24-hour urinary glucocorticoid metabolites are associated with hyperinsulinaemia independent of BMI in patients with the polycystic ovary syndrome
Michael O'Reilly, John Hazlehurst, Marie Lebbe, Paul Stewart, Jeremy Tomlinson & Wiebke Arlt
Polycystic ovary syndrome (PCOS) is a triad of insulin resistance, hyperandrogenism and anovulation. PCOS is associated with increased adrenocortical drive and 5alpha-reductase activity, which may have adverse metabolic consequences. Here we analysed the relationship of urinary androgen and glucocorticoid metabolite excretion with markers of insulin resistance in a large PCOS cohort. We compared results from 127 PCOS patients fulfilling Rotterdam diagnostic criteria with 100 BMI-matched controls. All subjects underwent baseline anthropometric assessment including BMI and metabolic testing with fasting plasma glucose and insulin levels, oral glucose tolerance test (OGTT), and HOMA-IR calculation. 24-hour urine samples from patients and controls were analysed by gas chromatography/mass spectrometry for total androgen and total glucocorticoid metabolite excretion. Partial correlation testing with adjustment for age and BMI was used to examine the relationship between urine metabolite excretion and markers of insulin resistance. OGTT results were abnormal in 26 PCOS patients (20.5%). Dysglycaemic PCOS women did not differ by age from normoglycaemic PCOS patients but had a significantly higher BMI (35.6±6.2 vs 30.5±6.7 kg/m2, P=0.001) and a higher HOMA-IR (3.99±3.33 vs 1.75±1.51, P<0.001). 40% of PCOS patients with a BMI>30 (27/67) showed evidence of dysglycaemia, which was detected in only 7% (4/53) in PCOS After adjustment for age and BMI, total glucocorticoid metabolites in the PCOS group had a significant positive correlation with fasting insulin (r=0.299, P=.0.004) and HOMA-IR levels (r=0.209, P=0.046), which was not detected in controls (r=0.084, P=0.488 and r=0.111, P=0.355). Total androgen metabolite excretion in the PCOS group correlated with fasting insulin when controlling for age alone (r=0.19, P=0.046) but that correlation disappeared when levels where adjusted for age and BMI (r=0.082, P=0.438). In PCOS, total glucocorticoid metabolite excretion is strongly correlated with fasting insulin and HOMA-IR levels. Increased adrenocortical drive in PCOS may contribute significantly to the adverse metabolic profile of these patients.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.