Effects of Metformin With or Without Supplementation With Folate on Homocysteine Levels and Vascular Endothelium of Women With Polycystic Ovary Syndrome
- Stefano Palomba, MD1,
- Angela Falbo, MD1,
- Francesco Giallauria, MD2,
- Tiziana Russo, MD1,
- Achille Tolino, MD3,
- Fulvio Zullo, MD, PHD1,
- Annamaria Colao, MD, PHD4 and
- Francesco Orio, MD, PHD4,5
- 1Department of Obstetrics and Gynecology, University “Magna Graecia” of Catanzaro, Catanzaro, Italy;
- 2Department of Clinical Medicine, Cardiovascular and Immunological Sciences, University “Federico II” of Naples, Naples, Italy;
- 3Department of Obstetrics and Gynecology, University “Federico II” of Naples, Naples, Italy;
- 4Department of Endocrinology, University “Federico II” of Naples, Naples, Italy;
- 5Chair of Endocrinology, University “Parthenope” of Naples, Naples, Italy.
- Corresponding author: Stefano Palomba, stefanopalomba{at}tin.it.
Abstract
OBJECTIVE To evaluate whether the administration of metformin exerts any effects on serum homocysteine (Hcy) levels in patients with polycystic ovary syndrome (PCOS) and whether supplementation with folate enhances the positive effects of metformin on the structure and function of the vascular endothelium.
RESEARCH DESIGN AND METHODS A total of 50 patients affected by PCOS, without additional metabolic or cardiovascular diseases, were enrolled in a prospective nonrandomized placebo-controlled double-blind clinical study. They were grouped into two treatment arms that were matched for age and BMI. Patients were treated with a 6-month course of metformin (1,700 mg daily) plus folic acid (400 μg daily; experimental group, n = 25) or placebo (control group, n = 25). Complete hormonal and metabolic patterns, serum Hcy, folate, vitamin B12, endothelin-1 levels, brachial artery diameter at the baseline (BAD-B) and after reactive hyperemia (BAD-RH), flow-mediated dilation, and intima-media thickness in both common carotid arteries were evaluated.
RESULTS After treatment, a significant increase in serum Hcy levels was observed in the control group compared with the baseline values and the experimental group. A beneficial effect was observed in the concentrations of BAD-B, BAD-RH, flow-mediated dilation, intima-media thickness, and serum endothelin-1 in both groups. However, the results were improved more significantly in the experimental group than in the control subjects.
CONCLUSIONS Metformin exerts a slight but significant deleterious effect on serum Hcy levels in patients with PCOS, and supplementation with folate is useful to increase the beneficial effect of metformin on the vascular endothelium.
Footnotes
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Clinical trial reg. no. NCT00953355, clinicaltrials.gov.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Received August 13, 2009.
- Accepted November 12, 2009.
- © 2010 by the American Diabetes Association.
