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Polycystic Ovary Syndrome (PCOS) and Fertility  [PDF]
Guilherme Barbosa, Larissa Bianca Paiva Cunha de Sá, Denise Rosso Tenório Wanderley Rocha, Alberto Krayyem Arbex
Open Journal of Endocrine and Metabolic Diseases (OJEMD) , 2016, DOI: 10.4236/ojemd.2016.61008
Abstract: The polycystic ovary syndrome (PCOS) is defined as a combination of hyperandrogenism (hirsutism and acne) and anovulation (oligomenorrhea, infertility, and dysfunctional uterine bleeding), with or without the presence of polycystic ovaries on ultrasound. It represents the main endocrine disorder in the reproductive age, affecting 6% - 15% of women in menacme. It is the most common cause of infertility due to anovulation, and the main source of female infertility. When in the presence of a menstrual disorder, the diagnosis of PCOS is reached in 30% - 40% of patients with primary or secondary amenorrhoea and in 80% of patients with oligomenorrhea. PCOS should be diagnosed and treated early in adolescence due to reproductive, metabolic and oncological complications which may be associated with it. Treatment options include drugs, diet and lifestyle improvement.
The comparison of free androgen index and serum free testosterone levels in women with hirsutism or polycystic ovary syndrome  [PDF]
Oya Güng?r,G?nül Erden,Ceylan Bal,Nihal U?uz1
Journal of Clinical and Experimental Investigations , 2011,
Abstract: In many laboratories free testosterone can not be measured, so that free androgen index is suggested instead. The aim of this study was to compare free androgen index and serum free testosterone levels measured by radioimmunoassay in women with hirsutism or polycystic ovary syndrome.Materials and methods: Totally 94 women referred to the polyclinics of Ankara Numune Hospital were retrospectively included. Three patient groups were composed; 55 of hirsutism, 20 of polycystic ovary syndrome and 19 of both hirsutism and polycystic ovary syndrome. Total testosterone and sex hormone binding globuline levels were measured by chemiluminescence method and free testosterone levels were measured by radioimmunoassay. Free androgen index was calculated from total testosterone and sex hormone binding globuline.Results: There was a significant positive correlation between free testosterone and free androgen index in patients with hirsutism, in patients with polycystic ovary syndrome, in patients with hirsutism and polycystic ovary syndrome, and in total patient group [r(hirsutism)=0,597, r(PCOS)=0,617, r(hirsutism and PCOS)=0,779, r(total patient group)=0,649, P<0,01].Receiver operating characteristics curves were drawn to assess the diagnostic power of parameters for all patient groups [For hirsutism (n=55) auROC (FT)=0,431 auROC (FAI)=0,485] [For PCOS (n=20) auROC (FT)=0,431 auROC (FAI)=0,359] [For hirsutism and PCOS (n=19) auROC (FT)=0,676 auROC (FAI)=0,669]. In our study, free testosterone and free androgen index were found useful to diagnose ‘hirsutism and polycystic ovary syndrome’ but not others.Conclusion: Free androgen index can be used instead of free testosterone in hirsutism and polycystic ovary syndrome for diagnosis. J Clin Exp Invest 2011;2(2):152-6
Changes in androgens and insulin sensitivity indexes throughout pregnancy in women with polycystic ovary syndrome (PCOS): relationships with adverse outcomes
Angela Falbo, Morena Rocca, Tiziana Russo, Antonietta D'Ettore, Achille Tolino, Fulvio Zullo, Francesco Orio, Stefano Palomba
Journal of Ovarian Research , 2010, DOI: 10.1186/1757-2215-3-23
Abstract: Forty-five pregnant patients with ovulatory PCOS (PCOS group) and other 42 healthy pregnant women (control group) were studied assaying serum androgen levels and insulin sensitivity indexes throughout pregnancy serially, and recording obstetrical outcomes.Serum androgen levels and insulin resistance indexes were significantly (p < 0.05) higher in PCOS than in control group at study entry, these differences were sustained throughout pregnancy, and their changes resulted significantly (p < 0.05) different between PCOS and control group. In PCOS patients, women who had a complicated pregnancy showed serum androgen levels and insulin sensitivity indexes significantly (p < 0.05) worse in comparison to subjects without any pregnancy and/or neonatal complications.PCOS patients have impaired changes in serum androgen levels and insulin sensitivity indexes during pregnancy. These alterations could be implicated in the pregnancy and neonatal complications frequently observed in women affected by PCOS.Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by biochemical alteration, i.e. hyperandrogenism and insulin resistance, and ovarian impairment, resulting in chronic anovulation. The chronic anovulation is not the only factors influencing the reduced reproductive chances in PCOS patients. In fact, an increased incidence of complications throughout pregnancy was also observed in PCOS women after meta-analytic analysis [1].Recently, we confirmed in a well selected population of PCOS patients an increased relative risk (RR) for complicated pregnancy [1.7, 95% confidence interval (CI) 1.12-2.96] with a total incidence of adverse outcomes of 31.4% [2]. In addition, the risk for adverse outcomes in PCOS resulted significantly related to ovarian dysfunction and biochemical hyperandrogenism [3].Moreover, our previous study evaluated only baseline androgen levels in PCOS population and no relationship with insulin sensitivity indexes was investigated [3]. In add
Thiazolidinediones and Fertility in Polycystic Ovary Syndrome (PCOS)  [PDF]
Pascal Froment,Philippe Touraine
PPAR Research , 2006, DOI: 10.1155/ppar/2006/73986
Abstract: Polycystic ovary syndrome (PCOS) is the most frequent cause of female infertility. The treatment of PCOS patients with insulin sensitizers, such as metformin or thiazolidinediones, increases the ovulation rate and the number of successful pregnancies. The positive action of the insulin-sensitizing treatments could be explained by a decrease in the peripheral insulin resistance but also by a direct action at the ovarian level. We report in this review different hypotheses of thiazolidinediones actions to improve PCOS (steroid secretion by ovarian cells ; insulin sensitivity in muscle and adipocyte and fat redistribution).
State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS)
David H Geller, Danièle Pacaud, Catherine M Gordon, Madhusmita Misra, of the Drug and Therapeutics Committee of the Pediatric Endocrine Society
International Journal of Pediatric Endocrinology , 2011, DOI: 10.1186/1687-9856-2011-9
Abstract: Recognition of the highly prevalent association between PCOS and insulin resistance (IR) has stimulated research into the mechanism(s) behind this relationship, defining the metabolic, cardiovascular, and reproductive consequences of the IR, and evaluating therapies that target IR. Much of the current therapeutic paradigm incorporating insulin sensitization is derived from studies in adult women; application to the adolescent requires critical evaluation of the data supporting insulin sensitizer use in this age group. Although not intended as a comprehensive review of PCOS therapy, this report will discuss the options available for the treatment of adolescents with PCOS, with focus on the possible efficacy and costs of insulin sensitizing agents in comparison to more traditional therapies for PCOS.PCOS is a heterogeneous condition affecting 7-10% of women worldwide [1,2], irrespective of ethnic background [3], making it the most common endocrine disorder among reproductive-aged women. The 2003 Androgen Excess Society (AES) consensus required two of the following three criteria as necessary for the diagnosis: hyperandrogenism, ovarian dysfunction (oligo- or anovulation), and/or a polycystic ovary [4]. Summarizing the report of the recent 4th annual meeting of the Androgen Excess and PCOS Society [5], Yildiz and Azziz noted the difficulty in defining certain sub-phenotypes of PCOS, such as women with irregular menstrual cycling and polycystic ovarian morphology without evidence of hyperandrogenism (previously considered essential for the diagnosis).While hyperandrogenism is central to classically defined PCOS pathophysiology [6-8], and testosterone and DHEA-S are increased in up to 75% of PCOS patients, obesity and IR are frequently associated [9-11]. As many as 60% of women with PCOS have BMI values in the overweight or obese range [2] and 70% demonstrate IR and diabetes beyond that predicted by weight alone [12-14]. Hyperinsulinemia consequent to obesity and IR plac
Polycystic Ovary Syndrome (PCOS), Insulin Resistance and Insulin-Like Growth Factors (IGFs)/IGF-Binding Proteins (IGFBPs).  [PDF]
Hsin-Shih Wang,Tzu-Hao Wang
Chang Gung Medical Journal , 2003,
Abstract: Polycystic ovary syndrome (PCOS) is the most frequent androgen disorder of ovarianfunction. Hyperinsulinemia with insulin resistance is believed to be a key link in the enigmaticgeneration of the symptoms of PCOS such as anovulatory infertility and hyperandrogenism.Regression of these symptoms may be achieved by reducing the hyperinsulinemia.A growing body of evidence suggests that PCOS patients with hyperinsulinemia have ahigher risk to develop diabetes mellitus, hypertension and cardiovascular disease as comparedto age-matched women. Although oral contraceptives, progestins, antiandrogens, andovulation induction agents remain standard therapies, weight loss should also be vigorouslyencouraged to ameliorate the metabolic consequences of PCOS. In addition, insulin-sensitizingagents are now being shown to be useful alone or combined with standard therapies toalleviate hyperinsulinemia in PCOS. Finally and most importantly, early identification ofpatients at risk and prompt initiation of therapies, followed by long-term surveillance andmanagement, may promote the patient's long-term health.
Digit ratios by computer-assisted analysis confirm lack of anatomical evidence of prenatal androgen exposure in clinical phenotypes of polycystic ovary syndrome
Marla E Lujan, Amanda J Podolski, Donna R Chizen, Denis C Lehotay, Roger A Pierson
Reproductive Biology and Endocrinology , 2010, DOI: 10.1186/1477-7827-8-156
Abstract: Ninety-six women diagnosed with PCOS according to the 2003 Rotterdam criteria had their finger lengths measured with computer-assisted analysis. Participants were categorized into four recognized phenotypes of PCOS and their 2D:4D compared to healthy female controls (n = 48) and men (n = 50).Digit ratios assessed by computer-assisted analysis in women with PCOS did not differ from female controls, but were significantly lower in men. When subjects were stratified by PCOS phenotype, 2D:4D did not differ among phenotypes or when compared to female controls.Computer-assisted measurements validated that digit ratios of women with PCOS do not show anatomical evidence of increased prenatal androgen exposure.Polycystic ovary syndrome (PCOS) is a complex endocrine disorder, having no single diagnostic trait [1,2]. Much controversy has surrounded the diagnosis of this condition but in 2003 experts proposed that a diagnosis of PCOS be based on the presence of two of three symptoms: 1) oligo or chronic anovulation (amenorrhea), 2) biochemical and/or clinical hyperandrogenism and 3) polycystic ovaries on ultrasonography [1,2]. These criteria recognized the broad clinical spectrum of PCOS including, the manifestation four unique phenotypes [3]. Frank PCOS represents the most severe form of this condition and is characterized by the presence all three symptoms. Non-PCO PCOS is characterized by oligoanovulation, hyperandrogenism, but normal ovarian morphology. Ovulatory PCOS describes the presence of hyperandrogenism, polycystic ovaries and normal menstrual cycles, whereas Mild PCOS describes the presence of oligoamenorrhea and polycystic ovaries, but no hyperandrogenism. While the validity of these phenotypes is still being debated [4,5], there is consensus among experts that PCOS imparts serious consequences for the long-term health and quality of life of patients and therefore should invite early identification and intervention [1-6].Despite familial clustering, the diverse man
Epigenetic Mechanism Underlying the Development of Polycystic Ovary Syndrome (PCOS)-Like Phenotypes in Prenatally Androgenized Rhesus Monkeys  [PDF]
Ning Xu, Soonil Kwon, David H. Abbott, David H. Geller, Daniel A. Dumesic, Ricardo Azziz, Xiuqing Guo, Mark O. Goodarzi
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0027286
Abstract: The pathogenesis of polycystic ovary syndrome (PCOS) is poorly understood. PCOS-like phenotypes are produced by prenatal androgenization (PA) of female rhesus monkeys. We hypothesize that perturbation of the epigenome, through altered DNA methylation, is one of the mechanisms whereby PA reprograms monkeys to develop PCOS. Infant and adult visceral adipose tissues (VAT) harvested from 15 PA and 10 control monkeys were studied. Bisulfite treated samples were subjected to genome-wide CpG methylation analysis, designed to simultaneously measure methylation levels at 27,578 CpG sites. Analysis was carried out using Bayesian Classification with Singular Value Decomposition (BCSVD), testing all probes simultaneously in a single test. Stringent criteria were then applied to filter out invalid probes due to sequence dissimilarities between human probes and monkey DNA, and then mapped to the rhesus genome. This yielded differentially methylated loci between PA and control monkeys, 163 in infant VAT, and 325 in adult VAT (BCSVD P<0.05). Among these two sets of genes, we identified several significant pathways, including the antiproliferative role of TOB in T cell signaling and transforming growth factor-β (TGF-β) signaling. Our results suggest PA may modify DNA methylation patterns in both infant and adult VAT. This pilot study suggests that excess fetal androgen exposure in female nonhuman primates may predispose to PCOS via alteration of the epigenome, providing a novel avenue to understand PCOS in humans.
The Role of Metformin in the Treatment of Polycystic Ovary Syndrome (PCOS)  [PDF]
Hsin-Shih Wang
Chang Gung Medical Journal , 2006,
Abstract: Hyperinsulinemia is believed to be a key link in the enigmatic generation of the symptomsof polycystic ovarian syndrome (PCOS), which include anovulatory infertility and theskin stigmata induced by hyperandrogenism. Regression of these symptoms may beachieved by reducing the hyperinsulinemia. Metformin, an insulin-sensitizing agent, hasbeen proven to be of clinical usefulness both in the short-term aiding of infertility treatmentsand, potentially, in the prevention of the long-term sequelae for patients with PCOS.
Trace glucose and lipid metabolism in high androgen and high-fat diet induced polycystic ovary syndrome rats
Hua-Ling Zhai, Hui Wu, Hui Xu, Pan Weng, Fang-Zhen Xia, Yi Chen, Ying-Li Lu
Reproductive Biology and Endocrinology , 2012, DOI: 10.1186/1477-7827-10-5
Abstract: Female Sprague-Dawley rats were divided into 3 groups: the control group(C), n = 10; the andronate-treated group (Andronate), n = 10 (treated with andronate, 1 mg/100 g body weight/day for 8 weeks); and the andronate-treated and high-fat diet group (Andronate+HFD), n = 10. The rate of glucose appearance (Ra of glucose), gluconeogenesis (GNG), and the rate of glycerol appearance (Ra of glycerol) were assessed with a stable isotope tracer. The serum sex hormone levels, insulin levels, glucose concentration, and the lipid profile were also measured.Compared with control group, both andronate-treated groups exhibited obesity with higher insulin concentrations (P < 0.05) but similar blood glucose concentrations. Of the two andronate-treated groups, the andronate+HFD group had the most serious insulin resistance (IR). Estrus cycles were completely acyclic, with polycystic ovaries and elevated serum lipid profiles in the andronate+HFD group (P < 0.05). Ra of glucose and GNG increased significantly in the andronate+HFD rats. However, the Ra of glycerol was similar in the three groups.Andronate with HFD rat model showed ovarian and metabolic features of PCOS, significant increase in glucose Ra, GNG, and lipid profiles, as well as normal blood glucose levels. Therefore, aberrant IR, increased glucose Ra, GNG, and lipid metabolism may represent the early-stage of glucose and lipid kinetics disorder, thereby might be used as potential early-stage treatment targets for PCOS.Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age [1] and is the most frequent cause of hyperandrogenism and anovulation [2]. PCOS is also strongly associated with abdominal obesity, hyperinsulinemia, insulin resistance, and type 2 diabetes [3]. The pathophysiology of PCOS is largely unknown but has been attributed to defects in various organ systems. Uncontrolled ovarian steroidogenesis with a thickened thecal layer that secrets excessive androgen is
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