title: Increased clearance of cortisol by 5beta-reductase in a subgroup of women with adrenal hyperandrogenism in polycystic ovary syndrome.
abstract: OBJECTIVE
  Increased peripheral metabolism of cortisol may explain compensatory ACTH-dependent adrenal steroidogenesis and hence hyperandrogenism in polycystic ovary syndrome (PCOS). Previous studies have described an increased 5alpha-reduction of cortisol or impaired regeneration of cortisol by 11beta-HSD1 in PCOS. However, these observations may be confounded by obesity. Moreover, the relationship between alterations in cortisol metabolism and the extent of adrenal androgen hyper-secretion in response to ACTH has not been established. This study aimed to examine the association between cortisol metabolism and ACTH-dependent adrenal hyperandrogenism in PCOS, independently of obesity.
  
  
  METHODS
  We compared 90 PCOS women (age 18-45 yr) stratified by adrenal androgen responses to ACTH1-24 and 45 controls matched for age and body weight.
  
  
  METHODS
  PCOS women were stratified as normal responders (NR), intermediate responders (IR), and high responders (HR) to 250 microg ACTH1-24: NR (no.=27) had androstenedione and DHEA responses within 2 SD of the mean in controls; IR (no.=43) had DHEA responses >2 SD above controls; HR (no.=20) had both androstenedione and DHEA responses >2 SD above controls.
  
  
  RESULTS
  All groups were similar for age, body weight, and body fat distribution. Basal testosterone, androstenedione, and 5alpha-dihydrotestosterone plasma levels were similarly elevated among the 3 groups of PCOS compared with controls, whereas basal DHEA-S was higher in HR (2.8+/-1.2 microg/ml) and IR (2.4+/-1.1 microg/ml) than in NR (1.8+/-0.8 microg/ml) and controls (1.7+/-0.6 microg/ml). The HR group had the lowest basal plasma cortisol levels (101+/-36 ng/ml vs IR 135+/-42 ng/ml, NR 144+/-48 ng/ml, and controls 165+/-48 ng/ml; all p<0.01), but the greatest cortisol response to ACTH1-24 (Delta(60-0)cortisol 173+/-60 ng/ml vs IR 136+/-51 ng/ml, NR 114+/-50 ng/ml, and controls 127+/-50 ng/ml; all p<0.01), and the highest urinary excretion of total and 5beta-reduced cortisol metabolites (eg 5beta-tetrahydrocortisol/ cortisol ratio 25.2+/-15.3 vs IR 18.8+/-10.7, NR 19.7+/-11.4, and controls 17.2+/-13.7; all p<0.05). There were no differences in urinary excretion of 5alpha-reduced cortisol metabolites or in 5alpha-dihydrotestosterone/testosterone ratio between groups.
  
  
  CONCLUSIONS
  Adrenal androgen excess in PCOS is associated with increased inactivation of cortisol by 5beta-reductase that may lower cortisol blood levels and stimulate ACTH-dependent steroidogenesis.
authors: Division of Endocrinology, Department of Internal Medicine, and Centre for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi Hospital, University Alma Mater Studiorum of Bologna, Bologna, Italy.
authors: A
authors: A
authors: Gambineri
authors: G
authors: G
authors: Forlani
authors: A
authors: A
authors: Munarini
authors: F
authors: F
authors: Tomassoni
authors: G E
authors: GE
authors: Cognigni
authors: W
authors: W
authors: Ciampaglia
authors: U
authors: U
authors: Pagotto
authors: B R
authors: BR
authors: Walker
authors: R
authors: R
authors: Pasquali
mesh_terms: D000293:Adolescent; D000308:Adrenocortical Hyperfunction / Q000150:complications* / Q000378:metabolism; D000328:Adult; D000735:Androstenedione / Q000097:blood / Q000378:metabolism; D001481:Basal Metabolism; D003366:Cosyntropin / Q000494:pharmacology; D003687:Dehydroepiandrosterone / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D017588:Hyperandrogenism / Q000150:complications* / Q000378:metabolism; D008875:Middle Aged; D010088:Oxidoreductases / Q000378:metabolism*; D010912:Pituitary-Adrenal Function Tests; D011085:Polycystic Ovary Syndrome / Q000150:complications* / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D003366:Cosyntropin; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D010088:Oxidoreductases; C021936:3-oxo-5 beta-steroid delta 4-dehydrogenase; D006854:Hydrocortisone