Abstract
Background: Atorvastatin has been shown to improve cardiovascular risk (CVR) indices in women with polycystic ovary syndrome (PCOS). Low-grade chronic inflammation of adipose tissue may link PCOS and adverse CVR. In pro-inflammatory states such as PCOS, spontaneous activation of the alternative pathway of complement results in increased generation of acylation stimulating protein (ASP) from adipocytes irrespective of body mass index.Methods: The objective of this study was to determine the effect of atorvastatin on markers of adipose tissue dysfunction and inflammation; acylation-stimulating-protein (ASP), interleukin-6 (IL-6), and monocyte-chemoattractant-protein-1 (MCP-1) in PCOS. This was a randomized, double-blind, placebo-controlled study where 40 medication-naive women with PCOS and biochemical hyperandrogenaemia were randomized to either atorvastatin 20 mg daily or placebo for 12 weeks. Following the 12 week randomization; both group of women with PCOS were subsequently started on metformin 1,500 mg daily for further 12 weeks to assess whether pre-treatment with atorvastatin potentiates the effects of metformin on markers of adipose tissue function We conducted a post-hoc review to detect plasma ASP and the pro-inflammatory cytokines IL6 and MCP-1 before and after 12 and 24 weeks of treatment.Results: There was significant reduction in ASP (156.7 ± 16.2 vs. 124.4 ± 14.8 ng/ml p <0.01), IL-6 (1.48 ± 0.29 vs.0.73 ± 0.34 pg/ml p = 0.01) and MCP-1 (30.4 ± 4.2 vs. 23.0 ± 4.5 pg/ml p = 0.02) after 12 weeks of atorvastatin that was maintained subsequently with 12 weeks treatment with metformin. There was a significant positive correlation between ASP levels with CRP (p < 0.01), testosterone (p < 0.01) and HOMA-IR (p < 0.01); IL-6 levels with CRP (p <0.01) and testosterone (p < 0.01) and MCP-1 with CRP (p < 0.01); testosterone (p < 0.01) and HOMA-IR (p < 0.02).Conclusions: This post-hoc analysis revealed that 12 weeks of atorvastatin treatment significantly decreased the markers of adipose tissue dysfunction and inflammation, namely ASP, IL-6 and MCP-1 in obese women with PCOS. Changes in adipose tissue markers were significantly associative with substantial improvements in HOMA-IR, testosterone and hs-CRP levels.ISRCTN Number: ISRCTN24474824.
Highlights
In sub-clinical? pro-inflammatory states, including polycystic ovary syndrome (PCOS), spontaneous activation of the alternative pathway of complement results in increased generation of acylation stimulating protein (ASP) from adipocytes irrespective of body mass index (BMI) [1, 2]
On multiple linear stepwise regression analysis the changes in ASP, IL-6, and MCP-1 accounted for 52% of the variance in CRP and 46% of testosterone levels but only ASP and MCP-1 accounted for 40% of the variance in HOMA-IR (Table 3). This post-hoc analysis revealed that 12 weeks of atorvastatin treatment significantly decreased markers of adipose tissue dysfunction and inflammation as determined by ASP, IL-6, and MCP-1 in younger, overweight obese women with PCOS
The reduction in ASP after 12 weeks of atorvastatin treatment was associated with substantial improvements in biochemical hyperandrogenaemia—the most distinctive feature of PCOS
Summary
In sub-clinical? pro-inflammatory states, including polycystic ovary syndrome (PCOS), spontaneous activation of the alternative pathway of complement results in increased generation of acylation stimulating protein (ASP) from adipocytes irrespective of body mass index (BMI) [1, 2]. Pro-inflammatory states, including polycystic ovary syndrome (PCOS), spontaneous activation of the alternative pathway of complement results in increased generation of acylation stimulating protein (ASP) from adipocytes irrespective of body mass index (BMI) [1, 2]. The suggested possible underlying mechanism of ASP resistance in such patients is reduced expression of C5L2 receptor on adipose tissue [10, 11] This process of decreased C5L2 expression is enhanced further by increased fatty acids and high inflammatory markers present in obesity. In pro-inflammatory states such as PCOS, spontaneous activation of the alternative pathway of complement results in increased generation of acylation stimulating protein (ASP) from adipocytes irrespective of body mass index
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