Determining the age group based cut-off values of serum antimullerian hormone concentrations to diagnose polycystic ovary syndrome

OBJECTIVE: Polycystic ovary syndrome (PCOS), is a common health issue that affects a significant number of women in the world. Anti-Mullerian Hormone (AMH), whose role regarding the etiopathogenesis of PCOS has been investigated at the moment, is known to be present in higher serum concentrations among women diagnosed with PCOS. We have aimed to determine cut-off values for AMH serum concentrations to diagnose PCOS in different age groups. MATERIALS AND METHOD: The study was conducted after the ethical approval was obtained from the Non-Invasive Studies Ethics Board of Dokuz Eylul University. 187 patients, who have visited the gynecology or infertility inpatient clinics of the teaching hospital of Dokuz Eylul University School of Medicine Department of Obstetrics and Gynecology, were included in this study. At least 31 patients with PCOS and 31 patients for control were appointed to each age group: 21- 25 years, 26 – 30 years and 31 – 35 years old. After the review of literature and calculations of area under curve (AUC) for 95% confidence interval and 95% power, 31 patients were required for the ROC curve analysis. The patients, who were visiting the clinics for routine controls constituted the control groups; while the patients, who were diagnosed with PCOS constituted the study groups. Serum samples were collected from the patients during the second or third days of their menstrual cycles. Serum estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), total testosterone, dehydroepiandrosterone sulphate (DHEAS), sex hormone binding globulin (SHBG), androstenedione and Anti-Mullerian Hormone (AMH) concentrations were assessed. In addition, the Ferriman – Gallwey scores, body mass indices and the ultrasonographic count of total antral follicles were recorded. FINDINGS: In total, results of 187 patients were evaluated. 93 of these patients were diagnosed with PCOS according to the Rotterdam criteria; 94 of them constituted the control group. (According to the age groups, 21 to 25 years of age: 31 PCOS, 32 Controls; 26 to 30 years of age: 31 PCOS, 31 Controls; 31 to 35 years of age: 31 PCOS and 31 Controls). The mean age was 27.78 ± 4.40. Age, height, weight, body mass index, Ferriman – Gallwey scores, total antral follicle count, serum concentrations of SHBG, total testosterone, DHEAS, androstenedione, FSH, LH, estradiol, TSH, prolactin and AMH were assessed. Weight, body mass index, Ferriman – Gallwey score and total antral follicle count were greater among patients with PCOS than the controls in all three age groups. The difference was statistically significant. The correlation between the total antral follicle count and serum AMH concentrations was statistically strong in all three age groups. In order to determine a cut-off value of AMH for the diagnosis of PCOS, ROC curve analysis was performed for each age group. Regarding the age group of 21 – 25 years, according to the analysis, the cut-off value for serum AMH concentration was found to be 5.57 ng/mL for the diagnosis of PCOS. The sensitivity was 80.65%, specificity was 75.00%, the positive predictive value (PPV) was 75.26% and the negative predictive value (NPV) was 80.00% for this cut-off. The area under curve (AUC) was 0.8543; p<0.001. After the ROC curve analysis for the age group of 26 – 30 years, the cut-off value for AMH concentration was found as 4,01 ng/mL. Concerning this cut-off level, the sensitivity was 74.19%, specificity was 70.07%, the PPV was 71.88% and the NPV was 73.33%. The AUC was 0.7862; p<0.001. The ROC curve analysis for the last age group, 31 – 35 years, concluded that the cut-off for AMH concentration was 3.42 ng/mL. The sensitivity was 74.19%, the specificity was 83.87%, the PPV was 82.14% and the NPV was 76.47% for this cut-off. The AUC was 0.8666 ; p<0.001. When all three age groups were analyzed at once (all 187 cases), the ROC curve analysis concluded that the cut-off for AMH concentration was 4.37 ng/mL. The sensitivity was 76.34%, specificity was 74.47%, the PPV was 74.74% and the NPV was 76.09%. The AUC was 0.8220; p<0.001. CONCLUSION: Sonographic assessment of ovaries is among the diagnostic criteria of Polycystic Ovary Syndrome, but it is currently being discussed whether it is an appropriate criterion. There are published criteria that does not include this criterion. However, the serum AMH concentration provides a more objective assessment of polycystic ovarian morphology. The cut-off values determined for AMH are unfortunately inadequate to be gold standard diagnostic test for PCOS. Nevertheless, keeping its contribution to predict ovarian hyperstimulation syndrome in mind, it may be a very valuable tool to support the diagnosis when there is a suspicion of PCOS.