Objective: The aim of this study was to investigate the endothelial status in young women with polycystic ovary syndrome (PCOS), using a simple and easily reproducible hemodynamic method combined with a biological marker and to evaluate the effect of metformin treatment on these parameters. Design: Descriptive clinical trial. Methods: Forty young women, 20 with PCOS and 20 normal women of similar age and body mass index were studied. Metformin (1700 mg daily) was administered for 6 months to the PCOS group. The endothelium status and the metabolic and hormonal profile were studied in both groups, as well as after metformin, by flow-mediated dilatation (FMD) on the brachial artery and by measurements of plasma endothelin-1 (ET-1) levels. Results: FMD was impaired in the PCOS group when compared with controls (3.24^0.71% vs 8.81^1.07% respectively, P , 0.0001), but this difference normalized after metformin treatment (PCOS post-metformin vs controls: 8.17^1.26 vs 8.81^1.07%, P ¼ 0.70) since the values significantly improved after metformin treatment (PCOS pre-metformin vs PCOS post-metformin : 3.24^0.71 vs 8.17^1.26%, P ¼ 0.003). ET-1 levels were significantly higher in the PCOS women compared with the control group (7.23^0.50 vs 4.99^0.69 fmol/l, P ¼ 0.01), they improved significantly after metformin treatment (PCOS pre-metformin vs PCOS post-metformin : 7.23^0.50 vs 3.57^0.60 fmol/l, P , 0.0001) and their difference compared with the control group was reversed (PCOS post-metformin vs controls: 3.57^0.60 vs 4.99^0.69 fmol/l, P ¼ 0.13). Metformin administration improved hyperandrogenemia. However, in this study, mathematical methods used to assess insulin resistance failed to show any detected alteration after treatment with metformin. Conclusions: PCOS women were found to exhibit endothelial dysfunction compared with controls, which was reversed 6 months after metformin administration. 152 749-756 European Journal of Endocrinology

Coffee is one of the most widely used pharmacologically active beverages. The present study was designed to evaluate the acute effect of coffee ingestion on endothelial function in healthy individuals, and the potential role of caffeine. We studied 17 healthy young adults (28.9+/-3.0 years old; nine men), who were regular non-heavy coffee drinkers. The endothelial performance was estimated by endothelium-dependent FMD (flow-mediated dilatation) of the brachial artery before and 30, 60, 90 and 120 min after ingestion of a cup of caffeinated coffee (80 mg of caffeine) or the corresponding decaffeinated beverage (< 2 mg of caffeine) in two separate sessions, following a randomized single-blind cross-over design. There was no difference in baseline FMD values between the two sessions [7.78 compared with 7.07% after caffeinated and decaffeinated coffee respectively; P = NS (not significant)]. Caffeinated coffee led to a decline of FMD (7.78, 2.86, 2.12, 4.44 and 4.57% at baseline, 30, 60, 90 and 120 min respectively; P < 0.001). This adverse effect was focused at 30 (P = 0.004) and 60 min (P < 0.001). No significant effect on FMD was found with the decaffeinated coffee session (7.07, 6.24, 5.21, 7.41 and 5.20%; P = NS). The composite effect of the type of coffee consumed over time on FMD was significantly different (P = 0.021). In conclusion, coffee exerts an acute unfavourable effect on the endothelial function in healthy adults, lasting for at least 1 h after intake. This effect might be attributed to caffeine, given that decaffeinated coffee was not associated with any change in the endothelial performance.

Objective. Increased endothelin activity may play a role in the pathogenesis of vascular injury, a primary feature of systemic sclerosis (SSc; scleroderma). Our goal was to test the hypothesis that treatment with the oral endothelin receptor antagonist bosentan might improve vascular endothelial function in SSc patients.Methods. A 4-week, prospective, parallel-group study compared 12 SSc patients who did not receive bosentan treatment with 12 patients who did receive treatment (125 mg/day) for pulmonary hypertension and/or digital ulcers. There were no differences in demographic and clinical characteristics or medications between the 2 groups. Baseline endothelial dysfunction was documented by decreased brachial artery ultrasound-derived flow-mediated dilation (FMD%; <5.5). Pulse wave analysis, venous occlusion plethysmography, and measurement of serum vascular markers were performed in parallel.Results. FMD%, the main end point, increased significantly from a mean ؎ SD of 3.1 ؎ 1.3% to 8.4 ؎ 2.6% after 4 weeks of bosentan treatment (P < 0.001, compared with a change from 2.4 ؎ 1.6% to 2.4 ؎ 2.2% in control patients). Arterial blood pressure, endothelium-independent vascular function, augmentation index, peripheral flow reserve, as well as circulating intercellular adhesion molecule 1, E-selectin, vascular endothelial growth factor, and endothelin 1 were not significantly affected by bosentan treatment. In patients continuously treated for 4 months, during which the dosage of bosentan remained at 125 mg/day (n ‫؍‬ 5) or increased to 250 mg/day (n ‫؍‬ 5), the 4-week results remained unchanged.Conclusion. Small doses of bosentan improve endothelial function without affecting hemodynamic parameters or endothelial activation-related processes, thus supporting a direct, reversible effect of endothelin in SSc-associated vascular injury. A long-term, controlled trial to examine the potentially global clinical benefit of endothelin receptor blockade in patients with early SSc may be warranted.

Objective: The aim of this study was to assess non-invasively endothelial function of young women with polycystic ovary syndrome (PCOS) in comparison with healthy age-matched women and a group of young women with idiopathic hirsutism (IH). The possible role of metabolic and hormonal parameters on endothelial function was also examined. Design: Descriptive clinical trial. Methods: Fifty-six women, 27 with PCOS, 16 with IH and 13 healthy age-matched women were studied. Endothelial function of resistance arteries was assessed by venous occlusion plethysmography. Metabolic and hormonal parameters were estimated in this study population. Results: The duration of reactive hyperemia (durRH) was shorter in PCOS group when compared with normal controls (63.75G13.33 s vs 113.18G20.92 s, PZ0.036). A similar finding was observed when PCOS were compared with IH group (63.75G13.33 s vs 105G17.20 s, PZ0.05). The durRH did not differ between IH and control group (105G17.20 s vs 113.18G20.92 s, ns). A significant positive linear correlation was found between the durRH and dehydroepiandrosterone-sulfate (DHEA-S) levels (rZC0.48, PZ0.04) in the PCOS group. The basal insulin resistance index (HOMA) differed significantly between PCOS, IH and control groups. There was no significant correlation between durRH and HOMA index or testosterone levels in the PCOS group. Conclusions: Endothelial dysfunction may be an early sign of cardiovascular system abnormalities in young PCOS women. It is possible that increased DHEA-S levels may offer a cardioprotective advantage that attenuates the effects of cardiovascular risk factors that accompany PCOS.European Journal of Endocrinology 154 883-890