FP19-5 The effect of atorvastatin on adipose tissue inflammation and dysfunction in women with polycystic ovary syndrome

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP19-Female Reproductive Endocrinology
Basic/Clinical
Sunday, June 16, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 11:05 AM
Room 102 (Moscone Center)

Poster Board SUN-514
Thozhukat Sathyapalan*1, Stephen L Atkin2, Eric S Kilpatrick3, Anne-Marie Coady3, John Shepherd4, James P Hobkirk5, Sean Carroll6, Philip Pemberton7, Alexander Smith7 and Katherine Cianflone8
1Michael White Diab Cntr, Hull, United Kingdom, 2Hull York Medical School, E Yorkshire, United Kingdom, 3Hull and East Yorkshire NHS Trust, Hull, United Kingdom, 4Hull and East Yorkshire Hospitals NHS Trust, Hull, United Kingdom, 5Hull York Medical School, Hull, United Kingdom, 6University of Hull, Hull, United Kingdom, 7Manchester Royal Infirmary, United Kingdom, 8McGill Univ Health Ctr, Montreal, QC, Canada
Background: There is growing evidence that women with polycystic ovary syndrome (PCOS) have adverse long-term cardiovascular disease (CVD) risk.  Low-grade chronic inflammation in PCOS could be considered as one of the potential links between PCOS and adverse CVD risk. Chronic sub-clinical inflammation could be a therapeutic target in PCOS patients with increased CVD risk.

Methods: A randomized, double blind placebo controlled study was conducted to investigate the effect of atorvastatin on markers of inflammation including plasma interleukin 6 (IL-6) and tumour necrosis factor α (TNF α) and adipose tissue dysfunction as measured by acylation-stimulating protein (ASP) in women with PCOS.  Forty medication naïve patients with PCOS were randomized to either atorvastatin 20 mg daily or placebo for 3 months. 

Results:  After 12 wk atorvastatin, there was a significant reduction in testosterone (4.1 ± 0.2 vs. 2.9 ± 0.1 nmol/liter, P < 0.01) and insulin resistance as measured by homeostasis model assessment for insulin resistance (HOMA-IR) (3.3 ± 0.4 vs. 2.7 ± 0.4, P < 0.01) and hs-C-reactive protein (4.9 ± 1.4 vs. 3.4 ± 1.1 mg/liter, P = 0.04). There was also a significant reduction in IL-6 levels (1.48 ± 0.09 vs. 0.73 ± 0.10 pg/ml p=0.01) and ASP levels (156.7 ± 10.2 vs. 124.4 ± 9.8 ng/ml p <0.01).  There were no significant changes in TNF α levels.

There was a significant positive correlation between D IL-6 levels with D testosterone (r= 0.49, p=0.01) and D hs-CRP (r= 0.5769, p <0.01) and D ASP levels with D testosterone (r= 0.66, p<0.01), hs-CRP (r= 0.52, p=0.01) and HOMA-IR (r= 0.59, p<0.01) after atorvastatin.  The reduction in IL-6 levels after atorvastatin treatment positively correlated with D ASP levels (r=0.67, p value=0.01). 

On forward stepwise regression analysis, D IL-6 and D ASP accounted for 62.4% of the variance in testosterone change and 52.2% of hs-CRP change with atorvastatin. D ASP accounted for 42.9% of change in HOMA-IR with atorvastatin. 

Conclusions:  Twelve weeks of atorvastatin treatment led to a significant reduction in surrogate markers of adipocyte inflammation (as determined by IL-6) and adipose tissue dysfunction (as measured by ASP) amongst patients with PCOS.  The changes in these markers independently predicted changes in insulin resistance and testosterone after atorvastatin treatment suggesting the beneficial effects of atorvastatin might be mediated through effects on adipose tissue fatty acid metabolism and sub-clinical inflammation.

Nothing to Disclose: TS, SLA, ESK, AMC, JS, JPH, SC, PP, AS, KC

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: This study was supported by an unrestricted grant from Pfizer.  Pfizer has supplied atorvastatin 20mg tablets and placebo for the study.  Otherwise sponsors had no input into study design, its execution, or interpretation of the findings.