ObjectivesWe assessed whether third-generation oral contraceptive (OC) treatment (30 μg ethinylestradiol + 75 μg gestodene daily) could affect the endothelial function of healthy women.MethodsIn 20 young healthy women (HW) and 10 hypercholesterolemic women (CW) we assessed forearm blood flow (strain-gauge plethysmography) changes induced by the intrabrachial infusion of acetylcholine (ACH) (0.15–15 μg/100 ml forearm tissue/min) and sodium nitroprusside (SNP) (1–4 μg/100 ml forearm tissue/min). ACH was repeated during the nitric oxide synthase inhibitor intra-arterialNG-monomethyl-l-arginine (l-NMMA) (100 μg/100 ml forearm tissue/min) or the antioxidant vitamin C (8 mg/100 ml forearm tissue/min). HW repeated the protocol after 6-month OC (n= 10) or placebo (n= 10) treatment.ResultsIn HW the maximal vasodilation to ACH, similar between placebo and OC subgroups, was significantly reduced in CW (P<0.01). Vasodilation to ACH was blunted (P<0.01) by l-NMMA and unaffected by vitamin C, in both OC and placebo groups. In CW the vasodilation to ACH, not modified by l-NMMA, was improved by vitamin C (P<0.01). OC treatment raised (P<0.01) plasma total and low-density lipoprotein cholesterol, and values were similar to those shown by CW. Both OC and placebo intake did not change the response to ACH and the modulation induced by l-NMMA or vitamin C. Vasodilation to SNP was similar in all groups.ConclusionsIn HW 6-month treatment with third-generation OC, although associated with an abnormal lipid profile, does not adversely affect endothelium-dependent vasodilation. This neutral effect could be the balance between a deleterious effect of hypercholesterolemia and a protective effect of OC on endothelial function.