Risk of Insulin Resistance and Metabolic Syndrome in Women with Hyperandrogenemia: A Comparison between PCOS Phenotypes and Beyond

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in premenopausal women, with a wide spectrum of possible phenotypes, symptoms and sequelae according to the current clinical definition. However, there are women who do not fulfill at least two out of the three commonly used “Rotterdam criteria” and their risk of developing type 2 diabetes or obesity later in life is not defined. Therefore, we addressed this important gap by conducting a retrospective analysis based on 750 women with and without PCOS. We compared four different PCOS phenotypes according to the Rotterdam criteria with women who exhibit only one Rotterdam criterion and with healthy controls. Hormone and metabolic differences were assessed by analysis of variance (ANOVA) as well as logistic regression analysis. We found that hyperandrogenic women have per se a higher risk of developing insulin resistance compared to phenotypes without hyperandrogenism and healthy controls. In addition, hyperandrogenemia is associated with developing insulin resistance also in women with no other Rotterdam criterion. Our study encourages further diagnostic and therapeutic approaches for PCOS phenotypes in order to account for varying risks of developing metabolic diseases. Finally, women with hyperandrogenism as the only symptom should also be screened for insulin resistance to avoid later metabolic risks.

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Metabolic Syndrome During Menopause

Current Vascular Pharmacology ◽

10.2174/1570161116666180904094149 ◽

2019 ◽

Vol 17 (6) ◽

pp. 595-603 ◽

Cited By ~ 4

Author(s):

Sezcan Mumusoglu ◽

Bulent Okan Yildiz

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Central Obesity ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

Natural Menopause ◽

The Metabolic Syndrome ◽

Increased Risk ◽

Aging Women

The metabolic syndrome (MetS) comprises individual components including central obesity, insulin resistance, dyslipidaemia and hypertension and it is associated with an increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). The menopause per se increases the incidence of MetS in aging women. The effect(s) of menopause on individual components of MetS include: i) increasing central obesity with changes in the fat tissue distribution, ii) potential increase in insulin resistance, iii) changes in serum lipid concentrations, which seem to be associated with increasing weight rather than menopause itself, and, iv) an association between menopause and hypertension, although available data are inconclusive. With regard to the consequences of MetS during menopause, there is no consistent data supporting a causal relationship between menopause and CVD. However, concomitant MetS during menopause appears to increase the risk of CVD. Furthermore, despite the data supporting the association between early menopause and increased risk of T2DM, the association between natural menopause itself and risk of T2DM is not evident. However, the presence and the severity of MetS appears to be associated with an increased risk of T2DM. Although the mechanism is not clear, surgical menopause is strongly linked with a higher incidence of MetS. Interestingly, women with polycystic ovary syndrome (PCOS) have an increased risk of MetS during their reproductive years; however, with menopausal transition, the risk of MetS becomes similar to that of non-PCOS women.

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An observational study of reduction of insulin resistance and prevention of development of type 2 diabetes mellitus in women with polycystic ovary syndrome treated with metformin and diet

Metabolism ◽

10.1016/j.metabol.2008.02.011 ◽

2008 ◽

Vol 57 (7) ◽

pp. 954-960 ◽

Cited By ~ 17

Author(s):

Charles J. Glueck ◽

Naila Goldenberg ◽

Luann Sieve ◽

Ping Wang

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Polycystic Ovary Syndrome ◽

Observational Study ◽

Polycystic Ovary ◽

Ovary Syndrome

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Prevalence of insulin resistance and prediction of glucose intolerance and type 2 diabetes mellitus in women with polycystic ovary syndrome

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm.2007.113 ◽

2007 ◽

Vol 45 (5) ◽

Cited By ~ 14

Author(s):

Jana Vrbikova ◽

Katerina Dvorakova ◽

Tereza Grimmichova ◽

Martin Hill ◽

Sona Stanicka ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Polycystic Ovary Syndrome ◽

Glucose Intolerance ◽

Polycystic Ovary ◽

Ovary Syndrome

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Obesity and Insulin Resistance Are the Main Determinants of Postprandial Lipoprotein Dysmetabolism in Polycystic Ovary Syndrome

International Journal of Endocrinology ◽

10.1155/2016/9545239 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Tommy Kyaw Tun ◽

Anne McGowan ◽

Niamh Phelan ◽

Neuman Correia ◽

Gerard Boran ◽

...

Keyword(s):

Insulin Resistance ◽

Cardiovascular Risk ◽

Polycystic Ovary Syndrome ◽

Apolipoprotein B ◽

Polycystic Ovary ◽

Density Lipoprotein ◽

Premenopausal Women ◽

Postprandial Glucose ◽

Ovary Syndrome ◽

Mixed Meal

Postprandial dyslipidaemia may be a plausible mechanism by which polycystic ovary syndrome (PCOS) increases cardiovascular risk. We sought to investigate whether the postprandial glucose and insulin and lipid and lipoprotein responses, including that of apolipoprotein B-48 (apoB-48) containing chylomicrons, to a mixed meal are different in obese PCOS women when compared to obese control subjects and whether differences, if any, are related to obesity, insulin resistance (IR), hyperandrogenaemia, or PCOS status. 26 women with PCOS (age30.4±1.2years (mean ± SEM), body mass index (BMI)36.8±1.5 kg/m2) and 26 non-PCOS subjects (age34.1±0.9years, BMI31.5±1.0 kg/m2) were studied before and up to 8 hours following a standard mixed meal. AUC-triglyceride (AUC-TG) was higher and AUC-high-density lipoprotein (AUC-HDL) lower in PCOS women. These differences were not apparent when BMI was accounted for. Insulin sensitivity (SI), AUC-apoB-48, and AUC-apolipoprotein B (AUC-apoB) were found to be independent predictors of AUC-TG, accounting for 55% of the variance. Only AUC-insulin remained significantly elevated following adjustment for BMI. Obesity related IR explains postprandial hypertriglyceridaemia and hyperinsulinaemic responses. Management of obesity in premenopausal women with PCOS is likely to reduce their cardiovascular risk burden.

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Polycystic ovary syndrome: reproductive aspects

Oxford Textbook of Endocrinology and Diabetes ◽

10.1093/med/9780199235292.003.0851 ◽

2011 ◽

pp. 1229-1234

Author(s):

Sophie Catteau-Jonard ◽

Cécile Gallo ◽

Didier Didier

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Reproductive Age ◽

Therapeutic Approaches ◽

Women Of Reproductive Age ◽

Ovary Syndrome ◽

Common Cause ◽

The Metabolic Syndrome

The polycystic ovary syndrome (PCOS) is the most common cause of anovulation and hyperandrogenism in women, affecting between 5 and 10% of women of reproductive age worldwide (1). Although this difficult topic in endocrine gynaecology is under extensive research, controversies still remain about the pathophysiology, diagnosis, and therapy of PCOS. The PCOS phenotype can be structured in three components: manifestations of anovulation, hyperandrogenism, and the metabolic syndrome (of which hyperinsulinaemia secondary to insulin resistance is the central abnormality). The latter two are addressed in other chapters. Our knowledge about the mechanism of disturbed folliculogenesis in PCOS that is responsible for its reproductive aspects has much increased these last years, thus opening new avenues for the diagnostic and therapeutic approaches.

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Developmental origin of polycystic ovary syndrome - a hypothesis

Journal of Endocrinology ◽

10.1677/joe.0.1740001 ◽

2002 ◽

Vol 174 (1) ◽

pp. 1-5 ◽

Cited By ~ 276

Author(s):

DH Abbott ◽

DA Dumesic ◽

S Franks

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Regulatory Region ◽

Later Life ◽

Ovary Syndrome ◽

Increased Risk ◽

Genetically Determined ◽

Lh Secretion

Polycystic ovary syndrome (PCOS) is a common but complex endocrine disorder and is a major cause of anovulation and consequent subfertility. It is also associated with a metabolic disturbance, characterized by hyperinsulinaemia and insulin resistance that carries an increased risk of type 2 diabetes in later life. Despite its prevalence little is known about its aetiology, but there is increasing evidence for an important genetic involvement. On the basis of experimental observations in the prenatally androgenized sheep and rhesus monkey, and supported by data from human studies, we propose that the clinical and biochemical features of PCOS can arise as a consequence of genetically determined hypersecretion of androgens by the ovary during, or very likely long before, puberty. The resulting hyperandrogenism results in 'programming' of the hypothalamic-pituitary unit to favour excess LH secretion, and encourages preferential abdominal adiposity that predisposes to insulin resistance. The severity of hyperinsulinaemia and insulin resistance (which has a profound influence on the phenotype of PCOS) is further influenced by both genetic factors (such as polymorphism in the insulin gene regulatory region) and environmental factors, notably obesity. This hypothesis therefore suggests a unifying, 'linear' model to explain the aetiology of the heterogeneous phenotype.

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Polycystic Ovary Syndrome, Insulin Resistance, and Obesity: Navigating the Pathophysiologic Labyrinth

International Journal of Reproductive Medicine ◽

10.1155/2014/719050 ◽

2014 ◽

Vol 2014 ◽

pp. 1-17 ◽

Cited By ~ 60

Author(s):

Joselyn Rojas ◽

Mervin Chávez ◽

Luis Olivar ◽

Milagros Rojas ◽

Jessenia Morillo ◽

...

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Ovarian Tissue ◽

Ovary Syndrome ◽

Main Culprit ◽

Exact Etiology

Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder that implies various severe consequences to female health, including alarming rates of infertility. Although its exact etiology remains elusive, it is known to feature several hormonal disturbances, including hyperandrogenemia, insulin resistance (IR), and hyperinsulinemia. Insulin appears to disrupt all components of the hypothalamus-hypophysis-ovary axis, and ovarian tissue insulin resistance results in impaired metabolic signaling but intact mitogenic and steroidogenic activity, favoring hyperandrogenemia, which appears to be the main culprit of the clinical picture in PCOS. In turn, androgens may lead back to IR by increasing levels of free fatty acids and modifying muscle tissue composition and functionality, perpetuating this IR-hyperinsulinemia-hyperandrogenemia cycle. Nonobese women with PCOS showcase several differential features, with unique biochemical and hormonal profiles. Nevertheless, lean and obese patients have chronic inflammation mediating the long term cardiometabolic complications and comorbidities observed in women with PCOS, including dyslipidemia, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Given these severe implications, it is important to thoroughly understand the pathophysiologic interconnections underlying PCOS, in order to provide superior therapeutic strategies and warrant improved quality of life to women with this syndrome.

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