Significance Of Adrenocorticotropic Hormone Stimulation Test In Identification Of Androgen Sources In Polycystic Ovary Syndrome

Research backgroundPolycystic ovary syndrome（PCOS）is a common reproductive endocrine disease in women of childbearing age,it is characterized by sparse ovulation or anovulation,hyperandrogenism and polycystic ovary（PCO）,hyperandrogenism-related symptoms are one of the main reasons for patients to see doctors.Ovarian-derived androgens play an important role in the development of PCOS,but recent studies have shown that the high sensitivity or overreactivity of hypothalamus-pituitary-adrenal axis in some patients is an important cause of hyperandrogenism.Further studies have found that these patients are more responsive to dexamethasone treatment,so adrenal hyperandrogenism may be an independent subtype of PCOS,but there is no effective way to distinguish the two.In clinical work,adrenocorticotropic hormone（ACTH）stimulation test is widely used in differential diagnosis of adrenal diseases,whether it can be used as a method for identification of PCOS androgen sources needs further study.ObjectiveTo investigate the changes of adrenal androgen metabolites after ACTH stimulation test in normal women and women with PCOS,and to evaluate the adrenal response to ACTH in patients with PCOS,explore the significance of ACTH stimulation test in differentiating androgen sources in PCOS patients.MethodThe clinical data of 46 PCOS patients who met Rotterdam criteria and 25age-matched normal controls were collected,including height,weight,body mass index（BMI）,waist-hip ratio（WHR）.Serum follicle stimulating hormone（FSH）,luteinizing hormone（LH）,total testosterone（TT）,free testosterone（FT）,estradiol（E₂）,progesterone（P）,prolactin（PRL）were measured.Oral glucose tolerance test（OGTT）was used to detect blood sugar and insulin（INS）,and LH/FSH,homeostasis model insulin resistance index（HOMA-IR）and free testosterone index（FAI）were calculated.All subjects were tested for serum levels of 17-hydroxyprogen（17-OHP）,cortisol（F）,dehydroepiandrosterone sulfate（DHEAS）,androstenedione（AD）and sex hormone binding globulin（SHBG）before and after ACTH stimulation,hormone values before and after stimulation were expressed by subscript 0 and 60,respectively.The clinical biochemical characteristics and hormone levels of PCOS group and control group were compared;the paired differences between PCOS group and control group were analyzed,the changes of hormone levels before and after ACTH stimulation test were compared;the correlation between clinical biochemical characteristics and hormones in PCOS patients was analyzed,and the risk factors of PCOS were analyzed by logistic regression analysis;the ROC curve was used to analyze the differential value of ACTH stimulation test in the androgen source of PCOS patients.Results（1）Compared with the control group,BMI,WHR,hirsutism score,HOMA-IR,LH,LH/FSH,TT,E₂,FT and FAI in PCOS group increased significantly（P<0.05）,while FSH,P and PRL had no significant difference（P>0.05）;ACTH stimulation test hormone comparison:17-OHP₀,17-OHP₆₀,AD₆₀ and DHEAS₆₀ in PCOS group were increased significantly,while SHBG₀ and SHBG₆₀ were decreased significantly（P<0.05）,but F₀,F₆₀,AD₀ and DHEAS₀ had no significant difference（P>0.05）.（2）Comparison of paired differences of hormone levels before and after ACTH stimulation test:after ACTH stimulation test,17-OHP,F,DHEAS and AD increased significantly and SHBG decreased significantly in PCOS group（P<0.05）;after ACTH stimulation test,17-OHP,F,DHEAS and AD in the control group increased significantly（P<0.05）,but SHBG had no significant difference（P>0.05）;the difference of hormones between the two groups before and after ACTH stimulation:DHEAS and AD increased in PCOS group（P<0.05）.（3）Logistic regression analysis:high levels of WHR and DHEAS are risk factors for PCOS.（4）ROC curve analysis:the largest hormone under ROC curve of ACTH stimulation test is DHEAS₆₀,AUC is 0.780,the best cut-off point is 308.5 ug/dL,the sensitivity,specificity and Yoden index are 0.652,0.800 and 0.452 respectively.The ACTH stimulation test has certain value in the identification of ovarian-derived and adrenal-derived androgen in patients with PCOS.ConclusionThe ACTH stimulation test can identify the source of androgen in PCOS patients,which is helpful for subtype analysis of PCOS.