Metabolic inflexibility is a feature of women with polycystic ovary syndrome and is associated with both insulin resistance and hyperandrogenism.

Context: Metabolic inflexibility, i.e. the impaired ability of the body to switch from fat to carbohydrate oxidation under insulin-stimulated conditions, is associated with insulin resistance. This alteration in metabolic plasticity can lead to organ dysfunction and is considered a key issue among the abnormalities of the metabolic syndrome. It is still unknown whether this phenomenon occurs in women with polycystic ovary syndrome (PCOS). Objective: To examine whether metabolic inflexibility is a feature of PCOS women and whether hyperandrogenism may contribute to this phenomenon.Design and Patients: Eighty-nine Caucasian women with PCOS were submitted to hyperinsulinemic euglycaemic clamp. Respiratory exchange ratios were evaluated, at baseline and during hyperinsulinemia, by indirect calorimetry, to quantify substrate oxidative metabolism. Total testosterone was measured by liquid chromatography mass spectrometry, and free testosterone by equilibrium dialysis. Setting: Outpatients in a tertiary care academic center.Main Outcome Measure: Metabolic flexibility, assessed by the change in respiratory quotient upon insulin stimulation.Results: Sixty-five of the 89 PCOS women (73%) had increased serum free testosterone, 68 (76%) were insulin resistant and 62 (70%) had an impaired metabolic flexibility. Comparison of hyperandrogenemic and normoandrogenemic women showed that the two subgroups were of similar age, but differed in terms of several anthropometric and metabolic features. In particular, hyperandrogenemic women had greater BMI (32.9±1.0 vs 24.7±0.9kg/m2, p<0.001) and lower glucose utilization during the clamp (9.2±0.4 vs 10.9±0.7mg/Kg FFM min, p=0.023) and metabolic flexibility (0.09±0.06 vs 0.12±0.01, p=0.014). In univariate analysis, metabolic flexibility was associated with several anthropometric, endocrine and metabolic features. In multivariate analysis, this feature was directly associated with baseline respiratory quotient and insulin sensitivity, and inversely with free testosterone and free fatty acids concentrations under insulin suppression (R2=0.634, p<0.001). Conclusions: Metabolic inflexibility is a feature of PCOS women. Both insulin resistance and androgen excess might contribute to this abnormality.