Hum. Reprod. Advance Access originally published online on June 20, 2008
Human Reproduction 2008 23(9):2127-2133; doi:10.1093/humrep/den230
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Metformin improves endothelial function in normoinsulinemic PCOS patients: a new prospective
1 Department of Obstetrics and Gynaecology, Università Cattolica del Sacro Cuore, L.go Agostino Gemelli, 8, 00168 Rome, Italy 2 ‘Oasi’ Institute for Research, 94018 Troina (EN), Italy
3 Correspondence address. Tel/Fax: +39-06-3057794; E-mail: danielaromualdi{at}libero.it
BACKGROUND: Metformin was reported to improve the alterations of endothelial reactivity in normal-weight subjects with polycystic ovary syndrome (PCOS). The aim of the present study was to investigate the mechanisms of action of this drug on the vascular function of this population.
METHODS: Thirteen normal-weight, normoinsulinemic and normolipemic PCOS women were studied before and after 6 months of metformin treatment (1000 mg/day). The endothelial function was assessed by evaluating the flow-mediated dilatation (FMD) of the brachial artery. We correlated this parameter with the endocrine-metabolic features of the patients.
RESULTS: Metformin significantly reduced testosterone (1.56 ± 0.52 after 6 months versus 2.98 ± 1.00 at baseline) and 17-hydroxyprogesterone (0.03 ± 0.01 versus 0.06 ± 0.02 nmol/ml) levels, without affecting gluco-insulinemic parameters. Concomitantly, the basal vessel diameter and the FMD significantly increased (4.12 ± 0.68 versus 3.2 ± 0.41 and 5.2 ± 0.6 versus 3.76 ± 0.5 mm, respectively), thus documenting an improved endothelial function.
CONCLUSIONS: Our data confirm the positive effects of metformin on the altered vascular reactivity, a precocious marker of cardiovascular risk, in normoinsulinemic PCOS subjects. This improvement seems to be mediated through hormonal changes, thus highlighting the detrimental role of hyperandrogenemia on the endothelial function, even beyond the metabolic factors. However, a direct effect of metformin on the endothelium should not be excluded.
Key words: polycystic ovary syndrome/cardiovascular disease/endothelial function/androgens/metformin
Submitted on January 11, 2008; resubmitted on May 12, 2008; accepted on May 19, 2008.
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