Adiponectin and polycystic ovary syndrome.

The prevalence of polycystic ovary syndrome (PCOS) in women of reproductive age ranges from 6.5% to 8%, and it is estimated that at least 4–5 million women are affected in the United States (Goodarzi & Azziz, 2006). Clinical presentation can vary but will include some combination of oligomenorrhea, hyperandrogenism, impaired glucose tolerance, predisposition to type 2 diabetes mellitus (T2DM), lipid abnormalities, and vascular disease (Ehrmann, 2005). The association of PCOS with metabolic and cardiovascular risk factors, most likely due to insulin resistance (Bethea & Nestler, 2008; Glintborg et al., 2006), puts women with PCOS at risk for T2DM and cardiovascular disease ([CVD]; Bethea & Nestler, 2008). There is a three- to fourfold increase in metabolic syndrome in women with PCOS compared with the general population (Cussons et al., 2008; Gulcelik, Aral, Serter, & Koc, 2008). Women with PCOS exhibit insulin resistance and androgen excess resulting in reproductive challenges and health consequences across the life span (Ehrmann, 2005). The insulin resistance in women diagnosed with PCOS is greater than that found in women without PCOS matched by body mass index (BMI) and body fat distribution (Ehrmann, 2005). Although obesity is common with this syndrome, the increased risk of metabolic syndrome and insulin resistance is not necessarily related to obesity in these cases (Svendsen, Nilas, Norgaard, Jensen, & Madsbad, 2008), suggesting a different mechanism may be present. Adipose tissue is an active endocrine organ that produces a variety of proteins, one being adiponectin (Magkos & Sidossis, 2007). Adiponectin, which has three major multidimer forms, is a circulating protein. Low levels (hypoadiponectinemia) are associated with conditions such as obesity, insulin resistance, metabolic syndrome, T2DM, and CVD. Conversely, high levels of adiponectin (hyperadiponectinemia) have anti-atherogenic, anti-inflammatory and anti-diabetic effects (Matsuzawa, 2005). Circulating levels of adiponectin are inversely related to adipocyte mass (Bloomgarden, 2005) and visceral adiposity (Matsuzawa, 2005). Plasma levels are lower in individuals with T2DM and are higher in individuals with insulin sensitivity (Bloomgarden, 2005; Matsuzawa, 2005). In insulin-sensitive individuals adipose tissue secretes high levels of adiponectin, but as adiposity increases, adiponectin secretion decreases (Rasouli & Kern, 2008). Decreased plasma levels and decreased adiponectin receptors occur with the development of insulin resistance, T2DM, metabolic syndrome, and obesity-related CVD (Kadowaki & Yamauchi, 2005). The specific role adiponectin plays in these metabolic conditions is not clear: it may have a causative role, or it could be regulated by insulin and serve as a marker for insulin resistance. Whichever function is correct; adiponectin is associated with insulin resistance and the metabolic syndrome (Pittas, Joseph, & Greenberg, 2004). Adiponectin circulates in different multimer complexes and molecular weights (Ebinuma et al., 2007). Following translation, it can be modified into several forms: trimers, hexamers, and high molecular weight (HMW) formations, which have varying biological effects (Hill, Kumar, & McTernan, 2009). Women have higher levels of total and HMW adiponectin than men, and for women there are significant negative correlations between HMW isomers and body fat measures (Peake, Kriketos, Campbell, Shen, & Charlesworth, 2005). Adiponectin levels have been examined in women diagnosed with PCOS, but delineation of a role for the protein in diagnosis and/or treatment has not occurred. The purpose of this article is to review the literature to determine what is known about the connection of adiponectin with PCOS and the potential application to clinical practice.