RESUMO
The aim of the study is to determine the impact of different anthropometric measurements of fat distribution on baseline sex-steroid concentrations and corticosteroidogenic enzyme activity in women with polycystic ovary syndrome compared to those with regular menstrual cycles. The current cross-sectional study included 106 normal cycling controls and 268 polycystic ovary syndrome patients. Patients with polycystic ovary syndrome, diagnosed by Rotterdam criteria, were divided in normoandrogenemic (n=91) and hyperandrogenemic (n=177). Anthropometric, biochemical, and hormone parameters were assessed and correlated with corticosteroidogenic enzyme activities in all three groups. Corticosteroidogenic enzyme activities were calculated using product-to-precursor ratios. Regarding sex-steroids individually, anthropometric parameters correlated with the concentrations of several androgens in polycystic ovary syndrome patients, most of them in patients with biochemical hyperandrogenism. The androgen precursors androstenedione, 17-hydroxyprogesterone, and dehydroepiandrosterone were less correlated with anthropometric parameters. The 17,20 lyase activity, in both Δ4 and Δ5 pathways, correlated with several anthropometric measurements in normo- and hyperandrogenemic polycystic ovary syndrome patients. The 17,20 lyase enzyme activity (Δ4 pathway) also correlated with conicity index, visceral adiposity index, and lipid accumulation product in the control group. 17-Hydroxylase activity positively correlated with waist-height ratio in both polycystic ovary syndrome groups. In contrast, 17-hydroxilase negatively correlated with the conicity index. Anthropometric markers of adiposity are associated with androgen levels and their precursors in blood. Body fat distribution correlates with the activities of some steroidogenic enzyme in both normo-and hyperandrogenemic polycystic ovary syndrome phenotypes. The molecular mechanisms involved in these associations are largely unclear and more investigations are required.
Assuntos
Androgênios/sangue , Biomarcadores/análise , Distribuição da Gordura Corporal , Hiperandrogenismo/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Esteroide 17-alfa-Hidroxilase/metabolismo , Adulto , Idoso , Antropometria , Estudos de Casos e Controles , Estudos Transversais , Feminino , Seguimentos , Humanos , Hiperandrogenismo/metabolismo , Pessoa de Meia-Idade , Síndrome do Ovário Policístico/metabolismo , PrognósticoRESUMO
A síndrome dos ovários policísticos (SOP) é um distúrbio endócrino-metabólico muito frequente no período reprodutivo. Quando associado ao distúrbio metabólico, as mulheres com SOP podem ter ainda risco acrescido para doença cardiovascular. O objetivo deste manuscrito é descrever as repercussões metabólicas, incluindo quais as principais, como investigar e as consequências desse distúrbio sobre a saúde da mulher. É uma revisão narrativa mostrando a implicação da resistência insulínica, das dislipidemias e da síndrome metabólica sobre o sistema reprodutor e sobre o risco cardiovascular da mulher com SOP, bem como do uso de sensibilizadores de insulina no seu tratamento. Conclui-se que a correção dos distúrbios metabólicos na SOP é benéfica tanto para o sistema reprodutor quanto para o cardiovascular. A primeira linha de tratamento é a mudança de estilo de vida e a perda de peso. Na resposta inadequada, o tratamento medicamentoso está recomendado. Nas mulheres com obesidade mórbida que não tiveram bons resultados com o tratamento clínico, a cirurgia bariátrica é uma opção.(AU)
Assuntos
Humanos , Feminino , Síndrome do Ovário Policístico , Hiperandrogenismo/diagnóstico , Hiperandrogenismo/fisiopatologia , Hiperandrogenismo/tratamento farmacológico , Obesidade Mórbida , Fatores de Risco , Saúde da Mulher , Contraceptivos Hormonais/uso terapêutico , Fatores de Risco de Doenças Cardíacas , Hirsutismo , Antagonistas de Androgênios/uso terapêutico , InsulinaRESUMO
Polycystic ovary syndrome is the most common endocrine disease in reproductive age, characterized by menstrual alterations, clinical or biochemical hyperandrogenism, and ultrasound-identified ovarian cysts. The neuroendocrine and metabolic alterations that accompany this condition involve the desensitization of the hypothalamus-pituitary-ovary axis, steroidogenesis and hyperandrogenism; recently, the role of insulin resistance has been explored. Hyperandrogenism has been established to be the main cause of polycystic ovary syndrome, due to enzymatic alterations in the steroidogenic pathway that cause luteinizing hormone over-stimulation because of quick pulses generated by gonadotropin-releasing hormones. Various growth factors of and cytokines inhibit the conversion of androgens into estrogens; activin and prostaglandins are also involved, even high levels of insulin participate in the characteristic deregulation of this syndrome.
El síndrome de ovarios poliquísticos es la enfermedad endocrina más frecuente en la edad reproductiva; se caracteriza por alteraciones menstruales, hiperandrogenismo clínico o bioquímico e identificación ultrasonográfica de quistes ováricos. Las alteraciones neuroendocrinas y metabólicas que lo acompañan implican desensibilización del eje hipotálamo-hipófisis-ovario, esteroidogénesis e hiperandrogenismo. Recientemente se ha explorado el papel de la resistencia a la insulina. Se ha establecido que la principal causa del síndrome de ovarios poliquísticos es el hiperandrogenismo, debido a alteraciones enzimáticas en la vía esteroidogénica, por lo que existe sobreestimulación por parte de la hormona luteinizante a causa de los pulsos rápidos generados por la hormona liberadora de gonadotropinas. Diversos factores de crecimiento y citocinas inhiben la conversión de andrógenos a estrógenos. En la desregulación característica de este síndrome también están involucradas la activina y las prostaglandinas e, incluso, altos niveles de insulina.
Assuntos
Hiperandrogenismo/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Resistência à Insulina , Hormônio Luteinizante/metabolismo , Sistema Hipófise-Suprarrenal/metabolismoRESUMO
OBJECTIVE: This study aims to evaluate the sleep of subjects with polycystic ovary syndrome (PCOS), with and without hyperandrogenism, in comparison with a healthy control group and examine the effects of hyperandrogenism and obesity on sleep parameters. METHODS: A total of 44 volunteers were recruited to participate in the study. Clinical, biochemical and polysomnographic parameters were used to diagnose PCOS and hyperandrogenism. The evaluation of sleep quality was made using validated questionnaires and polysomnography test. The frequency of obstructive sleep apnea was also compared between the groups. RESULTS: The study revealed that women with PCOS presented poorer subjective sleep quality, increased incidence of snoring and a higher risk of obstructive sleep apnea, based on the Berlin questionnaire. Also, after adjusting for body mass index, PCOS subjects had rapid eye movement (REM) time lower than those in the control group. PCOS women versus those without hyperandrogenism did not differ on any sleep measurement. Women with obstructive sleep apnea were only diagnosed in the PCOS group. CONCLUSIONS: Our results indicate that PCOS impairs subjective sleep quality, as well as objective sleep quality, due to a reduction in REM sleep stage time in women diagnosed with the syndrome. Obesity affected sleep-related parameters but hyperandrogenism had no effect. Only the PCOS group had obstructive sleep apnea diagnosis.
Assuntos
Hiperandrogenismo/complicações , Obesidade/complicações , Síndrome do Ovário Policístico/complicações , Apneia Obstrutiva do Sono/etiologia , Transtornos do Sono-Vigília/etiologia , Adolescente , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Hiperandrogenismo/fisiopatologia , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Polissonografia , Transtorno do Comportamento do Sono REM/fisiopatologia , Valores de Referência , Medição de Risco , Fatores de Risco , Apneia Obstrutiva do Sono/fisiopatologia , Transtornos do Sono-Vigília/fisiopatologia , Estatísticas não Paramétricas , Inquéritos e Questionários , Testosterona/sangue , Adulto JovemRESUMO
Resumen El síndrome de ovarios poliquísticos es la enfermedad endocrina más frecuente en la edad reproductiva; se caracteriza por alteraciones menstruales, hiperandrogenismo clínico o bioquímico e identificación ultrasonográfica de quistes ováricos. Las alteraciones neuroendocrinas y metabólicas que lo acompañan implican desensibilización del eje hipotálamo-hipófisis-ovario, esteroidogénesis e hiperandrogenismo. Recientemente se ha explorado el papel de la resistencia a la insulina. Se ha establecido que la principal causa del síndrome de ovarios poliquísticos es el hiperandrogenismo, debido a alteraciones enzimáticas en la vía esteroidogénica, por lo que existe sobreestimulación por parte de la hormona luteinizante a causa de los pulsos rápidos generados por la hormona liberadora de gonadotropinas. Diversos factores de crecimiento y citocinas inhiben la conversión de andrógenos a estrógenos. En la desregulación característica de este síndrome también están involucradas la activina y las prostaglandinas e, incluso, altos niveles de insulina.
Abstract Polycystic ovary syndrome is the most common endocrine disease in reproductive age, characterized by menstrual alterations, clinical or biochemical hyperandrogenism, and ultrasound-identified ovarian cysts. The neuroendocrine and metabolic alterations that accompany this condition involve the desensitization of the hypothalamus-pituitary-ovary axis, steroidogenesis and hyperandrogenism; recently, the role of insulin resistance has been explored. Hyperandrogenism has been established to be the main cause of polycystic ovary syndrome, due to enzymatic alterations in the steroidogenic pathway that cause luteinizing hormone over-stimulation because of quick pulses generated by gonadotropin-releasing hormones. Various growth factors of and cytokines inhibit the conversion of androgens into estrogens; activin and prostaglandins are also involved, even high levels of insulin participate in the characteristic deregulation of this syndrome.
Assuntos
Humanos , Feminino , Síndrome do Ovário Policístico/fisiopatologia , Hiperandrogenismo/fisiopatologia , Sistema Hipófise-Suprarrenal/metabolismo , Resistência à Insulina , Hormônio Luteinizante/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismoRESUMO
Kogure, GS, Silva, RC, Miranda-Furtado, CL, Ribeiro, VB, Pedroso, DCC, Melo, AS, Ferriani, RA, and Reis, RMd. Hyperandrogenism enhances muscle strength after progressive resistance training, independent of body composition, in women with polycystic ovary syndrome. J Strength Cond Res 32(9): 2651-2660, 2018-The effects of resistance exercise on muscle strength, body composition, and increase in cross-sectional area of skeletal muscle (hypertrophy) were evaluated in women with polycystic ovary syndrome (PCOS). This case-control study included 45 PCOS and 52 non-PCOS women, with age between 18-37 years and body mass index of 18-39.9 kg·m. Subjects performed a program of progressive resistance training (PRT), 3 times per week for 4 months. Biochemical characteristics were measured before and after PRT. Muscle strength evaluated by 1 maximum repetition test and body composition and hypertrophy indicator, evaluated by anthropometry, were measured at baseline, at 8 weeks, and at 16 weeks after PRT. Progressive resistance training produced an increase in maximum strength (bench press, p = 0.04; leg extension, p = 0.04) in the PCOS group; however, no changes were observed in body composition between groups. Concentration of testosterone decreased in both PCOS and non-PCOS groups (p < 0.01, both) after PRT, as well as glycemia (PCOS, p = 0.01; non-PCOS, p = 0.02) and body fat percentage (p < 0.01, both). An increase in hypertrophy indicators, lean body mass (LBM), and maximum strength on all exercises was observed in both PCOS and non-PCOS groups (p < 0.01). This training protocol promoted increases in muscle strength in PCOS women, and improved hyperandrogenism and body composition by decreasing body fat and increasing LBM and muscle strength in both PCOS and non-PCOS groups. Therefore, it is suggested that resistance exercise programs could promote health and fitness in women of reproductive age, especially functional capacity of strength those with PCOS.
Assuntos
Composição Corporal , Hiperandrogenismo/reabilitação , Força Muscular/fisiologia , Síndrome do Ovário Policístico/reabilitação , Treinamento Resistido , Adolescente , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Seguimentos , Humanos , Hiperandrogenismo/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: High levels of androgens increase muscle mass. Due to the characteristics of hyperandrogenism in polycystic ovary syndrome (PCOS), it is plausible that women with PCOS may have increased pelvic floor muscle (PFM) thickness and neuromuscular activity levels compared with controls. The aim of this study was to assess PFM thickness and neuromuscular activity among hyperandrogenic women with PCOS and controls. METHODS: This was an observational, cross-sectional, case-control study evaluating PFM by ultrasound (US) and surface electromyography (sEMG) in nonobese women with and without PCOS. Seventy-two women were divided into two groups: PCOS (n = 33) and controls (n = 39). PFM thickness during contraction was assessed by US (Vingmed CFM 800). Pelvic floor muscle activity was assessed by sEMG (MyoTrac Infinit) during contractions at different time lengths: quick, and 8 and 60 s. Descriptive analysis, analysis of variance (ANOVA), and Student's t test were used for statistical analyses. RESULTS: There were no significant differences in PFM sEMG activity between PCOS and controls in any of the contractions: quick contraction (73.23 mV/ 71.56 mV; p = 0.62), 8 s (55.77 mV/ 54.17 mV; p = 0.74), and 60 s (49.26 mV/ 47.32 mV; p = 0.68), respectively. There was no difference in PFM thickness during contractions evaluated by US between PCOS and controls (12.78 mm/ 13.43 mm; p = .48). CONCLUSIONS: This study did not find statistically significant differences in pelvic floor muscle thickness or in muscle activity between PCOS women and controls.
Assuntos
Hiperandrogenismo/diagnóstico por imagem , Hiperandrogenismo/fisiopatologia , Diafragma da Pelve/diagnóstico por imagem , Diafragma da Pelve/fisiopatologia , Síndrome do Ovário Policístico/diagnóstico por imagem , Síndrome do Ovário Policístico/fisiopatologia , Adolescente , Adulto , Estudos de Casos e Controles , Estudos Transversais , Eletromiografia , Feminino , Humanos , Contração Muscular , Ultrassonografia , Adulto JovemRESUMO
BACKGROUND: A high prevalence of hyperandrogenism has been reported in women with type 1 diabetes (T1D). Metformin has been used as a therapeutic agent in patients with polycystic ovarian syndrome and in T1D patients without hyperandrogenism. This study sought to determine the effect of metformin on hyperandrogenism and ovarian function in adolescents with T1D. METHODS: We recruited 24 girls with T1D. The participants had hyperandrogenism and displayed suboptimal metabolic control. The patients were enrolled in a randomized, double-blind, placebo-controlled trial. One group received metformin (850 mg bid) and the other group received a placebo. Treatment was administered for 9 months. Ovulation, steroids and gonadotropin levels were evaluated. RESULTS: Metformin treatment was associated with decreases in testosterone, free androgen index, androstenedione, 17-OH progesterone and estradiol levels. The girls who were treated with placebo showed stable steroid, gonadotropin and sex hormone-binding globulin levels during the analysis. No differences were observed in the Ferriman-Gallwey scores, ovulation rates, HbA1c levels or daily insulin doses of the girls treated with metformin compared with the placebo group. CONCLUSION: Treating hyperandrogenic T1D adolescents with metformin significantly decreased the serum androgens compared to the placebo, but metformin therapy did not significantly affect clinical parameters, such as hirsutism, ovulation and metabolic control.
Assuntos
Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hiperandrogenismo/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , 17-alfa-Hidroxiprogesterona/sangue , Adolescente , Adulto , Androsterona/sangue , Complicações do Diabetes/sangue , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Método Duplo-Cego , Feminino , Gonadotropinas/sangue , Humanos , Hiperandrogenismo/sangue , Hiperandrogenismo/etiologia , Hiperandrogenismo/fisiopatologia , Ovulação/sangue , Ovulação/efeitos dos fármacosRESUMO
Chronic hyperandrogenism alters the peroxisome proliferator-activated receptor γ (PPARγ) pathway in the uterine tissue of prepubertal mice. The gene and protein expression of PPARγ is not modified, but the gene and protein expression of 12-lipoxygenase (12-LOX), an enzyme that synthesizes PPARγ ligands, is decreased. The antihyperglycemic drug metformin can prevent this adverse effect.
Assuntos
Hiperandrogenismo/metabolismo , Hipoglicemiantes/farmacologia , Metformina/farmacologia , PPAR gama/agonistas , Desenvolvimento Sexual , Útero/efeitos dos fármacos , Animais , Araquidonato 12-Lipoxigenase/metabolismo , Araquidonato 15-Lipoxigenase/metabolismo , Desidroepiandrosterona , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Hiperandrogenismo/induzido quimicamente , Hiperandrogenismo/genética , Hiperandrogenismo/fisiopatologia , Ligantes , Camundongos , Camundongos Endogâmicos BALB C , PPAR gama/genética , PPAR gama/metabolismo , RNA Mensageiro/metabolismo , Útero/metabolismo , Útero/fisiopatologiaRESUMO
Acute hyperandrogenism decreases serum P levels and induces early apoptosis of antral follicles by a mechanism mediated by the peroxisome proliferator-activated receptor gamma system and independent of the steroidogenic acute regulator protein.
Assuntos
Gonadotropina Coriônica/farmacologia , Hiperandrogenismo/fisiopatologia , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/fisiologia , PPAR gama/metabolismo , Doença Aguda , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Desidroepiandrosterona/farmacologia , Feminino , Expressão Gênica/efeitos dos fármacos , Hiperandrogenismo/metabolismo , Hiperandrogenismo/patologia , Folículo Ovariano/patologia , PPAR gama/genética , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Ratos , Ratos Sprague-Dawley , Substâncias para o Controle da Reprodução/farmacologiaRESUMO
This study aimed to investigate how hyperandrogenism affects early folliculogenesis. Hyperandrogenism was induced in prepuberal female BALB/c mice by daily s.c. injection of dehydroepiandrosterone (60 mg/kg body weight in 0.1 ml sesame oil) for 10 consecutive days. Although hyperandrogenism increased the growth rate of primary follicles, it also increased ovarian oxidative stress (evaluated by the increase in lipid peroxidation, the decrease in superoxide dismutase activity and the fact that glutathione content was not modified). By using the annexin V/cytometry assay it was found that the excess of androgens decreased viable ovarian cells and increased early apoptotic ones. The increased lipid peroxidation induced enhanced ovarian prostaglandin E production. In addition, hyperandrogenism increased the number of T lymphocytes that infiltrate ovarian tissue and modified their phenotype (decreased CD4+ or helper and increased the suppressor/cytotoxic CD8+). The excess of androgens decreased the ovarian expression of the long isoform of leptin receptor (Ob-Rb, the only isoform expressed in the ovarian tissue) when compared with controls. All these alterations increased serum concentrations of oestradiol, a pro-apoptotic agent. It is concluded that the excess of androgens impairs early follicular development by modulating some endocrine and immune parameters that are either directly or indirectly related to follicular atresia.
Assuntos
Hiperandrogenismo/fisiopatologia , Ovário/fisiopatologia , Animais , Western Blotting , Estradiol/sangue , Feminino , Citometria de Fluxo , Glutationa/metabolismo , Imunofenotipagem , Peroxidação de Lipídeos , Masculino , Camundongos , Ovário/imunologia , Progesterona/sangue , Radioimunoensaio , Superóxido Dismutase/metabolismoRESUMO
During the last decade a battery of animal models used for the study of polycystic ovary syndrome (PCOS) have allowed a focus on different aspects of the pathology. Since dehydroepiandrosterone (DHEA) was found to be one of the most abundant circulating androgens in women with PCOS, a rodent model showing the salient features found in women with PCOS was developed by the injection of DHEA. Although insulin-sensitizing agents, such as biguanides, are clinically used in the treatment of diabetes and PCOS, the complete understanding of their mechanisms of action remains unknown. The present review discusses the molecular mechanisms involved in the development of PCOS by using the DHEA-PCOS murine model and analyzes the role of the biguanide metformin as treatment.
Assuntos
Desidroepiandrosterona , Modelos Animais de Doenças , Síndrome do Ovário Policístico/fisiopatologia , Androgênios/administração & dosagem , Androgênios/metabolismo , Animais , Desidroepiandrosterona/administração & dosagem , Desidroepiandrosterona/metabolismo , Perda do Embrião/etiologia , Feminino , Humanos , Hiperandrogenismo/fisiopatologia , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Metformina/farmacologia , Metformina/uso terapêutico , Camundongos , Ovulação/efeitos dos fármacos , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/tratamento farmacológico , Gravidez , Útero/efeitos dos fármacosRESUMO
We evaluated the effect of hyperandrogenism in ovaries with functional and regressing corpora lutea (CL) and the action of metformin in preventing these possible alterations using a mouse model. To obtain a CL functional for 9+/-1 days, immature female mice of the BALB/c strain were injected i.p. with 10 IU/mouse of pregnant mare's serum gonadotropin (PMSG). DHEA (60 mg/kg body weight s.c., 24 and 48 h prior to kill) decreased both serum progesterone (P) and estradiol (E(2)) levels and increased the activity of superoxide dismutase (SOD) from ovaries with functional CL (on day 5 after PMSG). It increased P and E(2) and the activities of SOD and catalase (CAT) and decreased lipoperoxidation of ovaries with regressing CL (on day 9 after PMSG). Treatment with DHEA did not affect the production of prostaglandin F(2alpha) (PGF(2alpha)) or PGE by ovaries with functional CL, whereas DHEA decreased PGF(2alpha) and increased PGE production by ovaries with regressing CL. Metformin (50 mg/kg body weight, orally) given together with DHEA restored E(2) levels from mice with ovaries with functional CL and serum P, PGF(2alpha) and PGE levels, and oxidative balance in mice with ovaries with regressing CL. Metformin alone was able to modulate serum P and E(2) levels, lipoperoxidation, SOD and CAT, and the 5,5-dimethyl-1-pyrroline N-oxide/(*)OH signal. These findings suggest that hyperandrogenism is able to induce or to rescue CL from luteolysis and metformin treatment is able to prevent these effects.
Assuntos
Corpo Lúteo/efeitos dos fármacos , Desidroepiandrosterona/farmacologia , Metformina/farmacologia , Animais , Corpo Lúteo/fisiologia , Dinoprosta/análise , Dinoprosta/metabolismo , Feminino , Hiperandrogenismo/patologia , Hiperandrogenismo/fisiopatologia , Hipoglicemiantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/patologia , Ovário/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Gravidez , Prostaglandinas E/análise , Prostaglandinas E/metabolismoRESUMO
The aim of the present work was to study some of the adverse effects produced by hyperandrogenism on the uterine function. Daily injection of dehydroepiandrosterone (DHEA: 6 mg/ 100 g body weight, sc) for 20 consecutive days induced polycystic ovaries in BALB/c mice. In this model, we found that DHEA produced alterations on uterine histology closely related to the development of tumour structures. In addition, hyperandrogenism induced a pro-inflammatory and a pro-oxidant condition represented by increased levels of prostaglandin F2 alpha production and uterine nitric oxide synthase (NOS) activity and by a decrease in both superoxide dismutase (SOD) and catalase (CAT) activities together with a decrease in the levels of the antioxidant metabolite glutathione (GSH). DHEA also induced an increase in CD4+ together with a decrease in the CD8+ T lymphocytes that infiltrate the uterine tissue. We conclude that this intricate network of regulators could be responsible for the low rate of implantation observed in women with polycystic ovary syndrome.
Assuntos
Adjuvantes Imunológicos/toxicidade , Desidroepiandrosterona/toxicidade , Hiperandrogenismo/fisiopatologia , Síndrome do Ovário Policístico/induzido quimicamente , Útero/fisiopatologia , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Catalase/antagonistas & inibidores , Catalase/metabolismo , Ciclo-Oxigenase 1/efeitos dos fármacos , Ciclo-Oxigenase 2/efeitos dos fármacos , Dinoprosta/biossíntese , Feminino , Glutationa/antagonistas & inibidores , Glutationa/metabolismo , Hiperandrogenismo/patologia , Proteínas de Membrana/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico Sintase/efeitos dos fármacos , Óxido Nítrico Sintase/metabolismo , Ovário/patologia , Estresse Oxidativo/efeitos dos fármacos , Síndrome do Ovário Policístico/imunologia , Síndrome do Ovário Policístico/patologia , Prostaglandinas E/biossíntese , Superóxido Dismutase/antagonistas & inibidores , Superóxido Dismutase/metabolismo , Útero/imunologia , Útero/patologiaRESUMO
Este trabalho trata-se de uma revisão da síndrome dos ovários policísticos (SOP) em relação aos seus aspectos etiopatogênicos, clínicos, diagnósticos e terapêuticos. Tecem-se considerações sobre a importância não só de efetivo tratamento médico como também de abordagem e apoio psicológico, no sentido de melhorar ainda mais o bem-estar e a qualidade de vida dessas mulheres
The authors have reviewed the main aspects of the polycystic ovary syndrome (PCOS) with respect to its etiopathogenic, clinical, diagnostic and therapeutic features. They also make considerations on the importance of an effective clinical treatment as well as on the approaches and psychological support, aiming to improve women's well-being and quality of life
Assuntos
Feminino , Hiperandrogenismo/diagnóstico , Hiperandrogenismo/fisiopatologia , Hiperandrogenismo/terapia , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/etiologia , Síndrome do Ovário Policístico/fisiopatologia , Síndrome do Ovário Policístico/terapia , Anovulação/etiologia , Diagnóstico Clínico , Exame Físico , Qualidade de VidaRESUMO
AIM: To verify possible associations among glucocorticoid doses, use of dexamethasone, and bone mineral density (BMD), measured by dual X-ray absorptiometry (DXA) and quantitative computed tomography (QCT), in female children with congenital adrenal hyperplasia due to CYP21 deficiency (CAH-CYP21). Classical CAH-CYP21 in females allows the study of the effects of hyperandrogenism and chronic glucocorticoid exposure. DESIGN: Cross-sectional observational study. PATIENTS: Sixteen girls (4-19 years) with CAH-CYP21 and 32 age-matched control girls. MEASUREMENTS: BMD was the main outcome measure assessed by total body and lumbar spine L1-L4 DXA (DXAtot and DXAIs), lumbar spine L1-L4 bone mineral apparent density (BMAD) and spinal L1-L4 QCT of trabecular (QCTtrab) and cortical (QCTcort) bone. The glucocorticoid dose used by patients with CAH-CYP21 was expressed as hydrocortisone equivalents/m2. RESULTS: Mean BMD in both groups was similar by any method. In patients, BMD decreased with the increasing mean dose of glucocorticoid, seen in QCTcort (r = -0.55; p = 0.03) and QCTtrab (r = -0.52; p = 0.04). There was also a negative correlation between cumulative glucocorticoid dose and BMD in QCTcort (beta = -0.0016; p = 0.005) and QCTtrab (beta = -0.0009; p = 0.03). CONCLUSIONS: The dose of glucocorticoid used in the treatment of girls with CAH-CYP21 correlated negatively with BMD, and dexamethasone was not selectively harmful.
Assuntos
Hiperplasia Suprarrenal Congênita/genética , Hiperplasia Suprarrenal Congênita/fisiopatologia , Densidade Óssea/fisiologia , Esteroide 21-Hidroxilase/genética , Absorciometria de Fóton , Adolescente , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Índice de Massa Corporal , Densidade Óssea/efeitos dos fármacos , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Humanos , Hiperandrogenismo/fisiopatologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/fisiopatologia , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
The aim of this study was to investigate the mechanisms by which N,N'-dimethylbiguanide metformin (50 mg/100 g body weight (BW) in 0.05 ml of water, given orally with a cannula) prevents the ovarian disorders provoked by the hyperandrogenization with dehydroepiandrosterone (DHEA) in prepuberal BALB/c mice. The injection of DHEA (6 mg/100 g BW in 0.1 ml of oil) for 20 consecutive days re-creates a mouse model that resembles some aspects of the human polycystic ovary syndrome (PCOS). The treatment with DHEA increased ovarian oxidative stress because it enhanced lipid peroxidation (LPO) and diminished both catalase (CAT) activity and glutathione (GSH) content. Therefore, the treatment with DHEA diminished both ovarian nitric oxide synthase (NOS) activity and prostaglandin E (PGE) production. When metformin was administered together with DHEA, the ovarian GSH content, NOS activity and PGE production did not differ when compared with controls. However, metformin was not able to prevent the effect of DHEA on ovarian LPO or CAT activity. Finally, DHEA increased the ovarian protein expressions of inducible NOS (iNOS), inducible cyclooxygenase (COX2) and the phosphorylated AMP-dependent kinase alpha (AMPK-alpha) (Thr172). Metformin administered together with DHEA was able to prevent the increase of ovarian iNOS and COX2 expressions and to enhance the activation of phosphorylated AMPK-alpha expression.
Assuntos
Hiperandrogenismo/fisiopatologia , Metformina/farmacologia , Ovário/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP , Adjuvantes Imunológicos/farmacologia , Administração Oral , Animais , Catalase/metabolismo , Ciclo-Oxigenase 2/metabolismo , Desidroepiandrosterona/farmacologia , Ativação Enzimática/efeitos dos fármacos , Feminino , Glutationa/metabolismo , Hiperandrogenismo/induzido quimicamente , Hiperandrogenismo/metabolismo , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Metformina/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Complexos Multienzimáticos/metabolismo , Óxido Nítrico Sintase/metabolismo , Ovário/metabolismo , Ovário/fisiopatologia , Fosforilação/efeitos dos fármacos , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/fisiopatologia , Prostaglandinas E/metabolismo , Proteínas Serina-Treonina Quinases/metabolismoRESUMO
In addition to neuroendocrine abnormalities, women with polycystic ovary syndrome have insulin resistance and beta-cell dysfunction associated with a high frequency of metabolic syndrome components, such as glucose intolerance, type 2 diabetes mellitus (DM-2), dyslipidemia and a higher risk for endothelial dysfunction, haemostatic abnormalities, hypertension and cardiovascular disease. Obesity, a common finding in this disorder, plays an important role in the development of metabolic and cardiovascular disorders. Early identification of patients and prompt initiation of insulin sensitizing therapy by pharmacological agents or changes in life style such diet and exercise might improve the metabolic and endocrine abnormalities and reduce the risk of DM-2 and cardiovascular disease in these patients.