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J Clin Endocrinol Metab. 2009 Sep;94(9):3558-66. Epub 2009 Jun 30.
Increased 5 alpha-reductase activity and adrenocortical drive in women
with polycystic ovary syndrome.
Vassiliadi DA, Barber TM, Hughes BA, McCarthy MI, Wass JA, Franks S,
Nightingale P, Tomlinson JW, Arlt W, Stewart PM.
Centre for Endocrinology, Diabetes & Metabolism, University of
Birmingham, Birmingham B15 2TT, United Kingdom.
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: 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.
Publication Types:
* Research Support, Non-U.S. Gov't
PMID: 19567518 |
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