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      Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan

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      BMC Medicine
      BioMed Central

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          Abstract

          Polycystic ovary syndrome (PCOS) is of clinical and public health importance as it is very common, affecting up to one in five women of reproductive age. It has significant and diverse clinical implications including reproductive (infertility, hyperandrogenism, hirsutism), metabolic (insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, adverse cardiovascular risk profiles) and psychological features (increased anxiety, depression and worsened quality of life). Polycystic ovary syndrome is a heterogeneous condition and, as such, clinical and research agendas are broad and involve many disciplines. The phenotype varies widely depending on life stage, genotype, ethnicity and environmental factors including lifestyle and bodyweight. Importantly, PCOS has unique interactions with the ever increasing obesity prevalence worldwide as obesity-induced insulin resistance significantly exacerbates all the features of PCOS. Furthermore, it has clinical implications across the lifespan and is relevant to related family members with an increased risk for metabolic conditions reported in first-degree relatives. Therapy should focus on both the short and long-term reproductive, metabolic and psychological features. Given the aetiological role of insulin resistance and the impact of obesity on both hyperinsulinaemia and hyperandrogenism, multidisciplinary lifestyle improvement aimed at normalising insulin resistance, improving androgen status and aiding weight management is recognised as a crucial initial treatment strategy. Modest weight loss of 5% to 10% of initial body weight has been demonstrated to improve many of the features of PCOS. Management should focus on support, education, addressing psychological factors and strongly emphasising healthy lifestyle with targeted medical therapy as required. Monitoring and management of long-term metabolic complications is also an important part of routine clinical care. Comprehensive evidence-based guidelines are needed to aid early diagnosis, appropriate investigation, regular screening and treatment of this common condition. Whilst reproductive features of PCOS are well recognised and are covered here, this review focuses primarily on the less appreciated cardiometabolic and psychological features of PCOS.

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          Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome.

          Hyperinsulinemia secondary to a poorly characterized disorder of insulin action is a feature of the polycystic ovary syndrome (PCO). However, controversy exists as to whether insulin resistance results from PCO or the obesity that is frequently associated with it. Thus, we determined in vivo insulin action on peripheral glucose utilization (M) and hepatic glucose production (HGP) with the euglycemic glucose-clamp technique in obese (n = 19) and nonobese (n = 10) PCO women and age- and body-composition-matched normal ovulatory women (n = 11 obese and n = 8 nonobese women). None had fasting hyperglycemia. Two obese PCO women had diabetes mellitus, established with an oral glucose tolerance test; no other women had impairment of glucose tolerance. However, the obese PCO women had significantly increased fasting and 2-h glucose levels after an oral glucose load and increased basal HGP compared with their body-composition-matched control group. There were statistically significant interactions between obesity and PCO in fasting glucose levels and basal HGP (P less than .05). Steady-state insulin levels of approximately 100 microU/ml were achieved during the clamp. Insulin-stimulated glucose utilization was significantly decreased in both PCO groups whether expressed per kilogram total weight (P less than .001) or per kilogram fat free mass (P less than .001) or when divided by the steady-state plasma insulin (l) level (M/l, P less than .001). There was residual HGP in 4 of 15 obese PCO, 0 of 11 obese normal, 2 of 10 nonobese PCO, and 0 of 8 nonobese normal women. The metabolic clearance rate of insulin did not differ in the four groups. We conclude that 1) PCO women have significant insulin resistance that is independent of obesity, changes in body composition, and impairment of glucose tolerance, 2) PCO and obesity have a synergistic deleterious effect on glucose tolerance, 3) hyperinsulinemia in PCO is not the result of decreased insulin clearance, and 4) PCO is associated with a unique disorder of insulin action.
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            Risk of cardiovascular and all-cause mortality in individuals with diabetes mellitus, impaired fasting glucose, and impaired glucose tolerance: the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab).

            Diabetes mellitus increases the risk of cardiovascular disease (CVD) and all-cause mortality. The relationship between milder elevations of blood glucose and mortality is less clear. This study investigated whether impaired fasting glucose and impaired glucose tolerance, as well as diabetes mellitus, increase the risk of all-cause and CVD mortality. In 1999 to 2000, glucose tolerance status was determined in 10,428 participants of the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab). After a median follow-up of 5.2 years, 298 deaths occurred (88 CVD deaths). Compared with those with normal glucose tolerance, the adjusted all-cause mortality hazard ratios (HRs) and 95% confidence intervals (CIs) for known diabetes mellitus and newly diagnosed diabetes mellitus were 2.3 (1.6 to 3.2) and 1.3 (0.9 to 2.0), respectively. The risk of death was also increased in those with impaired fasting glucose (HR 1.6, 95% CI 1.0 to 2.4) and impaired glucose tolerance (HR 1.5, 95% CI 1.1 to 2.0). Sixty-five percent of all those who died of CVD had known diabetes mellitus, newly diagnosed diabetes mellitus, impaired fasting glucose, or impaired glucose tolerance at baseline. Known diabetes mellitus (HR 2.6, 95% CI 1.4 to 4.7) and impaired fasting glucose (HR 2.5, 95% CI 1.2 to 5.1) were independent predictors for CVD mortality after adjustment for age, sex, and other traditional CVD risk factors, but impaired glucose tolerance was not (HR 1.2, 95% CI 0.7 to 2.2). This study emphasizes the strong association between abnormal glucose metabolism and mortality, and it suggests that this condition contributes to a large number of CVD deaths in the general population. CVD prevention may be warranted in people with all categories of abnormal glucose metabolism.
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              A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome.

              Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated with many characteristic features, including hyperandrogenaemia, insulin resistance and obesity which may have significant implications for pregnancy outcomes and long-term health of the woman. This meta-analysis was conducted to evaluate the risk of pregnancy and neonatal complications in women with PCOS. Electronic databases were searched for the following MeSH headings: PCOS, hyperandrogenism, pregnancy outcome, pregnancy complications, diabetes mellitus, type II. A handsearch of human reproduction and fertility and sterility was also conducted. Studies in which pregnancy outcomes in women with PCOS were compared with controls were considered for inclusion in this meta-analysis. Fifteen of 525 identified studies were included, involving 720 women presenting with PCOS and 4505 controls. Women with PCOS demonstrated a significantly higher risk of developing gestational diabetes [odds ratio (OR) 2.94; 95% confidence interval (CI): 1.70-5.08], pregnancy-induced hypertension (OR 3.67; 95% CI: 1.98-6.81), pre-eclampsia (OR 3.47; 95% CI: 1.95-6.17) and preterm birth (OR 1.75; 95% CI: 1.16-2.62). Their babies had a significantly higher risk of admission to a neonatal intensive care unit (OR 2.31; 95% CI: 1.25-4.26) and a higher perinatal mortality (OR 3.07; 95% CI: 1.03-9.21), unrelated to multiple births. In conclusion, women with PCOS are at increased risk of pregnancy and neonatal complications. Pre-pregnancy, antenatal and intrapartum care should be aimed at reducing these risks.
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                Author and article information

                Journal
                BMC Med
                BMC Medicine
                BioMed Central
                1741-7015
                2010
                30 June 2010
                : 8
                : 41
                Affiliations
                [1 ]Jean Hailes Clinical Research Unit, School of Public Health and Preventive Medicine, Monash University, Clayton, Australia
                [2 ]Diabetes Unit, Southern Health, Clayton, Australia
                Article
                1741-7015-8-41
                10.1186/1741-7015-8-41
                2909929
                20591140
                d2b6f213-e76c-4cd3-9ad2-6819193c6d3e
                Copyright ©2010 Teede et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 January 2010
                : 30 June 2010
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                Review

                Medicine
                Medicine

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