Waiyaput Wanwisa, Pumipichet Somphoch, Weerakiet Sawaek, Rattanasiri Sasivimol, Sophonsritsuk Areepan
Office of Research Academic and Innovation, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Department of Obstetrics and Gynecology, Faculty of Medicine Srinakharinwirot University, Bangkok, Thailand.
BMC Womens Health. 2017 Sep 26;17(1):89. doi: 10.1186/s12905-017-0446-3.
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.
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.
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).
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.
Thai Clinical Trials Registry TCTR20130627003 Registered: June 27, 2013.
辛伐他汀是一种有前景的治疗子宫内膜异位症的新药。它是一种降胆固醇药物，通过抑制HMG-CoA还原酶起作用，导致甲羟戊酸减少，甲羟戊酸是胆固醇和单核细胞趋化蛋白-1（MCP-1）的前体。本研究调查了术前口服辛伐他汀对子宫内膜异位症患者MCP-1基因表达和血清MCP-1蛋白水平的影响。
在拉玛蒂博迪医院医学院妇产科生殖内分泌科进行了一项前瞻性、随机、对照研究。招募了40名计划进行腹腔镜手术且已被诊断为子宫内膜异位症的女性（平均年龄：18 - 45岁），并将她们随机分为治疗组（术前2周口服20mg/d辛伐他汀）或未治疗的对照组。在治疗前后收集血清并测定MCP-1的蛋白水平。还使用实时PCR对子宫内膜异位囊肿组织中的MCP-1和CD68转录水平进行定量。
辛伐他汀治疗组和未治疗组之间子宫内膜异位囊肿上的MCP-1基因表达无显著差异（P = 0.99）。治疗组的CD68表达高于对照组，但无统计学意义（P = 0.055）。辛伐他汀治疗后的血清MCP-1水平高于治疗前采集的样本（分别为297.89±70.77和255.51±63.79pg/ml）（P = 0.01）。
每天20mg辛伐他汀治疗2周并未降低趋化因子MCP-1基因或巨噬细胞特异性基因的表达。总体而言，这表明辛伐他汀并非治疗子宫内膜异位症的理想药物，因为需要更高剂量的辛伐他汀（40 - 100mg/d）才能达到目标效果，这将显著增加患者发生肌病的风险。
泰国临床试验注册中心TCTR20130627003 注册时间：2013年6月27日
