Endocrine Abstracts

Polycystic ovary syndrome (PCOS) is a clinical triad of anovulation, hyperandrogenism and insulin resistance. Patterns of fat distribution in PCOS may be associated with androgen activation, glucocorticoid metabolism and insulin resistance. Here we analysed the relationship between fat distribution, steroid metabolism and insulin resistance in women with PCOS.

We compared results from 100 PCOS patients (Rotterdam criteria) with 80 sex- and BMI-matched controls. All patients underwent BMI measurement and body composition assessment by dual-energy X-ray absorptiometry (DEXA), fasting glucose and insulin measurement for homeostatic model assessment of insulin resistance (HOMA-IR) and 24-h urine analysis by gas chromatography/mass spectrometry. The latter included calculation of total glucocorticoid excretion (μg/24 h) and markers of 5α-reductase activity (androsterone/etiocholanolone and 5α-THF/THF ratios). Linear regression analysis was used to measure the impact of fat distribution on glucocorticoid excretion, 5α-reductase activity and insulin resistance.

PCOS and control patients were matched for BMI (32.1±7.1 and 32.2±6.2 kg/m² respectively). Compared to controls, PCOS women had higher urinary steroid ratios indicative of 5α-reductase activity (An/Et 1.3±0.6 vs 1.0±0.5, P=0.005; 5α-THF/THF 0.9±0.5 vs 0.7±0.4, P=0.004) and higher total glucocorticoid excretion (9624±4214 vs 8067±4165, P=0.013). After adjustment for age and BMI, increased truncal fat distribution on DEXA was highly predictive of HOMA-IR, glucocorticoid excretion and 5α-reductase activity. For each percentage increase in truncal fat, HOMA-IR values increased by 7.1% (95% CI, 4.6–9.6, P<0.001) and total glucocorticoid metabolites by 2.9% (95% CI, 1.3–4.9, P<0.001). Total leg fat was a negative predictor of insulin resistance, with each percentage increase in leg fat associated with a 3.6% reduction in HOMA-IR (95% CI 0.11–6%, P=0.005).

Body fat distribution in PCOS is closely associated with steroid metabolism and insulin resistance. Truncal obesity is highly predictive of insulin resistance, glucocorticoid excretion and 5α-reductase activity. Increased leg fat may confer beneficial effects on metabolism in patients with PCOS.