Activation of Systemic Inflammation and Oxidative Stress in Adolescent Girls with Polycystic Ovary Syndrome in Combination with Metabolic Disorders and Excessive Body Weight

Abstract

Relevance: Mitochondrial dysfunction and systemic inflammation are believed to play pivotal role in the pathogenesis of polycystic ovary syndrome (PCOS) and related complications of metabolic disorders in adult patients. Though such researches are limited or almost absent in adolescents. The aim of the study is to evaluate the impact of mitochondrial dysfunction and systemic inflammation on PCOS pathogenesis during adolescence with regard to body mass index and insulin resistance. Design: a case-control study. Methods: The study included 95 adolescent girls (15 to 17 years old inclusive) diagnosed with PCOS based on the Rotterdam criteria. The control group consisted of 30 healthy girls of the same age with a regular menstrual cycle. All participants were subjected to a full clinical and instrumental examination, as well as an assessment of the levels of leptin, C-reactive protein (CRP), and malondialdehyde (MDA) as oxidative stress marker. Serum levels of IL-6, IL-10, IL-18, TNF-α, and plasma concentrations of macrophage migration inhibitory factor (MIF), sFas, and sFasL were determined. Patients with PCOS were divided into groups according to the presence of metabolic disorders (MD) (impaired glucose tolerance and/or over insulin resistance) and normal weight or excessive weight (NW or OW). Results: Patients with PCOS of NW in the absence of metabolic disorders (MD−/NW) had a lower concentration of MDA and a higher level of IL-10 compared to healthy girls (p < 0.05). The group (MD−/NW) was characterized with lower levels of CRP, leptin, MDA, and higher levels of sFasL, when compared to OW patients with PCOS in the absence of metabolic disorders (MD−/OW) (p < 0.05). Overweight adolescent girls with PCOS and metabolic disorders (MD+/OW) showed higher CRP, leptin, and a two-fold increase in IL-6 and IL-18 concentrations compared to the control group of healthy girls (p < 0.05 for all parameters). The group (MD+/OW) was also characterized with higher levels of CRP, leptin, MDA, IL-18, MIF (p < 0.05), when compared to overweight patients with PCOS in the absence of metabolic disorders (MD−/NW). In comparison with the MD−/OW group, the obese insulin resistant girls with PCOS (MD+/OW) had a highera level of IL-18 (p < 0.05). Moreover, the MD+/OW girls demonstrated a significant increase in CRP, MDA and IL-18 levels when compared to the MD+/NW group (p < 0.05). OW girls with PCOS without MD (MD−/OW) had lower concentrations of sFasL compared to healthy girls (p < 0.05), and higher levels of MDA compared to MD+/NW (p < 0.05). Adolescent girls of NW with PCOS and with MD (MD+/NW) had lower levels of MDA compared to the control group of healthy girls (p < 0.05). These data are confirmed by a correlation analysis and two-factor ANOVA test. Conclusions: Lean girls with PCOS demonstrate the protective mechanism of decrease in oxidative stress mediated by the activation of antioxidant defense, reduction of lipid peroxidation and systemic inflammation. Excessive weight and metabolic disorders in adolescents with PCOS are the most significant factors in reducing the capacity of antioxidant systems, activation of oxidative stress, mitochondrial dysfunction, and systemic inflammation.

The Relevant Hormonal Levels and Diagnostic Features of Polycystic Ovary Syndrome in Adolescents

“…However, when analyzing separately normal and overweight patients with PCOS, we found differences not only in dyslipidemia and atherogenic lipid profile but also in more pronounced hyperandrogenism according to the increased level of FAI and decreased SHBG in overweight PCOS group. Besides, our findings corroborate with our previous results in which high leptin and CRP levels were associated with activated oxidative stress and systemic inflammation in overweight adolescents with PCOS complicated with metabolic disorders [ 18 ]. One of the generally accepted diagnostic criteria for PCOS is polycystic ovarian morphology according to ultrasound, though its evaluation in adolescence is doubtful [ 13 ].…”

Prevalence of Asthma in Polycystic Ovary Syndrome Women: A Meta-analysis

“…IL-18 is another important cytokine in PCOS which can stimulate TNF, IL-6 and CRP. IL-18 and CRP levels are raised in PCOS patients [37] . Moreover, IL-17 and TNF are well known markers of low grade systemic inflammation among patients with PCOS.…”

Impact of Increased Oxidative Stress on Cardiovascular Diseases in Women With Polycystic Ovary Syndrome

“…Thus, mitochondrial dysfunction in combination with systemic inflammation is thought to play an essential role in the occurrence of complications associated with metabolic disorders in patients with PCOS, and in the predisposition to cardiovascular disease. In this regard, as a result of mitochondrial dysfunctions, systemic increase of OS occurs in patients of reproductive age who develop symptoms of PCOS, and who have been found to have elevated serum levels of inflammatory markers such as C-reactive protein, interleukins, and proinflammatory cytokines, increased cell counts of leukocyte series such as lymphocytes and monocytes, change in tumor necrosis factor (TNF-α), as well as increases in some metabolites resulting from the processes of carbonylation and oxidation of proteins and lipids ( 172 – 174 ).…”