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Metformin reduces arterial stiffness and improves endothelial function in young women with polycystic ovary syndrome: A randomized, placebo-controlled, crossover trial

Agarwal, Neera, Rice, Sam P. L., Bolusani, Hemanth, Luzio, Stephen Denis, Dunseath, Gareth John, Ludgate, Marian Elizabeth and Rees, Dafydd Aled 2010. Metformin reduces arterial stiffness and improves endothelial function in young women with polycystic ovary syndrome: A randomized, placebo-controlled, crossover trial. Obstetrical & Gynecological Survey 65 (6) , pp. 381-382. 10.1097/OGX.0b013e3181e5a167

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Abstract

Polycystic ovary syndrome (PCOS) is characterized by increased insulin resistance and an increased risk of type 2 diabetes. These abnormalities most likely are associated with increased risk of cardiovascular mortality in women with PCOS, although this has not been demonstrated in epidemiological studies. Endothelial dysfunction is an early marker of vascular damage in women with PCOS. Increased arterial stiffness (assessed by pulse wave velocity [PWV]) correlates with insulin resistance and is a strong independent predictor of cardiovascular mortality in patients with type 2 diabetes. Since it is also increased in women with PCOS, insulin resistance may be an important therapeutic target. The oral biguanide, metformin, improves insulin sensitivity in women with PCOS and reduces circulating concentrations of markers of cardiovascular risk. However, its effects on vascular function are unclear because of conflicting data and the absence of randomized controlled studies. This randomized, double-blind, placebo-controlled crossover study investigated the effects of short-term metformin therapy on arterial stiffness and endothelial function in women with PCOS. The participants were 30 obese women (mean body mass index: 34.9) with PCOS, who were assigned, using a crossover design, to receive consecutive 12-week treatment periods of metformin or placebo separated by an 8-week washout. The primary study outcomes were changes in measures of arterial stiffness (augmentation index [Alx], brachial PWV, aortic PWV, central blood pressure), and endothelial function. Secondary outcome measures were changes in anthropometric measures (weight, body mass index, and waist and hip circumference), androgens (testosterone), and metabolic biochemistry (adiponectin, high-sensitivity C-reactive protein, homeostasis model of assessment for insulin resistance, triglycerides, and plasminogen activator inhibitor-1). Metformin improved measures of arterial stiffness including AIx (−6.1%; 95% confidence interval (CI) for the difference −8.5% to −3.5%); bPWV (−0.73 m/s; 95% CI for the difference −1.09 to −0.38); aPWV (−0.76 m/s; 95% CI for the difference −1.12 to −0.4 m/s); and central blood pressure (all comparisons, P < 0.001). Endothelium-dependent (AIx after albuterol, P < 0.003) and endothelium-independent (Alx after nitroglycerin; P < 0.001) vascular responses also improved. Metformin significantly reduced body weight (P < 0.001), waist circumference (P < 0.001), and triglycerides (P < 0.004). Increases were observed for adiponectin (P < 0.001). No changes were observed in testosterone or other metabolic measures. Both the study medication and placebo were well tolerated. These findings suggest that metformin improves important parameters of vascular function in young obese women with PCOS and may have therapeutic benefits for this study population.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > RG Gynecology and obstetrics
Publisher: Lippincott Williams & Wilkins
ISSN: 0029-7828
Last Modified: 09 Nov 2017 21:23
URI: http://orca.cf.ac.uk/id/eprint/28937

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