RESUMEN
OBJECTIVE: Obesity is frequently present in women with the polycystic ovary syndrome (PCOS) and aggravates insulin resistance (IR) and hyperandrogenemia. We aimed to assess the effects of orlistat combined with lifestyle changes in overweight and obese women with PCOS and body mass index (BMI)-matched controls. DESIGN: Prospective study. PATIENTS: We studied 101 women with PCOS (age 26·1 ± 6·4 years, BMI 34·5 ± 5·9 kg/m(2) ) and 29 BMI-matched women with normal ovulating cycles. All women were instructed to follow a low-calorie diet to exercise and were treated with orlistat 120 mg tid for 6 months. MEASUREMENTS: Metabolic and endocrine characteristics of PCOS, blood pressure (BP) and lipid profile. RESULTS: A significant and comparable reduction in BMI was observed in women with PCOS and controls. Systolic and diastolic BP decreased only in women with PCOS. Serum low-density lipoprotein cholesterol levels decreased in both women with PCOS and controls; however, this reduction was greater in controls. In contrast, serum high-density lipoprotein cholesterol levels did not change in women with PCOS and decreased in controls. Serum triglyceride levels decreased significantly and to a comparable degree in the two groups. Similarly, markers of IR improved significantly and to a comparable degree in women with PCOS and controls. Serum testosterone levels and the free androgen index decreased significantly in women with PCOS and did not change in controls. CONCLUSIONS: Orlistat combined with lifestyle changes induces substantial weight loss in women with PCOS, resulting in improvements in IR, hyperandrogenemia and cardiovascular risk factors.
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Fármacos Antiobesidad/uso terapéutico , Lactonas/uso terapéutico , Estilo de Vida , Obesidad/terapia , Sobrepeso/terapia , Síndrome del Ovario Poliquístico/terapia , Programas de Reducción de Peso , Adulto , Índice de Masa Corporal , Restricción Calórica , Terapia Combinada , Ejercicio Físico , Femenino , Humanos , Obesidad/complicaciones , Orlistat , Sobrepeso/complicaciones , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/epidemiología , Pérdida de Peso/efectos de los fármacos , Adulto JovenRESUMEN
OBJECTIVE: The polycystic ovary syndrome (PCOS) and the metabolic syndrome (MetS) are common disorders that share many characteristics, particularly abdominal obesity and insulin resistance. Our objective was to compare the prevalence of MetS between a large cohort of patients with PCOS and body mass index -matched controls. DESIGN: Cross-sectional study. PATIENTS: We studied 1223 patients with PCOS and 277 healthy women. Diagnosis of PCOS was based on the revised Rotterdam criteria. Women with PCOS were divided into those who fulfilled both the Rotterdam criteria and the diagnostic criteria of the 1990 National Institutes of Health definition of PCOS (group 1, n = 905) and into those with the additional phenotypes introduced by the Rotterdam criteria (group 2, n = 318). Diagnosis of MetS was based on four different definitions. MEASUREMENTS: Anthropometric, metabolic, hormonal and ultrasonographic features of PCOS. RESULTS: The prevalence of metabolic syndrome (MetS) was higher in women with PCOS than in controls when the National Cholesterol Education Program Adult Treatment Panel III definition of MetS was applied (15·8% and 10·1%, respectively; P = 0·021) but not with the three more recent MetS definitions. The prevalence of MetS was higher in group 1 than in controls regardless of the applied MetS definition. In contrast, the prevalence of MetS was similar in group 2 and in controls regardless of the applied MetS definition. In logistic regression analysis, PCOS did not predict the presence of MetS. CONCLUSIONS: Polycystic ovary syndrome per se does not appear to increase the risk of MetS independent of abdominal obesity.
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Síndrome Metabólico/epidemiología , Síndrome del Ovario Poliquístico/epidemiología , Adulto , Pesos y Medidas Corporales , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Síndrome Metabólico/diagnóstico por imagen , Obesidad Abdominal/complicaciones , Obesidad Abdominal/diagnóstico por imagen , Obesidad Abdominal/epidemiología , Síndrome del Ovario Poliquístico/diagnóstico por imagen , Prevalencia , Pronóstico , Factores de Riesgo , Ultrasonografía , Adulto JovenRESUMEN
STUDY QUESTION: Do women with the polycystic ovary syndrome (PCOS) differ from those with the metabolic syndrome (MetS) in markers of insulin resistance (IR) and circulating androgens? SUMMARY ANSWER: Women with MetS have more pronounced IR than those with PCOS whereas only the latter have elevated circulating androgens. WHAT IS KNOWN ALREADY: PCOS and MetS share many similarities, including abdominal obesity and IR, and PCOS is regarded as the ovarian manifestation of MetS. However, there are limited data on the differences between markers of IR and circulating androgens between women with these two syndromes. STUDY DESIGN, SIZE, DURATION: A prospective study in 1223 Caucasian women with PCOS and 277 women without PCOS, matched for BMI, was performed between May 2004 and December 2011. The presence/absence of MetS in PCOS+ and PCOS- women was recorded and comparisons among the resulting four groups were performed. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was performed in a university department of obstetrics and gynecology. The following markers of IR were determined: serum glucose and insulin levels, glucose/insulin ratio, area under the oral glucose tolerance test, homeostasis model assessment of IR index and quantitative insulin sensitivity check index. MAIN RESULTS AND THE ROLE OF CHANCE: PCOS+MetS+ women (n = 361) were more insulin-resistant than PCOS+MetS- women (n = 862) (P < 0.001 for the comparisons in all markers of IR). Similarly, PCOS-MetS+ women (n = 66) were more insulin-resistant than PCOS-MetS- women (n = 211) (P < 0.001 for the comparisons in all markers of IR). In contrast, PCOS+MetS+ showed only borderline significant differences in some markers of IR compared with PCOS-MetS+ women (P < 0.05). Similarly, PCOS+MetS- women showed only borderline significant differences in some markers of IR compared with PCOS-MetS- women (P = 0.037). Moreover, PCOS-MetS+ women were more insulin-resistant than PCOS + MetS- women (P < 0.001 for the comparisons in all markers of IR). Regarding circulating androgens, PCOS+MetS+ women had higher levels of circulating androgens than PCOS-MetS+ women (P < 0.001 for the comparisons in all circulating androgens). Similarly, PCOS+MetS- women had higher levels of circulating androgens than PCOS-MetS- women (P < 0.001 for the comparisons in all circulating androgens). In contrast, circulating androgens did not differ between PCOS+MetS+ women and PCOS+MetS- women. Similarly, circulating androgens did not differ between PCOS-MetS+ women and PCOS-MetS- women. LIMITATIONS, REASONS FOR CAUTION: Only Caucasian women were included in the study. IR was not assessed with the euglycemic hyperinsulinemic clamp. WIDER IMPLICATIONS OF THE FINDINGS: Even though MetS and PCOS have many similarities, they are distinct disorders. PCOS does not appear to simply represent the ovarian manifestation of MetS. Further studies are required to assess the contribution of hyperandrogenism to the pathogenesis of IR in PCOS. STUDY FUNDING/COMPETING INTEREST(S): No external funding was either sought or obtained for this study.
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Andrógenos/sangre , Resistencia a la Insulina , Síndrome Metabólico/metabolismo , Síndrome del Ovario Poliquístico/metabolismo , Adolescente , Adulto , Biomarcadores/sangre , Índice de Masa Corporal , Estudios de Cohortes , Femenino , Grecia , Hospitales Universitarios , Humanos , Síndrome Metabólico/sangre , Síndrome Metabólico/complicaciones , Síndrome Metabólico/diagnóstico , Obesidad/complicaciones , Servicio Ambulatorio en Hospital , Sobrepeso/complicaciones , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/diagnóstico , Guías de Práctica Clínica como Asunto , Estudios Prospectivos , Adulto JovenRESUMEN
A substantial proportion of women with the polycystic ovary syndrome (PCOS) are obese and obesity is considered as a prothrombotic state. Platelet-derived microparticles (PMPs) might be implicated in the activation of the coagulation cascade. We aimed to assess plasma PMPs in overweight/obese women with PCOS. We measured plasma PMPs and determined anthropometric, metabolic, hormonal and ultrasonographic features of PCOS in 67 overweight/obese women with PCOS (with body mass index [BMI] >25.0 kg/m²) and in 21 BMI-matched healthy women. Circulating androgens and markers of insulin resistance (IR) were higher in women with PCOS than in controls. Plasma PMPs were also higher in women with PCOS than in controls (p = 0.046). In women with PCOS, plasma PMPs correlated with the mean number of follicles in the ovaries (r = 0.343; p = 0.006). In controls, plasma PMPs did not correlate with any of the studied parameters. In conclusion, plasma PMPs are elevated in overweight/obese women with PCOS compared with BMI-matched controls. The cause of this increase is unclear but both IR and hyperandrogenemia might be implicated. More studies are required to elucidate the pathogenesis of the elevation of PMPs in PCOS and to assess its implications on the cardiovascular risk of these patients.
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Trastornos de la Coagulación Sanguínea/etiología , Plaquetas/patología , Obesidad/complicaciones , Sobrepeso/complicaciones , Síndrome del Ovario Poliquístico/metabolismo , Adulto , Índice de Masa Corporal , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Micropartículas Derivadas de Células , Femenino , Fase Folicular , Grecia/epidemiología , Humanos , Hiperandrogenismo/etiología , Resistencia a la Insulina , Ovario/diagnóstico por imagen , Ovario/patología , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/patología , Síndrome del Ovario Poliquístico/fisiopatología , Riesgo , Testosterona/sangre , Ultrasonografía , Adulto JovenRESUMEN
AIM: To compare the prevalence of metabolic syndrome (MetS) between women with polycystic ovary syndrome (PCOS) and controls across different age (≤20, 21-30 and 31-39 years old) and body mass index (BMI) (normal weight, overweight and obese) groups. METHODS: We studied 1223 women with PCOS and 277 BMI-matched controls. The prevalence of MetS in women with PCOS and controls was estimated according to four different MetS definitions. RESULTS: In subjects ≤20 and 21-30 years old, the prevalence of MetS did not differ between women with PCOS and controls regardless of the MetS definition, even though women with PCOS were more obese than controls in the ≤20 years old group. In subjects 31-39 years old, the prevalence of MetS was higher in women with PCOS than in controls but the former were more obese than controls. The prevalence of MetS did not differ significantly between women with PCOS and controls in any of the BMI groups (normal weight, overweight or obese) regardless of the MetS definition. CONCLUSION: The prevalence of Mets appears to be primarily determined by obesity and age whereas PCOS per se appears to be a less important contributing factor.
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Índice de Masa Corporal , Síndrome Metabólico/epidemiología , Síndrome del Ovario Poliquístico/epidemiología , Adolescente , Adulto , Factores de Edad , Estudios de Casos y Controles , Femenino , Humanos , Resistencia a la Insulina , Síndrome Metabólico/complicaciones , Síndrome del Ovario Poliquístico/complicaciones , Prevalencia , Circunferencia de la Cintura , Adulto JovenRESUMEN
We aimed to evaluate plasma plasminogen activator inhibitor-1 (PAI-1) antigen levels in women with polycystic ovary syndrome (PCOS) and different levels of adiposity and PCOS phenotypes. We studied 199 women with PCOS and 50 age-matched healthy women divided in normal weight (n=100 and n=25, respectively) and overweight/obese (n=99 and n=25, respectively). Normal weight and overweight/obese patients with PCOS were further divided in patients diagnosed according to the 1990 criteria (i.e. with anovulation and hyperandrogenemia; 1990 criteria group) and in patients with the additional phenotypes introduced in 2003 (i.e. with polycystic ovaries and either anovulation or hyperandrogenemia; additional 2003 criteria group). In normal weight subjects, plasma PAI-1 levels did not differ between women with PCOS (regardless of group) and controls, or between the 1990 criteria and the additional 2003 criteria groups of PCOS. In overweight/obese subjects, plasma PAI-1 levels were higher in both the 1990 criteria and the additional 2003 criteria groups of PCOS compared with controls (p<0.001 and p=0.004, respectively), but did not differ between the 1990 criteria and the additional 2003 criteria groups of PCOS. In conclusion, plasma PAI-1 levels are elevated in overweight/obese women with PCOS but not in normal weight women with this syndrome. Plasma PAI-1 levels do not differ between the phenotypes of PCOS.
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Adiposidad , Inhibidor 1 de Activador Plasminogénico/sangre , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/fisiopatología , Adulto , Anovulación/etiología , Biomarcadores/sangre , Índice de Masa Corporal , Estudios de Cohortes , Femenino , Humanos , Hiperandrogenismo , Resistencia a la Insulina , Obesidad/complicaciones , Sobrepeso/complicaciones , Fenotipo , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/metabolismo , Guías de Práctica Clínica como Asunto , Adulto JovenRESUMEN
Serum lipocalin-2 levels are elevated in obese patients. We assessed serum lipocalin-2 levels in polycystic ovary syndrome (PCOS) and the effects of weight loss or metformin on these levels. Forty-seven overweight/obese patients with PCOS [body mass index (BMI) >27 kg/m(2)] were instructed to follow a low-calorie diet, to exercise and were given orlistat or sibutramine for 6 months. Twenty-five normal weight patients with PCOS (BMI <25 kg/m(2)) were treated with metformin for 6 months. Twenty-five normal weight and 25 overweight/obese healthy female volunteers comprised the control groups. Serum lipocalin-2 levels did not differ between overweight/obese patients with PCOS and overweight/obese controls (p = 0.258), or between normal weight patients with PCOS and normal weight controls (p = 0.878). Lipocalin-2 levels were higher in overweight/obese patients with PCOS than in normal weight patients with PCOS (p < 0.001). In overweight/obese patients with PCOS, weight loss resulted in a fall in lipocalin-2 levels (p < 0.001). In normal weight patients with PCOS, treatment with metformin did not affect lipocalin-2 levels (p = 0.484). In conclusion, PCOS per se is not associated with elevated lipocalin-2 levels. Weight loss induces a significant reduction in lipocalin-2 levels in overweight/obese patients with PCOS.
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Lipocalinas/sangre , Obesidad/sangre , Sobrepeso/sangre , Síndrome del Ovario Poliquístico/sangre , Proteínas Proto-Oncogénicas/sangre , Pérdida de Peso/fisiología , Proteínas de Fase Aguda , Adolescente , Adulto , Fármacos Antiobesidad/uso terapéutico , Restricción Calórica , Terapia Combinada , Ciclobutanos/uso terapéutico , Regulación hacia Abajo , Terapia por Ejercicio , Femenino , Humanos , Lactonas/uso terapéutico , Lipocalina 2 , Metformina/uso terapéutico , Obesidad/complicaciones , Obesidad/terapia , Orlistat , Sobrepeso/complicaciones , Sobrepeso/terapia , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/terapia , Adulto JovenRESUMEN
Many patients with polycystic ovary syndrome (PCOS) have insulin resistance, obesity (mostly visceral) and glucose intolerance, conditions associated with abnormalities in the production of vaspin, a novel adipokine that appears to preserve insulin sensitivity and glucose tolerance. The aim of the study was to assess serum vaspin levels in PCOS and the effects on vaspin levels of metformin or of weight loss. We studied 79 patients with PCOS and 50 healthy female volunteers. Normal weight patients with PCOS (n=25) were treated with metformin 850 mg bid for 6 months. Overweight/obese patients with PCOS (n=54) were prescribed a normal-protein, energy-restricted diet for 6 months; half of them were also given orlistat 120 mg tid and the rest were given sibutramine 10 mg qd. At baseline and after 6 months, serum vaspin levels and anthropometric, metabolic and hormonal features of PCOS were determined. Overall, patients with PCOS had higher vaspin levels than controls (p=0.021). Normal weight patients with PCOS had higher vaspin levels than normal weight controls (p=0.043). Vaspin levels were non-significantly higher in overweight/obese patients with PCOS than in overweight/obese controls. In normal weight patients with PCOS, metformin reduced vaspin levels non-significantly. In overweight/obese patients with PCOS, diet plus orlistat or sibutramine did not affect vaspin levels. Vaspin levels were independently correlated with body mass index in women with PCOS (p=0.001) and with waist circumference in controls (p=0.015). In conclusion, serum vaspin levels are elevated in PCOS but neither a small weight loss nor metformin affect vaspin levels significantly.
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Metformina/uso terapéutico , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Serpinas/sangre , Pérdida de Peso , Adolescente , Adulto , Índice de Masa Corporal , Ciclobutanos/uso terapéutico , Dieta Reductora , Femenino , Humanos , Lactonas/uso terapéutico , Orlistat , Sobrepeso/dietoterapia , Sobrepeso/tratamiento farmacológico , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/dietoterapiaRESUMEN
Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome, with long-term sequelae from birth to senescence. The long-term effects of PCOS are attributed to several metabolic aberrations ensuing the syndrome. In a systematic review of literature regarding the cardiovascular risk factors that accompany PCOS, we found that macrovascular function has been assessed by flow-mediated dilatation (FMD), microvascular function by venous occlusion plethysmography (VOP), and arterial structure by ultrasonographic assessment of intima-media thickness (IMT) usually of the carotid artery. Contradictory results have been reported; however, in most studies, endothelial dysfunction, an early marker of atherosclerosis assessed either by haemodynamic methods such as FMD or by biochemical methods such as endothelin-1 levels, was found to be impaired. VOP is a less-studied method, with few indices altered. IMT was found to be altered in most of the included studies, but the population was more heterogeneous. Inflammatory markers, including C-reactive protein, were also found to be altered in most studies. On the other hand, a number of interventions have been shown beneficial for the markers of cardiovascular risk, in the context of insulin-sensitizers. However, other interventions such as oral contraceptive pills or statins did not consistently show a similar beneficial effect. In summary, the early identification and eventual treatment of cardiovascular clinical and biochemical risk factors may be used in clinical practice to prevent potential 'silent' triggers of cardiovascular disease.
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Introduction: Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in reproductive-aged women. Hyperandrogenism, polycystic ovaries, chronic anovulation, and metabolic aberrations are its common features. The treatment approach focuses on the main aberrations, which characterize the different phenotypes. Areas covered: Management strategies targeting the metabolic phenotype include lifestyle modifications for weight loss and improvement of dietary habits, as well as medication, such as insulin-sensitizers. The treatment of hyperandrogenic phenotype includes cosmetic procedures and the combined oral contraceptives with or without antiandrogens. The therapeutic approach to reproductive phenotype includes diet and lifestyle modifications, clomiphene citrate, and aromatase inhibitors. Alternative treatments include dietary supplements, herbs, resveratrol, myo-inositol, and acupuncture. Expert opinion: New studies have shown that higher anti-Müllerian hormone levels, gut microbiome composition, and plasma metabolomics are new parameters that are related to the most severe phenotypes. The clinical phenotypes can change over the lifespan with weight gain and can coexist in the same individual. Individualized treatment remains the main approach but grouping the phenotypes and following therapeutic recommendations may prove to be also clinically appropriate.
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Anovulación , Hiperandrogenismo , Síndrome del Ovario Poliquístico , Adulto , Hormona Antimülleriana , Femenino , Humanos , Fenotipo , Síndrome del Ovario Poliquístico/tratamiento farmacológicoRESUMEN
BACKGROUND: Lipocalin-2 is a novel adipokine that appears to play a role in the development of insulin resistance. Serum lipocalin-2 levels are elevated in obese patients. Obesity and insulin resistance are cardinal characteristics of the polycystic ovary syndrome (PCOS). However, there are limited data on serum lipocalin-2 levels in patients with PCOS. The aim of the present study was to assess serum lipocalin-2 levels in PCOS. METHODS: We studied 200 patients with PCOS and 50 healthy female volunteers. RESULTS: Serum lipocalin-2 levels were slightly higher in women with PCOS compared with controls (65.4 +/- 34.3 vs. 60.3 +/- 26.0 ng/ml, respectively) but this difference did not reach statistical significance. In contrast, lipocalin-2 levels were higher in overweight/obese women with PCOS than in normal weight women with the syndrome (76.2 +/- 37.3 vs. 54.5 +/- 27.2 ng/ml, respectively; p < 0.001). Serum lipocalin-2 levels were also higher in overweight/obese controls compared with normal weight controls (70.1 +/- 24.9 vs. 50.5 +/- 23.7 ng/ml, respectively; p = 0.004). In the total study population (patients with PCOS and controls), lipocalin-2 levels were independently correlated with the body mass index (p < 0.001). In women with PCOS, lipocalin-2 levels were independently correlated with the waist (p < 0.001). CONCLUSIONS: Obesity is associated with elevated serum lipocalin-2 levels. In contrast, PCOS does not appear to affect lipocalin-2 levels.
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Lipocalinas/sangre , Obesidad/sangre , Síndrome del Ovario Poliquístico/sangre , Proteínas Proto-Oncogénicas/sangre , Proteínas de Fase Aguda , Adulto , Estudios Transversales , Femenino , Humanos , Resistencia a la Insulina , Lipocalina 2 , Obesidad/complicaciones , Sobrepeso/sangre , Síndrome del Ovario Poliquístico/complicacionesRESUMEN
Sex steroids, except for their primary reproductive role, exert key effects on metabolic target tissues. Androgen receptors have been detected in various tissues, participating in both central and peripheral regulation of metabolism and insulin action. The physiological role of androgens in regulating multiple aspects of female insulin signaling and energy metabolism becomes evident early in utero, thus programming how insulin-targeted tissues will behave in later life. Across lifespan, distinct effects of androgens in all insulin-targeted tissues are controlled by their circulating serum levels, within a narrow window, outside of which disturbances in metabolism are observed. Thus, androgen excess in women, as documented in those with polycystic ovary syndrome, can adversely affect insulin sensitivity, promoting visceral adiposity, adipose tissue dysfunction, and, ultimately, insulin resistance.
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Adiposidad , Andrógenos/metabolismo , Hiperandrogenismo/metabolismo , Resistencia a la Insulina , Insulina/metabolismo , Síndrome del Ovario Poliquístico/metabolismo , Andrógenos/sangre , Femenino , Humanos , Hiperandrogenismo/sangre , Insulina/sangre , Síndrome del Ovario Poliquístico/sangreRESUMEN
Endocrine disrupting chemicals (EDCs), a heterogeneous group of exogenous chemicals that can interfere with any aspect of endogenous hormones, represent an emerging global threat for human metabolism. There is now considerable evidence that the observed upsurge of metabolic disease cannot be fully attributed to increased caloric intake, physical inactivity, sleep deficit, and ageing. Among environmental factors implicated in the global deterioration of metabolic health, EDCs have drawn the biggest attention of scientific community, and not unjustifiably. EDCs unleash a coordinated attack toward multiple components of human metabolism, including crucial, metabolically-active organs such as hypothalamus, adipose tissue, pancreatic beta cells, skeletal muscle, and liver. Specifically, EDCs' impact during critical developmental windows can promote the disruption of individual or multiple systems involved in metabolism, via inducing epigenetic changes that can permanently alter the epigenome in the germline, enabling changes to be transmitted to the subsequent generations. The clear effect of this multifaceted attack is the manifestation of metabolic disease, clinically expressed as obesity, metabolic syndrome, diabetes mellitus, and non-alcoholic fatty liver disease. Although limitations of EDCs research do exist, there is no doubt that EDCs constitute a crucial parameter of the global deterioration of metabolic health we currently encounter.
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Human, animal, and in vitro studies provide evidence that advanced glycation end-products (AGEs) may contribute to the pathogenesis of polycystic ovary syndrome (PCOS) and its metabolic and reproductive consequences. AGEs are able to induce, via activation of key intracellular signaling pathways, the generation of oxidative stress and proinflammatory cytokines, thus contributing to the adverse health impact of PCOS. This review presents the implications of AGEs in several disease pathophysiologies, including PCOS, as well as the cellular and systemic effects of AGEs on insulin resistance (IR), hyperandrogenemia, endoplasmic reticulum (ER) stress, hypoxia, and ovarian function. The gaps in our knowledge will serve as launching pad for future developments ranging from dietary and lifestyle changes to pharmaceutical interventions aiming at potential applications in women with PCOS.
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Síndrome del Ovario Poliquístico/metabolismo , Síndrome del Ovario Poliquístico/fisiopatología , Animales , Femenino , Productos Finales de Glicación Avanzada/metabolismo , Humanos , Resistencia a la Insulina/fisiología , Receptor para Productos Finales de Glicación Avanzada/metabolismoRESUMEN
Background: Twenty-one-hydroxylase-deficient non-classic adrenal hyperplasia (NC-CAH) is a very common autosomal recessive syndrome with prevalence between 1:1,000 and 1:2,000 individuals and the frequency varies according to ethnicity. On the other hand, polycystic ovary syndrome has a familial basis and it is inherited under a complex hereditary trait. This syndrome affects 6 to 10% of women in reproductive age and it is the most common endocrine disorder in young women. Our aim was to investigate, through a systematic review, the distinct characteristics and common findings of these syndromes. Methods: The search period covered January 1970 to November 2018, using the scientific databases PubMed. Inclusion criteria were adult women patients with PCOS or NC-CAH. Search terms were "polycystic ovary syndrome," "PCOS," "non-classical adrenal hyperplasia," "NC-CAH," "21-hydroxylase deficiency." From an initial 16,255 titles, the evaluations led to the final inclusion of 97 papers. Results: The clinical features of NC-CAH are hirsutism and ovulatory and menstrual dysfunction therefore; differentiation between these two syndromes is difficult based on clinical grounds only. Additionally, NC-CAH and PCOS are both associated with obesity, insulin resistance, and dyslipidaemia. Reproductive abnormalities are also common between these hyperandrogenemic disorders since in patients with NC-CAH polycystic ovarian morphology and subfertility are present as they are in women with PCOS. The diagnosis of PCOS, is confirmed once other disorders that mimic PCOS have been excluded e.g., conditions that are related to oligoovulation or anovulation and/or hyperandrogenism, such as hyperprolactinaemia, thyroid disorders, non-classic congenital adrenal hyperplasia, and androgen-producing neoplasms. Conclusions: The screening tool to distinguish non-classic adrenal hyperplasia from PCOS is the measurement of 17-hydroxyprogesterone levels. The basal levels of 17-hydroxyprogesterone may overlap, but ACTH stimulation testing can distinguish the two entities. In this review these two common endocrine disorders are discussed in an effort to unveil their commonalities and to illuminate their shadowed distinctive characteristics.
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Advanced glycation end products accumulate in the ovarian granulosa-cell layer of women with polycystic ovarian syndrome. Taken that the MAPK/ERK-pathway is a key regulator of oocyte maturation and function, consisting the main pathway used by the gonadotrophic hormones (luteinizing hormone, follicle stimulating hormone) to control ovulation, the present study aims to assess advanced glycation end products' interference into luteinizing hormone-and follicle stimulating hormone-signaling via the MAPK/ERK-pathway in the human granulosa KGN cell line. KGN cells were treated with luteinizing hormone or follicle stimulating hormone in the absence or presence of human glycated albumin. The specific activation of the main components of the MAPK/ERK1/2-pathway (namely c-Raf, MEK and ERK1/2) was assessed. Treatment of KGN cells with an MEK1/2-inhibitor or a blocking anti-RAGE-antibody was also performed to shed further light on the mechanism of the involvement of advanced glycation end products in luteinizing hormone and/or follicle stimulating hormone-related signaling pathways. Luteinizing hormone treatment increased p-ERK1/2 levels in human granulosa cells, while the combined treatment of luteinizing hormone and human glycated albumin provoked a decrease of p-ERK1/2 levels. A similar reducing effect was also observed for the upstream molecule phospho-cRaf upon combined treatment, while treatment with an MEK-inhibitor confirmed that the phenomenon is MAPK/ERK-pathway-dependent. Similarly, follicle stimulating hormone treatment increased p-ERK1/2 and p-MEK1/2 levels, while the combined treatment of follicle stimulating hormone and human glycated albumin downregulated their levels. Advanced glycation end products reduce the luteinizing hormone- and follicle stimulating hormone-induced ERK1/2 activation that is critical for granulosa cell mitogenesis and proliferation. Inappropriate activation of ERK1/2 in granulosa cells may block the granulosa cell differentiation pathway and/or impair follicular responses to hormones, potentially leading to ovulation failure that characterizes polycystic ovarian syndrome.
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Hormona Folículo Estimulante/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Células de la Granulosa/efectos de los fármacos , Células de la Granulosa/metabolismo , Hormona Luteinizante/metabolismo , Línea Celular , Femenino , Humanos , Transducción de SeñalRESUMEN
Nutrition can generate oxidative stress and trigger a cascade of molecular events that can disrupt oxidative and hormonal balance. Nutrient ingestion promotes a major inflammatory and oxidative response at the cellular level in the postprandial state, altering the metabolic state of tissues. A domino of unfavorable metabolic changes is orchestrated in the main metabolic organs, including adipose tissue, skeletal muscle, liver and pancreas, where subclinical inflammation, endothelial dysfunction, mitochondrial deregulation and impaired insulin response and secretion take place. Simultaneously, in reproductive tissues, nutrition-induced oxidative stress can potentially violate delicate oxidative balance that is mandatory to secure normal reproductive function. Taken all the above into account, nutrition and its accompanying postprandial oxidative stress, in the unique context of female hormonal background, can potentially compromise normal metabolic and reproductive functions in women and may act as an active mediator of various metabolic and reproductive disorders.
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Endocrinología , Enfermedades Metabólicas/fisiopatología , Fenómenos Fisiológicos de la Nutrición , Estrés Oxidativo/fisiología , Reproducción/fisiología , Tejido Adiposo/metabolismo , Femenino , Humanos , Músculo Esquelético/metabolismoRESUMEN
Postprandial dysmetabolism is a postprandial state characterized by abnormal metabolism of glucose and lipids and, more specifically, of elevated levels of glucose and triglyceride (TG) containing lipoproteins. Since there is evidence that postprandial dysmetabolism is associated with increased cardiovascular mortality and morbidity, due to macro- and microvascular complications, as well as with conditions such as polycystic ovary syndrome (PCOS) and non-alcoholic fatty liver disease (NAFLD), it is recommended that clinicians be alert for early detection and management of this condition. Management consists of a holistic approach including dietary modification, exercise and use of hypoglycemic and hypolipidemic medication aiming to decrease the postprandial values of circulating glucose and triglycerides. This review aims to explain glucose and lipid homeostasis and the impact of postprandial dysmetabolism on the cardiovascular system as well as to offer suggestions with regard to the therapeutic approach for this entity. However, more trials are required to prevent or reverse early and not too late the actual tissue damage due to postprandial dysmetabolism.
Asunto(s)
Glucemia/metabolismo , Hiperglucemia/sangre , Hipertrigliceridemia/sangre , Periodo Posprandial , Triglicéridos/sangre , Animales , Biomarcadores/sangre , Enfermedades Cardiovasculares/etiología , Humanos , Hiperglucemia/diagnóstico , Hiperglucemia/etiología , Hiperglucemia/terapia , Hipertrigliceridemia/diagnóstico , Hipertrigliceridemia/etiología , Hipertrigliceridemia/terapia , Lipoproteínas/sangre , Valor Predictivo de las Pruebas , Pronóstico , Factores de RiesgoRESUMEN
OBJECTIVE: Limited data suggest that menstrual cycle abnormalities are more pronounced in younger and more obese patients with polycystic ovary syndrome (PCOS). We aimed to evaluate the association between menstrual cycle pattern and age, obesity and PCOS phenotype in a large population of women with PCOS. DESIGN: We studied 1,297 women with PCOS and divided them according to: a) age in ≤ 20, 21-30 and > 30 years old, b) body mass index in normal weight, overweight and obese and c) PCOS phenotype in phenotype 1 (anovulation, hyperandrogenemia and polycystic ovaries), 2 (anovulation and hyperandrogenemia without polycystic ovaries), 3 (hyperandrogenemia and polycystic ovaries without anovulation) and 4 (anovulation and polycystic ovaries without hyperandrogenemia). RESULTS: The proportion of women with regular menstrual cycles progressively increased in the older age groups, being 8.1, 10.5 and 12.7% in women ≤ 20, 21-30 and > 30 years old, respectively (p = 0.037). The proportion of women with regular menstrual cycles did not differ between normal weight and obese women but was higher in overweight women (9.3, 9.4 and 13%, respectively; p = 0.020). The proportion of women with regular cycles alternating with irregular cycles was highest in women with phenotype 4, intermediate in women with phenotype 2 and lowest in women with phenotype 1 (74.3, 69.4 and 61.7%, respectively; p = 0.027). CONCLUSIONS: Menstrual cycle pattern is more irregular in women with the "classic" PCOS phenotypes than in phenotype 4 but appears to normalize with ageing. On the other hand, obesity does not appear to have an important effect on menstrual cycle pattern in PCOS.
Asunto(s)
Trastornos de la Menstruación , Obesidad , Síndrome del Ovario Poliquístico/epidemiología , Adulto , Factores de Edad , Comorbilidad , Femenino , Humanos , Trastornos de la Menstruación/epidemiología , Obesidad/epidemiología , Fenotipo , Síndrome del Ovario Poliquístico/clasificación , Adulto JovenRESUMEN
In 2007, the European Society for Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM) issued guidelines in Thessaloniki regarding the use of metformin and clomiphene for the induction of ovulation in patients with anovulatory polycystic ovary syndrome (PCOS). According to these guidelines, the use of metformin should be limited to patients with impaired glucose tolerance and should be interrupted well before the administration of clomiphene, thus restricting the use of metformin to a minority of patients with PCOS. More recent data suggest that these guidelines potentially require reconsideration. Indeed, metformin appears to be useful in patients with PCOS who have a body mass index within the normal range and present with infertility due to anovulation. Moreover, the combination of metformin with clomiphene appears to be the best treatment choice in patients with PCOS who are resistant to clomiphene, i.e. it should precede the administration of gonadotropins. In addition, the administration of metformin reduces the incidence and severity of ovarian hyperstimulation syndrome when given to patients with PCOS who undergo multiple ovulation induction for in vitro fertilization and have a high risk for this syndrome. However, it should be emphasized that more studies are needed to support the above arguments and, more importantly, to determine the factors that predict the success of ovulation induction.