Increased 5α-reductase activity and adrenocortical drive in women with polycystic ovary syndrome

Abstract

Context: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, anovulation, and susceptibility to the metabolic syndrome. Altered peripheral cortisol metabolism has been reported in PCOS, but also in simple obesity. Objective: The aim of the study was to describe cortisol metabolism and metabolic characteristics of a large PCOS cohort and to delineate the effect of obesity by comparison to body mass index (BMI)-matched controls. Design and Setting: We conducted an observational, cross-sectional study at outpatient clinics of two secondary/tertiary care centers. Patients or Other Participants: A total of 178 PCOS patients fulfilling Rotterdam criteria and 100 BMI-matched controls participated in the study. Intervention: The study included 24-h urine collection for steroid metabolite excretion and fasting blood samples, followed by an oral glucose tolerance test. Main Outcome Measures:Wemeasured urinary steroid metabolites including glucocorticoids and androgens and the ratios reflecting enzymatic activities involved in peripheral cortisol and androgen metabolism, 5α-reductase, and 11β- hydroxysteroid dehydrogenase types 1 and 2. We also measured circulating levels of glucose, insulin, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone and calculated homeostasis model assessment. Results: Total androgen metabolites were higher in PCOS patients compared to BMI-matched controls (4,105±2,047vs.2,532±1,610 μg/24hforthenonobese;5, 547±2,911vs.2,468±1,794 μg/24 h for the obese; both P < 0.001). Total glucocorticoid metabolites were higher in obese PCOS vs. controls (10,786±3,852 vs. 8,834±4,487 μg/24 h; P = 0.001). 5α-Reductase activity correlated with BMI, insulin levels, and homeostasis model assessment. Both obese and nonobese PCOS patients had higher 5α-reductase activity than controls (all P < 0.05). 11β-Hydroxysteroid dehydrogenase activities did not differ between PCOS and controls. Conclusions: PCOS is associated with enhanced androgen and cortisol metabolite excretion and increased 5α-reductase activity that cannot be explained by obesity alone. Increased adrenal corticosteroid production represents an important pathogenic pathway in PCOS. Copyright © 2009 by The Endocrine Society.