Endocannabinoid receptor blockade increases vascular endothelial growth factor and inflammatory markers in obese women with polycystic ovary syndrome

ContextAnimal 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. ObjectiveTo determine the impact of CB1 antagonism by rimonabant on VEGF and inflammatory markers in obese PCOS women. DesignRandomized, open-labelled parallel study. SettingEndocrinology outpatient clinic in a referral centre. SubjectsTwenty patients with PCOS (PCOS) and biochemical hyperandrogenaemia with a body mass index of 30 kg/m(2) were recruited. Patients were randomized to 15 g daily of metformin or 20 mg daily of rimonabant. Main outcome measuresPost hoc review to detect VEGF and pro-inflammatory cytokines TNF-, IL-1, IL-1ra, IL-2, IL6, IL-8, IL-10 and MCP-1 before and after 12 weeks of treatment. ResultsAfter 12 weeks of rimonabant treatment, there was a significant increase in VEGF (992 176 vs 1162 +/- 158 pg/ml, P < 001) and IL-8 (74 +/- 110 vs 181 +/- 132 pg/ml, P < 005) but not after metformin (VEGF P = 07; IL-8 P = 09). There was no significant difference in the pro-inflammatory cytokines TNF-, IL-1, IL-1ra, IL-2, IL6, IL-8, IL-10 and MCP-1 following either treatment. ConclusionThis 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.