Reactive Oxygen Species-Induced Oxidative Stress in the Development of Insulin Resistance and Hyperandrogenism in Polycystic Ovary Syndrome

Abstract

Context: Insulin resistance and chronic low level inflammation are often present in women with polycystic ovary syndrome (PCOS). Objective: The purpose of this study was to determine the effects of hyperglycemia on reactive oxygen species (ROS) generation from mononuclear cells (MNCs) in PCOS. Design: This was a prospective controlled study. Setting: The study was conducted at an academic medical center. Patients: The study population consisted of 16 women with PCOS (eight lean, eight obese) and 15 age- and body composition-matched controls (eight lean, seven obese). Main Outcome Measures: Insulin sensitivity was derived from a 2-h, 75-g oral glucose tolerance test (ISOGTT). ROS generation and p47phox protein expression were quantitated from MNCs obtained from blood drawn fasting and 2 h after glucose ingestion. Results: ISOGTT was lower in PCOS, compared with controls (3.1 ± 0.3 vs. 6.3 ± 0.9, P < 0.003). The percent change in ROS generation from MNCs was higher in lean and obese PCOS, compared with lean controls (138.8 ± 21.3 and 154.2 ± 49.1 vs. 0.6 ± 12.7, P < 0.003). The percent change in ROS generation from MNCs correlated positively with glucose area under the curve (r = 0.38, P < 0.05), and plasma levels of testosterone (r = 0.59, P < 0.002) and androstenedione (r = 0.50, P < 0.009). The percent change in p47phox from MNCs was also higher in lean and obese PCOS, compared with lean controls (36.2 ± 18.2 and 39.1 ± 8.0 vs. −13.7 ± 8.7, P < 0.02), and correlated negatively with ISOGTT (r = −0.39, P < 0.05). Conclusion: ROS generation from MNCs in response to hyperglycemia is increased in PCOS independent of obesity. The resultant oxidative stress may contribute to a proinflammatory state that induces insulin resistance and hyperandrogenism in women with this disorder.