Circulating ghrelin levels in patients with polycystic ovary syndrome

The syndrome of polycystic ovaries (PCOS) is associated with adiposity and metabolic changes predisposing to insulin resistance and diabetes mellitus. Because the recently discovered GH secretagogue, ghrelin, is intimately involved in the control of appetite and weight regulation, we studied ghrelin levels in a group of 26 otherwise healthy women with PCOS. They were compared with 61 healthy female control subjects and 5 gastrectomized women. Insulin sensitivity was assessed by homeostasis model assessment (HOMA) and continuous infusion of glucose with model assessment (CIGMA) in all patients. In PCOS women, serum ghrelin levels were significantly lower than in healthy lean or obese controls (P < 0.001). In insulin-sensitive PCOS women, ghrelin concentrations compared well with the healthy controls, whereas in insulin-resistant PCOS ghrelin levels were significantly lower and indistinguishable from the low levels found in the gastrectomized women. There was a close correlation of ghrelin to insulin sensitivity (HOMA, r(2) = 0.330, P < 0.002; CIGMA, r(2) = 0.568, P < 0.0001). Treatment of 10 insulin-resistant PCOS women with metformin significantly increased circulating fasting ghrelin concentrations (P < 0.02). Ghrelin levels did not correlate to any of the parameters of hyperandrogenemia, to the LH/FSH ratio, to body mass index, or to fasting insulin and glucose concentrations. In summary, ghrelin levels are decreased in PCOS women and are highly correlated to the degree of insulin resistance. This suggests that ghrelin could be linked to insulin resistance in PCOS women. However, whether low ghrelin in PCOS is a cause or the consequence of insulin resistance awaits further investigations.     

Circulating ghrelin concentrations in the polycystic ovary syndrome

Ghrelin is a novel gastric peptide which has orexigenic and adipogenic properties. Circulating ghrelin concentrations are influenced by nutritional status and, probably, regulate food intake and body weight. Obesity is a common feature in women with polycystic ovary syndrome (PCOS). To investigate the relationship of circulating ghrelin concentrations to the hormonal and metabolic features of PCOS women, plasma ghrelin and several hormone concentrations were evaluated in thirty-three women with PCOS and in thirty-two healthy women matched for age and body mass index (BMI). Plasma ghrelin concentrations were similar between the PCOS (179 +/- 27, pmol/l +/- SEM) and the control (181 +/- 24, pmol/l +/- SEM) groups. In both groups, there was a significant (P < 0.001) inverse correlation between fasting ghrelin concentrations and BMI (PCOS: r = -0.45; Controls: r = -0.59). Multivariate regression analysis did not demonstrate any correlation (P = NS) between fasting ghrelin concentrations and the other hormone levels in the PCOS patients. In conclusion, our data demonstrate that in women with PCOS plasma ghrelin concentrations are not different from those of weight matched controls and are inversely correlated with BMI. There is no relationship between circulating ghrelin and the abnormal hormonal pattern of the PCOS syndrome.     

Circulating leptin concentrations and ovarian function in polycystic ovary syndrome

OBJECTIVE: Polycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction. Although the role of leptin in the control of reproduction is unclear, it may be involved in the control of ovulation. The aim of this cross-sectional study was to determine the relationship between circulating leptin concentrations, and anthropometric, metabolic and endocrine variables as well as to examine a possible role of leptin in ovarian dysfunction associated with PCOS. DESIGN: Prospective observational study. METHODS: Seventy-one subjects with PCOS and 23 body mass index (BMI)-matched control subjects were recruited from infertility clinics. The association between serum leptin concentrations and the above variables was measured outwith the luteal phase. A subgroup of 24 PCOS subjects underwent more frequent blood sampling to monitor follicular growth and ovulation. The association between variables was measured by univariate, multivariate and partial correlation analyses. RESULTS: Serum leptin concentrations were not different in subjects with PCOS and controls, and were strongly associated with BMI in both groups. Twelve patients ovulated during the study period. There was no significant difference in serum leptin concentrations between ovulatory and anovulatory subjects. The relationship between BMI and leptin was similar in both groups. CONCLUSION: The results indicated that circulating leptin concentrations relate principally to total body fat in subjects with PCOS and controls, and that this is not associated with the facility for follicular development and ovulation in these patients.     

Adiponectin levels in women with polycystic ovary syndrome

Serum adiponectin levels were evaluated in 60 women with polycystic ovary syndrome (PCOS), 30 normal-weighted and 30 obese women, and 60 healthy women age and body mass index (BMI) matched with the patients. The homeostasis model assessment (HOMA) score was also calculated. Both in PCOS and controls, serum adiponectin levels were significantly (P < 0.05) lower in obese than normal-weight women, without any difference between PCOS and controls. The HOMA score was significantly (P < 0.05) higher in obese than normal-weight women both in PCOS and controls; additionally, the HOMA score was significantly (P < 0.05) higher in normal-weight PCOS than normal-weight controls. Both in PCOS and controls, adiponectin levels were significantly correlated with BMI (r = -0.51, P < 0.01 in PCOS; r = -0.45, P < 0.01 in controls) and HOMA values (r = -0.39, P < 0.05 in PCOS; r = -0.35, P < 0.05 in controls); HOMA was correlated with BMI (r = 0.51, P < 0.01 in PCOS, r = 0.61, P < 0.001 in controls). In conclusion, our results confirm that adiponectin concentrations change according to variations of fat mass. They further suggest that insulin sensitivity per se probably does not play any pivotal role in the control of adiponectin levels in PCOS women.     

多囊卵巢综合征性激素水平检测

目的：探讨血清性激素各项检测指标与不同年龄段的多囊卵巢综合征（PCOS）患者的关系及其临床意义。方法：以月经周期正常的健康妇女为对照组,采用化学发光法测定30岁以下年龄组和30岁及以上年龄组PCOS患者促黄体生成素（LH）、促卵泡生成素（FSH）、泌乳素（PRL）、雌二醇（E2）、睾酮（TESTO）、孕酮（Prog）水平,通过统计学软件进行比较分析。结果：多囊卵巢综合征患者,30岁以下年龄组和30岁及以上年龄组LH高于对照组（P〈0．01）,E2高于对照组（P〈0．05）,TESTO高于对照组（P〈0．01）。30岁以下PCOS患者组和30岁及以上PCOS患者组各检测指标之间差异无统计学意义（P〉0．05）。结论：血清中LH,E2高水平及TESTO增高可能是多囊卵巢综合征的预示因子,高LH、高E2、高雄激素血症可能是引起PCOS发生的因素之     

Increased C-reactive protein levels in the polycystic ovary syndrome: a marker of cardiovascular disease

The polycystic ovary syndrome (PCOS), one of the most common reproductive abnormalities, shares some components of the metabolic cardiovascular syndrome. Therefore, PCOS patients may represent the largest group of women at high risk for the development of early-onset cardiovascular disease (CVD) and/or diabetes. C-reactive protein (CRP) is a strong independent predictor of future CVD and/or stroke. Only one small published study has looked for such an association (17 PCOS patients vs. 15 controls). The objective of this study was to compare the levels of CRP and other risk factors of CVD in a large group of PCOS patients and controls. CRP measurements were undertaken in 116 PCOS patients and 94 body mass index-matched controls with regular menstrual cycles. Whereas 36.8% of the PCOS patients had CRP levels above 5 mg/liter, only 9.6% of the controls exhibited high CRP levels (P < 0.001). The mean +/- SD was 5.46 +/- 7.0 in the PCOS group vs. 2.04 +/- 1.9 mg/liter in the control (P < 0.001). The body mass index, white blood cell count, TSH, glucose, cholesterol, and homocysteine levels were not significantly different between the two groups. CRP levels are elevated in patients with PCOS and may be a marker of early cardiovascular risk in these patients. High CRP levels may explain why some PCOS women may possibly be at an increased risk for the development of early-onset CVD. Consequently, whether treatment regimens directed toward lowering CVD risk factors should be more aggressive for those PCOS women with increased CRP levels, awaits further clinical experience.     

Lower levels of urinary 2-hydroxyestrogens in polycystic ovary syndrome

CONTEXT: Women with polycystic ovary syndrome (PCOS) have anovulation due to arrested follicular maturation. The substrate (2-hydroxyestrogen) and product (2-methoxyestrogen) of catechol-O-methyl transferase (COMT) have been shown to modulate proliferation and angiogenesis of granulosa cells. OBJECTIVE: The objective of the study was to evaluate COMT ovarian expression as well as the production of estrogen metabolites (2-hydroxyestrogen and 2-methoxyestrogen) in subjects with PCOS. DESIGN: Immunohistochemistry was used to assess COMT expression in ovarian tissues. Urinary levels of 10 different estrogens and estrogen metabolites were measured using enzyme-labeled immunoassays and/or liquid chromatography with tandem mass spectrometry. SETTING: The study was conducted at a tertiary university referral center. PATIENTS AND OTHER PARTICIPANTS: Ovarian tissues were obtained from six control subjects and six subjects with PCOS. Fasting first-void urinary samples were collected from 49 subjects with PCOS and 36 healthy control subjects. MAIN OUTCOME MEASURE(S): COMT protein expression in ovarian tissues was measured. Urinary levels of 2-hydroxyestrogen and 2-methoxyestrogen levels in PCOS patients were also measured. RESULTS: Whereas immunohistochemistry showed that COMT was expressed in ovaries from control and PCOS subjects, its expression was significantly higher in ovaries from subjects with PCOS, in both the follicular structures and ovarian stroma. The urinary 2-hydroxyestrogen level was significantly lower in subjects with PCOS, compared with normal controls (P = 0.009). Additionally, urinary 2-hydroxyestrogen levels negatively correlated with serum insulin levels in subjects with PCOS (r = -0.333, P =0 .031). CONCLUSIONS: Urinary 2-hydroxyestrogen is decreased in subjects with PCOS, which could be due in part to increased ovarian expression of COMT. Further studies are needed to ascertain the role of estrogen metabolism in PCOS before this information can be used in clinical settings.     

Serum irisin levels in polycystic ovary syndrome after ovarian drilling

BackgroundMany cases of Poly-Cystic Ovary Syndrome (PCOS) are overweight and presenting with insulin resistance.Main objectivewas to evaluate the effects of ovarian drilling on the serum levels of Irisin in women with polycystic ovaries.Study design and settingSerum Irisin levels were investigated in 100 cases with PCOS before ovarian drilling and 3 months after drilling, and in 80 control cases. Serum Irisin, hormonal profile and HOMA-IR were estimated in PCOS cases before and after ovarian drilling. Statistical analysis was performed by using Statistical Package for Social Scientists (SPSS).ResultsThe serum irisin levels in overweight and in normal weight PCOS cases before ovarian drilling were significantly higher as compared with the corresponding control cases. Fasting serum Irisin levels were found to be significantly elevated in PCOS patients before ovarian drilling as compared to the levels after drilling. The serum irisin levels in overweight and in normal weight PCOS cases before ovarian drilling were found to be significantly positively correlated with BMI, insulin levels, and HOMA-IR.ConclusionElevated serum Irisin levels in PCOS may contribute to the development of insulin resistance. Ovarian drilling for polycystic ovaries results in a significant decrease in the serum Irisin levels. The analysis of ROC curves may suggest that serum Irisin may be a valuable biomarker for diagnosis and for monitoring cases with PCOS during treatment.     

Mean platelet volume in patients with polycystic ovary disease

Platelets contribute to blood coagulation at sites of vascular injury and to the recruitment of leukocytes at sites of inflammation. Under pathological conditions, platelets are involved in numerous diseases and clinical complications, such as deep venous thrombosis, embolism and atherosclerosis. But so far, little is known about the mechanisms of inflammation in large veins and the role of platelets in inflamed large veins. For this purpose, we investigated primary and secondary interactions between platelets, leukocytes and endothelial cells in the femoral vein in vivo with special regard to the role of CD62P (P-selectin) and CD162 (PSGL-1). Mice were challenged with lipopolysaccharide (LPS)/D-galactosamine (D-gal) and either CD162 or CD62P was blocked by intravenous administration of a corresponding antibody at the time point of LPS/D-gal injection. Four hours after LPS/gal injection, intravital fluorescence microscopy of the femoral vein was performed and primary and secondary platelet-leukocyte-endothelial cell-interactions were visualized after in vivo platelet and leukocyte staining with rhodamine 6G. Analysis of intravital fluorescence microscopy revealed that LPS/D-gal caused a strong inflammatory reaction of the venous endothelium with significant induction of platelet and leukocyte tethering, rolling and adhesion. Secondary interactions of platelets to adherent or rolling platelets or leukocytes were also increased after LPS/D-gal-injection. Immunoneutralization of either CD162 or CD62P significantly decreased platelet primary and secondary capture as well as leukocyte rolling and adhesion. CD162 and CD62P play a central role in mediating inflammatory primary and secondary interactions of platelets and leukocytes to the endothelium in inflamed large veins in vivo. Thus, blocking CD162 or CD62P might be an attractive tool for preventing platelet and leukocyte-driven venous diseases.     

多囊卵巢综合征患者血清Ghrelin水平测定及其意义

目的探讨血清生长素(Ghrelin)与多囊卵巢综合征(PCOS)的关系。方法选择PCOS患者35例(P-COS组)及正常体检者33例(对照组),两组服75 g葡萄糖粉后,分别检测空腹与服糖1、2 h血脂,基础血激素(雌激素、孕激素、卵泡刺激素、黄体生成素、泌乳素、睾酮、雄烯二酮)及Ghrelin水平,计算BMI、腰臀比(WHR)、胰岛素抵抗指数及敏感指数。结果 PCOS组BMI、TG、HDL、胰岛素抵抗指数、空腹胰岛素、Ghrelin、睾酮及雄烯二酮在空腹与服糖1、2 h均低于对照组(P<0.05或<0.01)。相关分析显示,血清Ghrelin与BMI、WHR、雄激素、雄烯二酮、空腹血糖呈负相关(r分别为-0.504、-0.336、-0.440、-0.432、-0.414,P均<0.05),与HDL呈正相关(r=0.357,P<0.05)。结论血清Ghrelin可能在PCOS的病理生理过程中发挥作用。     

Nonalcoholic fatty liver disease and polycystic ovary syndrome

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world comprising a spectrum of liver damage from fatty liver infiltration to end-stage liver disease, in patients without significant alcohol consumption. Increased prevalence of NAFLD has been reported in patients with polycystic ovary syndrome (PCOS), one of the most common endocrinopathies in premenopausal women, which has been redefined as a reproductive and metabolic disorder after the recognition of the important role of insulin resistance in the pathophysiology of the syndrome. Obesity, in particular central adiposity and insulin resistance are considered as the main factors related to NAFLD in PCOS. Moreover, existing data support that androgen excess, which is the main feature of PCOS and is interrelated to insulin resistance, may be an additional contributing factor to the development of NAFLD. Although the natural history of NAFLD remains unclear and hepatic steatosis seems to be a relatively benign condition in most patients, limited data imply that advanced stage of liver disease is possibly more frequent in obese PCOS patients with NAFLD. PCOS patients, particularly obese patients with features of the metabolic syndrome, should be submitted to screening for NAFLD comprising assessment of serum aminotransferase levels and of hepatic steatosis by abdominal ultrasound. Lifestyle modifications including diet, weight loss and exercise are the most appropriate initial therapeutic interventions for PCOS patients with NAFLD. When pharmacologic therapy is considered, metformin may be used, although currently there is no medical therapy of proven benefit for NAFLD. Long-term follow up studies are needed to clarify clinical implications and guide appropriate diagnostic evaluation, follow-up protocol and optimal treatment for PCOS patients with NAFLD.     

Plasma homocysteine levels in polycystic ovary syndrome and congenital adrenal hyperplasia

The purpose of this study was to determine whether polycystic ovary syndrome (PCOS) and nonclassic 21-hydroxylase deficiency (CAH) are related to hyperhomocysteinemia, and to investigate if there is a correlation between homocysteine levels and insulin sensitivity in women with PCOS and CAH. Fifty patients with PCOS, 50 patients with CAH and 25 control women were included in the study. Blood samplings were performed in the early follicular phase for measuring hormone profile, Vitamin B(12), folate, homocysteine levels and fasting blood glucose. Ovulatory status was assessed with timed serum progesterone measurements. Homeostasis model assessment-insulin resistance (HOMA-IR) was calculated as a measure of insulin resistance. Mean homocysteine levels were found as (8.9 + 1.9 micromol/l and 17.7 + 3.6 micromol/l) in the normal group and PCOS respectively (p<0.001), but there was no statistical significance between nonclassic 21-hydroxylase deficiency (9.0 + 2.2 micromol/l) and control group. Most of the patients in PCOS group (35 of 50) were significantly insulin resistant. However, there was no insulin resistant patient in CAH or control group. When we compare the two subgroups of PCOS women, the patients with insulin resistance had significantly higher homocysteine levels than the ones who were not insulin resistant. There were positive correlations among serum homocysteine, insulin and androgen levels in PCOS patients. There were no correlations among these parameters in CAH and control groups. Increased homocysteine levels may contribute to increased cardiovascular disease risk in patients with PCOS. The reason for hyperhomocysteinemia seems to be related to insulin resistance but not high androgen levels.     

Circulating leptin concentrations in polycystic ovary syndrome: relation to anthropometric and metabolic parameters

OBJECTIVE To determine the relation between metabolic and anthropometric parameters and circulating leptin concentrations in women with polycystic ovary syndrome (PCOS). DESIGN AND PATIENTS Correlation of fasting serum leptin concentrations with anthropometric measures and multiple metabolic parameters including insulin and glucose responses to a 2-hour 75-g oral glucose tolerance test (OGTT) in 85 women with PCOS (17–36 years, body mass index (BMI) 29.9 ± 0.9 kg/m², mean ± SD) and 18 control women (25–47 years, BMI 25 ± 1.7 kg/m²). Diagnostic criteria for PCOS: characteristic ovarian morphology on ultrasound plus at least two of (1) elevated serum testosterone; (2) elevated serum androstenedione; and (3) reduced serum SHBG concentrations. MEASUREMENTS Concentrations of androgens, lipids, PRL, gonadotrophins, and leptin were measured in the baseline fasting blood sample from an OGTT. Insulin and glucose were measured throughout OGTT. Serum leptin concentrations were measured by radioimmunoassay. RESULTS Log leptin levels in the PCOS group correlated significantly with BMI (r = 0.85, P < 0.0001) and with 8 other parameters including waist/hip ratio (r = 0.51, P = 0.0005). By stepwise regression analysis, only BMI (P < 0.0001) and plasma high density lipoprotein concentration (P = 0.02) were independently correlated with log leptin levels, both positively. There was no effect of fat distribution, as measured by waist/hip ratio, on leptin concentrations. Comparison of control subjects to a BMI-matched subgroup of 55 PCOS subjects revealed significantly higher circulating concentrations of LH, testosterone, DHEAS, progesterone and androstenedione, and higher glucose and insulin responses to OGTT in the PCOS group. Leptin levels were not different between the PCOS subgroup and control group (14.8 ± 1.3 vs 12.1 ± 2.3 μg/l, mean ± SE, P = 0.26) and the relation of BMI to leptin levels determined by linear regression analysis also did not differ between the two groups. CONCLUSIONS Our results indicate that circulating leptin concentrations in women with PCOS, a condition characterized by hyperandrogenaemia, increased LH concentrations and insulin resistance, are strongly related to BMI and not independently affected by circulating levels of insulin, gonadotrophins or sex hormones.