PCOS risk (P = 0·043), taking into account confounding variables. CONCLUSIONS: Haplotype I (CCGG) has a protective role for IR and MS in PCOS.
Assuntos
Resistência à Insulina/genética , Síndrome do Ovário Policístico/genética , Receptores Adrenérgicos beta 2/genética , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Frequência do Gene , Estudos de Associação Genética , Haplótipos , Humanos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Fenótipo , Síndrome do Ovário Policístico/epidemiologia , Síndrome do Ovário Policístico/metabolismo , Prevalência , Receptores Adrenérgicos beta 2/metabolismoRESUMO
Antioxidant actions of melatonin and its impact on testicular function and fertility have already been described. Considering that Sertoli cells contribute to provide structural support and nutrition to germ cells, we evaluated the effect of melatonin on oxidative state and lactate metabolism in the immature murine TM4 cell line and in immature hamster Sertoli cells. A prooxidant stimulus applied to rodent Sertoli cells expressing MT1/MT2 receptors, increased lipid peroxidation whereas decreased antioxidant enzymes (superoxide dismutase 1, catalase, peroxiredoxin 1) expression and catalase activity. These changes were prevented by melatonin. Furthermore, melatonin stimulated lactate dehydrogenase (LDH) expression/activity via melatonin receptors, and increased intracellular lactate production in rodent Sertoli cells. Interestingly, oral melatonin supplementation in infertile men positively regulated LDHA testicular mRNA expression. Overall, our work provides insights into the potential benefits of melatonin on Sertoli cells contributing to testicular development and the future establishment of a sustainable spermatogenesis.
Assuntos
Melatonina , Células de Sertoli , Masculino , Cricetinae , Camundongos , Animais , Células de Sertoli/metabolismo , Melatonina/farmacologia , Melatonina/metabolismo , Catalase/genética , Catalase/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Roedores/metabolismo , Estresse Oxidativo , Lactatos/metabolismoRESUMO
We have previously described that melatonin inhibits androgen production in hamster testes via melatonin subtype 1a (mel1a) receptors and the local corticotrophin-releasing hormone (CRH) system. This study attempted to determine the initial events of the melatonin/CRH signaling pathway. In Leydig cells from reproductively active Syrian hamsters, Western blotting, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and a colorimetric assay demonstrated that melatonin and CRH activate tyrosine phosphatases and subsequently reduce the phosphorylation levels of extracellular signal-regulated kinase (erk) and c-jun N-terminal kinase (jnk), down-regulate the expression of c-jun, c-fos and steroidogenic acute regulatory (StAR), and inhibit the production of testosterone. These effects were prevented by a highly selective CRH antagonist, thus indicating that melatonin does not exert a direct role. Specific mitogen-activated protein kinase kinase (MEK) and jnk blockers inhibited expression of c-jun, c-fos, StAR and the production of testosterone, confirming that these are events triggered downstream of erk and jnk. In Leydig cells from photoperiodically regressed adult hamsters, CRH inhibited the production of androstane-3α,17ß-diol (3α-diol), the main androgen produced, through the same signaling pathway. Testicular melatonin concentration was 3-4-fold higher in reproductively inactive hamsters than that detected in active animals. Since melatonin, CRH, and their receptors are present not only in hamster testes but also in testicular biopsies of infertile men, we can conjecture about the relevance of this previously uncharacterized pathway in human fertility disorders. In summary, our study identifies crucial intracellular events triggered by melatonin/CRH in the testis that lead to a down-regulation of the steroidogenic process.
Assuntos
Hormônio Liberador da Corticotropina/metabolismo , Células Intersticiais do Testículo/metabolismo , Melatonina/metabolismo , Animais , Cricetinae , Masculino , Transdução de Sinais/fisiologiaRESUMO
BACKGROUND: In non-obstructive azoospermia, histological patterns of Sertoli cell-only Syndrome (SCO) and hypospermatogenesis (H) are commonly found. In these pathologies, Leydig cell hyperplasia (LCH) is detected in some patients. Since TGF-ß1 is involved in cellular proliferation/development, the aim of this work was to analyze the expression of TGF-ß1, its receptors TGFBRII, TGFBRI (ALK-1 and ALK-5), and the co-receptor endoglin in human biopsies from patients with idiopathic infertility. METHODS: Specific immunostaining of TGF-ß1, its receptors TGFBRII, TGFBRI (ALK-1 and ALK-5), co-receptor endoglin and Smads proteins, were carried out in testicular biopsies from normal and infertile men with SCO or H. Gene expression of TGF-ß1 system were made in biopsies from infertile patients with semi-quantitative and quantitative PCR. RESULTS: Immunohistochemical studies revealed that TGF-ß1 and its specific receptors are present in Leydig cells in biopsies from normal tissue or patients with SCO or H with or without LCH. Smad proteins, which are involved in TGF-ß1 signaling, are also detected in both their phosphorylated (activated) and dephosphorylated form in all samples TGF-ß1, ALK-1 and endoglin gene expression are stronger in human biopsies with LCH than in those with SCO or H. Neither TGFBRII nor ALK-5 gene expression showed significant differences between pathologies. A significant correlation between ALK-1 and endoglin expression was observed. CONCLUSIONS: In conclusion, the high levels of mRNA and protein expression of the TGF-ß1 system in patients with LCH, particularly ALK1 and its correlation with endoglin, suggest that these proteins acting in concert might be, at least in part, committed actors in the Leydig cell hyperplasia.
Assuntos
Infertilidade Masculina/metabolismo , Proteínas Serina-Treonina Quinases/biossíntese , Receptores de Fatores de Crescimento Transformadores beta/biossíntese , Síndrome de Células de Sertoli/metabolismo , Doenças Testiculares/metabolismo , Fator de Crescimento Transformador beta1/biossíntese , Receptores de Activinas Tipo II/biossíntese , Adulto , Antígenos CD/biossíntese , Endoglina , Humanos , Hiperplasia/metabolismo , Células Intersticiais do Testículo/metabolismo , Células Intersticiais do Testículo/patologia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptores de Superfície Celular/biossíntese , Proteínas Smad/metabolismo , Testículo/metabolismoRESUMO
We have previously shown an inverse correlation between testicular melatonin concentration and inflammation/oxidative stress-related markers levels in infertile men showing unexplained azoospermia. Here, we evaluated the impact of melatonin oral supplementation (daily 3 mg dose used to treat sleep disorders) in the incidence of local inflammation, oxidative stress, and tubular wall fibrosis development in young and middle-aged infertile adult men. Compared with testes without histological alterations, gonads with morphological abnormalities showed lower melatonin concentration along with increased macrophage numbers, TBARS generation, and expression levels of inflammation-related markers and antioxidant enzymes, as well as tubular wall collagen fibers disorganization and thickening. Melatonin oral supplementation not only increased its own testicular levels but also decreased inflammation- and oxidative stress-related markers levels, and improved the tubular wall aspect. Overall, our work provides insights into the potential benefits of melatonin on the inflammatory and oxidative status in testes of patients suffering from unexplained infertility.
Assuntos
Inflamação/tratamento farmacológico , Melatonina/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacos , Adulto , Antioxidantes/uso terapêutico , Suplementos Nutricionais , Humanos , MasculinoRESUMO
AIM: to assess the presence of nonalcoholic fatty liver disease in patients with risk factors for this pathology (obesity, dyslipidemia, metabolic syndrome and diabetes type 2) and to determine the role of insulin, HOMA index, insulin-like growth factor-binding protein-1, sex hormone-binding globulin and plasminogen activator inhibitor type 1, as biochemical markers. METHODS: Ninety-one patients with risk factors for nonalcoholic fatty liver disease were evaluated. Serum transaminases, insulin, sex hormone-binding globulin, insulin-like growth factor-binding protein-1 and plasminogen activator inhibitor type 1 were measured. The diagnosis of fatty liver was performed by ultrasonography and liver biopsies were performed to 31 subjects who had steatosis by ultrasonography and high alanine aminotransferase. RESULTS: Nonalcoholic fatty liver disease was present in 65 out of 91 patients (71,4%). Liver biopsy performed to 31 subjects confirmed nonalcoholic steatohepatitis. Twenty-five patients had different degrees of fibrosis. Those individuals with fatty liver had higher waist circumference, serum levels of triglycerides, insulin and HOMA index, and lower serum insulin-like growth factor-binding protein-1 concentration. The degree ofhepatic steatosis by ultrasonography was positively correlated to waist circumference, triglycerides, insulin and HOMA index (p<0,003; p<0,003; p<0,002 and p<0,001, respectively), and was negatively correlated to HDL-cholesterol and insulin-like growth factor-binding protein-1 (p<0,025 and p<0,018, respectively). CONCLUSIONS: We found a high prevalence of NAFLD in patients with risk factors, most of them overweight or obese. Although SHBG and PAI-1 have a closely relationship to insulin resistance, they did not show to be markers of NAFLD. Regardless of low IGFBP-1 levels associated with NAFLD, serum IGFBP-1 measure is less accessible than insulin and triglycerides levels, HOMA index and waist circumference. Moreover, it is not a better marker for NAFLD than the above mentioned.
Assuntos
Fígado Gorduroso/epidemiologia , Resistência à Insulina , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Inibidor 1 de Ativador de Plasminogênio/sangue , Adolescente , Adulto , Idoso , Argentina/epidemiologia , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/etiologia , Ensaio de Imunoadsorção Enzimática , Fígado Gorduroso/complicações , Fígado Gorduroso/diagnóstico , Feminino , Humanos , Modelos Logísticos , Masculino , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade , Obesidade/complicações , Prevalência , Fatores de Risco , Globulina de Ligação a Hormônio Sexual/análise , Adulto JovemRESUMO
Catecholaminergic neuronal elements (CNE) and macrophages (MACs) are increased in testes of patients with idiopathic infertility. Now, we describe an anatomical proximity between CNE and MACs, expression of specific α- and ß-adrenergic receptors (ADRs) subtypes in MACs, and a positive correlation between the number of MACs and cyclooxygenase (COX2) expression - key enzyme in prostaglandin (PG) synthesis and an inflammatory marker - in testes of infertile men. To examine a potential effect of adrenergic input on COX2 expression, we used two additional experimental models: non-testicular human MACs (THP1 cell line) and non-human testicular MACs purified from adult Syrian hamsters. We found that epinephrine and norepinephrine up-regulate COX2 expression and PGD2 production through ß1-and ß2-ADRs. Our results demonstrate the existence of a yet unknown link between CNE and MACs in the human testis that could trigger inflammation and tissue homeostatic dysregulation associated with pathogenesis or maintenance of infertility states.
Assuntos
Ciclo-Oxigenase 2/metabolismo , Infertilidade Masculina/patologia , Macrófagos/patologia , Prostaglandinas/metabolismo , Receptores Adrenérgicos beta/metabolismo , Testículo/patologia , Testosterona/metabolismo , Adulto , Animais , Células Cultivadas , Ciclo-Oxigenase 2/genética , Humanos , Infertilidade Masculina/genética , Infertilidade Masculina/metabolismo , Macrófagos/metabolismo , Masculino , Mesocricetus , Receptores Adrenérgicos beta/genética , Testículo/metabolismoRESUMO
Fatty liver represents the liver component of metabolic syndrome and may be involved in plasminogen activator inhibitor-1 (PAI-1) synthesis. We studied plasma PAI-1 levels and relationships with risk factors for metabolic syndrome, including fatty liver, in 170 patients. Liver ultrasound scan was performed on all patients, and a liver biopsy was performed on those patients with chronically elevated transaminase levels. Plasma PAI-1 levels correlated significantly (P < .05) with body mass index, degree of steatosis, insulin resistance, insulin level, waist circumference, triglycerides, and high-density lipoprotein (HDL) -cholesterol. However, only body mass index (beta = .455) and HDL-cholesterol (beta = .293) remained predictors of PAI-1 levels. Liver biopsy revealed a significant correlation (P < .05) between insulin resistance (r = 0.381) or insulin level (r = 0.519) and liver fibrosis. In patients presenting features of metabolic syndrome, plasma PAI-1 levels were mainly conditioned by the whole-body fat content.
Assuntos
Fígado Gorduroso/sangue , Síndrome Metabólica/sangue , Inibidor 1 de Ativador de Plasminogênio/sangue , Adiposidade , Adulto , Índice de Massa Corporal , Fígado Gorduroso/complicações , Fígado Gorduroso/patologia , Feminino , Humanos , Insulina/sangue , Resistência à Insulina , Masculino , Síndrome Metabólica/etiologia , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Obesidade/patologia , Fatores de RiscoRESUMO
Reactive oxygen species (ROS) regulate testicular function in health and disease. We previously described a prostaglandin D2 (PGD2) system in Sertoli cells. Now, we found that PGD2 increases ROS and hydrogen peroxide (H2O2) generation in murine TM4 Sertoli cells, and also induces antioxidant enzymes expression suggesting that defense systems are triggered as an adaptive stress mechanism that guarantees cell survival. ROS and specially H2O2 may act as second messengers regulating signal transduction pathways and gene expression. We describe a stimulatory effect of PGD2 on lactate dehydrogenase (LDH) expression via DP1/DP2 receptors, which is prevented by the antioxidant N-acetyl-L-cysteine and the PI3K/Akt pathway inhibitor LY 294002. PGD2 also enhances Akt and CREB/ATF-1 phosphorylation. Our results provide evidence for a role of PGD2 in the regulation of the oxidant/antioxidant status in Sertoli cells and, more importantly, in the modulation of LDH expression which takes place through ROS generation and the Akt-CREB/ATF-1 pathway.
Assuntos
Lactato Desidrogenases/metabolismo , Prostaglandina D2/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Células de Sertoli/metabolismo , Adulto , Animais , Linhagem Celular , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/metabolismo , Masculino , Camundongos , Células de Sertoli/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição DP1/genética , Fator de Transcrição DP1/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
OBJECTIVE: To evaluate the effects of rosiglitazone on insulin resistance, growth factors, and reproductive disturbances in women with polycystic ovary syndrome (PCOS). DESIGN: Prospective study. SETTING: Women with PCOS attending as outpatients of the Endocrine Division, Hospital Durand, Buenos Aires. PATIENT(S): Twenty-four insulin-resistant women with PCOS. INTERVENTION(S): Hormonal evaluations and a standardized oral glucose tolerance test before and after a 3-month trial of 4 mg of rosiglitazone daily. MAIN OUTCOME MEASURE(S): Serum LH, FSH, T, IGF-1, IGFBP-1, IGFBP-3, leptin, 17alpha-hydroxyprogesterone, insulin, and glucose concentrations. The area under insulin curve (AUC-insulin), the HOMA index (insulin resistance), the QUICKI index (insulin sensitivity), and the beta-cell function were calculated. Body mass index (BMI) and the waist/hip ratio were evaluated. RESULT(S): A significant decrease was observed in serum fasting insulin, AUC insulin, HOMA index, beta-cell function, IGF-1, LH, and waist/hip ratio. The QUICKI index and IGFBP-1 increased significantly. Serum sex hormone-binding globulin, androgens, leptin, IGFBP-3, and BMI remained unchanged. Twenty-two of 23 females had their menses restored, and three patients became pregnant. One patient was excluded because she became pregnant at the second month. CONCLUSION(S): Associated with the decrease in LH, rosiglitazone improved insulin-resistance parameters and normalized the menstrual cycle, which suggests that this drug could improve the endocrine-reproductive condition in insulin-resistant women with PCOS.
Assuntos
Substâncias de Crescimento/metabolismo , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Síndrome do Ovário Policístico/fisiopatologia , Reprodução/efeitos dos fármacos , Tiazolidinedionas/uso terapêutico , Adolescente , Adulto , Índice de Massa Corporal , Feminino , Teste de Tolerância a Glucose , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Hormônio Luteinizante/sangue , Menstruação/efeitos dos fármacos , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/patologia , Gravidez , Estudos Prospectivos , Rosiglitazona , Resultado do TratamentoRESUMO
BACKGROUND: Infertility is a public health disorder affecting 10% of the population worldwide. Research on the impact of body mass index (BMI) on male fertility is very limited as compared to the multiple studies evaluating the impact of overweight in women's fertility. Although 25%-30% of the cases of couples consulting for infertility are attributable to male factors, studies evaluating the association between semen parameters and BMI are controversial. OBJECTIVE: To assess the impact of BMI on semen parameters in a selected group of men with unexplained infertility. METHOD: A retrospective analysis of 168 patients during the 2008-2010 period. They all had at least one semen analysis and related studies to rule out known causes of infertility. Median age of patients was 35 years (22-55), and they were divided into three groups: normal weight (BMI: 20-24.9kg/m(2)), overweight (BMI 25-29.9kg/m(2)), and obese (BMI ≥30kg/m(2)). RESULTS: There were no significant differences in semen parameters evaluated between the three groups, and no significant correlation was found between the same parameters and BMI. CONCLUSIONS: There was no significant association between BMI and conventional semen parameters, but we cannot exclude an impairment in other semen parameters that are not routinely assessed, which could result in a lower potential fertility in these individuals.
Assuntos
Índice de Massa Corporal , Peso Corporal , Infertilidade Masculina/fisiopatologia , Análise do Sêmen , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Introducción: El síndrome de ovario poliquístico (SOP) es una endocrinopatía que afecta a mujeres en edad reproductiva, frecuentemente asociado a insulinorresistencia (IR) y riesgo cardiovascular (RCV). El criterio de Rotterdam distingue 4 fenotipos: 3 presentan hiperandrogenismo clínico y/o bioquímico (HA) y uno es normo-androgénico (NHA). Por ser un síndrome heterogéneo, es necesario identificar a las pacientes con mayor RCV. Dos nuevos marcadores han sido propuestos para evaluarlo: el índice de adiposidad abdominal (VAI) y el producto de acumulación lipídica (LAP). Objetivo: Evaluar los marcadores LAP y VAI como predictores de IR y su correlación con los parámetros de RCV en relación con los fenotipos SOP. Metodología: Se estudió a 130 pacientes con SOP entre 18 y 36 años, clasificadas en 2 grupos: HA y NHA según la presencia de hiperandrogenismo clínico y/o bioquímico. Se evaluaron parámetros de RCV según ATP III: circunferencia de cintura (CC), glucemia, HDL, triglicéridos (TG) y presión arterial. Se calcularon: LAP = (CC [cm] - 58) * TG (mmol/l) y VAI = (CC [cm]/[36,58 + (1,89 * IMC [kg/m²]] * [TG [mg/dl]/0,81] * [1,52/HDL-c [mg/dl]]). Se realizaron curvas ROC/área bajo la curva para establecer valores de corte de LAP y VAI para la identificación de IR, análisis de correlación con parámetros de RCV y de las diferencias entre fenotipos, tomando como significativo p < 0,05. Resultados: Los valores de corte establecidos para definir IR fueron de 14,02 para LAP (especificidad: 93,22%; sensibilidad: 93,94%) y de 2,17 para VAI (especificidad: 91,38%; sensibilidad: 87,88). Dichos marcadores correlacionaron con marcadores de IR (HOMA-IR, QUICKI e índice glucosa/insulina) y presentaron una correlación positiva con TG, CC y negativa con HDL. El análisis entre fenotipos no reveló diferencias en la presencia de SM, IR o factores de RCV. Conclusión: LAP y VAI serían buenos predictores de IR y RCV asociado en pacientes jóvenes con SOP. El análisis de los parámetros entre fenotipos HA y NHA indica que ambos presentan similar riesgo metabólico y de desarrollar enfermedad cardiovascular.
Introduction: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age. It is associated with insulin resistance (IR) and high cardiovascular risk (CVR). According to the Rotterdam consensus, four PCOS phenotypes could be established: three with clinical and/or biochemical hyperandrogenism (HA), and one non-hyperandrogenic (NHA). It is necessary to identify which of these patients are at risk of metabolic disturbances and CVR. Two indexes: lipid accumulation product (LAP) and visceral adiposity index (VAI) have been suggested as reliable markers of IR and CVR in PCOS. Objective: The present study aims to assess the reliability of LAP and VAI as IR markers in a young local population of PCOS patients. Their association with CVR parameters is also evaluated. Methodology: LAP and VAI were calculated in 130 PCOS patients. The PCOS patients were divided in two groups as HA and NHA, taking into account the signs of hyperandrogenism (clinical or biochemical). An evaluation was also made of the metabolic and anthropometric characteristics of the population and their association with CVR and IR. Results: Both LAP and VAI showed to be effective markers to asses CVR and IR in these PCOS women (cutoff values: LAP: 14.02 (sensitivity: 93.94% specificity: 93.22%) VAI: 2.17 (sensitivity: 87.88% specificity: 91.38%). There was a positive correlation of both markers with abdominal circumference and triglycerides (TG), and negative with HDL-cholesterol. The risk of IR and metabolic disturbances was similar in both phenotypes (NHA versus HA). Conclusion: Our data show that both LAP and VAI are representative markers for assessing IR and associated CVR in PCOS patients. These results also suggest that the NHA phenotype in the population studied shows the same risk of metabolic disturbances and cardiovascular disease when compared to HA phenotypes.
RESUMO
BACKGROUND: It is not elucidated if liver fat deposits associated to metabolic syndrome (MS) aggravate the atherogenic state. We evaluated, in MS patients, if the presence of non-alcoholic hepatic steatosis (HS) determines differences in inflammatory markers and VLDL characteristics. METHODS: Seventy-five patients with MS were divided into 2 groups depending on the presence or absence of HS, assessed by ultrasound. Lipid profile, free fatty acids (FFA), VLDL composition, adiponectin, tumor necrosis factor-alpha (TNF-α), high sensitivity C-reactive protein (hs-CRP), and soluble adhesion molecules (sVCAM-1 and sICAM-1) were measured. RESULTS: HS patients presented increased triglycerides levels, HOMA-IR and FFA. Patients with HS showed a reduction in adiponectin (p = 0.04) and increase in hs-CRP (p = 0.02), independently of insulin-resistance (IR). FFA correlated positively with TNF-α (p = 0.04) and inversely with adiponectin (p = 0.01). hs-CRP correlated with all inflammatory markers, independently of IR: TNF-α (r = 0.34, p = 0.02), sVCAM-1 (r = 0.29 p = 0.03), sICAM-1 (r = 0.56, p = 0.01), adiponectin (r = -0.34, p = 0.04). HS patients presented higher VLDL mass and number of particles. Adiponectin correlated with VLDL cholesterol content (r = -0.47, p = 0.04), independently of IR. VLDL, once secreted, would suffer from changes, becoming more atherogenic. CONCLUSIONS: Simple HS would play an important role increasing cardiovascular risk, independently of IR. hs-CRP may represent a useful biomarker of this condition.
Assuntos
Aterosclerose/sangue , Aterosclerose/complicações , Síndrome Metabólica/sangue , Síndrome Metabólica/complicações , Adiponectina/sangue , Adulto , Biomarcadores/sangue , Fígado Gorduroso/sangue , Fígado Gorduroso/complicações , Feminino , Humanos , Inflamação/sangue , Lipoproteínas VLDL/sangue , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não AlcoólicaRESUMO
BACKGROUND: Hepatic steatosis (HS) is closely associated to metabolic syndrome (MS). Both, VLDL-triglyceride oversecretion and intrahepatic deposits, can take place. We evaluated VLDL characteristics, CETP, hepatic lipase (HL), IDL and small dense LDL (sdLDL), in patients with HS associated to MS. METHODS: We studied 3 groups matched by age and sex: 25 MS patients with HS (diagnosed by ultrasonography), 25 MS patients without HS and 25 healthy controls. Main measurements were: lipid profile, free fatty acids, VLDL composition, VLDL size by HPLC, CETP and HL activities, IDL-cholesterol and sdLDL-cholesterol. RESULTS: Patients with HS presented higher triglyceride levels, HOMA-IR and free fatty acids, VLDL mass and VLDL-apoB (p<0.05). No differences in VLDL composition were observed. MS groups presented higher proportion of large VLDL than controls (p<0.05). HS group showed higher CETP than controls (p=0.01) and almost higher than MS without HS (p=0.06). CETP correlated with VLDL-cholesterol content, r=0.48, p<0.005. The increase in sdLDL-cholesterol correlated with CETP (r=0.47) and HL (r=0.56), independent of insulin resistance (p<0.003). CONCLUSION: Despite intrahepatic fat, patients with HS secreted higher number of VLDL particles. CETP would have a remodeling action on VLDL in circulation, enriching it in cholesterol and also favoring, together with HL, the formation of sdLDL.
Assuntos
Fígado Gorduroso/sangue , Lipoproteínas LDL/sangue , Lipoproteínas VLDL/sangue , Síndrome Metabólica/sangue , Adulto , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Most women with hypothyroidism require an increase in their dose of levothyroxine (LT4) after conception. To minimize fetal and maternal complications of maternal hypothyroidism, it is thought that women should be rapidly restored to the euthyroid state. The objectives of this study was to determine the percentage of hypothyroid women who would need to increase their dose of LT4 dose even if they had a preconception (pre-C) serum thyrotropin (TSH) of <2.5 mIU/L as recommended by the Endocrine Society's guidelines and to ascertain whether there was a relationship between the pre-C TSH value and the need to increase the LT4 dose during pregnancy. METHODS: Fifty-three pregnant women with hypothyroidism on LT4 treatment in whom the pre-C serum TSH was <2.5 mIU/L, but which was within the normal range, within the 6 months before pregnancy were retrospectively studied. An additional selection criterion was that their LT4 dose at the time of their first prenatal visit was the same as that received pre-C. RESULTS: Seventeen patients had to increase their LT4 dose during pregnancy, because their serum TSH was increased at the time of the first prenatal visit (Group 1); and 36 patients did not have to increase their dose of LT4 during pregnancy (Group 2). The pre-C TSH was significantly higher in Group 1 (1.55 ± 0.62 mIU/L) than in Group 2 (0.98 ± 0.67 mIU/L). When pre-C TSH range was 1.2-2.4 mIU/L, 50% of the patients required an increase in the LT4 dose during pregnancy. In contrast, when the pre-C TSH was <1.2 mIU/L, only 17.2% (p< 0.02) had to increase the LT4 dose during pregnancy. CONCLUSIONS: We suggest that in women with hypothyroidism who are planning to become pregnant, serum TSH levels should be in the normal range but should not be greater than about 1.2 mIU/mL.
Assuntos
Hipotireoidismo/tratamento farmacológico , Complicações na Gravidez/sangue , Complicações na Gravidez/tratamento farmacológico , Tireotropina/sangue , Tiroxina/uso terapêutico , Adulto , Feminino , Humanos , Hipotireoidismo/sangue , Gravidez , Estudos Retrospectivos , Tiroxina/administração & dosagemRESUMO
As we previously reported, testes of men suffering from hypospermatogenesis and germ cell arrest or Sertoli cell-only syndrome show a major increase in the number of macrophages expressing interleukin-1ß (IL-1ß) and abundant expression of cyclooxygenase-2 (COX-2), the inducible isoform of the key enzyme in the biosynthesis of prostaglandins (PGs), in Leydig cells. In the present study we report [1] a positive correlation between IL-1ß levels and COX-2 expression in testes of infertile patients, [2] the induction of COX-2 by IL-1ß in mouse Leydig cells (TM3) and human macrophages (THP-1), and therefore [3] evidence for an IL-1ß-dependent induction of testicular inflammatory states.
Assuntos
Ciclo-Oxigenase 2/metabolismo , Infertilidade Masculina/metabolismo , Interleucina-1beta/metabolismo , Prostaglandinas/metabolismo , Testículo/metabolismo , Adulto , Animais , Biópsia , Células Cultivadas , Humanos , Infertilidade Masculina/patologia , Interleucina-1beta/farmacologia , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Células Intersticiais do Testículo/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Síndrome de Células de Sertoli/metabolismo , Síndrome de Células de Sertoli/patologia , Testículo/patologiaRESUMO
OBJECTIVE: To determine the prevalence of different subclinical hypothyroidism (SH) grades and thyroid autoimmunity (TAI) in infertile women. DESIGN: Retrospective study. Setting. Endocrinology division of a public hospital in Argentina. PATIENTS: Group I comprised 244 women consulting on infertility (>1 year without pregnancy); Group C (controls) comprised 155 healthy women with confirmed fertility. INTERVENTION: Thyroid-stimulating hormone and thyroid peroxidase antibodies were measured in all patients, and a thyrotropin-releasing hormone (TRH) stimulation test was performed in 71 patients to diagnose SH grade 1. The pregnancy rate in hypothyroid women on levothyroxine treatment was also evaluated. RESULTS: SH was diagnosed in 13.9% of the patients in Group I and in 3.9% of Group C (p < 0.002). The TRH stimulation test was useful to detect SH grade 1 in 12.7% of the infertile patients. Patients with precocious ovarian failure, tubal disturbances and ovulatory dysfunction presented higher SH rates (40.0, 18.2 and 15.4%, respectively) than control patients (p < 0.0001, p < 0.002 and p < 0.003). No significant difference in TAI prevalence was shown in Group I relative to Group C. Pregnancy rate of 44.1% was achieved under levothyroxine treatment. CONCLUSIONS: We observed a higher prevalence of SH, but not of TAI, in patients with infertility. Our results support thyroid screening in women with reproductive failure.