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This version published online on August 23, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-0965
A more recent version of this article appeared on November 1, 2005
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Submitted on May 2, 2005
Accepted on August 12, 2005

Improvement in endothelial structure and function after metformin treatment in young normal-weight women with polycystic ovary syndrome: results of a six-month study

Francesco Orio Jr*, Stefano Palomba, Teresa Cascella, Biagio De Simone, Francesco Manguso, Silvia Savastano, Tiziana Russo, Achille Tolino, Fulvio Zullo, Gaetano Lombardi, Ricardo Azziz, and Annamaria Colao

Department of Molecular & Clinical Endocrinology and Oncology (F.O. Jr, T.C., S.S., G.L., A.C.), University "Federico II" Naples, Naples 80131, Italy; Department of Obstetrics and Gynecology (S.P., T.R., F.Z.), University of Catanzaro "Magna Graecia", Catanzaro 88100, Italy; Institute of Internal Medicine and Metabolic Disease (B.D.S.) University "Federico II" Naples, Naples 80131, Italy; Department of Clinical and Experimental Medicine, Gastroenterology Unit, "Federico II" University (F.M.), Naples 80131, Italy; Department of Obstetrics and Gynecology (A.T.), University "Federico II" Naples, Naples 80131, Italy; Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center (R.A.), Los Angeles, California 90048

* To whom correspondence should be addressed. E-mail: francescoorio{at}virgilio.it.

Context: Recent data indicate that women affected by the polycystic ovary syndrome (PCOS) are at greater risk for cardiovascular disease and that metformin may improve the metabolic alterations in these patients.

Objective: To evaluate the effects of six months of metformin administration on endothelial structure and function in PCOS women.

Design: Prospective baseline-controlled clinical study.

Setting: University "Federico II" of Naples, Italy.

Patients: Thirty young normal-weight PCOS women without additional metabolic or cardiovascular diseases.

Interventions: Administration of metformin cloridrate (850 mg bid) for six months.

Mean outcome measures: Complete hormonal profile, including total testosterone (T), sex hormone binding globulin (SHBG), DHEAS, prolactin, and gonadotropin levels; serum insulin and glucose levels during a 75 gm 2-hour oral glucose tolerance test (OGTT); plasma endothelin-1 (ET-1) concentrations (pmol/l±SD); serum lipid profile; brachial artery baseline diameter (BAD, mm±SD), diameter after reactive hyperemia (DARH, mm±SD), and flow-mediated dilation (FMD, %±SD); and the intima-media thickness (IMT, mm±SD) on both common carotid arteries.

Results: After treatment, SHBG levels and free androgen index (FAI) changed significantly (P < 0.001). High-density lipoproteins (HDL) and the area under curve (AUC)glucose/AUCinsulin ratio also significantly (P < 0.001) increased, whereas low-density lipoproteins (LDL) and plasma ET-1 levels were significantly (P < 0.001) reduced. No other change was found in any of the biochemical parameters evaluated. A significant (P < 0.01) difference was observed in BAD (3.24 ± 0.30 vs. 3.0 ± 0.30), DARH (3.70 ± 0.30 vs. 3.55 ± 0.10), FMD (14.30 ± 1.90 vs.15.70 ± 1.50) and IMT (0.53 ± 0.09 vs. 0.40 ± 0.07) following metformin treatment in comparison with baseline values.

Conclusions: A six-month course of metformin improves endothelial structure and function in young normal-weight women with PCOS.
Key words: Endothelial function • metformin • PCOS • endothelin-1 • intima media thickness • insulin • androgens




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eLetters:

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Does Metformin Treatment Really Improve Arterial Structure in Women with Polycystic Ovarian Syndrome
Sophia Zoungas, et al.
JCEM Online, 30 Nov 2005 [Full text]
Re: Does Metformin Treatment Really Improve Arterial Structure in Women with Polycystic Ovarian Synd
Francesco Orio, et al.
JCEM Online, 14 Dec 2005 [Full text]

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