The role of genes and environment in the etiology of PCOS.

Both genes and the environment contribute to PCOS. Obesity, exacerbated by poor dietary choices and physical inactivity, worsens PCOS in susceptible individuals. The role of other environmental modifiers such as infectious agents or toxins are speculative. Phenotype confusion has characterized genetic studies of PCOS. Although several loci have been proposed as PCOS genes including CYP11A, the insulin gene, the follistatin gene, and a region near the insulin receptor, the evidence supporting linkage is not overwhelming. The strongest case can be made for the region near the insulin receptor gene (but not involving this gene), as it has been identified in two separate studies, and perhaps most importantly has not yet been refuted by larger studies. However, the responsible gene at chromosome 19p13.3 remains to be identified. To date, no gene has been identified that causes or contributes substantially to the development of a PCOS phenotype.

Short-term effect of orlistat on dietary glycotoxins in healthy women and women with polycystic ovary syndrome.

Exogenous advanced glycation endproducts (AGEs, known atherogenic molecules) abundant in everyday precooked, rich in fat, overheated meals can possibly contribute to the increased risk for diabetes and cardiovascular disease in women with polycystic ovary syndrome (PCOS). The aim of the present study was to investigate the effect of a lipase inhibitor on absorbed food glycotoxins in healthy women and those with PCOS. A 2-day protocol was followed. In the first day, a meal rich in AGE was provided, which on the second day was followed by two 120-mg capsules of lipase inhibitor, orlistat. Serum AGE levels were evaluated at baseline (0 hours), and at 3 and 5 hours postmeal during the study. Thirty-six women were studied, 15 controls (mean age, 28.80 +/- 5.47 years; body mass index, 25.85 +/- 6.73 kg/m(2)) and 21 with PCOS (mean age, 25.29 +/- 5.06 years; body mass index, 30.40 +/- 7.51 kg/m(2)) (University Hospital, Athens, Greece, institutional practice). Serum AGE levels, on day 1, were significantly increased both in the control group and in the PCOS group as compared with basal values (control group, 14.1%; PCOS group, 6.0%; P < .001). The corresponding rise was significantly lower on day 2 when the same meal was combined with orlistat (control group, 4.1%; PCOS group, 2.0%; P < .01). A limitation of the study is that it is a nonplacebo, nonrandomized therapeutic trial where each subject is considered as its own control. In conclusion, this study demonstrated the beneficial effect of orlistat on the absorption of food glycotoxins.

Indices of low-grade inflammation in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is probably the most common endocrinopathy of reproductive age. PCOS represents a disorder that not only enhances the risk for type 2 diabetes (T2D) but is also associated with an increased number of cardiovascular risk factors known to facilitate atherogenesis. On the other hand, inflammation is thought to play an important role in the progression and development of complications of atherosclerosis. Evidence of low-grade chronic inflammation in PCOS is indicated by the presence of elevated C-reactive protein (CRP) levels, inflammatory cytokines (i.e., IL-6 and IL-18), and increased leucocyte count. CRP, a nonspecific marker of inflammation, has been proven to be one of the strongest predictors of the risk of cardiovascular events in patients with or without cardiovascular disease. The levels of the adhesion molecules (AM), sIVAM-1, sVCAM-1, and sE-selectin in serum reflect low-grade chronic inflammation of the endothelium and independently predict coronary heart disease (CHD) and T2D. In a recent study in a large number of PCOS women we demonstrated elevated levels of sIVAM-1 and sE-selectin and we further substantiated the existence of a low-grade chronic inflammatory process in PCOS. However, it remains to be assessed with long-term studies whether the early presence of markers of chronic inflammation in young women with this syndrome has clinical significance.

Obesity and gonadal function of women.

Excessive visceral adiposity is associated with metabolic and reproductive abnormalities. Adipose tissue is an active endocrine gland and participates in multiple mechanisms in the reproductive function of women. The nature of the complex interaction of obesity with the female reproductive function remains a challenge. Several links have been implicated in the gonadal dysfunction of obese women, like insulin resistance and hyperinsulinemia, via which ovarian androgen production is stimulated resulting in hyperandrogenemia, increased peripheral aromatization of androgens to estrogens, altered gonadotrophin secretion, decreased sex hormone binding globulin, decreased GH and IGFBPs, increased leptin levels and altered neuroregulation of the hypothalamic-pituitary-gonadal axis. The impact of obesity in these mechanisms and their influence on female reproductive function are discussed in this article.

Conservative management of gynecologic diseases: insulin sensitizing agents in polycystic ovary syndrome.

A contemporary "Pandora's box" could be the polycystic ovary syndrome (PCOS), containing several negative features for a woman: compromised looks, compromised fertility; increased metabolic risk factors; and compromised general health. During the past decade, the central importance of insulin resistance (IR) in the pathogenesis of this syndrome has been established. Several in vivo and in vitro studies have demonstrated this phenomenon, initially by the hyperinsulinemic response to oral glucose in obese and lean women with PCOS compared with weight-matched normal women, and subsequently with more sensitive techniques like euglycemic hyperinsulinemic clamp. In vitro studies have corroborated these findings, showing molecular defects at the postreceptor level of insulin action, such as increased serine phosphorylation and decreased phosphoinositol 3-kinase action. Insulin sensitizers are the group of therapeutic agents that hold some promise of helping women with polycystic ovary syndrome (PCOS), since the role of insulin resistance and hyperinsulinemia appear to be major contributors to the pathophysiology of the syndrome. The therapeutic approach with insulin sensitizers appears to have beneficial effects on the metabolic as well as on the reproductive abnormalities in women affected by PCOS. Finally, insulin sensitizers should be considered by all subspecialists who aim at a comprehensive management of patients with PCOS.