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Polycystic ovary syndrome (PCOS) is a diagnosis made between late adolescence and the menopause in 5-10% of women. PCOS is a heterogeneous disorder of unknown etiology characterized by hyperandrogenic chronic anovulation. This syndrome consists of a diverse constellation of signs and symptoms, such as hirsutism, acne, acanthosis nigricans, obesity, menstrual irregularities, anovulation, and/or infertility. Features of the metabolic syndrome, including obesity, insulin resistance, and dyslipidemia, are common in this patient population. Recent insights into the pathophysiology of PCOS have shown insulin resistance and hyperinsulinemia to play a substantial role. Insulin resistance is increasingly recognized as a chronic, low-level, inflammatory state. Recent studies show that serum levels of inflammatory mediators, such as tumor necrosis factor-alpha and interleukin-6, are increased in the insulin-resistant conditions of obesity and PCOS. The optimal modality for long-term treatment should have positive effects on androgen synthesis, sex hormone-binding globulin production, the lipid profile, insulin sensitivity, inflammatory mediators, and clinical symptoms including acne, hirsutism, and irregular menstrual cycles. Treatment with insulin-sensitizing agents is a relatively new therapeutic strategy in women with PCOS. Current research has shown that the use of diabetes mellitus management practices aimed at reducing insulin resistance and hyperinsulinemia (such as weight reduction and the administration of oral antidiabetic drugs) can not only reverse testosterone and luteinizing hormone abnormalities and restore menstrual cycles, but can also improve glucose, insulin, proinflammatory cytokine, and lipid profiles.Clinical treatment with troglitazone, a member of the thiazolidinedione family, for the management of PCOS complications such as insulin resistance, hyperandrogenism, and anovulation was found to have beneficial effects; however, it was taken off the market over concerns of hepatotoxicity. Although troglitazone is no longer available in the US, numerous clinical trials have established the role of thiazolidinediones in the treatment of women with PCOS. Clinical data emerging regarding the utility of two of the newer, safer thiazolidinediones, pioglitazone and rosiglitazone, for this patient population, consistently demonstrate effective improvements of endocrine and ovulatory performance in women with PCOS. The benefit and importance of lifestyle modification and weight reduction, when it can be achieved, is still an important component in the long-term treatment of PCOS. Pharmacologic reduction in insulin levels using thiazolidinediones appears to offer another therapeutic modality for PCOS, which may ameliorate the progress of both hyperinsulinemia and hyperandrogenism. However, additional studies of patients so treated are necessary before these agents can be considered first-line treatment for PCOS. Convincing data from randomized controlled trials with sufficient power to detect both the benefits and risks of long-term treatment with thiazolidinediones in women with PCOS remain to be obtained.
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PMID:Thiazolidinediones for the therapeutic management of polycystic ovary syndrome : impact on metabolic and reproductive abnormalities. 1667 59

Diabetes mellitus is a complex disorder that arises from various causes, including dysregulated glucose sensing and impaired insulin secretion (maturity onset diabetes of youth, MODY), autoimmune-mediated beta-cell destruction (type 1), or insufficient compensation for peripheral insulin resistance (type 2). Type 2 diabetes is the most prevalent form that usually occurs at middle age; it afflicts more than 30 million people over the age of 65, but is appearing with greater frequency in children and adolescents. Dysregulated insulin signaling exacerbated by chronic hyperglycemia promotes a cohort of systemic disorders--including dyslipidemia, hypertension, cardiovascular disease, and female infertility. Understanding the molecular basis of insulin resistance can prevent these disorders and their inevitable progression to type 2 diabetes.
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PMID:Regulating insulin signaling and beta-cell function through IRS proteins. 1699 36

Polycystic ovary syndrome (PCOS), the main androgen disorder in women. Recently, it has been suggested that the condition is hereditary and that women with PCOS have disturbances, such as hyperandrogenism and additional metabolic abnormalities as hyperinsulinaemia, increased insulin resistance, dyslipidemia. Polycystic ovary syndrome (PCOS) usually arises during puberty and is marked by hyperinsulinemia and hyperandrogenism. Adolescents with PCOS are at an increased risk of developing health problems later on in life such as type 2 diabetes, cardiovascular disease, and infertility. Furthermore, the physical signs of PCOS can be detrimental to a teenage girl's self-image. Early diagnosis and treatment of PCOS in adolescents are essential in ensuring adulthood health and restoring self-esteem. Treatment for an adolescent with PCOS includes diet and exercise, metformin, and oral contraceptive pills. Still, surgery is not indicated in teenagers. Furthermore, psychological factors must be taken into consideration as well.
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PMID:[Early metabolic abnormalities--insulin resistance, hyperinsulinemia, impaired glucose tolerance and diabetes, in adolescent girls with polycystic ovarian syndrome]. 1708 Jul 48

Polycystic ovary syndrome (PCOS), a leading cause of infertility, affects approximately 10% of women of reproductive age. The etiology and pathophysiology of PCOS are poorly understood. PCOS is multifaceted and includes reproductive abnormalities and components of the metabolic syndrome such as insulin resistance, obesity, dyslipidemia, and hypertension. Exposure to excess testosterone (T) during the prenatal period may predispose individuals to PCOS phenotype. The goal of this study was to determine whether hypertension and dyslipidemia occur in a well-characterized model of PCOS produced by prenatal treatment of sheep with T. Radiotelemetry was used to measure blood pressure over a 24-h period in conscious, undisturbed animals. To normalize circulating estradiol levels across treatment, control (n = 4) and prenatal T-treated (100 mg T propionate im twice weekly from days 30 to 90 of fetal life, n = 4) 2-yr-old females were ovariectomized, instrumented with a radiotelemetry transmitter, and clamped with early follicular phase levels of estrogen using an implant. Six days later, a 24-h recording period commenced. Prenatal T-treated sheep were hypertensive compared with control sheep, and heart rate tended to be higher. T-treated sheep had hyperglycemia, insulin resistance, hypernatremia, and hyperchloremia, and both total and LDL cholesterol tended to be higher. Plasma aldosterone and epinephrine were significantly lower in T-treated sheep, whereas norepinephrine was unchanged. This first-ever use of radiotelemetric blood pressure recordings in sheep demonstrates that mild hypertension, a risk factor reported in some women with PCOS, is also a feature of the sheep model of PCOS produced by prenatal T treatment.
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PMID:Hypertension caused by prenatal testosterone excess in female sheep. 1732 68

Polycystic ovary syndrome (PCOS) is the common endocrine disorder of reproductive age women which is characterized by hyperandrogenism, chronic anovulation, and increased risk for infertility, endometrial cancer, developing metabolic dysfunction (type II diabetes, dyslipidemia), hypertension and heart disease. The syndrome is also associated with some skin disorders: hirsutismus, alopecia androgenetica and acne. The successful dermatologic therapy requires the holistic diagnosis of the women with skin disorders described above and use the antiandrogenic treatment with conventional methods and laser depilation in hirsutismus. In this paper we present literature studies and our own experiences.
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PMID:[Polycystic ovary syndrome and hair unit function disturbances in dermatological practice]. 1742 3

It is estimated that 60%-7% of women of reproductive age have polycystic ovarian syndrome (PCOS). Women with this condition exhibit an adverse cardiovascular risk profile, characteristic of the cardiometabolic syndrome and given the high prevalence of PCOS in the female population, this condition may contribute towards the acceleration of cardiovascular disease among young women. This article summarizes the recent development and findings in the cardiometabolic abnormalities in patients with PCOS. Patients with PCOS have the clinical features of oligomenorrhoea, hirsutism and infertility; however, they also exhibit hyperinsulinemia, obesity, hypertension, dyslipidemia, and an increased pro-thrombotic state. They have an increased risk of type 2 diabetes and impaired glucose tolerance, and sleep apnea is also found more commonly in this population. However, despite the presence of cardiovascular risk factors and increased surrogate markers of cardiovascular disease it is unclear if they have accelerated atherosclerosis. End point studies are currently lacking and the available evidence are conflicting. Adipose tissue has emerged as an important endocrine organ over the last decade and gained recognition in having an important role in the cardiometabolic syndrome. Adiponectin that is secreted exclusively by adipocytes has recently been recognized as an important marker of cardiometabolic syndrome, obesity, type 2 diabetes, and coronary artery disease. Other adipocytokines like leptin and resistin have also recently been recognized. This article will address the current evidence for the adverse cardiovascular risk in PCOS and the other factors that may be implicated. Finally the therapeutic options for treatment will be discussed.
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PMID:Cardiometabolic aspects of polycystic ovarian syndrome. 1758 75

Insulin resistance (IR) in childhood has importance to the understanding and prevention of the growing epidemic of insulin resistance syndrome (IRS) in adults with attendant obesity, type 2 diabetes (T2DM), atherosclerotic diseases, hypertension, gout, non-alcoholic, steato-hepatitis (NASH), gall bladder disease, nephropathy, polycystic ovarian disease (PCOS), infertility and premature senility. The severity of IR and its' complications in children unfortunately and usually progresses in their pubertal transition to adulthood; affected young children are more likely than adults to have underlying causal monogenic disorders; the sequence of natural history and events give insights into disease pathogeneses, and optimal life style choices that last are best made during the early formative years. Some features of IR in children discussed herein are: a strong tendency to low birth weight for gestational age, adverse effects of adrenarche and therapeutic steroid therapy, predisposition to premature pubarche, acanthosis nigricans, tall stature despite pituitary GH suppression, allergic diathesis, hyperandrogenism and PCOS, dyslipidemia and fatty liver disease, and diagnosis by clinical and biochemical markers of IR including insulin regulated hepatic hormonal binding proteins such as IGFBP-1. The national preoccupation with the "metabolic syndrome" T2DM and obesity, should be appropriately directed to an improved understanding of IR in children and their management, if the looming health crisis in affected adults is to be seriously addressed. The nation is facing its' first generation of children who will be less healthy and die younger than the previous generation (Marks (2005) Presentation to the American Association of Diabetes Educators 32nd Annual Meeting and Exhibition, August 10-13, Washington, DC).
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PMID:Childhood obesity and insulin resistance. 1770 76

Polycystic ovary syndrome (PCOS) is a complex, multifaceted, heterogeneous disorder that affects approximately 5 to 10% of women of reproductive age. It is characterized by hyperandrogenism, polycystic ovaries, and chronic anovulation along with insulin resistance, hyperinsulinemia, abdominal obesity, hypertension, and dyslipidemia as frequent metabolic traits (metabolic syndrome) that culminate in serious long-term consequences such as type 2 diabetes mellitus, endometrial hyperplasia, and coronary artery disease. It is one of the most common causes of anovulatory infertility. However, the heterogeneous clinical features of PCOS may change throughout the life span, starting from adolescence to postmenopausal age, largely influenced by obesity and metabolic alterations, and the phenotype of women with PCOS is variable, depending on the ethnic background. The etiology of PCOS is yet to be elucidated; however, it is believed that in utero fetal programming may have a significant role in the development of PCOS phenotype in adult life. Though a woman may be genetically predisposed to developing PCOS, it is only the interaction of environmental factors (obesity) with the genetic factors that results in the characteristic metabolic and menstrual disturbances and the final expression of the PCOS phenotype. Irrespective of geographic locations, a rapidly increasing prevalence of polycystic ovarian insulin resistance syndrome, excess body fat, adverse body fat patterning, hypertriglyceridemia, and obesity-related disease, such as diabetes and cardiovascular disease, have been reported in Asian Indians, suggesting that primary prevention strategies should be initiated early in this ethnic group. In lieu of the epidemic increase in the prevalence of obesity and diabetes mellitus in most industrialized countries including China and India owing to Westernization, urbanization, and mechanization, and evidence suggesting a pathogenetic role of obesity in the development of PCOS and related infertility, active intervention to combat the malice of these disorders is warranted. Pharmacologic therapy is a critical step in the management of patients with metabolic syndrome when lifestyle modifications fail to achieve the therapeutic goals, and studies in China and India have proved to be effective.
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PMID:Polycystic ovary syndrome in the Indian Subcontinent. 1818 Oct 79

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting 5-10% of reproductive aged women, about 1 out of 15 women worldwide. Traditionally it was considered as a reproductive disorder showing hyperandrogenism, chronic anovulation and infertility; it is now well accepted that PCOS represents a ''multifaceted'' syndrome with substantial metabolic and cardiovascular long term consequences. Several PCOS women present abdominal adiposity (visceral fat) with a level of peripheral insulin resistance (IR), similar to that present in women with type 2 diabetes, in association with an increased incidence of impaired glucose tolerance. Several cardiovascular risk factors are often related to metabolic alterations, such as dyslipidemia, hypertension, endothelial dysfunction, low grade chronic inflammation, that are present even at early age in PCOS women. Pathogenetic mechanisms of these impairments are not completely clarified yet, but IR appears to play a critical role, such as the key factor linking hypertension, glucose intolerance, obesity, lipid abnormalities and coronary artery disease. In conclusion, although increased incidence of metabolic abnormalities and metabolic disease like type 2 diabetes, and several cardiovascular abnormalities have been widely demonstrated in PCOS women, larger and multicenter trials of long term cardiovascular outcomes are required to better define the incidence of cardiovascular risk and cardiovascular disease in PCOS.
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PMID:Metabolic and cardiovascular consequences of polycystic ovary syndrome. 1827 51

1. Metformin is not efficient enough in order to regulate menstrual cycles. 2.Metformin is not efficient enough in order to treat hyperandrogenism. 3. Metformin should not be used as a first-line treatment in order to treat infertility. Clomiphene citrate (CC) is the reference treatment. 4. Metformin in addition to CC is not recommended as a second line treatment, after the failure of CC alone. 5. Metformin should not be used during pregnancy in non diabetic women with PCOS, in order to prevent the risk of gestational diabetes. 6. Metformin should be prescribed to PCOS women when they are diabetic, in order to prevent their cardiovascular risk, after lifestyle modification. 7. Metformin should not be used in PCOS non diabetic women in order to lose weight. Metformin should not be used in order to treat dyslipidemia in women with PCOS. 8. In PCOS women, without diabetes, but with fasting hyperglycemia or carbohydrate intolerance, metformin should be prescribed if: BMI>35.
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PMID:Should physicians prescribe metformin to women with polycystic ovary syndrome PCOS? 2007 83


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