Sex hormone-binding globulin as a biomarker for metabolic risk in European women with polycystic ovary syndrome

Objective: Sex hormone-binding globulin (SHBG) is suggested to be a biomarker for metabolic disturbances in women with polycystic ovary syndrome (PCOS). Insulin resistance and hyperinsulinemia is common in PCOS patients. Low SHBG increases free testosterone levels, which further induces hyperinsulinemia. There is no established cutoff level for SHBG in PCOS patients. The goal of this study is to examine SHBG as a biomarker for metabolic dysregulation in European women with PCOS in relation to hyperandrogenemia. Methods: Retrospective data was collected from the outpatient clinic for menstrual cycle disorders at Maastricht University Medical Center+. 208 women were included, aged between 18 and 40 years old. During a one-time visit to the clinic, physical examination and vaginal ultrasound evaluation were performed as well as endocrine evaluation performed after overnight fast. The women were diagnosed with PCOS according to the European Society of Human Reproduction and Embryology (ESHRE) 2018 guideline. Results: BMI was inversely associated with SHBG (beta -0.598, 95% CI [-0.710 to -0.485]) and waist circumference (beta -0.604, [-0.715 to -0.492]), even after correction for HOMA-IR and testosterone. A cutoff level <40 nmol/L was significantly, and unfavorably, associated with all metabolic outcomes. Its AUROC was optimal for waist circumference (sensitivity 0.75, specificity 0.82). Conclusions: SHBG levels <40 nmol/L are indicative for metabolic dysregulation in European women with PCOS. Waist circumference is an important predictor for SHBG, comparable to BMI. Visceral adiposity might play an important role in the expression of SHBG and etiology of PCOS.