Povezanost estara ftalne kiseline i sindroma policističnih jajnika

Abstract

Uvod: Ftalati su vrsta endokrinih disruptora koji se široko koriste kao plastifikatori i rastvarači ali i kao aditivi brojim proizvodima koji se svakodnevno koriste. Prema dosadašnjim studijama na eksperimentalnim životinjama, ali i u humanoj populaciji, diestri ftalne kiseline utiču na reproduktivni sistem, učestvuju u nastanku insulinske rezistencije i gojaznosti. Sindrom policističnih ovarijuma (PCOS) je najčešći endokrinološki poremećaj reproduktivnog sistema žena u generativnom periodu. Insulinska rezistencija i centralna gojaznost, kao faktori kardiometaboličkog sindroma imaju značajnu ulogu u etiologiji PCOS. Ciljevi: Utvrditi prisustvo metabolita ftalne kiseline kod žena u reproduktivnom periodu u našoj sredini, kao i da li postoji povezanost ovih endokrinih disruptora sa antropometrijskim parametrima, parametrima glikoregulacije, lipidima i lipoproteinima seruma, gonadotropinima, polnim hormonima, leptinom i indeksima kardiometaboličkog rizika kod žena sa sindromom policističnih jajnika. Metode: Istraživanje je obuhvatalo 61 ženu sa sindromom policističnih jajnika koje su podeljene u dve podgrupe: 31 ispitanica sa PCOS i prisutnim ftalatnim metabolitima u urinu i 30 ispitanica sa PCOS bez ftalatnih metabolita u urinu. Kontrolnu grupu je činilo 30 zdravih žena. Kod svih ispitanica vršena su antropometrijska merenja (TV, TM, OS) i određivane vrednosti parametara glikoregulacije (glikemija i insulinemija, izačunat je HOMA index), lipidi i lipoproteini seruma (ukupan holesterol, trigliceridi, LDL i HDL holesterol), gonadotropini (LH i FSH), polni hormoni (estradiol i testosteron) i leptin. U proceni kardiometaboličkog rizika korišćena su dva indeksa LAP i VAI. Iz jutarnjeg uzorka urina određivano je prisustvo i koncentracija 10 ftalatnih metabolita: Mono-metil ftalat- MMP, Mono-etil ftalat - MEP, Mono-n-butil ftalat - MBP, Mono-n-propil ftalat- MPP, Mono-izo-amil ftalat - MiAP, Mono-n-amil ftalat - MnAP, Mono-cikloheksil ftalat - MCHP, Monobenzil ftalat- MBzP, Mono-(2-etilheksil) ftalat- MHEP, Mono-n-octil ftalat-MOP. Za statističku obradu podataka korišćeni su odgovarajući parametarski i neparametarski testovi. Rezultati: Kod 51 % ispitanica sa PCOS potvrđeno je prisustvo ftalatnih metabolita u urinu. Najzastupljeniji ftalatni metabolit je bio MEHP, zatim MEP, ali je potvrđeno i prisustvo MMP, MPP i MOP. Kod ispitanica sa PCOS su potvrđene statistički značajne korelacije između ukupnih ftalatnih metabolita i BMI, obima struka, glikemije, insulinemije, HOMA indeksa, ukupnog holesterola, triglicerida, LDL holesterola, leptina i testosterona. Analizom pojedinačnih ftalatnih metabolita utvrđene su pozitivne korelacije između MMP i obima struka, parametara glukoznog metabolizma, ukupnog holesterola, LDL holesterola, triglicerida, LAP i VAI indeksa. Zaključak: Kod žena sa PCOS u reproduktivnom periodu u našoj sredini je potvrđeno prisustvo ftalanih metabolita. Najviše koncentracije su verifikovane za MEHP i MEP, ukazujući na visoku ekspoziciju di-etilheksil ftalatu (DEHP) i di-etil ftalatu (DEP). Ukupni ftalati značajno povećavaju vrednosti parametara koje učestvuju u razvoju metaboličkog sindroma kod PCOS, ali i povećavaju kardiovaskularni rizik ovih bolesnica. Direktna, značajna veza je potvrđena između MMP i testosterona, parametara i indeksa kardiometaboličkog sindroma.

Introduction: Phthalates are a type of endocrine disruptor widely used as plasticizers and solvents but also as additives to many products that are used daily. According to previous studies in experimental animals, but also in the human population, phthalic diesters affect the reproductive system, participate in the onset of insulin resistance and obesity. Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of the reproductive system of women in the generative period. Insulin resistance and central obesity, as factors of cardiometabolic syndrome, have a significant role in the etiology of PCOS. Objectives: To determine the presence of phthalic acid metabolites in women in the reproductive period in our environment, and whether there is a connection between these endocrine disruptors with anthropometric parameters, glycoregulation parameters, lipids and serum lipoproteins, gonadotrophins, sex hormones, leptin and indexes of cardiometabolic risk in women with polycystic ovarian syndrome. Methods: The study included 61 women with polycystic ovarian syndrome divided into two subgroups: 31 subjects with PCOS and present phthalate metabolites in urine and 30 subjects with PCOS without phthalate metabolites in urine. The control group consisted of 30 healthy women. In all subjects, anthropometric measurements were carried out (TV, TM, WC) and the values of glycoregulation parameters (glycemia and insulinemia, HOMA index), lipids and serum lipoproteins (total cholesterol, triglycerides, LDL I HDL cholesterol), gonadotropins FSH), sex hormones (estradiol and testosterone) and leptin. In the assessment of cardiometabolic risk LAP and VAI indexes were determined. From the morning urine sample, the presence and concentration of 10 phthalate metabolites were determined: Mono-methyl phthalate-MMP, Mono-ethyl phthalate-MEP, Mono-n-butyl phthalate-MBF, Mono-n- propyl phthalate- MPP, Mono-iso-amyl phthalate – MiAP, Mono-n-amyl phthalate – MnAP, Mono-cyclohexyl phthalate-MCHP, Monobenzyl phthalate-MBzP, Mono- (2-ethylhexyl) phthalate-MHEP, Mono-n-octyl phthalate-MOP. For statistical data processing, appropriate parametric and non-parametric tests were used. Results: 51% of subjects with PCOS confirmed the presence of phthalate metabolites in urine. The most common phthalate metabolite was MEHP, then MEP, but the presence of MMP, MPP and MOP also was confirmed. In subjects with PCOS, a statistically significant correlations between total phthalate metabolites and BMI, waist circumference, glycemia, insulinemia, HOMA index, total cholesterol, triglyceride, LDL cholesterol, leptin and testosterone were confirmed. By analyzing individual phthalate metabolites, a positive correlations between MMP and waist circumference, glycoregulation parameters, total cholesterol, LDL cholesterol, triglyceride, testosterone and LAP and VAI index were determined. Conclusion: In women with PCOS in the reproductive period, the presence of phthalic metabolites in our environment was confirmed. The highest concentrations were verified for MEHP and MEP, indicating a high exposure of DEHP and DEP. Total phthalates significantly increase the values of parameters involved in the development of metabolic syndrome in PCOS, but also increase the cardiovascular risk of these patients. A direct, significant association was confirmed between MMP and testosterone, parameters and index of cardiometabolic syndrome.