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.