Inter-related effects of insulin resistance, hyperandrogenism, sympathetic dysfunction and chronic inflammation in PCOS.

ABSTRACT

OBJECTIVE: Insulin resistance, hyperandrogenism, sympathetic dysfunction and chronic low-grade inflammation may act together in a vicious cycle in the pathophysiology of PCOS. However, the inter-relationships of these components are not fully understood. We aimed to study these mechanisms in the pathophysiology of PCOS. PARTICIPANTS AND METHODS: Premenopausal women with PCOS (Rotterdam diagnostic criteria) and without PCOS were recruited from a community setting into a cross-sectional substudy within a randomized control trial. Insulin resistance (fasting insulin and glucose), hyperandrogenism (testosterone, sex hormone-binding globulin [SHBG] and Free Androgen Index [FAI]), muscle sympathetic nerve activity (MSNA) and markers of chronic low-grade inflammation (high sensitivity C-reactive protein [hs-CRP] and high molecular weight adiponectin [HMW-adiponectin]) were measured. RESULTS: Forty-nine women with PCOS (mean age 30 ± 6 mean BMI 29 ± 5) and 23 controls (mean age 29 ± 8 mean BMI 33 ± 7) with included in this analysis. MSNA and testosterone level were most significantly associated with PCOS status, after adjustment for age and BMI. In women with PCOS, markers of sympathetic activity correlated inversely with HMW-adiponectin and HMW-adiponectin correlated inversely with FAI. Testosterone and FAI both correlated positively with insulin resistance in women PCOS. CONCLUSION: Sympathetic dysfunction and hyperandrogenism are significantly associated with PCOS. Chronic low-grade inflammation potentially mediates the effect of sympathetic dysfunction on hyperandrogenism and insulin resistance.