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, 5-reductase and 11-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 µg/24h for the non-obese, 5547±2911 vs. 2468±1794 µg/24hr for the obese, both p < 0.001). Total glucocorticoid metabolites were higher in obese PCOS vs. controls (10786±3852 vs. 8834±4487µg/24hr, p=0.001). 5-reductase activity correlated with BMI, insulin levels and HOMA. Both obese and non-obese PCOS patients had higher 5-reductase activity than controls (all p<0.05). 11-hydroxysteroid dehydrogenase activities did not differ between PCOS and controls.

Conclusions: PCOS is associated with enhanced androgen and cortisol metabolite excretion and increased 5-reductase activity that cannot be explained by obesity alone. Increased adrenal corticosteroid production represents an important pathogenic pathway in PCOS.