Hyperandrogenism is related to the circulating matrix metalloproteinase-9 response to hyperglycemia in women with polycystic ovary syndrome

Abstract

OBJECTIVE: Hyperglycemia stimulates proatherogenic inflammation in Polycystic Ovary Syndrome (PCOS). Matrix Metalloproteinase-9 (MMP-9) secreted by leukocytes is a promoter of atherosclerotic plaque rupture. We examined the effect of in vivo glucose challenge on circulating MMP-9 levels in women with PCOS compared to ovulatory controls, and the relationship of this effect with LH and androgens. DESIGN: Prospective, controlled study MATERIALS AND METHODS: Twelve women with PCOS (6 lean, 6 obese) between ages 18-40, diagnosed on the basis of oligo- or amenorrhea and hyperandrogenemia, and 12 ovulatory controls (6 lean, 6 obese) of similar age were selected for study. Subjects with diabetes, inflammatory illnesses or other endocrinopathies were excluded. A 2-hour glucose tolerance test was performed within 5-8 days of menses. MMP-9 levels were measured by ELISA in plasma from blood samples drawn fasting (pre) and 2 hours after (post) glucose ingestion. Levels of LH, testosterone and androstenedione were measured in serum by RIA. RESULTS: There were no significant differences in age and body mass index in women with PCOS compared to weight-matched controls. The percent change in the mean concentration of MMP-9 between the pre - and post-glucose challenge samples of lean and obese women with PCOS (55.6±22.3%; 81.2±17.0%) was significantly higher (p<0.02) compared to that of lean and obese controls which decreased (-4.9±5.4%; -35.1±13.1%). The MMP-9 response was positively correlated with serum levels of LH (r=0.49; p<0.02), testosterone (r=0.73; p<0.0001) and androstenedione (r=0.76; p<0.0001). CONCLUSIONS: These preliminary data indicate that in response to hyperglycemia, circulating MMP-9 levels are increased in women with PCOS, independent of obesity. Hyperandrogenism may perpetuate this proinflammatory, proatherogenic phenomenon in PCOS.