Metformin Reduces Arterial Stiffness and Improves Endothelial Function in Young Women with Polycystic Ovary Syndrome: A Randomized, Placebo-Controlled, Crossover Trial

被引:121
作者
Agarwal, Neera [1 ]
Rice, Sam P. L. [1 ]
Bolusani, Hemanth [1 ]
Luzio, Stephen D. [1 ]
Dunseath, Gareth [1 ]
Ludgate, Marian [1 ]
Rees, D. Aled [1 ]
机构
[1] Cardiff Univ, Sch Med, Ctr Endocrine & Diabet Sci, Cardiff CF14 4XN, S Glam, Wales
关键词
PULSE-WAVE ANALYSIS; IMPAIRED GLUCOSE-TOLERANCE; STAGE RENAL-DISEASE; NORMAL-WEIGHT WOMEN; INSULIN-RESISTANCE; VASCULAR FUNCTION; HYPERTENSIVE PATIENTS; CLINICAL-EVALUATION; AORTIC STIFFNESS; OVERWEIGHT WOMEN;
D O I
10.1210/jc.2009-1985
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context: Patients with polycystic ovary syndrome (PCOS) have an increased prevalence of insulin resistance and display subclinical evidence of early cardiovascular disease. Metformin improves insulin sensitivity and circulating markers of cardiovascular risk in patients with PCOS, but it is unclear whether this translates into improvements in vascular function. Objective: Our objective was to evaluate the effects of metformin on arterial stiffness and endothelial function in women with PCOS. Design and Intervention: Thirty women with PCOS were assigned to consecutive 12-wk treatment periods of metformin or placebo in a randomized, double-blind, crossover design separated by an 8-wk washout. Main Outcome Measures: The primary outcome measures were assessments of arterial stiffness [augmentation index (AIx), central blood pressure, and brachial and aortic pulse wave velocity (PWV)] and endothelial function. Anthropometry, testosterone, and metabolic biochemistry (lipids, homeostasis model of assessment for insulin resistance, high-sensitivity C-reactive protein, adiponectin, and plasminogen activator inhibitor-1) were also assessed. Results: Metformin improved AIx [-6.1%; 95% confidence interval (CI) for the difference -8.5 to -3.5%; P < 0.001], aortic PWV (-0.76 m/sec; 95% CI for the difference -1.12 to -0.4 m/sec; P < 0.001), brachial PWV (-0.73 m/sec; 95% CI for the difference -1.09 to -0.38; P < 0.001), central blood pressure (P < 0.001), and endothelium-dependent (AIx after albuterol; P = 0.003) and endothelium-independent (AIx after nitroglycerin; P < 0.001) vascular responses. Metformin also reduced weight (P < 0.001), waist circumference (P < 0.001), and triglycerides (P = 0.004) and increased adiponectin (P = 0.001) but did not affect testosterone or other metabolic measures. Conclusions: Short-term metformin therapy improves arterial stiffness and endothelial function in young women with PCOS. (J Clin Endocrinol Metab 95: 722-730, 2010)
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收藏
页码:722 / 730
页数:9
相关论文
共 60 条
[1]   Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction [J].
Al Suwaidi, J ;
Hamasaki, S ;
Higano, ST ;
Nishimura, RA ;
Holmes, DR ;
Lerman, A .
CIRCULATION, 2000, 101 (09) :948-954
[2]   The prevalence and features of the polycystic ovary syndrome in an unselected population [J].
Azziz, R ;
Woods, KS ;
Reyna, R ;
Key, TJ ;
Knochenhauer, ES ;
Yildiz, BO .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2004, 89 (06) :2745-2749
[3]   Global adiposity rather than abnormal regional fat distribution characterizes women with polycystic ovary syndrome [J].
Barber, Thomas M. ;
Golding, Stephen J. ;
Alvey, Christopher ;
Wass, John A. H. ;
Karpe, Fredrik ;
Franks, Stephen ;
McCarthy, Mark I. .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2008, 93 (03) :999-1004
[4]   Effect of weight loss and nutritional intervention on arterial stiffness in type 2 diabetes [J].
Barinas-Mitchell, Emma ;
Kuller, Lewis H. ;
Sutton-Tyrrell, Kim ;
Hegazi, Refaat ;
Harper, Patricia ;
Mancino, Juliet ;
Kelley, David E. .
DIABETES CARE, 2006, 29 (10) :2218-2222
[5]   Atherogenic lipoprotein phenotype and low-density lipoproteins size and subclasses in women with polycystic ovary syndrome [J].
Berneis, Kaspar ;
Rizzo, Manfredi ;
Lazzaroni, Veronica ;
Fruzzetti, Franca ;
Carmina, Enrico .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2007, 92 (01) :186-189
[6]   Impact of aortic stiffness on survival in end-stage renal disease [J].
Blacher, J ;
Guerin, AP ;
Pannier, B ;
Marchais, SJ ;
Safar, ME ;
London, GM .
CIRCULATION, 1999, 99 (18) :2434-2439
[7]   Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome [J].
Chang, J ;
Azziz, R ;
Legro, R ;
Dewailly, D ;
Franks, S ;
Tarlatzis, BC ;
Fauser, B ;
Balen, A ;
Bouchard, P ;
Dahlgren, E ;
Devoto, L ;
Diamanti, E ;
Dunaif, A ;
Filicori, M ;
Homburg, R ;
Ibanez, L ;
Laven, J ;
Magoffin, D ;
Nestler, J ;
Norman, RJ ;
Pasquali, R ;
Pugeat, M ;
Strauss, J ;
Tan, S ;
Taylor, A ;
Wild, R ;
Wild, S ;
Ehrmann, D ;
Lobo, R .
FERTILITY AND STERILITY, 2004, 81 (01) :19-25
[8]  
Chen CH, 1997, CIRCULATION, V95, P1827
[9]   Adiponectin stimulates production of nitric oxide in vascular endothelial cells [J].
Chen, H ;
Montagnani, M ;
Funahashi, T ;
Shimomura, I ;
Quon, MJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (45) :45021-45026
[10]   Insulin action is associated with endothelial function in hypertension and type 2 diabetes [J].
Cleland, SJ ;
Petrie, JR ;
Small, M ;
Elliott, HL ;
Connell, JMC .
HYPERTENSION, 2000, 35 (01) :507-511