Cortisol-Metabolizing Enzymes in Polycystic Ovary Syndrome

OBJECTIVE: The aim of this study was to assess the activity of cortisol-metabolizing enzymes in women with polycystic ovary syndrome (PCOS), using a fully quantitative gas chromatography/mass spectrometry (GCMS) method. DESIGN: We investigated the glucocorticoid degradation pathways that include 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) type 1, 5 alpha-reductase (5 alpha-R) and 5 beta-reductase (5 beta-R), 3 alpha-hydroxysteroid dehydrogenase, and 20 alpha -and 20 beta-hydroxysteroid dehydrogenase (20 alpha-HSD and 20 beta-HSD, respectively) in young nonobese women with PCOS, using a fully quantitative GCMS method. SETTING: This study was conducted in a tertiary referral hospital in Israel. PATIENTS: This study group consisted of 13 young women, aged 20.1 +/- 2.8 years (mean +/- SD), with the body mass index (BMI) of 22.6 +/- 3.7 kg/m(2), diagnosed with PCOS according to the Rotterdam criteria. The control group consisted of 14 healthy young women matched for weight, height, and BMI. INTERVENTIONS: Urine samples were analyzed using GCMS. We measured urinary steroid metabolites that represent the products and substrates of the study enzymes and calculated the product/substrate ratios to represent enzyme activity. MAIN OUTCOME MEASURES: The calculation of enzymatic activity, based on glucocorticoid degradation metabolites, was done by GCMS in PCOS vs. controls. RESULTS: All glucocorticoid degradation metabolites were higher in the PCOS group than in controls. Of the adrenal enzymes, the activities of 21-hydroxylase and 17 alpha-hydroxylase were reduced, whereas the activity of 17,20-lyase was enhanced in PCOS. Of the degradation enzymes, the activity of 11 beta-HSD type 1 was reduced in women with PCOS only when calculated from cortoles and cortolones ratios. The activities of 5 alpha-R/5 beta-R were increased only when calculating the 11-hydroxy metabolites of androgens. The activity of 20a-HSD was elevated in the patients with PCOS and its relation with the substrate levels was lost. CONCLUSIONS: We confirm PCOS association with low 21-hydroxylase activity. PCOS is associated with dysregulation in glucocorticoid degradation. The activity of 5 alpha-R is enhanced only through the backdoor pathway. Marked increase in the activity of 20 alpha-HSD suggests a hitherto unknown derangement in PCOS.