Objective: To evaluate levels of soluble receptor (sOB-R) and free leptin inwomen with polycystic ovarian syndrome (PCOS)- and note any relationships with insulin resistance,adiposity, and androgens. Leptin is an adipokine that circulates in a free form and bound to an sOB- R. Only free leptin is biologically active. Design: Prospective, case-control study. Setting: University-based reproductive endocrinology practice. Patient(s): Forty women with PCOS and severe insulin resistance and 15 body mass index (BMI)-matched ovulatory controls. Intervention(s): Measurements of serum insulin, leptin, sOB-R at fasting and during a standard oral glucose tolerance test (OGTT), and measurements before and after treatment with rosiglitazone. Main Outcome Measure(s): Fasting glucose, insulin, leptin, sOB-R, T, and DHEAS levels in women with PCOS and controls were measured to investigate the relationship of sOB-R and the free leptin index (FLI) to insulin, adipocity, and androgens and to investigate the effect of acute hyperinsulinemia during OGTT and the effect of improvement of insulin resistance with rosiglitazone on the leptin system. FLI was calculated by dividing leptin levels by sOB-R. Result(s): Total leptin and FLI correlated significantly with BMI in both patients with PCOS and in controls. There was a significant negative correlation between DHEAS and sOB-R in PCOS. Leptin, sOB-R, and FLI were not significantly different in the two groups, and neither sOB-R nor FLI correlated with insulin or glucose levels. The sOB-R levels increased significantly 3 hours after oral glucose ingestion, resulting in a significant decline in FLI. Conclusion(s): [1] Adiposity rather than insulin resistance appears to be the main determinant of leptin levels and FLI. [2] Acute increase in insulin levels during OGTT is associated with an increase in levels of sOB-R. [3] DHEAS may play a role in leptin bioavailability by modulating sOB-R levels. Objective: To evaluate levels of soluble receptor (sOB-R) and free leptin inwomen with polycystic ovarian syndrome (PCOS) - and note any relationships with insulin resistance, adiposity, and androgens. Leptin is an adipokine that circulates in a free form and bound Setting: University-based reproductive endocrinology practice. Patient (s): Forty women with PCOS and severe insulin resistance and 15 body mass index ( Intervention (s): Measurements of serum insulin, leptin, sOB-R at fasting and during a standard oral glucose tolerance test (OGTT), and measurements before and after treatment with rosiglitazone. Main Outcome Measure (s ): Fasting glucose, insulin, leptin, sOB-R, T, and DHEAS levels in women with PCOS and controls were investigated to investigate the relationship of sOB-R and the free leptin index (FLI) to insulin, adipocity, and androgens and to investigate the effect of acute hyperinsulinemia during OGTT and the effect of improvement of insulin resistance with rosiglitazone on the leptin system. FLI was calculated by dividing leptin levels by sOB-R. (s): Total leptin and FLI correlated significantly with BMI in both patients There was a significant negative correlation between DHEAS and sOB-R in PCOS. Leptin, sOB-R, and FLI were not significantly different in the two groups, and neither sOB-R nor FLI correlated with insulin or glucose Levels. The sOB-R levels increased significantly for 3 hours after oral glucose ingestion, resulting in a significant decline in FLI. Conclusion (s): [1] Adiposity rather than insulin resistance appears to be the main determinant of leptin levels and FLI. 2] Acute increase in insulin levels during OGTT is associated with an increase in levels of sOB-R. [3] DHEAS may play a role in leptin bioavailability by modulating sOB-R levels.