Amaç: Polikistik Over Sendromu (PCOS), üreme çağındaki kadınlarda en sık görülen endokrinopatilerden biridir. PCOS olan kadınlar kardiyovasküler has- talık için, hipertansiyon, dislipidemi, diyabet ve obezite gibi klasik risk fak- törlerinin yanı sıra C-reaktif protein (CRP), homosistein ve tümör nekroz faktörü-α klasik olmayan risk faktörlerinin de bir artış olduğunu belirtmiş- lerdir. Adropin enerji hemostazının sürdürülmesinde ve insülin cevabında rolü olduğu düşünülen bir proteindir. Bizim çalışmamızın amacı; insülin direnci ve artmış diyabet riski taşıyan PCOS hasta topluluğunda adropin düzeyinin insu- lin direnci ile ilişkisini araştırmaktır. Gereç ve Yöntem: Elli yedi hasta (30 adet PCOS hastası ve 27 sağlıklı kontrol) çalışmaya dahil edildi. Her hastanın vücut kitle indeksi ve insulin direnci hesaplandı. Adropin düzeyleri EIA (enzyme im- munoassay) metodu kullanılarak ölçüldü. Bulgular: Adropin düzeyi hasta gru- bunda 10,79 ng/L iken kontrol grubunda 13,02 ng/L olarak bulundu ve arada- ki fark istatistiksel olarak anlamlı bulundu (p=0,04). Adropin düzeyi ile insü- lin, aspartat aminotransferaz (AST), trigliserid (TG) ve insülin direncini yansı- tan HOMA değeri (HOMA-IR) düzeyleri arasında anlamlı olarak ters korelas- yon saptandı (sırasıyla p=0,03; p=0,03; p=0,04; p=0,02). Tartışma: Çalışma- mızda insülin direnci ile ilişkili olan adropin düzeylerinin, PCOS lu hastalarda azalmış olduğu saptanmıştır. PCOS lu hastalarda insülin direnci ile giden kli- nik durumların değerlendirilmesinde adropin düzeyleri üzerine yeni çalışmalar yapılmasının değerli olacağını düşünmekteyiz.
A possible explanation for these conflicting data could be that PCOS encompasses various phenotypic subtypes that are dictated by the parental genetic traits of the individual, the mater- nal contribution during fetal life and the adult environment. In large epidemiological studies, small subtypes (with low or high birth weight) probably yield no significant differences. Anoth- er explanation may be that the relation of birth weight and PCOS risk is not linear but a U-shaped, as it has been shown for insulin resistance and type 2 diabetes . If this is the case then, a much larger number of patients is needed to prove this hypothesis.
though the mechanism by which LH causes recurrent abortion is not known. In the pres- ent study high LH levels showed a negative correlation with progesterone level during the luteal phase in PCOS women, possibly implying that low progesterone levels may be associated with LH hypersecretion in this syndrome. It has been hypothesized that high LH concentrations may stimulate the high androgen synthesis observed in PCOS (14), using progesterone as a precursor. It may also be possible that LH-induced hyperan- drogenism suppresses progesterone synthe- sis, although these possibilities need further confirmation. The positive correlation be- tween LH and insulin observed in the pres- ent study suggests that high LH levelsin PCOS women may be due to hyperinsuline- mia/insulin resistance. Several studies using metformin, a commonly employed insulin- sensitizing agent, have shown reduced LH levelsin PCOS women, suggesting an en- hancing influence of insulin on LH secretion (15,16).
25(OH)D deiciency has diverse effects in hu- man bodies. There is evidence that demonstrate a correlation between 25(OH)D and insulin resist- ance. Although the mechanisms underlying these associations are not fully understood (13, 14), vitamin D has some effects on beta-cell function and may have a beneicial effect on insulin action by stimulating the expression of insulin receptors (8). In a study by Hahn et al. (7), they showed that 25(OH)D was associated with higher BMI values and body fat. In severely obese patients, Manco et al. (15) has illustrated that the fat mass is the best predictor for serum level of 25(OH)D. However, the mechanisms mediating these inding remain
PURPOSE: To evaluate the prevalence of common mental disorders in women diagnosed with polycysticovarysyndrome as compared with paired controls without this syndrome. METHODS: Cross-sectional study with a Control Group examining women between the ages of 18 and 30 who did not use antidepressants and who sought the Gynecology Service of the researched sites. For every woman diagnosed with the polycysticovarysyndrome, another with the same age, educational status and presence or absence of sexual partners was sought without this diagnosis. In total, 166 patients agreed to participate, consisting of 95 diagnosed with polycysticovarysyndrome and 71 in the Control Group. The diagnosis of polycysticovarysyndrome was made by the presence of two from three criteria: oligomenorrhea or amenorrhea, clinical or biochemical hyperandrogenism and polycystic ovaries on transvaginal ultrasound, following exclusion of patients with Cushing’s syndrome, congenital adrenal hyperplasia, and androgen-secreting tumors. Weight and height were measured to calculate the body mass index. The Self-Reporting Questionnaire, which evaluated 20 items, was used as an indicator of common mental disorders. A χ 2 analysis stratiied by the category of body mass
attempted to compare the study group to the control group, which consisted of eumenorrheic, non-hirsute and non-obese females with BMI <25 (Group I). During OGTT it was noted that, in Group I, after the stimulus of ingest of carbo- hydrates there is rapid rise in glycemia, noti- ceable at 15 minutes, followed by a gradual drop towards the end of the test. These data are concordant with wide populational studies 13 . This
The findings of this study confirm that the prevalence of MetS and its individual components, particularly a decreased high-density lipoprotein cholesterol level, is substantially higher in women with PCOS than in the general population. However, the prevalence of MetS in Brazilian women with PCOS appears to be much lower than that found in the U.S. population, as previously reported in other non-U.S. studies. Thus, these women are at increased risk of diabetes mellitus and cardiovascular disease; it is therefore important to screen all women with PCOS for cardiovascular risk fac- tors. Identification and clinical management of this high- risk group is an important aspect of coronary heart disease prevention, and better understanding of these issues is crit- ical to preventing mortality from cardiovascular disease in these patients.
Regarding the effect of chronic hyperandrogenemia, inpolycysticovarysyndrome a specific pattern of gonado- tropins secretion has been described, with an increased concentration of basal LH and diminished FSH and with an increase in the frequency of LH pulses, 3 while in adrenal or ovarian androgen-secreting tumors, gonadotropin levels vary from high, 4-6 normal for age 7-9 or suppressed. 7,10-11 The reason for the different gonadotropins pattern in androgen-secreting tumors is not clear. It is possible that the level of testosterone and the time exposure could influence the secretion of gonadotropins, as postulated by Spinder et al in transsexual 2 and Bachelot et al in virilizing ovarian tumors. 10
The etiology and pathogenesis of polycysticovarysyndrome (PCOS) is still a matter of controversies, but it is apparent that hyperinsulinism and insulin resis- tance (IR) are major determining factors in the development of ovarian hyperandrogenism and chronic anovulation. The consequences of the PCOS extend be- yond the reproductive axis. Follow up studies have shown an increase in the incidence of type 2 diabetes mellitus and other elements of metabolic syndromein PCOS and increased cardiovascular risk, too. It is possible that PCOS and type 2 diabetes mellitus are different clinical manifestations of the same IR syn- drome, with their phenotypic differences. It is even more compound as PCOS is not a homogenous group of patients. It is reflected in the diagnostic criteria of PCOS by the Rotterdam PCOS Conference as the diagnostic criteria identify 4 phenotypes of PCOS. The PCOS phenotypes differ in the degree of hyper- androgenism, but differences in hyperinsulinism and obesity have not been studied yet. Management of PCOS depends on the principal goals of the patients (treatment of infertility, diminishing signs of hyperandrogensim, prevention of long term metabolic consequences), but the management should be individu- alized according to the phenotypes as well. The value of the insulin sensitizer therapy (e. g. metformin, myo-inositol), statins and/or lifestyle modification await further evaluation and it should be integrated in the spectrum of therapeutical options.
chemiluminescent immunoassay Insulin cobas R Roche Elecsys2010 Roche Diagnostics GmbH, Mannheim, Germany) were measured after an overnight fast. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR) and calculated as fasting insulin x fasting glucose/22.5 . T2DM and impaired fasting glycaemia was excluded by fasting plasma glucose levels ,7 mmol/l and ,6 mmol/l respectively and no previous history of symptoms of hyperglycemia and or casual plasma glucose $11.1 mmol/l . Circulating VPC were isolated and cultured as follows. Mononuclear cells (MNCs) were isolated from 40 ml peripheral blood from healthy or PCOS subjects by density gradient centrifugation with Ficoll Paque PLUS (density 1.077 g/ml; GE Healthcare) according to manufacturer recommendations. MNCs (10610 6 ) were plated in 2 ml endothelial growth medium (EGM- 2 MV bulletkit; Lonza), on fibronectin-coated six-well plates at 37 uC in a 5% CO 2 humidified incubator. Under daily
adverse effects of obesity on ovarian function in PCOS (10, 11). Brzechffa et al have reported increased levels of leptin in PCOS (12) while others report normal leptin levels (13, 14). In these studies, significant positive correlations are found between leptin levels and body mass index. Bias in the selection of patients and matching control groups may define these dif- ferences. In addition Micic suggested in PCOS leptin secretion is less than expected because of insulin resistance and the presence of vis- ceral fat (15).
release, have long been appreciated in PCOS. he increase in LH pulse frequency relects an increase in GnRH release and suggests the presence of a hypothalamic defect in this group of women . We found that nonobese PCOS women had higher levels of LH compared to the other two groups, and the level of this hormone was similar in controls and obese PCOS women. We also found a negative correlation between LH levels and BMI in PCOS women. Based on these results and in previous studies [22, 24–26], we can assume that there are two distinct groups of PCOS: one composed of nonobese, noninsulin resistant women, showing higher levels of LH and adrenocortical hormones (cortisol and DHEA- S) and another composed of obese, insulin resistant women showing lower levels of LH and adrenocortical products. Our control group was composed only of nonobese women, who showed levels of cortisol and LH comparable to those of obese PCOS women.
Recently, we adapted the HRQoL Questionnaire for Women with PCOS (PCOSQ) into a Chinese version with cultural adaptations. The newly developed Chinese version of PCOSQ was named as Chi-PCOSQ) . Chi-PCOSQ was shown to be reliable and valid for a sample of ethnic Chinese women with PCOS . The uniqueness of Chi-PCOSQ is that it incorpo- rates three additional items (“acne”, “hair loss”, and “feel frightened of getting diabetes”) into the original PCOSQ. Acne and hair loss (androgenetic alopecia), as characterized by clinical hyperandrogenism, are common presentations of PCOS and were frequently reported in our previous study of Chinese women with PCOS . Acne or hair loss problems associated with PCOS can lead to psychological disturbances (i.e., low self-esteem, depression, feelings of unat- tractiveness) in PCOS patients . However, concerns associated with acne or hair loss are not addressed in the original PCOSQ . In terms of future complications associated with PCOS, the women with PCOS are at risk for metabolic syndrome and diabetes . Previous studies of Asian women with PCOS have shown that PCOS increases the risks of impaired glu- cose tolerance, gestational diabetes, and type 2 diabetes [19, 20]. In addition to assessing the fear of getting cancer in the original PCOSQ , our previous study found that Chinese women with PCOS also had a fear of getting diabetes . Chi-PCOSQ was developed as a cul- turally specific HRQoL instrument and thus may better address the impact of PCOS on the HRQoL of Chinese women with PCOS.
According to the Glueck et al. (13) and Apridonidze et al.(14) studies, the prevalence of MetS in Ameri- can women with PCOS was 46% and 43%, respec- tively, both of which were much higher than our study. Conversely, Vrbíková et al. (23) did not find a higher prevalence of MetS in Czech women with PCOS even those women had higher BMI,WC, and blood pressure, and lower HDL-cholesterol levels than women without PCOS. In a study of Italian women, Carmina et al. (24) observed that MetS was more frequent in women with PCOS than in the gen- eral population, however this prevalence was much lower than in the United States. According to their study findings, this lower prevalence of MetS intheir study subjects compared to PCOS women from the US suggested that genetic factors, differences in lifestyle and diet pattern influence the prevalence of MetS in women with PCOS profoundly (24).
The relevance of current animal models of PCOS that involve the administration of androgens or other steroid hormones to the etiology of PCOS in humans is uncertain [32,33]. We have recently shown that specific genetic deletion of insulin receptors (IR) and leptin receptors (LepR) from pro-opiomelanocortin (POMC) neurons reproduces many features of PCOS. POMC neurons modulate food intake, energy use, and hepatic glucose production [34,35,36]. These IR/LepR POMC mice have normal GnRH gene expression, and normal estradiol and prolactin levels . However, by four months old and before the onset of obesity, they show reduced litter production, reduced litter sizes, and lengthened reproductive cycles . In addition, their serum testosterone levels are significantly elevated, with increased expression of ovarian 3b-HSD , the enzyme that produces androstenedione. IR/LepR POMC mice also show significantly increased basal insulin levels, reduced glucose tolerance, overall insulin resistance, and profound hepatic insulin resistance resulting in increased glucose production . Although these mice do not overeat, they have a decreased metabolic rate . As in PCOS [38,39,40], their insulin resistance is out of proportion to their body weight. The body weights of females do not diverge from controls until 6 months old when they display increased fat deposition . Therefore, like PCOS patients, these mice display both reproductive and metabolic abnormalities.
Besides that, the metabolic abnormalities in PCOS patients can coincide with the diagnostic components of the MS, 9 in which IR and compensatory hyperinsulinemia also play a crucial role in the physiopathology of the MS. 27 Nevertheless, the prevalence of this syndrome can vary depending on the ethnicity, age, BMI, country, as well as the criteria used in deﬁning both PCOS and the MS. 28 Despite having excluded the analysis the patients’ charts with fasting glucose higher than 100 mg/dL, 22.89% of the patientsin our study had at least three parameters altered the normalcy standards, which would comply with the MS diagnostic criteria, 9 reinforcing the higher cardiovascular risk in PCOS women.
Given the significant association of certain haplotypes, we analyzed the pattern of haplotype distribution vis-a`-vis the different clinical phenotypes of PCOS. Irrespective of the association pattern, we observed two haplotype combinations: while 21111/21221 was more prominent among the PCOS cases with hirsutism, the other combination (11111/21221) showed a relatively greater frequency among the cases with infertility, obesity and elevated cholesterol levels, suggesting variable effect of UCSNP-44 depending on its presence in homozygous/heterozy- gous state. Overall, the results of our pioneering study among the Indian women are concurrent to the earlier observations that emphasize the role of CAPN10 UCSNP-44 in the manifestation of PCOS. Nevertheless, further studies are warranted to replicate the association patterns in larger cohorts of ethnically diverse populations of India so as to reach unequivocal conclusion on the role of CAPN10 polymorphisms in PCOS. Functional studies based on the regulatory regions of this gene would be required further to help gain more meaningful further insights on the precise etiological role of CAPN10 towards PCOS phenotype.
Although response rate is encouraging, failure to respond occurs and its cause is frequently uncertain. Therefore, identifying pretreatment clinical, biochemical and/or ultrasonographic features associated with improved ovulation and pregnancy rates could help select the group of infertile women with PCOS more likely to benefit from surgery and avoid unnecessary procedures. In our study, only infertility duration less than three years was correlated with improved spontaneous pregnancy rates, meaning that no other preoperative feature were useful. Other studies found that in addition to infertility duration, age, BMI and preoperative hormone levels may help predict outcomes. 35–38 A systematic review and meta-analysis
The physiopathology of insulin resistance in women with polycysticovarysyndrome (PCOS) is related to a dis- turbance in the function of the insulin receptor. In fact, the post-receptor defect associated with PCOS may be a critical factor that interferes with the recruitment of proteins for intracellular glucose transport. The conceivable end result is a compensatory increase in insulin (1). One possible option for correcting this insulin resistance is the use of drugs (such as metformin and glitazones) that may increase glucose intake in the tissue (1,2). However, there are studies showing that a few patients interrupted their metformin treatment due to a high incidence of gastrointestinal side effects, such as nausea or vomiting (2).
It is noticed that, despite the great amount of stu- dies conducted on t he subject, there is not a single conclusion that is shared between authors, quite the contrary, some are even contradictory. Therefo- re, it is concluded that vitamin d levelsin PCOS pa- tients remain a controversial subject, in which some authors argue that there is no difference between vitamin d levelsin women with and without PCOS, as well as this vitamin deficiency is not related to insulin resistance.