Analysis of the indicators of the oxidative stress in adolescent girls with polycystic ovary syndrome on different oral hormonal contraception therapy regiments

Sindrom policističnih jajnika (PCOS) je složeni poremećaj prisutan u 6-10% žena reproduktivnog perioda, a karakteriziran je hiperandrogenizmom, hiperinsulinemijom, oštećenom funkcijom hipotalamo-hipofizno-ovarijumske osovine i disfunkcijom hormonske aktivnosti masnog tkiva. Pretpostavlja se da različiti endokrini i metabolički poremećaji mogu dodatno uticati na pojavu oksidativnog stresa kod žena sa PCOS a posebno hiperandrogenizam, koji se smatra glavnim pokretačem povećane produkcije reaktivnih kiseoničnih vrsta (ROS). Kod adolescentkinja sa PCOS, oralna hormonska kontraceptivna (OHK) pilula može efikasno poboljšati biohemijske i kliničke parametre. Cilj ovog rada bio je određivanje parametara oksidativnog stresa i aktivnost ključnih enzima antioksidantne zaštite kod adolescentkinja sa PCOS, koje su bile normalno uhranjene i bez poremećaja tolerancije glukoze, pre i posle primene oralne hormonske kontraceptivne pilule. Pored toga, ispitali smo markere inflamacije, hs-CRP i fibrinogen kao i njihovu vezu sa antropometrijskim i parametrima lipidnog statusa. Materijal i metode: Studijom je praćeno 35 adolescentkinja sa PCOS i 17 zdravih kontrola, odgovarajuće starosti i indeksa telesne mase. Izvršena su antropometrijska merenja, biohemijska i hormonska ispitivanja. Parametri oksidativnog stresa, koncentracije nitrotirozina i proteinskih tiol grupa kao i aktivnosti glutation-peroksidaze i superoksid dismutaze, određivane su našte i tokom oralnog testa opterećenja glukozom (OGTT). Genetski polimorfizmi glavnih citosolnih glutation S-transferaza (GST) određeni su PCR-om. Insulinska rezistencija procenjivana je primenom homeostatskog indeksa rezistencije na insulin (HOMA-IR), homeostatskog indeksa funkcije β ćelija (HOMA-β), insulinogenog indeksa (IGI), “Matsuda” indeksa sezitivnosti na insulin [ISI(Matsuda)] i AUC glukoze. Rezultati: U uslovima našte, nije pronađena značajna razlika u koncentraciji parametara oksidativnog stresa između adolescentkinja sa PCOS i zdravih kontrola. Akutna hiperglikemija tokom OGTT izazvala je značajne promene u koncentraciji parametara oksidativnog oštećenja proteina kod ispitanica sa PCOS. Posebno su promene koncentracije nitrotirozina bile povezane sa testosteronom, DHEAS, androstenedionom, FAI i LH, dok je promena proteinskih tiol grupa bila povezana sa DHEAS (p<0,05)...Polycystic ovary syndrome (PCOS) is a complex disorder present in 6-10% of the reproductive age women and characterized by hyperandrogenism, hyperinsulinemia, impaired function of the hypothalamic-pituitary-ovarian axis and dysfunction of adipose tissue hormonal activity. It has been supposed that different endocrine and metabolic disorders can further affect the occurrence of oxidative stress in women with PCOS, with special emphasis on hyperandrogenism which is considered the main progenitor of increased production of reactive oxygen species (ROS). In an adolescent with PCOS, oral contraceptive therapy can effectively improve biochemical and clinical parameters. The aim of this study was to determine oxidative stress by-products and activity of key antioxidant enzymes in adolescent girls with PCOS, which were non-obese and normoinsulinemic, before and after oral contraceptive therapy. In addition, we evaluated inflammatory markers, high-sensitivity C-reactive protein (hs-CRP) and fibrinogen as well as their relationship with anthropometric and lipid parameters. Methods: The study comprised a total of 35 adolescent girls with PCOS and 17 healthy controls, appropriate age and body mass index. The anthropometric measurements, biochemical and hormonal testing were performed. Oxidative stress parameters, nitrotyrosine and thiol groups’ concentrations as well as glutathione peroxidase and superoxide dismutase activities were determined under fasting conditions and during oral glucose tolerance test (OGTT). Glutathione S-transferases (GSTs) polymorphisms were determined by PCR. Insulin resistance was assessed by the homeostasis model assesment of insulin resistance (HOMA-IR), homeostasis model assessment of β-cell function (HOMA-β), insulinogenic index (IGI), insulin sensitivity index-Matsuda [ISI(Matsuda)] and blood glucose area under the curve (AUCglucose). Results: Under fasting conditions, no significant difference of oxidative stress parameters was found between adolescent patients with PCOS and healthy controls. However, acute hyperglycemia during OGTT induced significant alteration in parameters of oxidative protein damage in PCOS patients..

Polimorfizm S-transferazy glutationowej (GST) może być wczesnym markerem w rozwoju zespołu policystycznych jajników (PCOS) — doświadczenia nieotyłych dorosłych pacjentów z cukrzycą insulinoniezależną

Introduction: It has been supposed that endocrine disturbances might be responsible for polycystic ovary syndrome (PCOS)-associated oxida­tive stress, with special emphasis on hyperandrogenism. Considering the potential relationship between hyperandrogenism and increased free radical production, parameters of oxidative stress were determined in non-obese normoinsulinemic adolescent girls newly diagnosed with PCOS. Materials and methods: Nitrotyrosine, thiol group concentrations, glutathione peroxidase, and superoxide dismutase activities were determined under fasting conditions and during oral glucose tolerance test (OGTT) in 35 PCOS patients and 17 controls. Insulin resistance was assessed by the homeostasis model (HOMA-IR), HOMA β, insulinogenic index (IGI), Matsuda insulin sensitivity index (ISI), and AUC for glucose. Glutathione S-transferases (GSTs) polymorphisms were determined by PCR. Results: Under fasting conditions, no significant difference of oxidative stress parameters was found between PCOS and controls. Acute hyperglycaemia during OGTT induced significant alteration in parameters of oxidative protein damage in PCOS patients. Alteration in nitrotyrosine concentrations correlated with testosterone, DHEAS, androstenediones, FAI, and LH, while changes in thiol groups cor­related with DHEAS. Significant inverse association was found between LH and ISI, as well as AUC glucose and thiol groups. PCOS girls, carriers of GSTM1-null genotype, had significantly lower testosterone in comparison to ones with GSTM1-active genotype. Conclusions: PCOS girls exhibited high free radical production together with unchanged antioxidant enzymatic capacity, independently from obesity and insulin resistance. Based on associations between oxidative stress parameters and testosterone, DHEAS, and androsten­edione, it can be suggested that increased free radical production, probably as a consequence of hyperandrogenaemia, is an early event in the development of PCOS

Analysis of the indicators of the oxidative stress in adolescent girls with polycystic ovary syndrome on different oral hormonal contraception therapy regiments

Sindrom policističnih jajnika (PCOS) je složeni poremećaj prisutan u 6-10% žena reproduktivnog perioda, a karakteriziran je hiperandrogenizmom, hiperinsulinemijom, oštećenom funkcijom hipotalamo-hipofizno-ovarijumske osovine i disfunkcijom hormonske aktivnosti masnog tkiva. Pretpostavlja se da različiti endokrini i metabolički poremećaji mogu dodatno uticati na pojavu oksidativnog stresa kod žena sa PCOS a posebno hiperandrogenizam, koji se smatra glavnim pokretačem povećane produkcije reaktivnih kiseoničnih vrsta (ROS). Kod adolescentkinja sa PCOS, oralna hormonska kontraceptivna (OHK) pilula može efikasno poboljšati biohemijske i kliničke parametre. Cilj ovog rada bio je određivanje parametara oksidativnog stresa i aktivnost ključnih enzima antioksidantne zaštite kod adolescentkinja sa PCOS, koje su bile normalno uhranjene i bez poremećaja tolerancije glukoze, pre i posle primene oralne hormonske kontraceptivne pilule. Pored toga, ispitali smo markere inflamacije, hs-CRP i fibrinogen kao i njihovu vezu sa antropometrijskim i parametrima lipidnog statusa. Materijal i metode: Studijom je praćeno 35 adolescentkinja sa PCOS i 17 zdravih kontrola, odgovarajuće starosti i indeksa telesne mase. Izvršena su antropometrijska merenja, biohemijska i hormonska ispitivanja. Parametri oksidativnog stresa, koncentracije nitrotirozina i proteinskih tiol grupa kao i aktivnosti glutation-peroksidaze i superoksid dismutaze, određivane su našte i tokom oralnog testa opterećenja glukozom (OGTT). Genetski polimorfizmi glavnih citosolnih glutation S-transferaza (GST) određeni su PCR-om. Insulinska rezistencija procenjivana je primenom homeostatskog indeksa rezistencije na insulin (HOMA-IR), homeostatskog indeksa funkcije β ćelija (HOMA-β), insulinogenog indeksa (IGI), “Matsuda” indeksa sezitivnosti na insulin [ISI(Matsuda)] i AUC glukoze. Rezultati: U uslovima našte, nije pronađena značajna razlika u koncentraciji parametara oksidativnog stresa između adolescentkinja sa PCOS i zdravih kontrola. Akutna hiperglikemija tokom OGTT izazvala je značajne promene u koncentraciji parametara oksidativnog oštećenja proteina kod ispitanica sa PCOS. Posebno su promene koncentracije nitrotirozina bile povezane sa testosteronom, DHEAS, androstenedionom, FAI i LH, dok je promena proteinskih tiol grupa bila povezana sa DHEAS (p<0,05)...Polycystic ovary syndrome (PCOS) is a complex disorder present in 6-10% of the reproductive age women and characterized by hyperandrogenism, hyperinsulinemia, impaired function of the hypothalamic-pituitary-ovarian axis and dysfunction of adipose tissue hormonal activity. It has been supposed that different endocrine and metabolic disorders can further affect the occurrence of oxidative stress in women with PCOS, with special emphasis on hyperandrogenism which is considered the main progenitor of increased production of reactive oxygen species (ROS). In an adolescent with PCOS, oral contraceptive therapy can effectively improve biochemical and clinical parameters. The aim of this study was to determine oxidative stress by-products and activity of key antioxidant enzymes in adolescent girls with PCOS, which were non-obese and normoinsulinemic, before and after oral contraceptive therapy. In addition, we evaluated inflammatory markers, high-sensitivity C-reactive protein (hs-CRP) and fibrinogen as well as their relationship with anthropometric and lipid parameters. Methods: The study comprised a total of 35 adolescent girls with PCOS and 17 healthy controls, appropriate age and body mass index. The anthropometric measurements, biochemical and hormonal testing were performed. Oxidative stress parameters, nitrotyrosine and thiol groups’ concentrations as well as glutathione peroxidase and superoxide dismutase activities were determined under fasting conditions and during oral glucose tolerance test (OGTT). Glutathione S-transferases (GSTs) polymorphisms were determined by PCR. Insulin resistance was assessed by the homeostasis model assesment of insulin resistance (HOMA-IR), homeostasis model assessment of β-cell function (HOMA-β), insulinogenic index (IGI), insulin sensitivity index-Matsuda [ISI(Matsuda)] and blood glucose area under the curve (AUCglucose). Results: Under fasting conditions, no significant difference of oxidative stress parameters was found between adolescent patients with PCOS and healthy controls. However, acute hyperglycemia during OGTT induced significant alteration in parameters of oxidative protein damage in PCOS patients..

Polimorfizm S-transferazy glutationowej (GST) może być wczesnym markerem w rozwoju zespołu policystycznych jajników (PCOS) — doświadczenia nieotyłych dorosłych pacjentów z cukrzycą insulinoniezależną

Introduction: It has been supposed that endocrine disturbances might be responsible for polycystic ovary syndrome (PCOS)-associated oxida­tive stress, with special emphasis on hyperandrogenism. Considering the potential relationship between hyperandrogenism and increased free radical production, parameters of oxidative stress were determined in non-obese normoinsulinemic adolescent girls newly diagnosed with PCOS. Materials and methods: Nitrotyrosine, thiol group concentrations, glutathione peroxidase, and superoxide dismutase activities were de­termined under fasting conditions and during oral glucose tolerance test (OGTT) in 35 PCOS patients and 17 controls. Insulin resistance was assessed by the homeostasis model (HOMA-IR), HOMA β, insulinogenic index (IGI), Matsuda insulin sensitivity index (ISI), and AUC for glucose. Glutathione S-transferases (GSTs) polymorphisms were determined by PCR. Results: Under fasting conditions, no significant difference of oxidative stress parameters was found between PCOS and controls. Acute hyperglycaemia during OGTT induced significant alteration in parameters of oxidative protein damage in PCOS patients. Alteration in nitrotyrosine concentrations correlated with testosterone, DHEAS, androstenediones, FAI, and LH, while changes in thiol groups cor­related with DHEAS. Significant inverse association was found between LH and ISI, as well as AUC glucose and thiol groups. PCOS girls, carriers of GSTM1-null genotype, had significantly lower testosterone in comparison to ones with GSTM1-active genotype. Conclusions: PCOS girls exhibited high free radical production together with unchanged antioxidant enzymatic capacity, independently from obesity and insulin resistance. Based on associations between oxidative stress parameters and testosterone, DHEAS, and androsten­edione, it can be suggested that increased free radical production, probably as a consequence of hyperandrogenaemia, is an early event in the development of PCOS.Wstęp: Istnieją przypuszczenia, że zaburzenia hormonalne mogą odpowiadać za stres oksydacyjny, związany z zespołem policystycznych jajników (polycystic ovary syndrome; PCOS), ze szczególnym naciskiem na hiperandrogenizm. Biorąc pod uwagę potencjalny związek między hiperandrogenizmem a zwiększoną produkcją wolnych rodników, parametry stresu oksydacyjnego określono u nieotyłych, dorastających dziewcząt z normoinsulinemią, u których niedawno zdiagnozowano zespół policystycznych jajników (PCOS). Materiał i metody: W warunkach na czczo oraz podczas doustnego testu obciążenia glukozą (oral glucose tolerance test; OGTT) określono stężenie nitrotyrozyny, stężenia grup tiolowych, aktywność peroksydazy glutationowej i dysmutazy ponadtlenkowej u 35 pacjentów z PCOS oraz 17 osób z grupy kontrolnej. Insulinooporność oceniano za pomocą modelu homeostazy (HOMA-IR), HOMA β, współczynnika insulinogennego IGI (insulinogenic index; IGI), wskaźnika insulinowrażliwości (Matsuda insulin sensitivity index; ISI) i pola pod krzywą (area under the curve; AUC) stężenia glukozy we krwi. Polimorfizmy S-transferaz glutationowych (GSTs) określono za pomocą metody PCR. Wyniki: W warunkach na czczo nie stwierdzono istotnej różnicy parametrów stresu oksydacyjnego między pacjentami z PCOS a osobami z grupy kontrolnej. Ostra hiperglikemia podczas trwania OGTT wywołała istotne zmiany parametrów oksydacyjnych uszkodzeń białek u pacjentów z PCOS. Zmiana stężeń nitrotyrozyny korelowała ze stężeniem testosteronu, siarczanu dehydroepiandrosteronu (dehydroe­piandrosterone sulphate; DHEAS), androstenedionów, współczynnikiem wolnych androgenów (free androgen index; FAI) oraz hormonem luteinizującym (luteinising hormone; LH), podczas, gdy zmiany stężeń grup tiolowych korelowały z DHEAS. Stwierdzono istotną odwrotną zależność między LH a ISI, jak również między AUC stężenia glukozy a grupami tiolowymi. Dziewczęta z PCOS, nosicielki genotypu GSTM1-null, wykazywały niższe stężenie testosteronu w porównaniu z dziewczętami z genotypem GSTM1-active. Wnioski: U dziewcząt z PCOS wykazano wyższą produkcję wolnych rodników wraz z niezmienioną enzymatyczną zdolnością antyoksydacyjną, niezależnie od otyłości i oporności na insulinę. Biorąc pod uwagę związek między parametrami stresu oksydacyjnego i testosteronu, DHEAS i androstenedionów, można uznać, że zwiększona produkcja wolnych rodników, prawdopodobnie jako konsek­wencja hiperandrogenemii, występuje na wczesnym etapie rozwoju PCOS