Effect of simvastatin on monocyte chemoattractant protein-1 expression in endometriosis patients: a randomized controlled trial

BACKGROUND: Simvastatin is a promising new drug for the treatment of endometriosis. It is a cholesterol-lowering drug that acts by inhibiting HMG-CoA reductase, resulting in a decrease in mevalonate, a precursor of cholesterol and monocyte chemoattractant protein-1 (MCP-1). This study investigated the effect of pre-operative oral simvastatin administration on MCP-1 gene expression and serum MCP-1 protein levels in patients with endometriosis. METHODS: A prospective, randomized, controlled study was conducted at the Reproductive Endocrinology Unit of the Department of Obstetrics and Gynecology at the Faculty of Medicine Ramathibodi Hospital. Forty women (mean age: 18–45 years) scheduled for laparoscopic surgery who had been diagnosed with endometriosis were recruited and randomly assigned to either a treatment group (20 mg/d of orally administered simvastatin for 2 weeks before surgery) or an untreated control group. Serum was collected before and after treatment and protein levels of MCP-1 were determined. MCP-1 and CD68 transcript levels were also quantified using real-time PCR on endometriotic cyst tissues. RESULTS: MCP-1 gene expression on endometriotic cyst was not significantly different between the simvastatin-treated and untreated groups (P = 0.99). CD68 expression was higher in the treatment group compared to the control group, but this was not statistically significant (P = 0.055). Serum MCP-1 levels following simvastatin treatment were higher than in samples obtained before treatment (297.89 ± 70.77 and 255.51 ± 63.79 pg/ml, respectively) (P = 0.01). CONCLUSIONS: Treatment with 20 mg/d of simvastatin for 2 weeks did not reduce the expression of either the chemokine MCP-1 gene or macrophage-specific genes. Cumulatively, this suggests that simvastatin is not ideal for treating endometriosis because a higher dose of simvastatin (40–100 mg/d) would be needed to achieve the target outcome, which would significantly increase the risk of myopathy in patients. TRIAL REGISTRATION: Thai Clinical Trials Registry TCTR20130627003 Registered: June 27, 2013.