IJCS | Volume 32, Nº1, January/ February 2019

7 Figure 2 - Bar graph comparing augmentation index (mean ± standard error) by testosterone levels in polycystic ovarian syndrome (POS) women after division by the median; *P = 0.045 by Student’s t-test. Burlá et al. Vascular changes in polycystic ovarian syndrome Int J Cardiovasc Sci. 2019;32(1)3-9 Original Article pulse wave reflection than those with PCOS and lower testosterone levels. Previous studies have shown that women with PCOS have high prevalence of CV risk factors, in addition to besides the clinical features of menstrual irregularity, hyperandrogenismand infertility. Thus, some studies have suggested an association between PCOS and accelerated CV disease. 7,21,22 Recent cohort studies had controversial results regarding CV events in PCOS patients. 5,6 Both endothelial dysfunction and arterial stiffness have been associated to worse CV outcomes in the general population and are proposed as complementary CV risk evaluation. 10,11 Vascularendotheliumplaysacrucial role inmaintaining vascular homeostasis and endothelial dysfunction is an important early step in the development of atherosclerosis and CV diseases. 21 There are many pathophysiological mechanisms that explain the relationship between PCOS and endothelial dysfunction. 7,21 Insulin resistance impairs intracellular signaling, which in endothelium may cause lower production of nitric oxide and increased secretion of endothelin-1, leading to vasoconstriction and decreased blood flow. 23 Moreover, hyperinsulinemia exerts a direct hypertrophic effect on the vascular wall, which deteriorates endothelial function and may lead to vascular stiffening. 7,21,23 Other proposed mechanisms involve atherogenic dyslipidemia, lipo-oxidative stress, products of glycation and glycoxidation, and inflammatory cytokines. 7 One of the first studies relating PCOS and endothelial dysfunctionwaspublished in2001andenrolled12patients with PCOS and 13 age- and weight-matched controls. 24 They observed that PCOS subjects had endothelial dysfunction that was related to hyperandrogenism and insulin resistance. 24 These results have been confirmed by subsequent studies and a recent meta-analysis, which showed that PCOS women had a pooled mean FMD 3.4% lower than controls. 12,18,25 However, there are controversies if endothelial dysfunction is a consequence of high androgen levels, hyperinsulinemia-obesity syndrome or both. 18,24,26 A previous study compared PCOS women and controls, both groups with BMI < 30 kg/m 2 , and observed that PCOS subjects had lower FMD and higher androgen levels despite no biochemical evidence of insulin resistance. 18 A similar study involving overweight young women with PCOS also observed endothelial dysfunction, but FMD was statistically correlated not only to high androgen levels but also to inflammatory markers and insulin resistance. 26 In contrast, a previous small study of PCOS women with high testosterone levels and normal insulin resistance did not observe endothelial dysfunction. 27 A study of PCOS subjects with high androgen levels also did not observe lower FMD when compared to age- and BMI- matched controls; in that study, the PCOS group had hyperinsulinemia. 28 In addition, a study comparing non-obese PCOS women and age- and BMI-matched controls showed similar FMD despite higher androgen levels in PCOS subjects; insulin levels and HOMA-IR indices were similar between the groups. 29 In the present study, women with PCOS had endothelial dysfunction, and our sample consisted essentially of young and overweight women. Furthermore, insulin levels and both HOMA-IR and HOMA-Beta were within normal range for their BMI, suggesting a non-significant insulin resistance. Thus, our results reinforce that PCOS women may have endothelial dysfunction due to mechanisms other than insulin resistance. Changes in the arterial wall, with loss of elastin fibers and increase in collagen proteins, leads to vascular stiffening. 30 Age and hypertension are two of the most important factors that trigger these modifications. 30 Endothelial dysfunction and arterial stiffening are related to each other. Carotid-femoral PWV is the gold-standard method to evaluate arterial stiffness and is a powerful and independent predictor of CV events. 11,31 A previous study enrolled overweight women and demonstrated that subjects with PCOS had higher PWV and lower FMD than controls. 32 However, other studies did not confirm the hypothesis of stiffer vessels in PCOS