Endocrine Metabolism Characteristics And Related Research In Polycystic Ovarian Syndrome With Emotional Disorder

Polycystic ovary syndrome(PCOS)is a heterogeneous disease characterized by hirsutism,acne,acanthosis nigra,obesity,infertility and so on,which causes a greater psychological burden to patients.At present,it is considered that the disease is the result of the interaction of genetic and environmental factors,involving the central nervous system,hypothalamus-pituitary-ovary axis and insulin metabolism.It has been found that patients with PCOS have insulin resistance and hyperinsulinemia in varying degrees,which are associated with abnormal hypothalamic-pituitary-ovarian axis function.Insulin can synergize luteinizing hormone to promote androgen synthesis in follicular membrane cells;insulin can inhibit the production of insulin-like growth factor binding protein,sex hormone binding globulin and high affinity binding protein in the liver,which play a key role in modifying insulin-like growth factor and sex hormone in target cells.With the deepening of research,the treatment of PCOS patients has been expanded from single drug treatment to comprehensive treatment of lifestyle intervention,drugs and surgery.With the progress of society,the psychological problems caused by PCOS have been paid more and more attention.This study explored whether the NLRP3 inflammatory body participated in the psychological disorder mechanism of polycystic ovary syndrome PCOS comorbidity and provided evidence for the development of new drugs.The second is to observe the therapeutic effect and possible mechanism of pioglitazone metformin compound preparation on PCOS with emotional disorder,so as to broaden the therapeutic thinking.Objective:1.To investigate the mental health status of PCOS patients and analyze the influencing factors,so as to provide basis for psychological intervention of PCOS;2.To explore the relationship between PCOS endocrine,metabolic indicators and emotional disorders,and to provide possible ideas for the treatment of emotional distress caused by PCOS;3.To explore whether NLRP3 inflammatory body is involved in the mechanism of PCOS with emotional disorder,and to provide evidence for the development of new drugs;4.To evaluate and analyze the effects of pioglitazone metformin compound preparation on mood,endocrine and metabolic indexes of PCOS,to study its possible mechanism,and to broaden the thinking and methods of PCOS treatment.Methods:1.The diagnostic criteria of 111 patients with PCOS were adopted according to the consensus reached by the European Society of Human Reproductive and Embryonic Sciences and the American Society of Reproductive Medicine in May 2003,which is,(1)ultrasound examination revealed polycystic ovaries with at least 2-9 mm follicles in diameter(>10-12)and(or)ovarian volume(>10m L);(2)clinical and/or biochemical manifestations of androgen excess;(3)rare or anovulatory,in line with any 2 of the above three items.Meanwhile,the informed consent of the subjects was signed.Questionnaires(age,marital and reproductive status,family history),anthropometric measurements(height,body weight,waist circumference,hip circumference,blood pressure,pulse,etc.)were investigated and SCL90 scale was used to assess psychological status.Blood routine,liver and kidney function,blood lipid,electrolyte(sodium ion,potassium ion and calcium ion),urine biochemistry,sex hormone,glucose tolerance and insulin release test,liver ultrasound and gynecological ultrasound were also measured.2.The basic conditions of 40 cases of PCOS with normal psychology,40 cases of PCOS with mental disorder and 30 healthy controls were measured.The oxidative stress index(SOD,MDA),inflammatory factors(CRP,IL-6,TNF-@,IL-1?)were measured by ELISA.The inflammatory body protein of NLRP3 was measured by Western blot.The expression of NLRP3 and Capase-1 RNA was measured by fluorescence quantitative PCR.3.A randomized,single-blind prospective study was conducted.Eligible PCOS subjects were divided into control group(group A),metformin group(group B),pioglitazone metformin compound group(group C).The intervention program was divided into two parts.The treatment period was 12 weeks respectively.The scheme was that all three groups each took pioglitazone metformin compound(pioglitazone 15 mg,metformin 500mg/tablet)? metformin(500mg/tablet)? control drug(placebo)and one tablet immediately after breakfast and dinner in the first week,two tablets immediately after breakfast,one tablet after dinner next the second week.Those who were intolerable within two weeks could withdraw from the study.The therapeutic effect was evaluated at 12 weeks.The criteria included ovulation,sex hormone changes and endocrine metabolism.For patients with better therapeutic effect,we continue the original treatment for 12 weeks.For those with poor therapeutic effect,group A and group B were directly changed to group C.Group C continues the original treatment for 12 weeks to evaluate the therapeutic effect.Results:1.Among 111 cases of PCOS,37 cases had psychological disorders,and the prevalence rate was as high as 33.3%.According to the positive detection rate of psychological symptoms,the highest score was anxiety 27.0%,followed by depression 26.1%,and compulsion 25.2%;the lowest score was psychotic 9.9%,followed by paranoia 10.8%.According to the severity of psychological symptoms,the order is first depression,second anxiety,third interpersonal sensitivity;the order of moderate symptoms is depression,anxiety and compulsion,and the order of mild symptoms is compulsion,anxiety and depression.According to the total detection rate of psychological symptoms,anxiety,depression,compulsion,hostility,interpersonal sensitivity,somatization,paranoia and psychosis were ranked.According to the severity of psychological symptoms and the positive detection rate of psychological symptoms,the main emotional disorders of PCOS are depression,anxiety,compulsion and interpersonal sensitivity.There was no statistical difference in the total psychological scores of PCOS patients of different ages,marriage,fertility,BMI,waist circumference,waist-hip ratio,hirsutism,acne and acanthosis nigra(P>0.05).There was statistical difference in the total psychological scores of PCOS patients of different course of disease(P < 0.05),with one year as the limit.Further Pearson correlation analysis showed that there was no correlation between the course of disease and the total psychological score(r = 0.122,P > 0.05).2.There was no statistical difference in total cholesterol,triglyceride,high density lipoprotein,low density lipoprotein,insulin resistance index,luteinizing hormone,follicle stimulating hormone,estradiol,dehydroepiandrosterone sulfate and total psychological status(P>0.05).There were significant differences in prolactin levels,testosterone levels between total psychological scores and the two groups(P < 0.05).Further Pearson correlation analysis showed that there was no correlation between testosterone and total psychological score(r = 0.117,P > 0.05);there was no correlation between prolactin level and total psychological score(r = 0.129,P > 0.05).3.Compared with healthy control group,there were significant differences in MDA and SOD between PCOS mental disorder and normal PCOS mental state(P < 0.05).There were no significant differences in MDA and SOD between PCOS mental disorder and normal PCOS mental state(P > 0.05).Compared with the three groups,there was no significant difference in CRP(P>0.05).The expressions of IL-6,TNF-a,IL-1?,NLRP3 and Capase-1 RNA were significantly different(P < 0.05).Western blot was used to detect the expression of NLRP3 protein.There was a significant difference in the expression of NLRP3 between the three groups(P< 0.05).The Pearson correlation analysis showed that there was a significant correlation between IL-1?and total psychological score(r = 0.273,P < 0.05),and between NLRP3 and total psychological score(r = 0.291,P < 0.05).There was a significant correlation between Capase-1 and total psychological score(r=0.417,P<0.05).4.After 12 weeks of treatment,BMI showed a downward trend,but there was no significant difference between group A,B and C(P> 0.05).The improvement rates of menstrual cycle in group A,B and C were 15.7%,52.1% and 60% respectively.There were significant differences in total psychological score,IL-6,IL-1beta,TNF-a,NLRP3 and Capase-1 RNA expression between group C and group A and group B(P < 0.05).There were significant differences in 120-minute insulin,testosterone(P < 0.05).Group C decreased the most,followed by Group B and Group A.For those with poor therapeutic effect,group A and group B were changed to group C,and others were treated with the original regimen.The intervention time was 12 weeks.In group A,changed therapeutic method,there were significant differences in BMI,total psychological score,60-minute C-peptide,fasting insulin,60-minute insulin,120-minute insulin,testosterone,IL-6,TNF-a,IL-1beta,NLRP 3 and Capase-1 RNA expression compared before and after treatment(P< 0.05).The menstrual cycle returned to normal increased by 9 persons,56.3%.In group B,changed therapeutic method,there were significant differences in total psychological score,fasting blood sugar,testosterone,IL-6,TNF-a,IL-1?,NLRP3 and Capase-1 RNA expression before and after treatment,among which the number of patients whose menstrual cycle returned to normal increased by 3 persons,25%.In group C,the menstrual cycle returned to normal increased by 2 persons,7.1%.The expression of IL-1?,NLRP3 and Capase-1 RNA had statistical significance before and after treatment.Conclusions:1.The prevalence of PCOS with emotional disorders is high,mainly manifested as depression,anxiety and compulsion.The causes of emotional disorders may not be related to age,course of disease,marriage and childbearing,BMI,waist circumference,waist-hip ratio,hirsutism,acne and acanthosis nigra.Psychological intervention and counseling should be strengthened in the treatment of PCOS patients.2.The high incidence of emotional disorders in PCOS may not be related to different lipid levels,insulin resistance index and sex hormone levels.3.The high incidence of PCOS with emotional disorder may not be related to oxidative stress level,but may be related to inflammatory factors(IL-6,TNF-a,IL-1?),NLRP3 inflammatory body and capase-1 RNA expression.NLRP3 inflammatory body may participate in the mechanism of PCOS with psychological disorder.Drugs targeting NLRP3 inflammatory body may be used in the prevention and treatment of PCOS with psychological disorder in the future.4.Compared with metformin,pioglitazone metformin compound can significantly reduce the levels of inflammatory factors(IL-6,TNF-a,IL-1beta),reduce the expression of NLRP3 inflammatory body and Capase-1 RNA,improve the menstrual cycle,endocrine of PCOS,and improve the mental health and metabolic level of patients.