title: Increased 5 alpha-reductase activity and adrenocortical drive in women with polycystic ovary syndrome.
abstract: BACKGROUND
  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.
  
  
  METHODS
  We conducted an observational, cross-sectional study at outpatient clinics of two secondary/tertiary care centers.
  
  
  METHODS
  A total of 178 PCOS patients fulfilling Rotterdam criteria and 100 BMI-matched controls participated in the study.
  
  
  METHODS
  The study included 24-h urine collection for steroid metabolite excretion and fasting blood samples, followed by an oral glucose tolerance test.
  
  
  METHODS
  We measured urinary steroid metabolites including glucocorticoids and androgens and the ratios reflecting enzymatic activities involved in peripheral cortisol and androgen metabolism, 5 alpha-reductase, and 11 beta-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 +/- 2,047 vs. 2,532 +/- 1,610 microg/24 h for the nonobese; 5,547 +/- 2,911 vs. 2,468 +/- 1,794 microg/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 microg/24 h; P = 0.001). 5 alpha-Reductase activity correlated with BMI, insulin levels, and homeostasis model assessment. Both obese and nonobese PCOS patients had higher 5 alpha-reductase activity than controls (all P < 0.05). 11 beta-Hydroxysteroid dehydrogenase activities did not differ between PCOS and controls.
  
  
  CONCLUSIONS
  PCOS is associated with enhanced androgen and cortisol metabolite excretion and increased 5 alpha-reductase activity that cannot be explained by obesity alone. Increased adrenal corticosteroid production represents an important pathogenic pathway in PCOS.
authors: Centre for Endocrinology, Diabetes & Metabolism, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors: Dimitra A
authors: DA
authors: Vassiliadi
authors: Thomas M
authors: TM
authors: Barber
authors: Beverly A
authors: BA
authors: Hughes
authors: Mark I
authors: MI
authors: McCarthy
authors: John A H
authors: JA
authors: Wass
authors: Stephen
authors: S
authors: Franks
authors: Peter
authors: P
authors: Nightingale
authors: Jeremy W
authors: JW
authors: Tomlinson
authors: Wiebke
authors: W
authors: Arlt
authors: Paul M
authors: PM
authors: Stewart
mesh_terms: D000293:Adolescent; D000328:Adult; D000728:Androgens / Q000378:metabolism; D042944:Cholestenone 5 alpha-Reductase / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D005938:Glucocorticoids / Q000096:biosynthesis; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*
chemical_list: D000728:Androgens; D005938:Glucocorticoids; D042944:Cholestenone 5 alpha-Reductase; D006854:Hydrocortisone