The role of orlistat combined with lifestyle changes in the management of overweight and obese patients with polycystic ovary syndrome.

OBJECTIVE: Obesity is frequently present in women with the polycystic ovary syndrome (PCOS) and aggravates insulin resistance (IR) and hyperandrogenemia. We aimed to assess the effects of orlistat combined with lifestyle changes in overweight and obese women with PCOS and body mass index (BMI)-matched controls. DESIGN: Prospective study. PATIENTS: We studied 101 women with PCOS (age 26·1 ± 6·4 years, BMI 34·5 ± 5·9 kg/m(2) ) and 29 BMI-matched women with normal ovulating cycles. All women were instructed to follow a low-calorie diet to exercise and were treated with orlistat 120 mg tid for 6 months. MEASUREMENTS: Metabolic and endocrine characteristics of PCOS, blood pressure (BP) and lipid profile. RESULTS: A significant and comparable reduction in BMI was observed in women with PCOS and controls. Systolic and diastolic BP decreased only in women with PCOS. Serum low-density lipoprotein cholesterol levels decreased in both women with PCOS and controls; however, this reduction was greater in controls. In contrast, serum high-density lipoprotein cholesterol levels did not change in women with PCOS and decreased in controls. Serum triglyceride levels decreased significantly and to a comparable degree in the two groups. Similarly, markers of IR improved significantly and to a comparable degree in women with PCOS and controls. Serum testosterone levels and the free androgen index decreased significantly in women with PCOS and did not change in controls. CONCLUSIONS: Orlistat combined with lifestyle changes induces substantial weight loss in women with PCOS, resulting in improvements in IR, hyperandrogenemia and cardiovascular risk factors.

Uterine volume and endometrial thickness in the early follicular phase in patients with polycystic ovary syndrome.

OBJECTIVE: We aimed to evaluate uterine volume and endometrial thickness during the early follicular phase in patients with polycystic ovary syndrome (PCOS) and healthy controls. METHODS: We studied 1,016 PCOS patients and 182 healthy controls. The anthropometric, endocrine, and metabolic characteristics of PCOS were determined. Uterine volume and endometrial thickness were also recorded. RESULTS: Uterine volume progressively increased with age both in PCOS patients and controls. Patients with PCOS and body mass index (BMI) ≥25 kg/m2 had greater uterine volumes than PCOS patients with BMI <25 kg/m2 (P<.001). Patients with the classic PCOS phenotypes (i.e., with oligo-ovulation and/or anovulation [ANOV] and hyperandrogenemia [HA] with or without polycystic ovaries [PCO]) had smaller uterine volume than PCOS patients with the additional phenotypes introduced by the Rotterdam criteria (i.e., with PCO and either ANOV or HA; P = .033) and controls (P = .045). CONCLUSION: Uterine volume increases progressively with age and obesity in PCOS patients. The smaller uterine volumes and endometrial thicknesses in the classic PCOS phenotypes might be attributed to the more severe HA of these patients.

ENhancinG vAGinal dElivery in Greece through educational and behavioral interventions among maternity care providers regarding labor management: the ENGAGE stepped-wedge randomized prospective trial protocol.

BACKGROUND: There is an emerging need to systematically investigate the causes for the increased cesarean section rates in Greece and undertake interventions so as to substantially reduce its rates. To this end, the ability of the participating Greek obstetricians to follow evidence-based guidelines and respond to other educational and behavioral interventions while managing labor will be explored, along with barriers and enablers. Herein discussed is the protocol of a stepped-wedge designed intervention trial in Greek maternity units with the aforementioned goals in mind, named ENGAGE (ENhancinG vAGinal dElivery in Greece). METHODS: Twenty-two selected maternity units in Greece will participate in a multicenter stepped-wedge randomized prospective trial involving 20,000 to 25,000 births, with two of them entering the intervention period of the study each month (stepped randomization). The maternity care units entering the study will apply the suggested interventions for a period of 8-18 months depending on the time they enter the intervention stage of the study. There will also be an initial phase of the study lasting from 8 to 18 months including observation and recording of the routine practice (cesarean section, vaginal birth, and maternal and perinatal morbidity and mortality) in the participating units. The second phase, the intervention period, will include such interventions as the application of the HSOG (the Hellenic Society of Obstetrics and Gynecology) Guidelines on labor management, training on the correct interpretation of cardiotocography, and dealing with emergencies in vaginal deliveries, while the steering committee members will be available to discuss and implement organizational and behavioral changes, answer questions, clarify relevant issues, and provide practical instructions to the participating healthcare professionals during regular visits or video conferences. Furthermore, during the study, the results will be available for the participating units in order for them to monitor their own performance while also receiving feedback regarding their rates. Τhe final 2-month phase of the study will be devoted to completing follow-up questionnaires with data concerning maternal and neonatal morbidities that occurred after the completion of the intervention period. The total duration of the study is estimated at 28 months. The primary outcome assessed will be the cesarean section rate change and the secondary outcomes will be maternal and neonatal morbidity and mortality. DISCUSSION: The study is expected to yield new information on the effects, advantages, possibilities, and challenges of consistent clinical engagement and implementation of behavioral, educational, and organizational interventions described in detail in the protocol on cesarean section practice in Greece. The results may lead to new insights into means of improving the quality of maternal and neonatal care, particularly since this represents a shared effort to reduce the high cesarean section rates in Greece and, moreover, points the way to their reduction in other countries. TRIAL REGISTRATION: NCT04504500 (ClinicalTrials.gov). The trial was prospectively registered. Ethics Reference No: 320/23.6.2020, Bioethics and Conduct Committee, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Prevalence of metabolic syndrome in women with polycystic ovary syndrome.

OBJECTIVE: The polycystic ovary syndrome (PCOS) and the metabolic syndrome (MetS) are common disorders that share many characteristics, particularly abdominal obesity and insulin resistance. Our objective was to compare the prevalence of MetS between a large cohort of patients with PCOS and body mass index -matched controls. DESIGN: Cross-sectional study. PATIENTS: We studied 1223 patients with PCOS and 277 healthy women. Diagnosis of PCOS was based on the revised Rotterdam criteria. Women with PCOS were divided into those who fulfilled both the Rotterdam criteria and the diagnostic criteria of the 1990 National Institutes of Health definition of PCOS (group 1, n = 905) and into those with the additional phenotypes introduced by the Rotterdam criteria (group 2, n = 318). Diagnosis of MetS was based on four different definitions. MEASUREMENTS: Anthropometric, metabolic, hormonal and ultrasonographic features of PCOS. RESULTS: The prevalence of metabolic syndrome (MetS) was higher in women with PCOS than in controls when the National Cholesterol Education Program Adult Treatment Panel III definition of MetS was applied (15·8% and 10·1%, respectively; P = 0·021) but not with the three more recent MetS definitions. The prevalence of MetS was higher in group 1 than in controls regardless of the applied MetS definition. In contrast, the prevalence of MetS was similar in group 2 and in controls regardless of the applied MetS definition. In logistic regression analysis, PCOS did not predict the presence of MetS. CONCLUSIONS: Polycystic ovary syndrome per se does not appear to increase the risk of MetS independent of abdominal obesity.

Comparison of markers of insulin resistance and circulating androgens between women with polycystic ovary syndrome and women with metabolic syndrome.

STUDY QUESTION: Do women with the polycystic ovary syndrome (PCOS) differ from those with the metabolic syndrome (MetS) in markers of insulin resistance (IR) and circulating androgens? SUMMARY ANSWER: Women with MetS have more pronounced IR than those with PCOS whereas only the latter have elevated circulating androgens. WHAT IS KNOWN ALREADY: PCOS and MetS share many similarities, including abdominal obesity and IR, and PCOS is regarded as the ovarian manifestation of MetS. However, there are limited data on the differences between markers of IR and circulating androgens between women with these two syndromes. STUDY DESIGN, SIZE, DURATION: A prospective study in 1223 Caucasian women with PCOS and 277 women without PCOS, matched for BMI, was performed between May 2004 and December 2011. The presence/absence of MetS in PCOS+ and PCOS- women was recorded and comparisons among the resulting four groups were performed. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was performed in a university department of obstetrics and gynecology. The following markers of IR were determined: serum glucose and insulin levels, glucose/insulin ratio, area under the oral glucose tolerance test, homeostasis model assessment of IR index and quantitative insulin sensitivity check index. MAIN RESULTS AND THE ROLE OF CHANCE: PCOS+MetS+ women (n = 361) were more insulin-resistant than PCOS+MetS- women (n = 862) (P < 0.001 for the comparisons in all markers of IR). Similarly, PCOS-MetS+ women (n = 66) were more insulin-resistant than PCOS-MetS- women (n = 211) (P < 0.001 for the comparisons in all markers of IR). In contrast, PCOS+MetS+ showed only borderline significant differences in some markers of IR compared with PCOS-MetS+ women (P < 0.05). Similarly, PCOS+MetS- women showed only borderline significant differences in some markers of IR compared with PCOS-MetS- women (P = 0.037). Moreover, PCOS-MetS+ women were more insulin-resistant than PCOS + MetS- women (P < 0.001 for the comparisons in all markers of IR). Regarding circulating androgens, PCOS+MetS+ women had higher levels of circulating androgens than PCOS-MetS+ women (P < 0.001 for the comparisons in all circulating androgens). Similarly, PCOS+MetS- women had higher levels of circulating androgens than PCOS-MetS- women (P < 0.001 for the comparisons in all circulating androgens). In contrast, circulating androgens did not differ between PCOS+MetS+ women and PCOS+MetS- women. Similarly, circulating androgens did not differ between PCOS-MetS+ women and PCOS-MetS- women. LIMITATIONS, REASONS FOR CAUTION: Only Caucasian women were included in the study. IR was not assessed with the euglycemic hyperinsulinemic clamp. WIDER IMPLICATIONS OF THE FINDINGS: Even though MetS and PCOS have many similarities, they are distinct disorders. PCOS does not appear to simply represent the ovarian manifestation of MetS. Further studies are required to assess the contribution of hyperandrogenism to the pathogenesis of IR in PCOS. STUDY FUNDING/COMPETING INTEREST(S): No external funding was either sought or obtained for this study.

Platelet-derived microparticles in overweight/obese women with the polycystic ovary syndrome.

A substantial proportion of women with the polycystic ovary syndrome (PCOS) are obese and obesity is considered as a prothrombotic state. Platelet-derived microparticles (PMPs) might be implicated in the activation of the coagulation cascade. We aimed to assess plasma PMPs in overweight/obese women with PCOS. We measured plasma PMPs and determined anthropometric, metabolic, hormonal and ultrasonographic features of PCOS in 67 overweight/obese women with PCOS (with body mass index [BMI] >25.0 kg/m²) and in 21 BMI-matched healthy women. Circulating androgens and markers of insulin resistance (IR) were higher in women with PCOS than in controls. Plasma PMPs were also higher in women with PCOS than in controls (p = 0.046). In women with PCOS, plasma PMPs correlated with the mean number of follicles in the ovaries (r = 0.343; p = 0.006). In controls, plasma PMPs did not correlate with any of the studied parameters. In conclusion, plasma PMPs are elevated in overweight/obese women with PCOS compared with BMI-matched controls. The cause of this increase is unclear but both IR and hyperandrogenemia might be implicated. More studies are required to elucidate the pathogenesis of the elevation of PMPs in PCOS and to assess its implications on the cardiovascular risk of these patients.

Age- and body mass index-related differences in the prevalence of metabolic syndrome in women with polycystic ovary syndrome.

AIM: To compare the prevalence of metabolic syndrome (MetS) between women with polycystic ovary syndrome (PCOS) and controls across different age (≤20, 21-30 and 31-39 years old) and body mass index (BMI) (normal weight, overweight and obese) groups. METHODS: We studied 1223 women with PCOS and 277 BMI-matched controls. The prevalence of MetS in women with PCOS and controls was estimated according to four different MetS definitions. RESULTS: In subjects ≤20 and 21-30 years old, the prevalence of MetS did not differ between women with PCOS and controls regardless of the MetS definition, even though women with PCOS were more obese than controls in the ≤20 years old group. In subjects 31-39 years old, the prevalence of MetS was higher in women with PCOS than in controls but the former were more obese than controls. The prevalence of MetS did not differ significantly between women with PCOS and controls in any of the BMI groups (normal weight, overweight or obese) regardless of the MetS definition. CONCLUSION: The prevalence of Mets appears to be primarily determined by obesity and age whereas PCOS per se appears to be a less important contributing factor.

Diet, physical exercise and Orlistat administration increase serum anti-Müllerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS).

The present study investigates the combined effect of diet, physical exercise and Orlistat for 24 weeks, on serum anti-Müllerian hormone (AMH) levels in overweight and obese women with polycystic ovary syndrome (PCOS) and in overweight and obese controls. Sixty-one (61) selected women with PCOS and 20 overweight and obese controls followed an energy-restricted diet, physical exercise plus Orlistat administration (120 mg, 3 times per day) for 24 weeks. At baseline, week 12 and week 24, serum levels of AMH, FSH, LH, PRL, androgens, sex hormone-binding globulin (SHBG), glucose, and insulin were measured and Free Androgen Index (FAI) and Insulin Resistance (IR) indices were calculated. In PCOS women, serum AMH levels increased after 12 and 24 weeks of treatment. After 12 weeks LH and SHBG were increased, while Testosterone decreased. After 12 and 24 weeks, FAI was decreased and all indices of IR were significantly improved. We concluded that in overweight and obese women with PCOS Orlistat administration, combined with diet and physical exercise, for 24 weeks, resulted in significant weight loss, improvement of hyperandrogenism and insulin sensitivity, and increased serum AMH levels.

Insulin resistance and endocrine characteristics of the different phenotypes of polycystic ovary syndrome: a prospective study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by oligo- or anovulation (ANOV), biochemical or clinical manifestations of hyperandrogenemia (HA) and PCOs. Four phenotypes of PCOS exist [phenotype 1 (ANOV + HA + PCO), phenotype 2 (ANOV + HA), phenotype 3 (HA + PCO) and phenotype 4 (ANOV + PCO)] but the differences between them are not well studied. We compared markers of insulin resistance (IR) and endocrine characteristics between the different PCOS phenotypes. METHODS: We prospectively studied 1212 consecutive women with PCOS and 254 BMI-matched healthy women. RESULTS: Phenotypes 1-4 were present in 48.2, 30.7, 9.7 and 11.4% of patients, respectively. BMI did not differ between the four phenotypes and controls. Both normal weight and overweight/obese women with phenotypes 1 and 2 were more insulin resistant than controls. Overweight/obese, but not normal weight, women with phenotype 4 were more insulin resistant than controls, while IR in women with phenotype 3 did not differ from controls regardless of obesity. In normal weight subjects, women with phenotypes 1 and 2 were more insulin resistant than women with phenotype 4. In overweight/obese subjects, women with phenotype 1 were more insulin resistant than women with phenotypes 2 and 3 and women with phenotype 4 were more insulin resistant than those with phenotype 3. Circulating androgens were higher in normal weight and overweight/obese PCOS patients with phenotypes 1-3 compared with those with phenotype 4, and higher in normal weight PCOS patients with phenotype 1 than in those with phenotype 2. CONCLUSIONS: Phenotype 1 is associated with more IR and more pronounced HA than phenotype 2. Phenotypes 2 and 4 with obesity, are also characterized by IR. In contrast, phenotype 3 is not associated with IR.

Plasma plasminogen activator inhibitor-1 levels in the different phenotypes of the polycystic ovary syndrome.

We aimed to evaluate plasma plasminogen activator inhibitor-1 (PAI-1) antigen levels in women with polycystic ovary syndrome (PCOS) and different levels of adiposity and PCOS phenotypes. We studied 199 women with PCOS and 50 age-matched healthy women divided in normal weight (n=100 and n=25, respectively) and overweight/obese (n=99 and n=25, respectively). Normal weight and overweight/obese patients with PCOS were further divided in patients diagnosed according to the 1990 criteria (i.e. with anovulation and hyperandrogenemia; 1990 criteria group) and in patients with the additional phenotypes introduced in 2003 (i.e. with polycystic ovaries and either anovulation or hyperandrogenemia; additional 2003 criteria group). In normal weight subjects, plasma PAI-1 levels did not differ between women with PCOS (regardless of group) and controls, or between the 1990 criteria and the additional 2003 criteria groups of PCOS. In overweight/obese subjects, plasma PAI-1 levels were higher in both the 1990 criteria and the additional 2003 criteria groups of PCOS compared with controls (p<0.001 and p=0.004, respectively), but did not differ between the 1990 criteria and the additional 2003 criteria groups of PCOS. In conclusion, plasma PAI-1 levels are elevated in overweight/obese women with PCOS but not in normal weight women with this syndrome. Plasma PAI-1 levels do not differ between the phenotypes of PCOS.

Weight loss significantly reduces serum lipocalin-2 levels in overweight and obese women with polycystic ovary syndrome.

Serum lipocalin-2 levels are elevated in obese patients. We assessed serum lipocalin-2 levels in polycystic ovary syndrome (PCOS) and the effects of weight loss or metformin on these levels. Forty-seven overweight/obese patients with PCOS [body mass index (BMI) >27 kg/m(2)] were instructed to follow a low-calorie diet, to exercise and were given orlistat or sibutramine for 6 months. Twenty-five normal weight patients with PCOS (BMI <25 kg/m(2)) were treated with metformin for 6 months. Twenty-five normal weight and 25 overweight/obese healthy female volunteers comprised the control groups. Serum lipocalin-2 levels did not differ between overweight/obese patients with PCOS and overweight/obese controls (p = 0.258), or between normal weight patients with PCOS and normal weight controls (p = 0.878). Lipocalin-2 levels were higher in overweight/obese patients with PCOS than in normal weight patients with PCOS (p < 0.001). In overweight/obese patients with PCOS, weight loss resulted in a fall in lipocalin-2 levels (p < 0.001). In normal weight patients with PCOS, treatment with metformin did not affect lipocalin-2 levels (p = 0.484). In conclusion, PCOS per se is not associated with elevated lipocalin-2 levels. Weight loss induces a significant reduction in lipocalin-2 levels in overweight/obese patients with PCOS.

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 ± 1.74 vs. 6.20 ± 1.78 ng/ml, P < 0.0005) values were significantly lower, whereas Gla osteocalcin (37.93 ± 6.87 vs. 9.64 ± 8.21 ng/ml, P < 0.0005) and receptor activator for nuclear factor-κB ligand (0.54 ± 0.26 vs. 0.16 ± 0.15 pmol/l, P < 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.

The effect of weight loss and treatment with metformin on serum vaspin levels in women with polycystic ovary syndrome.

Many patients with polycystic ovary syndrome (PCOS) have insulin resistance, obesity (mostly visceral) and glucose intolerance, conditions associated with abnormalities in the production of vaspin, a novel adipokine that appears to preserve insulin sensitivity and glucose tolerance. The aim of the study was to assess serum vaspin levels in PCOS and the effects on vaspin levels of metformin or of weight loss. We studied 79 patients with PCOS and 50 healthy female volunteers. Normal weight patients with PCOS (n=25) were treated with metformin 850 mg bid for 6 months. Overweight/obese patients with PCOS (n=54) were prescribed a normal-protein, energy-restricted diet for 6 months; half of them were also given orlistat 120 mg tid and the rest were given sibutramine 10 mg qd. At baseline and after 6 months, serum vaspin levels and anthropometric, metabolic and hormonal features of PCOS were determined. Overall, patients with PCOS had higher vaspin levels than controls (p=0.021). Normal weight patients with PCOS had higher vaspin levels than normal weight controls (p=0.043). Vaspin levels were non-significantly higher in overweight/obese patients with PCOS than in overweight/obese controls. In normal weight patients with PCOS, metformin reduced vaspin levels non-significantly. In overweight/obese patients with PCOS, diet plus orlistat or sibutramine did not affect vaspin levels. Vaspin levels were independently correlated with body mass index in women with PCOS (p=0.001) and with waist circumference in controls (p=0.015). In conclusion, serum vaspin levels are elevated in PCOS but neither a small weight loss nor metformin affect vaspin levels significantly.

The impact of oral contraceptives and metformin on anti-Müllerian hormone serum levels in women with polycystic ovary syndrome and biochemical hyperandrogenemia.

OBJECTIVE: To assess the impact of metformin and of two different oral contraceptives (OCs) containing cyproterone acetate and drospirenone, on serum anti-Müllerian hormone (AMH) levels, in a cohort of women with polycystic ovary syndrome (PCOS) with hyperandrogenism. DESIGN: Prospective randomised study. SETTING: Division of Endocrinology and Human Reproduction, Aristotle University of Thessaloniki. PATIENTS: Forty-five (45) women with PCOS diagnosed according to the criteria proposed in 1990 by the NIH. INTERVENTIONS: Women with PCOS were randomised into three groups, all treated for 6 months: Group A received an OC containing 35 µg ethinylestradiol plus 2 mg cyproterone acetate, Group B received an OC containing 30 µg ethinylestradiol plus 3 mg drospirenone and Group C received metformin 850 mg × 2. Main outcome measure(s). Anti-Müllerian hormone levels were measured by a specific ELISA. RESULTS: AMH was significantly decreased under treatment with 35 µg ethinylestradiol plus 2 mg cyproterone acetate (p = 0.002 at 3 months and p < 0.001 at 6 months). Treatment with 30 µg ethinylestradiol plus 3 mg drospirenone, and treatment with metformin 850 mg × 2 did not significantly affect serum AMH levels. AMH was significantly decreased under OCs treatment compared to metformin 850 mg × 2 (p = 0.005). CONCLUSION(S): AMH serum levels were significantly decreased under treatment with 35 µg ethinylestradiol plus 2 mg cyproterone acetate, due to decrease in androgens and suppression of gonadotropins.

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

BACKGROUND: 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. METHODS: We studied 200 patients with PCOS and 50 healthy female volunteers. RESULTS: 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). CONCLUSIONS: Obesity is associated with elevated serum lipocalin-2 levels. In contrast, PCOS does not appear to affect lipocalin-2 levels.

Study of association of IRS-1 and IRS-2 genes polymorphisms with clinical and metabolic features in women with polycystic ovary syndrome. Is there an impact?

OBJECTIVE: Insulin receptor substrate (IRS) proteins are critical to signal transduction in insulin target tissues. The present study was undertaken to determine whether IRS-1 Gly972Arg and IRS-2 Gly1057Asp influence hormonal and metabolic characteristics in Greek patients with polycystic ovary syndrome (PCOS) and controls. MATERIAL AND METHODS: One hundred and eighty-three women with PCOS and 88 healthy volunteers were enrolled. Venous blood samples were obtained for genetic study and hormonal profile, glucose, and insulin assays, on days 3 to 7 from cycling patients. DNA was extracted by whole blood samples for genotyping and detection of IRS-1 Gly972Arg and IRS-2 Gly1057Asp polymorphisms. RESULTS: Fifty-six women with PCOS (30.60%), whereas 12 women in the control group (13.64%) carried the IRS-1 polymorphism (p = 0.0026). No statistically significant differences in genotypes or allele frequencies for IRS-2 polymorphism were observed between controls and PCOS women. No significant differences in any clinical or hormonal measures between subjects on the basis of genotype were observed, except the increased levels of fasting glucose that exhibit the carriers of the Asp allele of the IRS-2 polymorphism. CONCLUSIONS: Only the IRS-1 polymorphism is associated with increased susceptibility to PCOS in a Greek population. These loci should not be considered as major contributors to the hormonal and metabolic phenotype of PCOS.

Increased serum advanced glycation end-products is a distinct finding in lean women with polycystic ovary syndrome (PCOS).

BACKGROUND: Nonenzymatic advanced glycation and oxidation end-products, advanced glycation end-products (AGEs), impart a potent impact on vessels and other tissues in diabetic state and in euglycaemic conditions with increased oxidative stress. Insulin resistant (IR) polycystic ovary syndrome (PCOS) women, have elevated serum AGEs, increased receptor (RAGE) expression, and increased deposition with differential localization in the polycystic ovarian tissue (theca and granulosa) compared to normal. OBJECTIVE: To determine whether the raised AGE levels in noninsulin resistant women with PCOS is a distinct finding compared with those presenting the isolated components of the syndrome and among PCOS subphenotypes. Noninsulin resistant women were selected in order to show that serum AGEs are elevated in PCOS independently of the presence of IR. DESIGN: Clinical trial. PATIENTS: One hundred and ninety-three age- and BMI-matched young lean noninsulin resistant women were studied. Among them, 100 women were diagnosed with PCOS according to Rotterdam criteria, and divided to subphenotypes (hyperandrogenaemia with or without PCO morphology and with or without anovulation). Sixty-eight women with the isolated components of the PCOS phenotype were also studied along with 25 healthy women. MEASUREMENTS: Serum AGE levels, metabolic, hormonal profiles and intravaginal ultrasound were determined in all subjects. RESULTS: The studied population did not differ in BMI, fasting insulin concentration, waist : hip and glucose : insulin ratios. PCOS women exhibited statistically higher AGEs levels (7.96 +/- 1.87 U/ml, P < 0.001) compared with those with isolated hyperandrogenaemia (5.61 +/- 0.61 U/ml), anovulation (5.53 +/- 1.06 U/ml), US-PCO morphology (5.26 +/- 0.25 U/ml) and controls (5.86 +/- 0.89 U/ml). CONCLUSIONS: In PCOS, serum AGEs are distinctly elevated compared with women having the isolated characteristics of the syndrome. No difference was observed between PCOS subphenotypes. As chronic inflammation and increased oxidant stress have been incriminated in the pathophysiology of PCOS, the role of AGEs as inflammatory and oxidant mediators, may be linked with the metabolic and reproductive abnormalities of the syndrome.

Serum and seminal plasma ghrelin levels in men with normospermia and dyspermia.

AIMS: To investigate the existence of ghrelin in seminal plasma and the levels of serum ghrelin in men with normospermia and dyspermia. SUBJECTS AND METHODS: Ninety-eight men were classified into three groups: Group 1, men with normospermia and proven fertility (n = 26); Group 2, men with idiopathic oligo-astheno-teratozoospermia (n = 62); and Group 3, men with idiopathic azoospermia (n = 10). Spermiograms and determination of ghrelin in serum and seminal plasma were performed in all men. RESULTS: Ghrelin was present in the seminal plasma of men from all groups at a concentration of 27%, 18% and 30% of the corresponding serum levels (mean +/- standard error: Group 1, 127.7 +/- 14.7 vs. 468.3 +/- 35.5 pmol/l, p = 0.003; Group 2, 117.0 +/- 10.1 vs. 637.0 +/- 29.3 pmol/l, p < 0.001; Group 3, 166.2 +/- 32.5 vs. 557.7 +/- 25.4 pmol/l, p = 0.068). When Group 1 men were compared with men from Groups 2 and 3 combined, there were no significant differences in serum (mean +/- standard error: 468.3 +/- 35.5 vs. 628.0 +/- 26.4 pmol/l, p = not significant) or seminal plasma ghrelin (mean +/- standard error: 127.7 +/- 14.7 vs. 123.9 +/- 9.9 pmol/l, p = not significant). In the total group of studied men (Groups 1 to 3), serum ghrelin was positively correlated with semen volume (r = 0.309, p = 0.037), whereas seminal plasma ghrelin was negatively correlated with age (r = -0.268, p = 0.008) and semen volume (r = -0.385, p < 0.000). CONCLUSIONS: Ghrelin is present in human seminal plasma at lower levels than in serum. There is no difference in seminal plasma ghrelin levels between men with normospermia and dyspermia.

Genetic variants in TCF7L2 and KCNJ11 genes in a Greek population with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS), the most common reproductive endocrine disorder of premenopausal women, is strongly associated with hyperinsulinemia and type 2 diabetes mellitus (T2DM). Given the phenotypic overlap between PCOS and T2DM, our objective was to investigate whether the TCF7L2 rs7903146(C/T) and the KCNJ11 E23K variants are involved in susceptibility to PCOS and related traits in a Greek population. A total of 183 PCOS patients and 148 healthy controls participated. All participants were Greeks. Blood was taken before hormonal therapy. PCOS patients and healthy controls were genotyped for the TCF7L2 and KCNJ11 variants. The T allele of the TCF7L2 rs7903146 variant was found to be marginally over-represented in Greek patients with PCOS. There was no association between KCNJ11 E23K polymorphism and PCOS in the present study. In addition, there were no associations observed between hormone levels and insulin resistance in PCOS carriers of TCF7L2 rs7903146 and KCNJ11 E23K variants. These data provide evidence that the rs7903146 variant of the TCF7L2 gene might influence PCOS predisposition, while no association is observed between the E23K variant of KCNJ11 and susceptibility to PCOS and related traits.

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.