BIOCHEMICAL CHARACTERISTICSOF POLYCYSTIC OVARY SYNDROME

Martial and methods: This study includes 20 woman attending Mansoura university woman Hospital, their age‘s ragas range from 20-35 years. This study was approved by the ethical and research committee of council of obstetrics and gynecology Mansoura university. Group I (study group): Consists of 10 women with polycystic ovary syndrome and Group II control group: Consist of 10 women.Eachcase-taking sample of fasting blood from veins to determine Biochemical analysis that characterized of polycystic ovary syndrome.


Praveen et al. (2016) resulted that, polycystic ovarian syndrome (PCOS) is a complex and multifactorial disorder believed to be the consequence of a complex interaction between genetic, immunological, and environmental factors
Khayyatet al. (2012) recorded the height, weight of every patient was measured and recorded on their first visit, and BMI was calculated. Patients were grouped according to their BMI into three groups of normal with BMI of 20 to 24.9, overweight (25 to 29.9) and obese (≥30). Increase body mass index (BMI) with clinical symptoms in polycystic ovary syndrome (PCOS) women. The findings of this study indicated that the overweight/obese women with PCOS are at an increased risk for sonographic view of polycystic ovaries. (Seddigheh et al. 2015) Gangale et al. (2011) reported that, case-control study from Chile showed a statistically significant difference in elevated ALT levels between 41 PCOS patients compared to 31 age-and body mass index (BMI)-matched healthy women (39% vs 3.1%, respectively), using a cut-off > 25 U/L, according to normal values for healthy Chilean women.Gangale et al. (2011) reported that, case-control study from Chile showed a statistically significant difference in elevated ALT levels between 41 PCOS patients compared to 31 age-and body mass index (BMI)matched healthy women (39% vs 3.1%, respectively), using a cut-off > 25 U/L, according to normal values for healthy Chilean women.

Banaszewska et al. (2003)
resulted LH/FSH ratio greater than 2 was accepted as abnormal, and it was found in 54 women (45.4%; I group). Normal gonadotropin ratio was detected in 65 women (55%; group II). Statistically significant differences were noted between groups with normal and elevated LH/FSH ratio in the following parameters: BMI (body mass index), serum insulin, and LH levels. Further analysis revealed that the majority of women with elevated insulin concentrations belong to the group with normal LH/FSH ratio.

Sunita et al. (2012)
resulted that, Hormonal profile of PCOS was studied in 102 Indian women. Serum levels of Luteinizing hormone (LH), Follicle stimulating hormone (FSH), LH: FSH ratio, Prolactin (PRL), Thyroidstimulating hormone (TSH), Dehydroepiandrosterone (DHEA), Testosterone, fasting blood glucose (FBG), fasting insulin levels and Homeostasis Model Assessment (HOMA) value were estimated. The mean LH and FSH levels are 12.54 ± 5.87 and 5.70 ± 1.80 (IU/L) respectively. The mean LH: FSH ratio is reversed and is more than two (2.23±0.94). Mean PRL, TSH, and testosterone levels show normal ranges. Mean fasting insulin (16.27±13.27 µU/ml) and HOMA (3.509±2.621) are high with 79.31% prevalence of insulin resistance. In all the patients, both LH and FSH are positively correlated with testosterone. In normal weight patients, PRL and LH: FSH are positively correlated. In overweight/obese serum, LH and DHEA are positively correlated. A positive correlation was observed between testosterone and PRL in overweight/obese. On sub-grouping data of gonadotropin levels with respect to different days of menstrual cycle, LH levels and LH: FSH ratio but not FSH levels show significant intergroup variation. The authors conclude that, low levels of FSH is persistent irrespective of day and phases of menstrual cycle, the reversal of LH: FSH is mainly because of lower FSH and the physiological cyclical pattern of gonadotropin altered in PCOS with partial preservation of the cyclical variation of LH but not of FSH. Insulin resistance is independent of BMI and is common in Indian PCOS women.
Nida (2014) concluded that, Anti-mullerian Hormone (AMH) is a member of the transforming growth factor β family of growth and differentiation factors. It has an integral role in the intrauterine development and sex differentiation of the male fetus. It is secreted from the Sertoli cells of the developing testes inhibiting ipsilateral mullerian duct development and thereby allowing the Wolffian duct system to prevail. However, the role of AMH across the female reproductive life span has only more recently become known. In the ovary, AMH has an inhibitory effect on primordial follicle recruitment as well as on the responsiveness of growing follicles to Follicle-Stimulating Hormone (FSH). The ovary-specific expression pattern in granulosa cells of growing non-selected follicles makes AMH an ideal marker for the size of the ovarian follicle pool and a prognostic factor for fertility potential.
Chang et al. (2005) reported that, the adrenal cortex synthesizes all the three major androgens; dehydroepiandrosterone sulfate (DHEAS), androstenedione and testosterone, and this is the other major site of female androgen production, besides the ovaries. DHEAS is almost exclusively (97-99%) produced by the adrenal cortex and androstenedione is produced in both the adrenal gland and the ovaries , whereas 25% of testosterone is synthesized by the adrenal gland, 25% in the ovary and the remaining part being produced through peripheral conversion from androstenedione in liver, adipose tissue and skin . Around 60-80% of PCOS women have high concentrations of circulating testosterone. In PCOS women, the prevalence of DHEAS excess is 20-30%, depending on ethnicity and DHEAS levels decline up to the age of ~ 45 years. The increased DHEAS levels in PCOS women compared with controls is verified up to the perimenopausal ages. However, the mechanisms of the adrenal androgen excess in PCOS is still unclear, although it has been proposed that it may result from increased metabolism of cortisol, which could lead to decreased negative feedback on ACTH secretion.

Moran et al. (1999)
concluded that, Clinically, the measurement of circulating levels of the AA metabolite DHEA sulfate (DHEAS) has been traditionally used as a marker for AA excess because this steroid is 97-99% of adrenocortical origin, the second most abundant steroid after cortisol (F), relatively stable throughout the day and the menstrual cycle, because of its relatively long half-life, and easily measured. Excess AA levels, particularly elevations in the levels of the dehydroepiandrosterone (DHEA) metabolite DHEAS and 11-hydroxyandrostenedione (11OHA4), were initially reported in 40-60% of patients with PCOS. However, in most of these early studies criteria for the selection of PCOS patients were different from those currently used. Moreover, it is clear that several factors, including age and race, should be considered when estimating the prevalence of AA excess in PCOS, because AAs begin to decline after the age of 30 years in both normal women and women with PCOS.
Carmina et al. (1992) resulted that, in a retrospective study of 145 hyperandrogenic patients, we found that hyperandrogenic patients with high DHEAS levels were younger, in addition to being thinner and more hirsute, than hyperandrogenic women with lower DHEAS levels. The impact of race on the prevalence of AA excess in PCOS is unclear. In one report the prevalence of AA excess among PCOS patients was found to be similar among Italian, US, Hispanic-American, and Japanese women. However, only small groups of patients compared. To reevaluate the prevalence of AA excess in PCOS taking into account race and age-related changes in AAs, we undertook a study of 213 (27 black and 186 white) women with PCOS and 182 (88 black and 94 white) age-matched healthy eumenorrheic nonhirsute women (controls) .
Huertaet al. (1999) concluded that, the diagnosis of PCOS based on hyperandrogenism and chronic anovulation, consistent with the National Institutes of Health 1990 criteria. DHEAS levels were significantly lower in black than white controls, whereas fasting insulin and body mass index (BMI) were higher in black controls, and DHEAS levels decreased similarly with age in control and PCOS women of either race. Body mass and fasting insulin had little impact on circulating DHEAS levels in healthy women. Among PCOS patients, these parameters were negatively associated with circulating DHEAS levels among white, but not black patients. For each race and age group, the upper 95% normative values for log DHEAS was calculated, and the number of PCOS subjects with log DHEAS values above this level assessed. The prevalence of supranormal DHEAS levels was 33 and 20% among black and white women with PCOS, respectively-not a significant difference.

Sanchez et al. (2002)
.resulted that, these data indicate that AA excess, defined by the circulating level of DHEAS, is somewhat less common in PCOS than previously reported, affecting between 20 and 30% of affected women when using age-and race-adjusted normative values. However, it also appears that women with absolute DHEAS excess simply represent the upper edge of the normal DHEAS distribution in the general population, not a separate population. For example, cluster analysis failed to reveal any specific subpopulations of DHEAS levels among our patients with PCOS. Finally, there may be significant differences in mean DHEAS levels between white and black control women.

Mehmet et al. (2015)
resulted that, finally, we should note that DHEAS, does not uniformly reflect AA secretion in response to adrenocorticotropic hormone (ACTH) in normal or hyperandrogenic patients. For example, only 50% of patients with 21-OH-deficient NCAH have a supranormal DHEAS levels. Witness also the profound suppression in DHEAS levels that occurs in NCAH patients treated with glucocorticoids despite the still elevated production of low-dose A4. Likewise, note should be taken of the increase in DHEAS in response to exogenous testosterone administration to oophorectomies women, despite the absence of any change in the AA response to acute ACTH stimulation. Consequently, it is apparent that a number of factors may alter DHEAS levels without modifying adrenocortical AA production, most likely through regulation of DHEA sulfotransferase (DHEA-ST) activity. Hence, the investigation of those mechanisms underlying the AA excess of PCOS requires evaluation not only of DHEAS levels, but also of adrenocortical biosynthesis (usually measurable by the response to acute ACTH stimulation). In our study, increased BMI observed with a correlation between DHEAS levels and a similar relationship because of work done by Park and colleagues also found.

Material and methods:-
This study includes 20 woman attending Mansoura university woman Hospital, their age's ragas range from 20-35 years. This study was approved by the ethical and research committee of council of obstetrics and gynecology Mansoura university.The 20 women are divided into two groups

Results:-
In the present investigation of the Anthropometric of polycystic ovary syndrome (PCOS) women and controls showed in table (1)      In addition, there is some evidence that ovarian T production may be reduced by administration of statins (Legroet al. 2007). This effect may be due, at least in part, to inhibition of theca cell growth and by decreasing the concentration of precursor for production of androstenedione (Balenet al. 2003). Furthermore, statins appear to have antioxidant properties. Clinical trials of statins alone or in combination with other medications among women with PCOs are limited in number, and conclusive evidence that statins ameliorate PCOs symptoms is lacking, although improvements in hyperandrogenemia have been noted (Mikolaet al. 2001). Further recent data show that statin use may increase the risk for developing T2 DM (Haakovaet al. 2003).while triglyceride increase duo to fats that provide energy for the cell. Like cholesterol, they are delivered to the body's cells by lipoproteins in the blood. A diet with a lot of saturated fats or carbohydrates will raise the triglyceride levels, liver dysfunction resulting from hepatitis, extra hepatic biliary obstruction or cirrhosis, diabetes mellitus is associated with the increase.(Young2001).They also demonstrate an increase in LDL particle number and a borderline decrease in LDL size and suggest that androgens may play a more significant role in pathogenesis of lipid abnormalities in PCOS (Sidhwaniet al. 2001). The mechanism by which hyperandrogenism may contribute to development of lipid abnormalities in PCOS is not clear. Hyperandrogenism may lead to the abnormalities in lipoprotein profile by working directly at the liver, or it may alter body composition by favoring central adiposity. (Echiburú et al.  2012)The obtained results of this showed increase of aspartate aminotransferase and alanine aminotransferase compared with women of PCOS with normal women. While not significant increase in total protein, serum albumin Increase the insulin due to several conditions in which insulin disturbance is pathologic: diabetes mellitus, insulinoma, metabolic syndrome and polycystic ovary syndrome. There are two types of diabetes mellitus: type 1 (autoimmune-mediated destruction of insulin producing beta cells in the pancreas resulting in absolute insulin deficiency), and type 2 (multifactor syndrome with combined influence of genetic susceptibility and influence of environmental factors, the best known being obesity, age, and physical inactivity, resulting in insulin resistance in cells requiring insulin for glucose absorption. This form of diabetes is strongly inherited). (Gerbitz 1980).
In the present studies Showed highly significant decrease in the follicle stimulating hormone at the comparison with control group. While highly significant in increase in luteinizing hormone at the comparison with control group. On the other hand high significant increase the dehydroepiandrosterone sulfate at the comparison with control group. While the AMH showed high significant increase at the comparison with control group. The total testosterone showed high significant increase at the comparison with control group. This result agree with Muhammad and Nabila (2015) resulted the elevated LH in PCOS has also been reported earlier.12 However, the elevation in LH level, in this study, was significantly intense than the reported values. The LH: FSH ratio in PCOS group, in comparison to control subjects, was raised by 18-folds in this study. Interestingly, PCOS women with hyperinsulinemia and overproduction of LH had significantly higher serum levels of dehydroepiandrosterone sulphate. In the remaining groups, DHEAS concentration was normal. It is still not fully under-stood how insulin influences the adrenal androgen secretion. The negative correlation between insulin levels and dehydroepiandrosterone sulphate production have been found. On the other hand, there are also studies that do not confirm correlation between insulin activity and adrenal androgen production (Azziz et al., 1998).
The elevated LH due to Nowadays it is believed that elevated LH level occurs more rarely in a group of patients with insulin resistance and hyperinsulinemia, than in-group without hyperinsulinemia. This observation was confirmed in a presented group of women, in which normal gonadotropin ratio 1:1 was observed in up to 72% of patients with hyperinsulinemia. One may speculate that additionally to, that is considered to be a strongest androgen production stimulator, in women with normal LH level additional stimulators of steroidogenesis exist. Most probably it is insulin and IGF-I. Thus, it could have been expected that the most severe clinical symptoms and greater androgen concentration would appear in women with hyperinsulinemia and overproduction of LH. However, the mean testosterone levels in the studied women were independent of insulin and LH concentrations. Hirsutism of greater sever it was observed in a group of women with hyperinsulinemia and LH/FSH ratio > 2 when compared with women with hyperinsulinemia and normal gonadotropin ratio (Banaszewskaet al.2003). Interestingly, PCOS women with hyperinsulinemia and overproduction of LH had significantly higher serum levels of dehydroepiandrosterone sulphate. In the remaining groups, DHEAS concentration was normal. It is still not fully understood how insulin influences the adrenal androgen secretion. The negative correlation between insulin levels and dehydroepiandrosterone sulphate production have been found. On the other hand, there are also studies that do not confirm correlation between insulin activity and adrenal androgen production (Azziz et al., 1998).
In the present study concluded elevated serum testosterone in polycystic ovary syndrome Serum testosterone level so is the best marker for ovarian hyperandrogenism, and dehydroepiandrosteronesulfate is the best adrenal marker this results agree with Carminaet al. (1992) concluded that, The measurement of free testosterone provides a higher diagnostic yield for ovarian hyperandrogenism because levels of sex-hormone binding globulin are decreased. However, clinical assays used to test this measure vary considerably, affecting its reliability. It is important to point out that hyperandrogenemia is not synonymous with hirsutism or acne. Some ethnic groups (for example, Asians) have substantialhyperandrogenism (elevated levels of testosterone and dehydroepiandrosterone sulfate) without any significant skin manifestations.
In the present study, we used diagnostic criteria recommended by Carmina et al. (1992) for selecting the patients. It has been suggested that serum AMH levels were increased in PCOS .Although AMH seems a promising diagnostic tool, Hart et al failed to demonstrate serum AMH was a reliable predictor of polycystic ovarian morphology or for the presence of PCOS in the general adolescent population (Hart et al.2010). Routine serum testing for AMH levels for the diagnosis of PCOS is controversial. In the present study, AMH levels among study groups were different. PCOS subjects had significantly higher AMH levels duo to the positive correlation between AMH and ovarian volume. AMH also positively correlated with total testosterone. We found AMH levels and testosterone high in adolescent PCOS group. In previous studies, AMH levels were found to be associated significantly with testosterone especially in adolescents. This finding is harmonious with our results. We think that AMH can be a useful marker to determine the adolescent population who have a tendency to develop PCOS. Further studies are required with larger sample sizes. We also think that subgroups in adolescent PCOS group should be determined which are associated more significantly with elevated AMH levels in subsequent studies. Moreover, AMH levels in PCOS women were found to be approximately three-fold higher that those of healthy fertile control. Although the increase in AM H levels in PCOS women was thought to be due to the increase in small antral follicles, a recent stud y showed that AMH production is 75 times higher per granulosa cell in PCOS patients than in granulosa cells innormal ovaries. (Pellattet al. 2007).Furthermore, AMH concentrations in the follicular fluid were five times higher in the follicles of womenwith anovulatory PCOS compare d with women who were ovulatory(Daset al. 2008)In this study, the rate of age-related decline inAMH concentrations was found to be smaller in PCOSpatients compared with healthy fertile patient s. Whether or not the aforementioned finding is due to a slower depletion of thefollicular pool in PCOS patients requires further rese arch. The sensitivity and specificity of AMH-base d detect ion of PCOS in Taiwanese women aged 29e 38 years were calculated to be74% and 79%, respectively, using an AMH cut-off value of3.5 ng/mL. Whether it is helpful or not to use AMH screening tool for PCOS require s future investigations. (Seiferet al. 2009).