title: Endocannabinoid receptor blockade increases vascular endothelial growth factor and inflammatory markers in obese women with polycystic ovary syndrome.
abstract: BACKGROUND
  Animal studies suggest that cannabinoid receptor-1 (CB-1) blockade reduces inflammation and neovascularization by decreasing vascular endothelial growth factor (VEGF) levels associated with a reduction in inflammatory markers, thereby potentially reducing cardiovascular risk.
  
  
  OBJECTIVE
  To determine the impact of CB1 antagonism by rimonabant on VEGF and inflammatory markers in obese PCOS women.
  
  
  METHODS
  Randomized, open-labelled parallel study.
  
  
  METHODS
  Endocrinology outpatient clinic in a referral centre.
  
  
  METHODS
  Twenty patients with PCOS (PCOS) and biochemical hyperandrogenaemia with a body mass index of ≥30 kg/m2were recruited. Patients were randomized to 1·5 g daily of metformin or 20 mg daily of rimonabant.
  
  
  METHODS
  Post hoc review to detect VEGF and pro-inflammatory cytokines TNF-α, IL-1β, IL-1ra, IL-2, IL6, IL-8, IL-10 and MCP-1 before and after 12 weeks of treatment.
  
  
  RESULTS
  After 12 weeks of rimonabant treatment, there was a significant increase in VEGF (99·2 ± 17·6 vs 116·2 ± 15·8 pg/ml, P < 0·01) and IL-8 (7·4 ± 11·0 vs 18·1 ± 13·2 pg/ml, P < 0·05) but not after metformin (VEGF P = 0·7; IL-8 P = 0·9). There was no significant difference in the pro-inflammatory cytokines TNF-α, IL-1β, IL-1ra, IL-2, IL6, IL-8, IL-10 and MCP-1 following either treatment.
  
  
  CONCLUSIONS
  This study suggests that rimonabant CB-I blockade paradoxically raised VEGF and the cytokine IL-8 in obese women with PCOS that may have offset the potential benefit associated with weight loss.
authors.affiliation: Department of Academic Endocrinology, Diabetes and Metabolism, University of Hull, Hull, UK.
authors.forename: Thozhukat
authors.initials: T
authors.lastname: Sathyapalan
authors.affiliation: Department of Academic Endocrinology, Diabetes and Metabolism, University of Hull, Hull, UK.
authors.forename: Zeeshan
authors.initials: Z
authors.lastname: Javed
authors.affiliation: Sidra Research Centre, Doha, Qatar.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Kilpatrick
authors.affiliation: Department of Obstetric Ultrasound, Hull & East Yorkshire Women's & Children's Hospital, Hull, UK.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Coady
authors.affiliation: Weill Cornell Medicine Qatar, Doha, Qatar.
authors.forename: Stephen L
authors.identifier: http://orcid.org/0000-0002-5887-7257
authors.initials: SL
authors.lastname: Atkin
mesh_terms: D015415:Biomarkers; D063387:Cannabinoid Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects; D005260:Female; D006801:Humans; D017588:Hyperandrogenism; D007249:Inflammation / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis; D008687:Metformin / Q000008:administration & dosage; D009765:Obesity; D010880:Piperidines / Q000008:administration & dosage; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011720:Pyrazoles / Q000008:administration & dosage; D000077285:Rimonabant; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000187:drug effects; D015431:Weight Loss
chemical_list: D015415:Biomarkers; D063387:Cannabinoid Receptor Antagonists; D016207:Cytokines; D016209:Interleukin-8; D010880:Piperidines; D011720:Pyrazoles; D042461:Vascular Endothelial Growth Factor A; D008687:Metformin; D000077285:Rimonabant