The effects of obesity and polycystic ovary syndrome on serum lipocalin-2 levels: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Lipocalin-2 is a novel adipokine that appears to play a role in the development of insulin resistance. Serum lipocalin-2 levels are elevated in obese patients. Obesity and insulin resistance are cardinal characteristics of the polycystic ovary syndrome (PCOS). However, there are limited data on serum lipocalin-2 levels in patients with PCOS. The aim of the present study was to assess serum lipocalin-2 levels in PCOS.</p> <p>Methods</p> <p>We studied 200 patients with PCOS and 50 healthy female volunteers.</p> <p>Results</p> <p>Serum lipocalin-2 levels were slightly higher in women with PCOS compared with controls (65.4 +/- 34.3 vs. 60.3 +/- 26.0 ng/ml, respectively) but this difference did not reach statistical significance. In contrast, lipocalin-2 levels were higher in overweight/obese women with PCOS than in normal weight women with the syndrome (76.2 +/- 37.3 vs. 54.5 +/- 27.2 ng/ml, respectively; p < 0.001). Serum lipocalin-2 levels were also higher in overweight/obese controls compared with normal weight controls (70.1 +/- 24.9 vs. 50.5 +/- 23.7 ng/ml, respectively; p = 0.004). In the total study population (patients with PCOS and controls), lipocalin-2 levels were independently correlated with the body mass index (p < 0.001). In women with PCOS, lipocalin-2 levels were independently correlated with the waist (p < 0.001).</p> <p>Conclusions</p> <p>Obesity is associated with elevated serum lipocalin-2 levels. In contrast, PCOS does not appear to affect lipocalin-2 levels.</p

Vaspin: a novel adipokine, member of the family of serine protease inhibitors

In 2000, the novel adipokine vaspin, which belongs to the superfamily of serpins, was isolated from visceral adipose tissue. Vaspin is mainly produced in the visceral adipose tissue and is related to insulin resistance, blood glucose levels, sex hormones (women have higher levels compared to men) and nutritional status. Moreover, vaspin levels are modulated by weight loss and several agents, and it possibly constitutes a connecting link between obesity and its associated metabolic disorders. Many patients with polycystic ovary syndrome have insulin resistance, obesity (mostly visceral) and glucose intolerance, conditions associated with abnormalities in the production of vaspin. The role of vaspin in the regulation of human metabolism is unclear at present, but it appears that vaspin might represent a novel marker of obesity and insulin resistance. However, the controversial findings of existing studies on vaspin stress the need for further research in women with obesity and metabolic disorders in order to elucidate the role of this adipokine in these diseases and particularly in the polycystic ovary syndrome

Mechanisms of infertility in polycystic ovary syndrome

It has been proposed that the follicular problem in polycystic ovary syndrome is 2-fold. First, the intra-ovarian hyperandrogenism may promote early follicular growth, leading to a 2-5mm follicle excess. Second, the ensuing excessive number of selectable follicles would inhibit the selection process, presumably through follicle to follicle interaction involving granulosa cell products such as the anti-Mϋllerian hormone. These factors would induce a reversible refractoriness to the FSH-induced differentiation of granulosa cells. This explanation challenges but does not exclude other hypotheses about the follicular arrest, such as the premature LH action on the granulosa cells of selectable follicles. Hyperinsulinism or insulin resistance would act as a second hit, worsening the follicular arrest either through amplification of the intra-ovarian hyperandrogenism or through dysregulation of the granulosa cells. The loss of cyclic rhythm would prevent the inter-cycle elevation of FSH, thus perpetuating of the ovulation process

Effect of metformin administration on plasma advanced glycation end product levels in women with polycystic ovary syndrome

Metformin therapy in polycystic ovary syndrome (PCOS) improves metabolic and hormonal profiles. Its therapeutic effect on cardiovascular risk factors is under investigation. Advanced glycation end products (AGEs), well-known atherogenic molecules, were recently found to be elevated in plasma of women with PCOS. The purpose of the study was to investigate the effect of metformin treatment in plasma AGE levels of women with PCOS. This was a descriptive clinical trial. The study involved 22 patients with PCOS (age, 25.09 +/- 1.05 years; body mass index [BMI], 28.44 +/- 1.51 kg/m(2)) and 22 healthy women (age, 26.50 +/- 0.85 years; BMI, 25.62 +/- 1.30 kg/m(2)). Measurements of plasma AGE levels (U/mL) were performed, and the metabolic and hormonal profiles were determined in all subjects. All women with PCOS received a dose of 1700 mg metformin daily for 6 months. AGEs levels were reduced after metformin administration in 22 women with PCOS (9.98 +/- 0.13 [before metformin] vs 9.86 +/- 0.11 [after metformin], P =.05). In a subgroup analysis, of 16 women with PCOS and normal glucose tolerance, the drop of AGE levels was potentiated (9.98 +/- 0.19 [before] vs 9.81 +/- 0.15 [after], P =.02). Body mass index as well as the other parameters studied remained unchanged after metformin therapy apart from a drop of testosterone levels (P =.01) and free androgen index (P =.009). In conclusion, after metformin therapy, the atherogenic AGE molecules were reduced in the serum of women with PCOS. The clinical relevance of this finding in PCOS, a high-risk group for type 2 diabetes mellitus and cardiovascular disease, remains to be seen. Future studies are required to confirm the need of therapeutic intervention for short-term abnormalities and for prevention of long-term sequelae characterizing this syndrome. (c) 2007 Elsevier Inc. All rights reserved

Anti-mullerian hormone is associated with advanced glycosylated end products in lean women with polycystic ovary syndrome

Objective: Oocyte maturation process characterizes polycystic ovary syndrome (PCOS). The mechanisms of this abnormality leading to chronic anovulation are under investigation. Advanced glycosylated end products (AGEs). a marker of oxidative stress linked with oocyte Maturation are localized in granulosa cells and are increased in sera. in women with pCOS. The aim of this Study was to investigate the relationship, whether there is an association between the anti-mullerian hormone (AMH), a hormone produced by granulosa cells and AGEs in ovulatory and anovulatory PCOS (PCOS-Anov), its well as in non-PCOS anovulatory (Non-PCOS Anov) women. Design: Cross-sectional study. Methods: Data from sixty women with PCOS (37 anovulatory and 23 regularly ovulating) were compared with eleven Non-PCOS Anov women and 25 normal women. In each Subject biochemical, hormonal, and ultrasonographic parameters were Studied. Results: AMH values were statistically significantly higher in PCOS-Anov (7.63 +/- 3.12) in comparison with ovulatory PCOS (PCOS-Ov: 4.92 +/- 2.50), Non-PCOS Anov (3.66 +/- 1.4), and controls (4.02 +/- 1.27 ng/ml). AGEs demonstrated a similar pattern: 8.70 +/- 1.65 in PCOS-Anov, 7.43 +/- 1.79. PCOS-Ov, 5.21 +/- 0.09, Non-PCOS Anov, and 5.85 +/- 0.89 U/ml in controls (P &lt; 0.005 for all comparison respectively). Follicle number was significantly higher in PCOS-Anov in comparison with other groups. A significant, positive correlation between AMH and AGEs was observed (r: 0.326, P &lt; 0.01). and with the estimated AMH/AGEs ratio to follicle number (r: 0.42, P: 0.0001) and the presence of anovulation. Conclusions: These data suggest that an oxidative marker, AGEs. and AMH, may interact in the anovulatory mechanisms in women with PCOS

Plasma metastin levels are negatively correlated with insulin resistance and free androgens in women with polycystic ovary syndrome

Objective: This study was designed to: [1] measure, for the first time, metastin (kisspeptin) levels in women with polycystic ovary syndrome (PCOS), a condition associated with hypersecretion of LH and hyperandrogenemia; and [2] investigate the possible correlations between metastin and PCOS-related reproductive and metabolic disturbances. Design: Clinical study. Setting: University hospital. Patient(s): Twenty-eight obese and overweight (body mass index [BMI] &gt; 25 kg/m(2)) women with the syndrome, and 13 obese and overnight controls (ovulatory women without clinical or biochemical hyperandrogenemia) were selected. Intervention(s): Blood samples were collected between day 3 and day 6 of a sponataneous bleeding episode in the PCOS groups and a menstrual cycle of the controls, at 9:00 AM, after an overnight fast. Main Outcome Measure(s): Circulating levels of LH, FSH, PRL, T, Delta(4)-androstenedione (A), DHEAS, 17 alpha OH-P, sex hormone-binding globulin (SHBG), insulin, glucose, and metastin were measured. Result(s): Both normal weight women with PCOS and obese controls were less insulin resistant and had significantly higher metastin levels, compared to obese and overweight women with the syndrome. Plasma kisspeptin levels were negatively correlated with BMI, free androgen index, and indices of insulin resistance. Conclusion(s): These results indicate that metastin is negatively associated with free androgen levels. The PCOS-associated insulin resistance and consequent hyperinsulinemia probably contribute to this effect by [1] stimulating androgen synthesis by the polycystic ovary (PCO) and [2] suppressing SHBG production in the liver

Serum concentrations of carboxylated osteocalcin are increased and associated with several components of the polycystic ovarian syndrome

Intriguing studies suggest that osteocalcin (OC) and its carboxylated (Gla)/uncarboxylated form are involved in the regulation of insulin secretion and action. Additionally, advanced glycated end products (AGEs) directly regulate the secretion of these osteoblast-derived molecules. In polycystic ovarian syndrome (PCOS), among the pathophysiological aberrations, deregulation of insulin secretion and action as well as elevated AGEs levels have been demonstrated. In this study, we evaluated the serum levels of osteocalcin and Gla osteocalcin and their possible associations with metabolic, hormonal, and ultrasonographic components of PSOS: 97 women were studied, 50 PCOS patients and 47 controls, matched for age and body mass index (BMI). In each subject, the levels of bone metabolism markers have been evaluated, and metabolic and hormonal profiles as well as ovarian ultrasound were carried out. Osteocalcin (4.30 +/- A 1.74 vs. 6.20 +/- A 1.78 ng/ml, P &lt; 0.0005) values were significantly lower, whereas Gla osteocalcin (37.93 +/- A 6.87 vs. 9.64 +/- A 8.21 ng/ml, P &lt; 0.0005) and receptor activator for nuclear factor-kappa B ligand (0.54 +/- A 0.26 vs. 0.16 +/- A 0.15 pmol/l, P &lt; 0.0005) values were significantly higher in PCOS subjects compared to the control group, independently of obesity. A significant association was disclosed between osteocalcin and Gla osteocalcin with androgens, insulin resistance, AGEs, and ovarian morphology. Receiver operating curve analysis revealed that Gla osteocalcin [AUC, 0.975 (95% CI, 0.93-1.00)] as well as AGEs are significant prognostic factors of PCOS [AUC, 0.986 (95% CI, 0.97-1.00)]. Lower osteocalcin and elevated serum levels of its carboxylated form are displayed in PCOS subjects and are associated with several PCOS components. These findings suggest a potential interaction between bone-derived markers and the metabolic/hormonal abnormalities observed in PCOS. However, the pathophysiological mechanisms and moreover the possible clinical implications require further investigation