Background: Polycystic ovary syndrome (PCOS) is associated with reproductive and metabolic abnormalities. Aim: The aim of this study was to assess novel inflammatory markers [adipokines leptin, adiponectin, and leptin-adiponectin ratio (L/A)] in overweight women with and without PCOS and to examine alterations in these markers [aldosterone, leptin, adiponectin, and L/A] with pharmacological interventions modulating insulin resistance (IR) in PCOS. Materials/subjects and methods: Overweight age, and body mass index (BMI)-matched women with (no.=80) or without PCOS (no.=27) were assessed cross-sectionally. Subjects with PCOS were then randomised to 6 months metformin (1 g b.d, no.=26) or oral contraceptive pill (OCP) (35 g ethinyl estradiol/2 mg cytoproterone acetate, no.=30). Outcome measures were leptin, adiponectin, L/A, aldosterone, highly sensitive C-reactive protein, lipid profile, IR, and androgen levels. Results: Leptin levels were lower (156.4+/-85.9 vs 208.5+/-105.2 ng/ml, p=0.015) while adiponectin and L/A were not different between women with and without PCOS. Following intervention, IR increased for the OCP and decreased for metformin, however leptin and aldosterone decreased equivalently with the OCP and metformin with no difference between each treatment (p=0.583 and p=0.801, respectively). There was no change in adiponectin or L/A with the OCP or metformin. On multiple regression, the only baseline predictor of leptin was BMI (r(2)=0.485, p<0.001) and the strongest predictor of change in leptin was change in weight (r(2)=0.402, p<0.001). Conclusions: Alterations in leptin between women with and without PCOS and following pharmacological interventions are primarily related to adiposity and not IR. Aldosterone was reduced equivalently with metformin and the OCP despite differential effects on IR. (J. Endocrinol. Invest. 33: 258-265, 2010) (C) 2010, Editrice Kurtis