الفهرس 
Acknowledgements
Polycystic ovary syndromeOnly 14 pages are availabe for public view
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Abstract
PCOS is a common endocrine disorder affecting the women of reproductive age and occurring with a prevalence of 5–15%. The reproductive features of PCOS include increased androgen production and disordered gonadotropin secretion leading to menstrual irregularity, hirsutism and infertility. It is also associated with an increased risk of obesity, T2DM and cardiovascular diseases. Till now the pathophysiology of PCOS is unclear. But, IR and hyperandrogenism may act together in a vicious cycle in the production of PCOS. Therefore, many researches focused on the pathological process of the disease and aimed to identify those who are at risk for PCOS development. Numerous hormones measured in the blood, had been predicted the mechanism of PCOS development. The discovered hormone, nesfatin-1, inhibits food intake and affects energy balance, insulin signaling and glucose metabolism. It is expressed in the CNS and adenohypophysis and in peripheral tissues mainly in the gastric mucosa, white adipose tissue and pancreatic β-cells as well as in the male and female reproductive organs. The development of OS in PCOS may have an adverse effect on the oocyte quality and maturation. Nicotinamide is the amide form of nicotinic acid and the precursor of NADPH. It suppresses ROS generation and enhances mitochondria quality and extends the replicative life span of human fibroblasts. Also, NADPH is essential for maintaining redox homeostasis and its deficiency lead to oxidative or reductive stress and it is critical for the scavenging of cellular ROS by glutathione reductase and peroxidase systems as a reducing equivalent. Unlikely, DA is relatively unstable molecule and undergoes auto-oxidative metabolism in which may contribute to the impairment of ovarian functions seen in the PCOS via ROS production causing apoptosis of GCs and follicular atresia. The clinical importance of nesfatin-1, DA and NADPH in the development of PCOS has not been established and nevertheless, there is still scarcity in the published literature regarding them and PCOS. Therefore, the present clinical trial study was conducted in order to clarify nesfatin-1, DA and NADPH concentrations in the PCOS patients as well as the correlation between each other and other parameters. In our study, 84 participants, 60 patients with clinical features or ultrasonography findings of PCOS and 24 healthy controls were included. The age of the participants ranged from 18 to 40 years. Patients with chronic diseases, brain disorders and usage of oral contraception were excluded. All participants were subjected to the following: Complete medical history. Complete general, physical and gynecological examinations. Anthropometric measurements as the body weight, height, WC and HC. Laboratory investigations as: Determination of lipid profile. Measurement of serum concentrations of insulin and fasting blood glucose and calculation of HOMA-IR. Measurement of hormonal assay as FSH, LH, prolactin, progesterone, estradiol and testosterone. Measurement of serum concentrations of nesfatin-1, DA and NADPH for determination of nicotinamide. Five ml of overnight fasting venous blood samples were drawn from the cubital vein from the third to the fifth day of the follicular phase of each participant. The blood samples centrifuged at 2000-3000 rpm for 20 minutes. Afterwards, the serum aliquot and stored at -20º C until analysis for nesfatin-1, NADPH and DA by corresponding ELISA tests. The following results were observed: Insignificant difference between the control and the PCOS patients groups regarding age, residence, education level and occupational status. Significant higher body weight, BMI, WC, HC and WHR and significant lower height in the PCOS patients than the control group. Irregular menstrual cycle, nulliparous, acne, hirsutism and oily skin in the PCOS patients than the control group. Significant increase in FBG, FSI, HOMA-IR and lipid profile in the PCOS patients than the control group. Significant increase in FSH, LH, prolactin, estradiol and testosterone concentrations in the PCOS patients than the control group. Significant increase in the serum concentrations of nesfatin-1 and DA and a significant decrease in NADPH concentrations in the PCOS patients. Significant positive correlations between the serum prolactin concentrations and BMI, WHR, fasting insulin, FSH, LH and estradiol. Significant positive correlations between testosterone and estradiol concentrations. Significant positive correlations between the nesfatin-1 and prolactin and DA concentrations. Significant positive correlations between DA and BMI, fasting insulin, FSH, LH, estradiol and prolactin. Significant negative correlations between NADPH and BMI, fasting insulin, estradiol and prolactin. Conclusionsfrom the results of this study it can be concluded that obesity, hyperinsulinemia, IR, hyperandrogenism are the main contributors in the pathophysiology of PCOS. Also elevated serum concentrations of prolactin with its direct association with BMI, WHR, fasting insulin, gonadotropins and estradiol indicating that hyperprolactinemia might contributed to obesity, IR, hyperinsulinemia and gonadal dysfunction in PCOS. Furthermore, elevated serum nesfatin-1 concentrations and its association with hyperprolactinemia indicating that nesfatin-1 resistance might be present with a compensatory up regulation of nesfatin-1 receptors as a defense mechanism that need further researches. Elevated serum DA concentrations might be due to increase sympathetic activity in PCOS and with its direct association between BMI, fasting insulin, gonadotropins, estradiol and prolactin contributed to impaired folliculogenesis through ROS production and IR and obesity via post-insulin receptor insensitivity. Meanwhile, decrease in the serum NADPH concentrations in PCOS with its inverse association between BMI, FSI, estradiol and prolactin indicating that NADPH could be used in the management of PCOS via its effect in reducing ROS productions. So, elevated serum nesfatin-1, DA and decreased NADPH concentrations could be used in combination with other parameters to predict the pathogenesis and outcome of PCOS.