Study On The Correlation Between Tumor Necrosis Factor Alpha,Interleukin 1 Beta And Polycystic Ovary Syndrome

Objective Polycystic ovary syndrome(polycystic ovarian syndrome, PCOS) is one of the common reproductive endocrine disorders and metabolic disorders of women of childbearing age, and it is also one of the common causes of female infertility. PCOS is mainly manifested as persistent anovulation, hyperandrogenism(HA), hyperinsulinemia(HI) and bilateral polycystic ovary-like changes. In addition, PCOS has many metabolic effects, such as increasing the risks of obesity, Type 2 diabetes and coronary heart disease. But so far, the causes of PCOS are unclear. Many studies suggested that the pathogenesis may be outcome of combined action of pathogenic genes and environmental factors. In recent years, more and more studies have shown that chronic subclinical inflammation is closely related to the pathogenesis of PCOS. Through this research, we had a discussion about the relationship between PCOS and chronic inflammation by determining serum tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β), in order to provide a basis for further research. Methods 1. Specimen collection and preservation Our diagnostic criteria of PCOS conformed to the diagnostic criteria which was recommended by European Society of Human Reproduction and Embryology and American Society for Reproductive Medicine(ESHRE/ASRM) on the expert meeting in Rotterdam holded in May 2003:(1) rare ovulation or anovulation;(2) Clinical manifestations of hyperandrogenism and(or) hyperandrogenism;(3) Polycystic ovary-like changes: B-mode ultrasound examination showed that follicles having a diameter of 2~9mm in one or both ovaries≥12, and(or) ovarian volume≥10mL. Anyone conforms to any two of the above three can be diagnosed with PCOS. PCOS group was consisted of 34 PCOS patients(18 obese PCOS patients, 16 non-obese PCOS patients). Inclusion criteria for the control group: Women suffering from infertility caused by their tubal problems or their husband’s problems. Moreover, they all had regular menstrual cycles, biphasic basal body temperature and normal serum hormone levels. Furthermore, the ultrasound examination showed their uterus, fallopian tubes and ovaries were in normal states. Control group was consisted of 26 women. Our diagnostic criteria of obesity conformed to the diagnostic criteria for Asia-Pacific populations, which was formulated by western pacific officials of the World Health Organization(WHO), international association of the study of obesity(IASO) and the international obesity task force(IOTF) in 2000: Body mass index(BMI) = weight(kg) / height(m)2. Those individuals whose BMI≥25kg/m2 were considered to be obese while those whose BMI<25kg/m2 were considered to be non-obese. Individuals who were suffering from ovarian tumor which produced androgen, adrenal hyperplasia or tumor, pituitary disease and other endocrine disease were excluded from our experiment. At the same time, make sure that nobody was suffering from heart, liver or kidney disease and no one had a history of hormone use in the last three months. We collected fasting venous blood samples of all subjects at 9:00~11:00 a.m. in the first 2~5 days of their menstrual cycles. For those individuals whose menstrual cycle was disordered, we collected their blood sample when B-mode ultrasound examination showed that there was no dominant follicle in any of their ovaries. Each sample was 10 m L. After measuring biochemical indicators, we collected 1.5 m L of upper serum of each sample and stored it in EP tubes in-80℃ refrigerator. 2. Detection items and detection methods Measuring the weight, height, waist circumference(WC) and hip circumference(HC) of all subjects; Detecting fasting plasma glucose(FPG) with Hitachi H7060 automatic chemical immune analyzer; Detecting fasting insulin(FINS), prolactin(PRL), luteinizing hormone(LH), follicle-stimulating hormone(FSH), progesterone(P), testosterone(T) and estradiol(E2) by radioimmunoassay; Detecting serum TNF-α, IL-1β by enzyme-linked immunosorbent assay(ELISA) and immunonephelometry. 3. The calculation formulas Body mass index(BMI) = Body mass(kg) / Height(m) 2; Waist-hip ratio(WHR) = Waist circumference(cm) / Hip circumference(cm); Insulin sensitivity index(ISI) = 1 / FPG(mmol/L) × FINS(m IU/L). 4. Statistical analysis All experimental data were analyzed with statistical software SPSS16.0. All data were presented as mean ± standard deviation( x ±s). Two groups of means were compared by“ t ”test. Multiple groups of means were compared by analysis of variance and q test. Linear correlation analysis were adopted during correlation analysis. “α= 0.05” was considered to be the inspection standard in all comparisons. “P <0.05” was considered to be statistically significant. Results 1. Comparison among various indicators Serum levels of TNF-α and IL-1β in PCOS group were higher than those in control group, the differences were statistically significant(P<0.05). Serum level of IL-1β in obese PCOS group was higher than that in non-obese group, the difference was statistically significant(P<0.05). There was no significant difference of serum level of TNF-α between obese PCOS group and non-obese PCOS group(P<0.05).(Table 3) BMI、WHR in PCOS group were higher than those in control group, the differences were statistically significant(P<0.05). BMI in obese PCOS group was higher than that in non-obese PCOS group, while ISI was lower in obese PCOS group, the differences were statistically significant(P<0.05).(Table 2) 2. Correlation analysis among some indicators Serum levels of TNF-α was positively correlated with BMI and WHR in PCOS group, while it was negatively correlated with ISI in PCOS group(P<0.05)(Table 4). Conclusions 1. Serum level of TNF-α in PCOS group was higher than that in control group(P<0.05). It was positively correlated with BMI and WHR, and negatively correlated with ISI(P<0.05). There was no significant difference of serum level of TNF-α between obese PCOS group and non-obese PCOS group(P>0.05). This suggested that there may be some ways to lead to elevated levels of TNF-α beyond obesity. 2. Serum level of IL-1β was higher in PCOS group than that in control group(P<0.05). It was positively correlated with BMI and WHR, and negatively correlated with ISI(P<0.05). Serum level of IL-1β was higher in obese PCOS group than that in non-obese PCOS group(P<0.05). This suggested that obesity may play a role in the pathogenesis of PCOS. 3. TNF-α and IL-1β of PCOS patients could aggravate IR and aggravate the state of this illness at the same time. Determinations of serum levels of TNF-α and IL-1β might provide a basis for judging the progress and prognosis of PCOS.