Clinical,Psychological Characteristics And AR Gene Mutation In Patients Of Childbearing Age With Polycystic Ovary Syndrome

Polycystic ovary syndrome(PCOS)is a most common reproductive and endocrine disease in women of childbearing age,and a leading cause of ovulation disorders and infertility.Irregular menstruation,hyperandrogenemia,and polycystic ovary are the mainly clinical features of PCOS.Overweight or obesity is common in PCOS,and with complications such as endometrial hyperplasia,endometrial cancer,metabolic syndrome,cardiovascular diseases,and type 2 diabetes.In addition to anxiety and depression,mental disorders.Because of its high heterogeneity,there is no unified diagnostic criteria.It is still characterized by hyperandrogenism or hyperandrogenemia.The mechanism underlying the pathophysiology of PCOS remains to be illustrated.It is generally believed that heredity,epigenetic factors and environmental affect the pathogenesis of PCOS.In recent years,there were many studies focus on the androgen receptor(AR)gene and PCOS,but there were few reports about AR mutation and pathogenesis of PCOS.Therefore,this study will explore the relationship between AR mutation and PCOS.Androgen excess is a typical feature of PCOS.The clinical manifestations are hirsute,acne and male type baldness,which seriously affect patients physical and mental health.It is found that hyperandrogenemia increased LH secretion,which leads to follicular dysgenesis and menstrual disorder in PCOS.Hyperandrogenemia inhibit the degradation of insulin in liver,and lead to insulin resistance.Androgen excess,insulin resistance and ovulation disorders which effect,promote and influent each other,they participate and promote the development of PCOS.This study will discuss from the following three aspects.First,we analyzed the clinical and laboratory data of PCOS and non-PCOS population,and revealed the characteristics and possible related high-risk factors of PCOS.Secondly,we collectd the self-rating anxiety scale of PCOS,combined with the results of clinical and laboratory indicators,to explore the correlation between androgen and psychological health of PCOS patients.It provides scientific basis for the prevention of PCOS.Third,we sequenced the AR gene in PCOS patients,and calculated the incidence and potential pathogenic of AR mutation in PCOS population.Then we constructed the wild and mutant AR gene type lentivirus vectors,which infect human ovarian granulosa cell tumor cells(KGN).After that,we detected the hormone seretion from the culture medium of infected KGN cells,and explored the relationship between AR mutation and hormone expression.Chapter?:Clinical laboratory characteristics and risk factors of PCOSpatients in childbearing ageObjective:To analyze the clinical laboratory characteristics of PCOS patients in childbearing age,to explore the risk factors of PCOS patients.Methods:258 PCOS(study group)and 520 non PCOS infertility patients(control group)were collected in the assisted reproduction center of Jiangxi maternal and child health hospital from October 2016 to September 2018.China PCOS diagnostic criteria which published in 2011 was used to identified PCOS patients.The clinical and laboratory characteristics of PCOS group and control group were analyzed retrospectively,and the risk factors of PCOS were analyzed through case-control study.SPSS 19.0 statistical software was used for data analysis.Result:1)The mean BMI,menstrual interval,AFC,mF-G score,waist to hip ratio and acne score of PCOS group were higher than those of the control group(P<0.05).2)The basic LH,T,AMH,FT3,TSH,fasting blood glucose and triglyceride in PCOS patients were higher,while the basic FSH,HDL and LDL were lower than those of the control group,the differences were statistically significant(P<0.05).There was no significant difference in basal E2,PRL,FT4,CA125 and total cholesterol between the two groups(P>0.05).3)The proportion of smoking/passive smoking,middle and above stress,lack of exercise,family history of hypertension and family history of obesity in PCOS patients were higher than those in the control group,the results were statistically significant(P<0.05).There was no significant difference in drinking,less stress,PCOS family history,diabetes family history and male early baldness family history between the two groups(P>0.05).Conclusion:The clinical characteristics of PCOS patients in childbearing age were prolonged menstrual cycle,increased number of antral follicles,obesity(especially central obesity),hirsutism,acne and other hyperandrogenic signs;the laboratory indicators are high LH,T,and AMH.PCOS has family heredity.The pathogenesis of PCOS may be related to stress,more smoking/passive smoking,lack of exercise and so on.Chapter?A study of anxiety of PCOS patients in childbearing ageObjective:To explore the influencing factors of psychological and quality of life of PCOS patients in childbearing age.To analyze the correlation between androgen and mental health of PCOS.It provides scientific basis for the prevention of PCOS,the adjustment of life style and the improvement of treatment effect.Methods:Among 258 PCOS patients,147 of them were investigated with SAS in a relatively private environment.The patient's history and basic information were collected as mentioned before,glucose tolerance and insulin were tested.SPSS 19.0statistical software was used for data analysis.Result:1)In this study,the average age of 147 PCOS patients were 28.08±3.24 years,and the average BMI was 23.33±3.4 kg/m~2.The mean short interval of menstrual cycle was 28.51±6.34 days,and the long cycle was 102.08±42.25 days.66 cases(44.90%)had a menstrual cycle of less than 90 days,and 69 cases(46.94%)were90-180 days,and 12 cases(8.16%)were more than 180 days.The average duration of infertility was 3.93±1.45 years.48 cases(32.65%)were complicated with obesity,126 cases(85.71%)were central obesity(WHR>0.8).36 cases(24.49%)had impaired glucose tolerance and 114 cases(77.55%)had insulin resistance.There were135 cases of menstrual disorder+PCO type(91.84%),0 cases of menstrual disorder+hyperandrogenic state type(0%),and 12 cases of menstrual disorder+hyperandrogenic state+PCO type(8.16%).2)Among the 147 PCOS patients,18.37%of them were anxious,with an average anxiety score of 40.59±0.79 points.27 patients with mild anxiety.No one was found to have moderate or severe anxiety.3)Among the 147 PCOS patients,the detection proportion of acne score,waist-hip ratio,central obesity proportion,menstrual cycle,LH/FSH,basic E2,T,serum TSH,triglyceride,menstrual disorder+hyperandrogenic status+PCO polycystic subtype in the anxiety group were all higher than those in the non-anxiety group,with statistically significant differences(P<0.05).There were no statistically significant differences in age,modified F-G score,BMI,blood pressure,menarche age,menstrual disorder duration,total cholesterol,HDL,abnormal glucose tolerance and insulin resistance between the two groups(P>0.05).4)The longer the menstrual cycle of PCOS patients,the higher the detection proportion of anxiety.The detection proportion of anxiety was higher in the central obesity group,acne group,hyperandrogenic group and menstrual disorder+hyperandrogenic status+PCO polycystic subtype group,with a statistically significant difference(P<0.05).While there were no differences of anxiety detection proportion in the thyroid dysfunction group,hyperlipidemia group,abnormal glucose tolerance group and insulin resistance group(P>0.05).Conclusion:The longer the period of PCOS patients,the higher the detection proportion of anxiety.High anxiety detection proportion in patients with central obesity,acne,hyperandrogenemia,menstrual disorder+hyperandrogenic status+PCO PCOS patients.Hyperlipidemia,thyroid dysfunction,abnormal glucose tolerance and insulin resistance of PCOS patients were not related to anxiety.Chapter?Research on AR mutation in PCOS patients of childbearingageObjective:To investigate the role of AR mutation in PCOS with reproductive age.It provides a new thought and theoretical basis for the clinical diagnosis and treatment of PCOS patients with AR mutation.Methods:AR gene sequencing was performed in 258 cases of PCOS and 520non-PCOS patients.Furthermore,the mutation sites were analyzed by bioinformatics,evolutionary conservation and variability to search for potential pathogenic mutations.Wild type and mutant lentivirus vectors of AR gene were constructed to infect human ovarian granulosa cell tumor cells(KGN),to observe the changes of various hormone secretion in KGN cell culture medium in different groups,and to analyze the relationship between AR mutation and various hormone seretion.Results:1)5 AR heterozygous missense mutations(p.V3M(c.7G>A),p.Q72R(c.215A>G),p.S158L(c.473C>T),p.S176R(c.528C>A)and p.G396R(c.1186G>C))were detected in 5 PCOS samples,while no AR mutation was detected in 520Han Chinese control samples.2)3 AR mutations(p.V3M,p.S158L and p.S176R)were potentially pathogenic,while the other 2 mutations(p.Q72R and p.G396R)were probably benign.3)The average serum E2 level on HCG injection day of the 3 samples with pathogenic AR mutations was 2227.00±184.82 pg/mL,significantly lower than that of the 255 PCOS samples without or with benign AR mutations(3180.24±1710.25pg/mL)(P<0.01).The basal serum levels of FSH,LH,RPL,CA125,and LH and progesterone levels on HCG injection day,was higher in the 3 patients with pathogenic AR mutations,while the LH/FSH ratio,basal serum E2,T and AMH levels,triglycerides,BMI,AFC,length of menstrual cycle,total dose of gonadotrophins,and the number of oocytes retrieved were lower,when compared with the 255 PCOS samples without or with benign AR mutations,even if these differences did not reach statistical significance.4)The levels of T,E2 and insulin in the culture medium of KGN cells infected with AR gene mutation were lower than that of the wild type.Conclusion:3 patients with p.V3M,p.S158L and p.S176R mutations,but not p.Q72R and p.G396R mutations,may be pathogenic.The demographic characteristics of the 3 patients with pathogenic AR mutation of PCOS were closer to the non-PCOS population,belonging to atypical PCOS.Compared with the patients without or with benign AR mutation,they had lower BMI,shorter menstrual cycle,fewer AFC,and lower serum T level.AR gene mutation may have protective effect on PCOS patients.