Urinary glucocorticoid metabolite excretion is associated with insulin resistance independent of body mass index (BMI) in patients with polycystic ovary syndrome
M. OReilly, J. Hazlehurst, M. Lebbe, B. Hughes, P. Stewart, J. Tomlinson & W. Arlt
Polycystic ovary syndrome (PCOS) is a triad of insulin resistance, hyperandrogenism and anovulation. PCOS is associated with increased adrenocortical drive, which may have adverse metabolic consequences. Here we analysed the relationship of urinary androgen and glucocorticoid metabolite excretion with insulin resistance in a large PCOS cohort.
We compared results from 127 PCOS patients (Rotterdam criteria) with 100 BMI-matched controls. All subjects underwent anthropometric assessment including BMI, and metabolic testing with oral glucose tolerance test (OGTT) and homeostatic model assessment of insulin resistance (HOMA-IR). 24-h urine samples from patients and controls were analysed by gas chromatography/mass spectrometry for total androgen (androsterone+etiocholanolone) and total glucocorticoid metabolite excretion (μg/24 h). HOMA-IR values were log-transformed to normalise their distribution. Linear regression was used to measure the impact of urinary steroid metabolite excretion on HOMA-IR.
OGTT results were abnormal in 26 PCOS patients (21%). Dysglycaemic PCOS women did not differ by age from normoglycaemic patients but had a significantly higher BMI (35.6±6.2 vs 30.5±6.7 kg/m2, P=0.001). Of those PCOS patients with a BMI>30, 33% (22/67) had dysglycaemia on OGTT, compared to 7% (4/53) of those with BMI<30. Total glucocorticoid excretion was significantly higher in PCOS patients compared to controls (9612±4194 vs 8067±4165, P=0.013). After adjustment for age and BMI, total glucocorticoid excretion was highly predictive of HOMA-IR levels, with HOMA-IR values increasing by 7% (95% CI, 211%, P=0.003) for each increase of 1000 μg/24 h in glucocorticoid metabolites (Table 1). Total urinary androgen metabolites were not predictive of HOMA-IR, P=0.068.
In PCOS, total glucocorticoid metabolite excretion is strongly correlated with markers of insulin resistance. Increased adrenocortical drive in PCOS may have adverse metabolic consequences.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.