1: J Clin Endocrinol Metab. 2009 Jun 30. [Epub ahead of print]
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 and Metabolism, University of Birmingham,
Edgbaston, Birmingham, B15 2TT, UK (D.A.V., B.A.H., J.W.T., W.A., P.M.S.); Oxford
Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, OX3 7LJ,
UK (T.M.I.M., J.A.H.W.); Institute of Reproductive and Developmental Biology,
Imperial College London, W12 0NN, UK (S.F.); Wellcome Trust Clinical Research
Facility, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK
(P.N.).
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: To describe cortisol metabolism and metabolic characteristics of a
large PCOS cohort and to delineate the effect of obesity by comparison to
BMI-matched controls. Design: Observational, cross-sectional study. Setting:
Outpatient clinics of two secondary/tertiary care centres Patients or Other
Participants: 178 PCOS patients fulfilling Rotterdam criteria and 100 BMI-matched
controls. Intervention: 24-h urine collection for steroid metabolite excretion,
fasting blood samples followed by an OGTT. Main Outcome Measures: Urinary steroid
metabolites including glucocorticoids and androgens and the ratios reflecting
enzymatic activities involved in peripheral cortisol and androgen metabolism,
5alpha-reductase and 11beta-hydroxysteroid dehydrogenase type 1 and 2.
Circulating levels of glucose, insulin, DHEA, DHEAS and testosterone, calculation
of HOMA. Results: Total androgen metabolites were higher in PCOS compared to
BMI-matched controls (4105+/-2047 vs. 2532+/-1610 microg/24h for the non-obese,
5547+/-2911 vs. 2468+/-1794 microg/24hr for the obese, both p < 0.001). Total
glucocorticoid metabolites were higher in obese PCOS vs. controls (10786+/-3852
vs. 8834+/-4487microg/24hr, p=0.001). 5alpha-reductase activity correlated with
BMI, insulin levels and HOMA. Both obese and non-obese PCOS patients had higher
5alpha-reductase activity than controls (all p<0.05). 11beta-hydroxysteroid
dehydrogenase activities did not differ between PCOS and controls. Conclusions:
PCOS is associated with enhanced androgen and cortisol metabolite excretion and
increased 5alpha-reductase activity that cannot be explained by obesity alone.
Increased adrenal corticosteroid production represents an important pathogenic
pathway in PCOS.
PMID: 19567518
