摘要
目的:探讨二甲双胍马来酸罗格列酮对多囊卵巢综合征(PCOS)患者胰岛素抵抗(IR)、高雄激素血症及血浆超长链脂肪酸(VLCFAs)等的影响。
方法:选取符合2003年鹿特丹诊断标准的PCOS患者70例(年龄18-40岁),根据体重指数(BMI)分为肥胖组(BMI≧ 25 kg/m2,34例)和非肥胖组(BMI<25 kg/m2,36例),选择同期因输卵管或男方因素不孕患者35例为对照组。两组PCOS患者口服二甲双胍马来酸罗格列酮片(每日2片)3个月。治疗前后检测:身高、体重、腰围、臀围、肝功能、血脂,葡萄糖氧化酶法检测空腹血糖(FPG);化学发光法检测空腹胰岛素(FINS)、黄体生成素(LH)、卵泡刺激素(FSH)、总睾酮(T);酶联免疫吸附法(ELISA)测定游离睾酮(FT),并检查卵巢面积及卵泡数目。计算体重指数(BMI)、胰岛素抵抗指数(HOMA-IR)、胰岛素敏感指数(ISI)。气相色谱质谱联用仪(GC-MS)检测血浆VLCFAs,包括超长链饱和脂肪酸(VLCSFAs)、超长链单不饱和脂肪酸(n-9VLCMUFAs)、n-3和n-6系超长链多不饱和脂肪酸(n-3VLCPUFAs,n-6VLCPUFAs)。
结果:①与对照组相比,治疗前两组PCOS患者LH、LH/FSH、T、FT、FINS、HOMA-IR明显增高,FSH、ISI明显下降(P均<0.05)。PCOS患者肥胖组与非肥胖组相比,HOMA-IR及卵泡数目增高,ISI下降(P均<0.05),但LH、LH/FSH、T、FT及卵巢面积差异无统计学意义。②治疗后两组PCOS患者体重、BMI、腰围、臀围、FPG、FINS、HOMA-IR明显下降(P均<0.05),ISI明显上升(P<0.05);肥胖组LH、LH/FSH、FT及非肥胖组FT明显下降(P均<0.05),且肥胖组FT下降的差值大于非肥胖组(P<0.05);两组卵巢面积、卵泡数目均减少(P<0.05); T、FSH无明显变化。③治疗前两组PCOS患者VLCSFAs,肥胖组n-3VLCPUFAs、n-9VLCMUFAs明显均高于对照组,肥胖组n-9VLCMUFAs也明显高于非肥胖组(P均<0.05)。n-6VLCPUFAs三组无差异。治疗后两组PCOS患者的n-3VLCPUFAs均明显升高,肥胖组VLCSFAs下降,非肥胖组n-9VLCMUFAs升高(P均<0.05)。④治疗过程中胃肠道不良反应发生率非肥胖组为9.3%,肥胖组为6.3%,无肝毒性、水肿及低血糖等不良反应。
结论:①肥胖较非肥胖的PCOS患者IR及卵巢多囊样改变更明显,但T、FT差异无显著性。②二甲双胍马来酸罗格列酮能降低PCOS患者的BMI和FT,改善IR及卵巢多囊样改变,对肥胖PCOS患者作用更显著,无明显不良反应。③肥胖和非肥胖的PCOS患者均存在超长链脂肪酸代谢的紊乱,二甲双胍马来酸罗格列酮能升高PCOS患者的n-3VLCPUFAs,降低肥胖PCOS患者的VLCSFAs,升高非肥胖PCOS患者的n-9VLCMUFAs。
OBJECTIVE:The aim of the study is to evaluate the therapeutic effects of metformin hydrochloride and rosiglitazone maleate tablets on insulin resistance(IR), androgen concentration and plasma very long chain fatty acids(VLCFAs) levels in women with polycystic ovarian syndrome (PCOS).
METHOD:Seventy women(aged 18 to 40 years) with PCOS were enrolled into this study according to the diagnostic criteria of Rotterdam conference(2003).The women with PCOS were divided into the obese group(BMI= 25 kg/m2, n=34) and the nonobese group(BMI< 25 kg/m2,n=36) according to BMI. In the corresponding period,35 infertile women due to the problems of uterine tube or spouses was taken as the control group.All women with PCOS had metformin hydrochloride and rosiglitazone maleate tablets twice daily for 3 months. There were some tests as the following before and after the treatment:height (Ht),weight(Wt),waist circumference(WC), liver function, lipids were tested; the fasting plasma glucose (FPG) was detected by glucose oxidase;the luteinizint hormone(LH),follicle stimulating hormone (FSH),total testosterone(T) and fasting plasma insulin (FINS) were examined by chemiluminescence method;the follicular number and ovarian area were checked in follicle period or amenorrhoea period; the plasma free testosterone was examined by enzyme-linked immunosorbentassay (ELISA);the BMI, waist to hip ratio (WHR),and homeostasis model assessment for insulin resistance (HOMA-IR), insulin sensitivity index(ISI) were calculated;the plasma VLCFAs were analysed by gas chromatography-mass spectrometry (GC-MS),including very long chain saturated fatty acids (VLCSFAs),n-9 very long chain monounsaturated fatty acids (n-9VLCMUFAs),n-3 very long chain polyunsaturated fatty acids (n-3VLCPUFAs) and n-6 very long chain polyunsaturated fatty acids (n-6VLCPUFAs).
RESULT:①Compared with the control group, LH, LH/FSH, T,FT, FINS, HOMA-IR were significantly higher and FSH, ISI were obviously lower in women with PCOS(P<0.05). Compared with the nonobese group, dramatic increases in HOMA-IR and follicle number were observed in obese group(P<0.05), while LH, LH/FSH, T, FT had no significant difference between two gruops.②After the treatment with metformin hydrochloride and rosiglitazone maleate tablets, Wt, BMI, WC, hip circumference, FPG, FINS, HOMA-IR significantly decreased and ISI rised apparently in two groups(P<0.05). There were also significant declines of LH, LH/FSH, FT,ovarian area, follicular number,especially in the obese women with PCOS(P<0.05),while T and FSH did not change significantly.③Compared with the control,the levels of VLCSFAs in both groups, and the levels of n-3VLCPUFAs and n-9VLCMUFAs in obese group were significant higher(P<0.05),while n-6VLCPUFAs had no significant difference among these groups. Compared with the nonobese group, there was an increase of n-9VLCMUFAs in obese group(P<0.05).Clinically significant increases of n-3VLCPUFAs in both groups,n-9VLCMUFAs in nonobese group and significant reduction in VLCSFAs of obese group were observed after the treatment with metformin hydrochloride and rosiglitazone maleate tablets(P<0.05), while n-6 VLCPUFAs did not change significantly in either group after the treatment.④The incidence of gastrointestinal adverse reactions happened in nonobese and obese group was 9.3% and 6.3% respectively, and no liver toxicity, edema, hypoglycemia and other adverse reactions was observed in the treatment.
CONCLUSION:①Compared with the nonobese group, there were severer insulin resistance and polycystic ovary in obese women with PCOS, while T and FT had no significant difference between two gruops.②Metformin hydrochloride and rosiglitazone maleate tablets can ameliorate insulin resistance and polycystic ovary,and also reduce BMI and FT in women with PCOS particularly in the obese,which may have no significant adverse reaction.③The metabolic disorders of plasma very long chain fatty acids existed in women with PCOS. After the treatment with metformin hydrochloride and rosiglitazone maleate tablets for three months, the concentration of n-3VLCPUFAs in both groups and n-9VLCMUFAs in nonobese group was significantly increased, while the concentration of VLCSFAs in obese group decreased.
引文
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