Estrés oxidativo en pacientes con síndrome de ovario poliquístico

Résumé

Introduction and Objectives: Polycystic ovary syndrome (PCOS) is an important cause of both ovulatory and menstrual irregularity and androgen excess in women. The disorder affects 5-10% of reproductive-aged women. Women with PCOS have numerous metabolic complications such as obesity, hyperinsulinemia, impaired glucose tolerance, dyslipidemia, and increased blood pressure. These complications expose patients with PCOS to risk of type 2 diabetes mellitus, fatty liver disease, subclinical atherosclerosis, vascular dysfunction and cardiovascular disease (CVD). The pathophysiology of PCOS is still unclear, and medical care of these patients has been limited to symptomatic control and infertility. The reasons for the increased risk of CVD in PCOS are not entirely understood. Recent studies strongly suggest that oxidative stress (OS) plays a pivotal role in the pathogenesis of PCOS. Besides, it has been hypothesized that OS also contributes to the risk of CVD in women with PCOS. Numerous studies have shown that the level of OS is significantly elevated in women with PCOS in comparison to healthy patients. However, results would not be consistent, when OS is evaluated by different oxidative markers. Lipid peroxidation is a well-established mechanism of cellular injury in humans, and is used as an indicator of OS in cells and tissues. Lipid peroxidation is most commonly assessed in research studies and one of its products, isoprostanes (IsoP), has been validated as the gold standard. The level of IsoP is a good marker reliable for endogenous lipid peroxidation, and therefore a useful tool that reflects damage and oxidative status in vivo. For this reason, it is considered the most sensitive marker of OS currently available. Many PCOS women are undiagnosed due to lack of consensus in diagnostic criteria and the presence of various PCOS phenotypes complicates the diagnosis even further. It is for these reasons that a standardized diagnostic tool with minimal inter-observer variation is needed, and thus be able to follow-up on short and long-term health risk. The aims of the present study were to evaluate OS in age-matched groups of women with versus without PCOS, using plasma levels of different oxidative markers, mainly 8-isoprostanes (8-IsoP), and evaluate it like diagnostic tools to PCOS. Besides, it investigated whether there is a relationship between 8-IsoP and increased risk of CVD in women with PCOS. Methodology: This case-control study included 125 patients with PCOS and 168 healthy women from the Gynecology, Endocrinology and Sterility Service outpatient clinics at the University Virgen de la Arrixaca Hospital Clinic, Murcia (Spain) between June 2014 and February 2016. In this controlled study participants were voluntarily recruited. PCOS was diagnosed in accordance with the Rotterdam Consensus Conference criteria by European Society for Human Reproduction and Embryology and the American Society for Reproductive Medicine. Control group subjects were healthy volunteers with normal menstrual cycles, normal ovaries morphology and who had no clinical or biochemical features of hyperandrogenism. Biochemical, hematological, hormonal and OS parameters were measured in all subjects. The results were analyzed using the Statistical Package for Social Sciences software version 22.0 (SPSS Inc., Chicago,IL, USA). Conclusions: Our study demonstrated that patients with PCOS have higher levels of oxidation markers and lower levels of antioxidants, and that this OS is greater in those phenotypes of PCOS with hyperandrogenism. This increase of OS is independent of the presence of obesity, but it is associated with the presence of IR and Metabolic Syndrome. Patients with polycystic ovarian syndrome who have higher levels of 8-ISOP have higher levels of CVR markers than those with this syndrome, but with normal levels of 8-ISOP. PCOS alone is a factor that predisposes to the development of CVD, but the presence of EO increases this risk even more in these patients. For this reason, it has been suggested that the routine measurement of markers of OS may be an accurate tool help to identify cardiovascular risk in women with PCOS and can be adopted and included in clinical practice. Finally, of the biomarkers measured in this study, the combination of MULLE, BILT and 8-ISOP is a useful tool for the diagnosis of PCOS.