There is growing interest in the possible health threat posed by endocrine-disrupting chemicals (EDCs), which are substances in our environment, food, and consumer products that interfere with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. In this first Scientific Statement of The Endocrine Society, we present the evidence that endocrine disruptors have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology. Results from animal models, human clinical observations, and epidemiological studies converge to implicate EDCs as a significant concern to public health. The mechanisms of EDCs involve divergent pathways including (but not limited to) estrogenic, antiandrogenic, thyroid, peroxisome proliferator-activated receptor gamma, retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways that are highly conserved in wildlife and humans, and which can be modeled in laboratory in vitro and in vivo models. Furthermore, EDCs represent a broad class of molecules such as organochlorinated pesticides and industrial chemicals, plastics and plasticizers, fuels, and many other chemicals that are present in the environment or are in widespread use. We make a number of recommendations to increase understanding of effects of EDCs, including enhancing increased basic and clinical research, invoking the precautionary principle, and advocating involvement of individual and scientific society stakeholders in communicating and implementing changes in public policy and awareness.

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Based on the available data, it is the view of the AES Task Force on the Phenotype of PCOS that there should be acceptance of the original 1990 National Institutes of Health criteria with some modifications, taking into consideration the concerns expressed in the proceedings of the 2003 Rotterdam conference. A principal conclusion was that PCOS should be first considered a disorder of androgen excess or hyperandrogenism, although a minority considered the possibility that there may be forms of PCOS without overt evidence of hyperandrogenism but recognized that more data are required before validating this supposition. Finally, the task force recognized, and fully expects, that the definition of this syndrome will evolve over time to incorporate new research findings.

Polycystic ovary syndrome (PCOS) is now recognized as an important metabolic as well as reproductive disorder conferring substantially increased risk for type 2 diabetes. Affected women have marked insulin resistance, independent of obesity. This article summarizes the state of the science since we last reviewed the field in the Endocrine Reviews in 1997. There is general agreement that obese women with PCOS are insulin resistant, but some groups of lean affected women may have normal insulin sensitivity. There is a post-binding defect in receptor signaling likely due to increased receptor and insulin receptor substrate-1 serine phosphorylation that selectively affects metabolic but not mitogenic pathways in classic insulin target tissues and in the ovary. Constitutive activation of serine kinases in the MAPK-ERK pathway may contribute to resistance to insulin's metabolic actions in skeletal muscle. Insulin functions as a co-gonadotropin through its cognate receptor to modulate ovarian steroidogenesis. Genetic disruption of insulin signaling in the brain has indicated that this pathway is important for ovulation and body weight regulation. These insights have been directly translated into a novel therapy for PCOS with insulin-sensitizing drugs. Furthermore, androgens contribute to insulin resistance in PCOS. PCOS may also have developmental origins due to androgen exposure at critical periods or to intrauterine growth restriction. PCOS is a complex genetic disease, and first-degree relatives have reproductive and metabolic phenotypes. Several PCOS genetic susceptibility loci have been mapped and replicated. Some of the same susceptibility genes contribute to disease risk in Chinese and European PCOS populations, suggesting that PCOS is an ancient trait.

Women with PCOS with obesity, cigarette smoking, dyslipidemia, hypertension, impaired glucose tolerance, and subclinical vascular disease are at risk, whereas those with metabolic syndrome and/or type 2 diabetes mellitus are at high risk for CVD. Body mass index, waist circumference, serum lipid/glucose, and blood pressure determinations are recommended for all women with PCOS, as is oral glucose tolerance testing in those with obesity, advanced age, personal history of gestational diabetes, or family history of type 2 diabetes mellitus. Mood disorder assessment is suggested in all PCOS patients. Lifestyle management is recommended for primary CVD prevention, targeting low-density and non-high-density lipoprotein cholesterol and adding insulin-sensitizing and other drugs if dyslipidemia or other risk factors persist.

Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. Great efforts have been made in the last 2 decades to define the syndrome. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic heterogeneity of the syndrome. Major criteria are required for the diagnosis, which in turn identifies different phenotypes according to the combination of different criteria. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject. This paper offers a critical endocrine and European perspective on the debate on the definition of PCOS and summarises all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. We have also paid specific attention to the role of obesity, sleep disorders and neuropsychological aspects of PCOS and on the relevant pathogenetic aspects of cardiovascular risk factors. In addition, we have discussed how to target treatment choices based according to the phenotype and individual patient's needs. Finally, we have suggested potential areas of translational and clinical research for the future with specific emphasis on hormonal and metabolic aspects of PCOS.

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, chronic anovulation, and oligomenorrhea (O/M). PCOS has variable clinical phenotypes, biochemical features, and metabolic abnormalities. To determine the prevalence of PCOS in the Greek population as well as the metabolic parameters, we performed a cross-sectional study of 192 women of reproductive age (17-45 yr), living on the Greek island of Lesbos. They were divided into 4 groups according to the presence of hirsutism (defined as a Ferriman-Gallwey score > or = 6) and O/M: group N (n = 108), regular menses and absence of hirsutism; group 1 (n = 56), regular menses and hirsutism; group 2 (n = 10), O/M and absence of hirsutism; and group 3 (n = 18), O/M and hirsutism. Body mass index, waist to hip ratio, and mean blood pressure did not differ among the studied groups. Hormonal profile was assessed by measuring free testosterone (FT). The prevalence of PCOS, defined by the presence of O/M and biochemical hyperandrogenism (FT > or = 95th percentile of the normal women), was estimated to be 6.77% (13 women of 192). Higher FT levels were observed in group 3 (O/M and hirsutism) compared with groups N (P < 0.00001) and 1 (P < 0.0001) and in groups 1 (hirsutism) and 2 (O/M) compared with group N (P < 0.0001 and P < 0.005, respectively). Sex hormone-binding globulin levels were lower in women with PCOS and in groups 1 and 3 than those in group N (P < 0.002, P < 0.02, and P < 0.002, respectively) independently of the body mass index. The metabolic profile was investigated by measurements of fasting glucose (FG), fasting insulin (FI), and estimation of the fasting glucose to insulin ratio (FG:I ratio). After covariance adjusted for the BMI, FI levels were higher in group 3 and in women with PCOS than in the normal (P < 0.005 and P < 0.002, respectively) and the hirsute (P < 0.05 and P < 0.02, respectively) women, whereas FG levels did not differ among the studied groups. The FG:I ratio was lower in group 3, group 1, and in women with PCOS than in normal women (P < 0.05). Finally, a high incidence of family history of diabetes mellitus (P = 0.001) and menstrual disorders (P = 0.01) was observed in women with PCOS, in contrast to the normal and hirsute women. In conclusion, PCOS appears to be a particularly common endocrine disorder in the Greek population under study (prevalence, 6.77%); furthermore, it is associated with certain metabolic abnormalities. These data also suggest that the severity of the fasting hyperinsulinemia is associated with the severity of the clinical phenotype of hyperandrogenism independently of obesity.

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, chronic anovulation, and oligomenorrhea (O/M). PCOS has variable clinical phenotypes, biochemical features, and metabolic abnormalities. To determine the prevalence of PCOS in the Greek population as well as the metabolic parameters, we performed a cross-sectional study of 192 women of reproductive age (17-45 yr), living on the Greek island of Lesbos. They were divided into 4 groups according to the presence of hirsutism (defined as a Ferriman-Gallwey score > or = 6) and O/M: group N (n = 108), regular menses and absence of hirsutism; group 1 (n = 56), regular menses and hirsutism; group 2 (n = 10), O/M and absence of hirsutism; and group 3 (n = 18), O/M and hirsutism. Body mass index, waist to hip ratio, and mean blood pressure did not differ among the studied groups. Hormonal profile was assessed by measuring free testosterone (FT). The prevalence of PCOS, defined by the presence of O/M and biochemical hyperandrogenism (FT > or = 95th percentile of the normal women), was estimated to be 6.77% (13 women of 192). Higher FT levels were observed in group 3 (O/M and hirsutism) compared with groups N (P < 0.00001) and 1 (P < 0.0001) and in groups 1 (hirsutism) and 2 (O/M) compared with group N (P < 0.0001 and P < 0.005, respectively). Sex hormone-binding globulin levels were lower in women with PCOS and in groups 1 and 3 than those in group N (P < 0.002, P < 0.02, and P < 0.002, respectively) independently of the body mass index. The metabolic profile was investigated by measurements of fasting glucose (FG), fasting insulin (FI), and estimation of the fasting glucose to insulin ratio (FG:I ratio). After covariance adjusted for the BMI, FI levels were higher in group 3 and in women with PCOS than in the normal (P < 0.005 and P < 0.002, respectively) and the hirsute (P < 0.05 and P < 0.02, respectively) women, whereas FG levels did not differ among the studied groups. The FG:I ratio was lower in group 3, group 1, and in women with PCOS than in normal women (P < 0.05). Finally, a high incidence of family history of diabetes mellitus (P = 0.001) and menstrual disorders (P = 0.01) was observed in women with PCOS, in contrast to the normal and hirsute women. In conclusion, PCOS appears to be a particularly common endocrine disorder in the Greek population under study (prevalence, 6.77%); furthermore, it is associated with certain metabolic abnormalities. These data also suggest that the severity of the fasting hyperinsulinemia is associated with the severity of the clinical phenotype of hyperandrogenism independently of obesity.