Endocrine Abstracts

Context: There is growing evidence 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.

Design: Randomised, open-labelled parallel study.

Setting: Endocrinology outpatient clinic in a referral centre.

Subjects: Twenty patients with PCOS and biochemical hyperandrogenaemia with a body mass index of ≥ 30 kg/m² were recruited. Patients were randomised to 1.5 g daily of metformin or 20 mg daily of rimonabant.

Main Outcome Measures: Post hoc review to detect VEGF and pro-inflammatory cytokines TNF-α, IL-1β, IL-1ra, IL-2, IL6, IL-8, IL-10, MCP-1 and Eotaxin before and after 12 weeks treatment.

Results: After 12 weeks of rimonabant there was a significant increase in VEGF (99.2±17.6 vs 116.2±15.8 pg/ml, P<0.01) but not after metformin (110.3±25.2 vs 111.5±24.8, P=0.7). There was no significant difference in the pro-inflammatory cytokines following either treatment except IL-8 (7.4±11.0 vs 18.1±13.2 pg/ml, P<0.05) and Eotaxin (52.7±9.2 vs 64.9±14.6 pg/ml, P<0.05), which were raised significantly after rimonabant and metformin treatment, respectively.

Conclusion: This study suggests that rimonabant CB-I blockade paradoxically raises VEGF and some pro-inflammatory markers in obese women with PCOS, which may offset the potential benefits associated with weight loss.