Polycystic Ovary Syndrome: The Correlation Between Renal Doppler Ultrasound and Laboratory Parameters l

Transcription

1 e r Ar þ t ý r m Polycystic Ovry Syndrome: The Correltion Between Renl Doppler Ultrsound nd Lbortory Prmeters l n i j ri O O i g in Polikistik Over Sendromu: Lbortuvr Prmetreleri, Renl Doppler Ultrsonogrfi İlişkisi h c r s Re l Renl Doppler Ultrsonogrfi, Polikistik Over Sendromu / Renl Doppler Ultrsound, Polycystic Ovry Syndrome Elif Krdeli 1, Ayl Uckuyu 2, Fik Ceyln Ciftci 2, Erzt Toprk 2, Erdem Turhn 2, Emel Ozcimen 2, Emin Alp Niron 1 1 Deprtment of Rdiology, 2 Deprtment of Obstetrics nd Gynecology, Bskent University, Fculty of Medicine, Turkey Özet Amç: Tnsiyonu norml oln üreme çğındki polikistik over sendromlu (PKOS) kdınlrd sğ ve sol böbrek uzunluğu, prnkim klınlığı, renl rteriyel, venöz kn kımı ölçümlerinde frklılık olup olmdığını rştırmk. Gereç ve Yöntem: Rotterdm kriterlerine göre PKOS tnısı lmış 40 kdın olgu ve 36 sğlıklı kdın olgu çlışmy dhil edildi. Hormonl, biyokimysl nliz, renl Doppler ultrsonogrfi ypıldı, sğ ve sol böbrek uzunluğu, prnkim klınlığı, pik sistolik velosite (PSV), rezistiv indeks (RI),venöz impedns indeksi(vi), insülin rezistnsı, bozulmuş glikoz tolernsı, serum lipid konsntrsyonu rştırıldı. Student t testi ve person korelsyon testi isttistik nliz için kullnıldı. Bulgulr: Böbreklerin ölçümleri çısındn PKOS lu ve sğlıklı kdınlr rsınd frk yoktu. An renl rterin pik sistolik velositesi PKOS lu grupt dh düşüktü. An renl venöz impedns PKOS lu grupt kontrol grubundn dh yüksekti. An renl rezistif indeks PKOS lu grupt dh yüksekti, fkt isttistiksel olrk önemli değildi. Tüm olgulrı içeren bivrite nlizde, n böbrek uzunluğu, n prnkim klınlığı ölçümleri ile BMI, bel klç ornı, serum çlık glikoz, insülin, LDL, tirgliserit seviyeleri pozitif ilişkiliydi. Trtışm: Biz PKOS lu normotnsif üreme çğındki kdınlrd böbrek kn kımınd değişiklikler olduğunu bulduk. Bu bulgulr PKOS un uzun önem renl ve krdiyovsküler kompliksyonlrının sonucunu gösteriyor olbilir. Anhtr Kelimeler Doppler Ultrsonogrfi; Polikistik Over Sendromu Abstrct Aim: To investigte whether there is ltertion both right nd left kidney lenght, prenchyml thickness, renl rteril,venous blood flow mesurements in normotensive reproductive ge women with polycystic ovry syndrome (PCOS). Mteril nd Method: Forty women with PCOS ccording to Rotterdm criteri nd thirty-six helthy volunteers women were included in our study. Hormonl, biochemicl nlysis, renl Doppler ultrsonogrphy were performed nd were investigted in terms of both left nd right renl lenght, prenchyml thickness, pek systolic velocity (PSV), resistive index (RI), venous impednce index (VI), metbolic chrcteristics hving insulin resistnce, impired glucose tolernce, serum lipid concentrtion. The student t test nd person coreltion test were used for sttisticl nlysis. Results: The mesurements for kidneys were not different between women with PCOS nd helthy women. The pek systolic velocity of men renl rtery ws lower in PCOS group. The men renl venous impednce lso ws higher in PCOS group thn control group. The men renl resistive index ws slightly higher in PCOS but not sttisticl significnt. In bivrite coreltion nlyse including ll ptients, it ws seen tht BMI, WHR, level of serum fsting glucose, insulin, LDL, trigliserides were positively relted with men renl length nd men prenchyml thickness mesurements. Discussion: We found tht there ws ltertions kidney blood flow in normotensive reproductive ge women with PCOS. This findings my indicte results of long term renl nd crdiovsculr complictions of PCOS. Keywords Polycystic Ovry Syndrome; Renl Doppler Ultrsound DOI: /JCAM.3409 Received: Accepted: Published Online: Corresponding Author: Elif Krdeli, Deprtment of Rdiology, Bskent University, Fculty of Medicine, Adn, Turkey. T.: F.: E-Mil: [email protected] Journl of Clinicl nd Anlyticl Medicine 1

2 Introduction Polycystic ovry syndrome (PCOS) is one of the most common endocrinopthies in women of fertile ge nd ffects up to 6 7% of this popultion [1]. Using the Rotterdm consensus criteri could increse the prevlence of PCOS by t lest 65%. PCOS ccording to Rotterdm consensus criteri should be defined by the presence of t lest three to two (1- chronic novultion 2-clinicl nd/or biochemicl hyperndrogenism 3- polycystic ovries on ultrsound) with the exclusion of other ndrogen excess or relted disorders [2]. It hs been recognized tht PCOS is ssocited with metbolic bnormlities such s insulin resistnce, dyslipidemi, chronic low-grde inflmmtion, nd rteril hypertension[3]. Recently, most studies hve linked PCOS with potentilly incresed risk of crdiovsculr disese [4]. Hypertension hs high prevlence in womn with PCOS in the perimenopusl period. Metbolic disturbnces is expected to be less common in the phenotypiclly heterogenous group of PCOS ptients dignosed by Rotterdm criteri. Overll, of mjor concern is to wht extent the PCOS-relted metbolic bnormlities trnslte into incresed crdiovsculr (CV) morbidity nd mortlity in these women. Recent dt in postmenopusl women show tht PCOS is ssocited with n incresed rte of CV events, which is prtly independent of the presence of obesity, dibetes nd MS, nd prtly dependent on the degree of hyperndrogenemi [5] Thus, the burdens of CV risk conferred by PCOS nd by MS, respectively, pper to be not identicl, but dditive. PCOS emerges s n independent predictor of CV complictions fter menopuse. PCOS long term consequence led to hypertension, therosclerosis, proteinuri. It ws reported previously tht first finding of impred renl function ws vrince of renl hemodinmics [6]. As is known, B-mode ultrsonogrphy is stil first rdiologic method in the evlution of ntive renl dysfunction. Renl length, corticl thickness nd prenchyml echogenicity nd collecting system dilttion re exmined. In spite of these prmeters correlte well with hystopthology, usully, these vlues my help in ssesment disese chronicity rther thn hystopthology[7]. Since yers, renl Doppler sonogrphy hs been used primrily for the screening of renovsculr disese in ntive nd trnsplnt kidneys [8]. Doppler sonogrphy is nonivsive method of evlution of locl vsculr resistnce, such s resistnce index [RI). Especilly, renl RI vlues re useful for the ssesment of renl prenchyml dmge nd my provide relible prmeter of renl therosclerosis [9]. In ddition, RI vlues of intrrenl rteries gives informtion bout severity of trget orgn dmge in diseses s hypertension, dibetes mellitus nd chronic renl filure [10]. The purpose of the present cross sectionl cse-control study ws to compre between women with PCOS nd helthy control nd mke correltions the Doppler prmeters of renl rtery, the interlobr rteries, renl vein including synchronously obtined serum glucose, insulin, lipid levels, other prmeters. Mteril nd Method In this study, fter the evlution of medicl history, physicl / gynecologycl exmintion nd trnsvginlly ultrsonogrphy ws performed. The dignosis of PCOS ws mde ccording to the criteri of the Rotterdm ESHRE ASRM- sponsored PCOS consensus workshop group (2004) where 2 out of 3 criteri were present: 1- oligo nd/or novultion (menstrul cycle between dys or secondry menorrhe nd/or novultion); 2- clinic nd/or biochemicl signs of hyperndrogenism [Ferrimn-Gllwy modified score 8 nd/or cne, nd /or hyperndrogenemi: totl testosterone (T) >0,6 ng/ml (2 nmol/l); 3- polycystic ovries (PCO), identified by trnsvginl ultrsonogrphy (presence of 12 follicles in ech ovry, mesuring 2-9 mm in dimeter nd/or incresed ovrin volume>10cm³) [2]. This study ws pproved by Bskent University Institutionl Review Bord nd Ethics Committee (Project no: KA09/262) nd supported by Bskent University Reserch Fund. After receiving locl ethicl pprovl, written informed consent ws obtined from ll ptients before enrollment. Ptients hd no pregnncy. None of the ptients hd ny other chronic kidney, systemic, endocrin disese such s Type 2 Dibetes mellitus or hypertension, the bsis of clinicl history nd physicl exmintion, routine blood tests. None of the ptients hd phrmcologicl tretment for PCOS-relted disorders, including orl contrseptive, ntindogenic drugs, insulin sensitizer drugs, ntipltelet drugs. Smoking ptients were excluded. Clinic blood pressure (BP) mesurements were performed with mercury phygmomnometer. Ptients hving hypertension is defined s systolic BP greter thn 140 mm Hg nd/or distolic BP greter thn 90 mm Hg were not included in the study. Women hving previous history of kidney stone, kidney opertion, pregnncy induced hypertention were excluded. Ultrsonogrphy ws performed by 6,5mHz micro-convex trnsvginl probe (Voluson 730 Pro, Generl Electric Co,USA). Ultrsound exmintion ws crried out on second or thirth dy of nturl menses. Follicle which is smller thn 10mm dimeter ws countered. Antrl follicle count (AFC) were recorded totlly for both ovry. Hormone profile ( luteinizing hormone (LH), Totl testosterone, free tetosterone, tiroid stimuln hormone (TSH), insulin), nd biochemistry profile (Fsting Glucose, HDL, LDL, Triglyceride, OGTT (75g)) were performed on the sme dy with ultrsound evlution. Renl Doppler evlution ws lso performed on the sme dy with other procedurs. Anthropometric mesurements were obtined t the umbilicus (wist circumference) nd t the most prominent buttock level (hip circumference); their rtio (wist-to-hip rtio, WHR) ws considered s mesure of body ft distribution. Insulin resistnce ws clculted using the HOMA index. HOMA index ws clculted s: [fsting plsm insulin (μu/ml) fsting plsm glucose (mmol/l)]/ As we obtined glucose levels in g/dl, we hd to multiply our dt by to chnge them to mmol/l for the clcultion of HOMA index [11]. Lbortory Anlysis A blood venous smple ws obtined fter n overnight fsting to ssess biochemicl dt. Fsting glucose, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, nd triglyceride (TG) levels were mesured with originl kits using n Abbott-Aeroset utonlyzer (Chicgo, IL, USA). Serum levels of FSH, LH, insulin 2

3 were mesured by microprticle enzyme immunossy method (MEIA) in n AXSYM utonlyzer. Serum totl testosterone levels were mesured by solid-phse competetive chemiluminescent enzyme immunssy in n Immulite 2000 utonlyzer using BIODPC regents. Renl Doppler Ultrsonogrphy All ptients with polycystic overin syndrome nd helthy control subjects were exmined by B-mode nd duplex Doppler ultrsound using commercilly vlible colour doppler scnner (Sonoline Antres, Siemens, Germny) with 5 MHz convex probe. All exmintions were performed with the ptient in the fsting stte fter 30 minutes of rest. Both kidneys were scnned in ll women in the lterl decubitus position. All exmintions were performed by the sme rdiologist to void interobserver vribility. Corticl thickness nd long xis of kidney were meusured nd prenchym echogenicity ws determined. Doppler spectr were obtined from the rcute rteries t the corticomedullry junction. The Doppler ngle ws mintned between 30 nd 60 degrees to correct for the ngle between the xis of the bem nd the vessels. At lest three resistive index ( RI) mesurements were obtined in the lower pole, midportion, nd upper pole, then were verged for ech kidney t ech session. The pek systolic velocity nd resistive index ( RI) of both min renl rteries nd the pek venous flow signl nd lest flow signl of both min renl veins were clculted. Corticl thickness, echogenicity, nd intrrenl RI vlues, pek systolic velocity nd RI vlues of the min renl rtery, pek venous velocity nd lest venous velocity were recorded in ech of the kidney in ll ptients with polycystic overin syndrome nd helthy control subjects. Venous impednce index ws clculted s: (pek venous velocity- lest venous velocity) / pek venous velocity. Sttistics Sttisticl nlysis were performed using SPSS 10.0 (SPSS for Windows 10.0; Chicgo, IL, USA). Groups were compred using student t test. When prmetric tests were not pproprite, Mnn-Whitney U test ws used. For the nlysis of ctegoricl vribles, we used the χ2 test nd Fisher exct test, where vilble. Person s correltion nlysis ws used to test univrite reltions. A p vlue <0.05 ws considered significnt. Tble1. Anthropometricl chrcteristics of PCOS nd control group. chrcteristics PCOS group N:40 Men ±SD Control group N:36 Men ±SD P vlue Age (yer) 26,43±4,76 28,034,03±,117 BMI 28,93±6,73 29,03±3,56,855 Wist Circumference (cm) 84,85±13,81 82,83±7,04,635 Hip Circumference (cm) 108,35±14,50 107,53±9,43,868 WHR,78±,04,77±,03,768 Systolic BP (mmhg) 120,67±10,21 118,89±8,45,687 Distolic BP (mmhg) 81,56±4,59 79,34±5,13,876 Legend 1: BMI: Body mss index, WHR: Wist-to- hip rtio, BP: Blood pressure Tble 2. Clinic nd biochemicl chrcteristics of PCOS nd control group Chrcteristics PCOS group N:40 Men ±SD Control group N:36 Men ±SD P vlue Fsting Glucose (mg/dl) 93,93±6,02 91,42±6,69,092 Insulin (μu/ml) 10,72±4,36 9,29±3,57,122 HOMA index 2,45±,97 2,08±,82,077 Totl Testosterone (ng/ml),738±,30,54±,16,001 Free Testosterone (pg/ml) 1,58±,76 1,27±,68,056 HDL (mg/dl) 47,35±8,96 51,97±7,71,018 LDL (mg/dl) 108,53±24,68 120,06±18,7,024 Triglycerides (mg/dl) 116,65±59,34 109,47±37,61,527 TSH (μu/ml) 3,03±4,68 1,81±,50,110 LH (miu/ml) 8,80±5,71 4,70±1,11,000 CRP (mg/dl) 3,68±2,31 2,85±2,02,115 AFC 54,10±25,54 18,19±5,94,000 Hirsutism or cne (%) 34,2 5,3,000 Oligomenorrhe (%) 44,7 6,6,000 IGT (%) 2,6 9,2,082 Legend 2: Student t test, HOMA index, homeostsis model ssessment index: HDL: Highdensity lipoprotein, LDL: Low-density lipoprotein, TSH: thyroid-stimulting hormone, LH: (in second dy of cycle), CRP: c-rective protein, AFC: Antrl follicle count (in second dy of cycle), IGT: Impired glucose tolernce. Results There ws not significnt difference between PCOS nd control groups in terms of ge, body mss index (BMI), wist-to-hip rtio (WHR), systolic nd distolic blood pressure (BP) [Tble 1]. The rte of hirsutism/cne, oligomenorrhe, impired glucose tolernce (IGT) nd serum LH level nd ovrin AFC in second dy of cycle nd serum totl testorone were higher in with PCOS women thn control helty women [Tble 2]. 1- Kidneys size: There ws no difference between the right renl length (RRL) (107,1mm) nd the left renl length (LRL) (106,9mm). Both kidneys length were slightly lower (sttisticlly nonsignificnt) in PCOS women [Tble 3]. Both lengths correlted significntly nd positively with BMI, WHR, fsting glucose, insulin, HOMA, LDL. 2- Kidneys prenchyml thickness: Right nd left kidney prenchyml thickness hd similr ptterns (respectivelly 13,84mm nd 14,04mm). Both kidney prenchyml thickness lso hd no difference between two groups (Tble 3). Both kidney prenchyml thickness correlted significntly nd positively with BMI, fsting glucose, insulin, HOMA, trigliseride. 3- Kidney rteries PSV: There ws no difference between right nd left renl rteries PSV (respectivelly 94,8cm/sec; 95,7cm/ sec p>,05). In women with PCOS, verge renl PSV nd left renl PSV were significntly lower thn helty women (respectively p=,001, p=,015) (Tble 3). PSV correlted significntly nd negtively with insulin, HOMA [Tble 4]. 3- Kidney rteries RI: There ws no difference between right nd left renl rteries RI (respectivelly 0,636; 0,629 : p>,05). In women with PCOS, verge renl RI ws slightly higher thn helty women (sttisticlly unsignificnt) (p=,062). RI correlted significntly nd positively with insulin nd HOMA, negtively HDL (Tble 4). Men RI of upper, middle, bottom lobr renl rteries were not difference between two groups. 4- Venous impednce (VI) index: Right nd left kidney veins hd different impednce index (respectivelly 0,48; 0,41 p<,05). In women with PCOS, verge renl VI index nd left renl VI in- 3

4 dex were significntly higher thn helty women (respectively p=,009, p=,007) [Tble 3]. Tble 3. Comprison of rteril nd venous blood flow prmeters nd renl biometric mesurements right nd left kidney in PCOS nd control groups. Right Renl Length (mm) Left Renl Length (mm) Men Renl Length (mm) Right Prenchym Thickness (mm) Left Prenchym Thickness (mm) Men Prenchym Thickness (mm) PCOS group N:40 Men±SD Control group N:36 Men±SD 95% Confidence Intervl of the Difference P vlue 106,40±7,11 107,94±8,07-1,95-5,04, ,88±9,75 107,06±8,02-3,89-4,25, ,63±7,7 107,50±7,05-4,2-2,5,613 13,58±1,85 14,14±2,01 -,32-1,45,210 14,38±2,33 13,67±1,62-1,62-,20,127 13,97±1,4 13,90±1,6 -,63-,78,203 Right Renl RI,64±,06,62±,05 -,048-,003,089 Left Renl RI,64±,05,61±,05 -,044-,001,067 Men Renl RI,64±,04,62±,04 -,00049-,040,062 Right Renl PSV (cm/sec) Left Renl PSV (cm/sec) Men PSV (cm/ sec) Men Upper Men Middle Men Bottom Right Venous Impednce Index Left Venous Impednce İndex Men Venous Impednce Index 92,85±28,12 97,00±23,00-7,55-15,85,482 87,40±21,71 105,11±23,25 7,38-28,03,001 90,12±20,21 101,05±17,80-19,6- -2,24,015,58±,05,60±,03 -,038-,003,106,61±,05,62±,04 -,025-,018,770,62±,04,62±,03 -,021-,017,855,50±,17,47±,15 -,106-,043,410,46±,17,36±,15 -,180- -,308,007,48±,12,41±,09,017-,11,009 Legend 3: RI: Resistive index, PSV : Pek systolic velocity, Discussion PCOS is metbolic disorder which hve contrversil definition yet. PCOS my cover to the differ extends of the glucose nd lipid metbolism bnormlities. Obesity is common in PCOS nd ffects between 30 70% of women depending on the setting of the study nd the ethnicl bckground of the subjects. In Western society, incidence nd prevlns of overweight/obesity increse recently [12] Our popultion lso hve included lrge mount overweight women who hve verge BMI ws 29. The overweight/obesity led to impired glycemic control nd insulin resistnce. There is evidence concerning the reltionship between renl dysfunction nd crdiovsculr risk in non-dibetic ptients. Even minor renl dysfunction cuses drmtic increse in crdiovsculr risk. PCOS not only is reproductive endocrinopthy but, like the metbolic syndrome, is ssocited with longterm helth risks including insulin resistnce, dibetes mellitus, dyslipidemi, hypertension, nd premture therosclerosis [13]. Bsed on the prevlence of these risk fctors, PCOS ptients hve n estimted 4 11-fold incresed risk for coronry hert disese[14]. Epidemiologic studies hve documented tht dibetes nd hypertension re the mjor risk fctors for the development nd progression of chronic kidney disese (CKD)[15,16]. Chen et l suggested tht the insulin resistnce nd concomitnt hyperinsulinemi re presented in CKD ptients without clinicl dibetes [17]. They lso suggest tht even mildly elevted blood pressure (130/85 mm Hg) or serum glucose levels (110 mg/dl) re ssocited with n incresed risk for chronic kidney disese nd microlbuminuri [18]. In recent yers, dvnced ultrsonogrphy trnsducers hve led to inresed tissue informtion nd sptil nd contrst resolution. Consequently, these improvements simplified to evlution of renl ntomic detils s dimension, thickness nd echogenicity of the renl cortex. These morphologic prmeters re importnt, becuse ultrsonogrphy shows findings of irreversible renl prenchyml disese s decrese in renl size, prenchyml trophy, sclerosis nd fibrosis [7]. In ddition, it cn help to ssess prognosis nd void unnecessry dignostic or therpeutic procedures. Especilly, this rdiologic method show smller kidney with prenchyml trophy is dibetic nephropthy, the leding cuse of chronic nd end-stge renl filure in developed countries in recent yers [19]. To our knowledge, there is no study investigting renl size mesurements in women with PCOS. Wheres, the studies relted to the norml ultrsonogrphic mesurements of the kidney in dult volunteers hs been reported by Emmin SA et l [20]. They demonstrted tht renl dimensions nd prenchyml volume were correlted with ge, height, weight, body mss index, nd totl body re. Medin renl lengths were 11.2 cm on the left side nd 10.9 cm on the right side. Renl size decresed with ge, lmost entirely becuse of prenchyml reduction. Renl length decresed with ge nd the rte of decline ccelertes lter 60 yers of ge. Renl volume correlted best with totl body re. Renl length correlted best with body height [21]. It ws known tht there is trend both for the right nd left kidney longitudinl lengths to increse until reptoductive ge. Enmin et l demonstrted tht renl size unchnge in norml sitution. In our study, renl size, corticl echogenicity nd prenchyml thickness of ll kidneys were norml. There ws no difference between the right renl length (RRL) nd the left renl length (LRL). Both right nd left kidney length were slightly lower (sttisticlly nonsignificnt) in women with PCOS (Tble 3). Color Doppler ultrsonogrphy is noninvsive method for ssesment renl vsculr function. It meures blood flow velocity in the renl circultion within smll prenchyml rteries. The resistive index ( RI) shows vsculr resistnce nd increse of this vlue demonstrtes diseses of tubulointerstitil or vsculr system. As is known, RI is n ge-dependent prmeter. Bude et l showed tht RI in ptents older thn 60 yers tends to be higher thn in younger dults [22]. The pek systolic velocity (PSV) is direct proportionl with flow volume ( left ventricle bet volume). In ddition, PSV is inversely 4

5 proportionl with vsculr dimeter nd elsticity of blood vessel wll. The norml frequency spectrum presents the typicl form of flow pulse, with low subsequent vsculr resistnce. In dults, the norml PSV is verge 120 ±12 cm/sec ( cm/sec) nd the end-distolic flow velocity is cm/ s [8,23]. The kidneys offer low resistnce vsculr bed, thus the Doppler spectrl wveform from the norml kidney is tht of constnt forwrd distolic flow. In renl prenchyml disese, there is increse vsculr resistnce which in turn cuses decrese in the distolic flow component nd incresed pulstility of the Doppler spectrl wveform. Prenchyml distolic flow velocities less thn 20 per cent of the pek systolic velocity re consistent with renl prenchyml disese. In renl rtery stenosis, the PSV shows n increse of more thn 150cm/sec. When vsculr resistnce is low, pek systolic velocity nd pek flow volume increse with incresing blood pressure. Spontneous vritions in subject s systolic blood pressure were positively correlted with pek systolic volume nd pek flow volume. Low resistnce flow is blood pressure dependent [24]. Decresed PSV could show incesed vsculr resistnce. We found the lower PSV in PCOS women. Color doppler ultrsound shows renl vsculr resistnce using RI vlue, which corresponds to pek systolic velocity minus enddistolic velocity divided by pek systolic velocity. The RI vlues re clculted in the segmentl, interlobr, nd rcute rteries, these vlues re normlly below 0.70 except significntly higher in elderly persons nd in those younger thn 6 yers [24]. The effects of vrition in vessel ngultion nd size re nullified in the clcultion of these indexes [25]. Vrious bnorml wveforms my be compred by clculting the RI nd PI. Physiologic events tht lter vsculr resistnce nd thus ffect wveforms include exercise, chnges in grvity orienttion nd stress level, nd digestion [25]. Chnges in the intrrenl rteril RI vlues re ssocited with diseses s urinry obstruction, vrious renl disorders, renl vsculr disese, renl scrring. The RI provides informtion bout rteril impednce. The pressure differentil between the systole nd distole ws shown to be mjor fctor influencing RI, long with the vsculr complince nd the cross-sectionl re of the downstrem vsculr bed [26]. In our study, there ws no difference between RI vlues of right nd left renl rteries (respectivelly 0,636; 0,629 : p>,05). In women with PCOS, verge renl RI ws slightly higher thn helty women (sttisticlly unsignificnt) (p=,062). RI correlted Tble 4. Coreltions of renl blood flow prmeters with biochemicl nd clinic chrcteristics in ll ptients. Men Renl Length Men Prenchym Thickness Men Renl Artery PSV Men Renl Men Upper Men Middle Men Bottom BMI r,365(**),378(**) -,063,150,185,104,075,053 p,001,001,589,197,110,372,521,651 WHR r,292(*),047,029 -,149 -,293(*) -,341(**) -,127 -,035 Fsting Glucose (mg/dl) p,010,687,803,198,010,003,275,762 r,316(**),281(*),032 -,054 -,053,021,267(*),022 p,005,014,784,641,646,857,020,850 Insulin (μu/ml) r,214,239(*) -,375(**),508(**),252(*),278(*),304(**),139 p,063,037,001,000,028,015,008,231 HOMA index r,269(*),282(*) -,355(**),475(**),230(*),251(*),325(**),149 p,019,014,002,000,046,029,004,200 HDL (mg/dl) r -,079 -,015,053 -,290(*) -,298(**) -,168 -,090 -,033 p,498,897,650,011,009,147,440,777 LDL (mg/dl) r,483(**),012,094,113,154,113,264(*) -,037 Triglycerides (mg/dl) Men Renl Length Men Prenchym Thickness Men Renl Artery PSV Men Renl Men Upper Men Middle Men Bottom p,000,920,420,330,183,332,021,752 r,170,191,087 -,057,066,128,147 -,179 p,141,098,453,622,569,270,206,122 r,477(**),179,087,035,178,279(*),059 p,000,121,455,767,125,015,610 r 1,111 -,024,069,200,068 -,064 p,341,834,554,083,560,581 Men Venous Impednce Index r 1 -,400(**) -,047 -,108 -,141 -,502(**) p,000,690,353,225,000 r 1,518(**),396(**),349(**),200 p,000,000,002,084 r 1,612(**),439(**),034 p,000,000,772 r 1,674(**),148 p,000,201 r 1,237(*) p,039 Legend: RI: Resistive index, HOMA index, homeostsis model ssessment index: HDL: High-density lipoprotein, LDL: Low-density lipoprotein. 5

6 significntly nd positively with insulin nd HOMA, negtively HDL (Tble 4). Men RI of upper, middle, bottom lobr renl rteries were not difference between two groups. We thought tht higher RI vlues in women with PCOS might be indicte erly period of therosclerosis. Especilly, reltionship between RI nd insulin vlues my be importnt to determine mild vsculr chnges. The verge flow velocity (Vmen) vlues of renl vein re given in the literture s cm/ s. The flow in the renl veins is generlly continuous, but mild fluctutions my be seen s reflection of respirtion nd right tril contrction [27]. The flow pttern in intrrenl veins depends on renl prenchyml histology nd crdic physiology. The intrrenl venous impednce index obtined by Doppler ultrsound is relted to complince in vein, nd cn be helpful in the ssessment of renl prenchyml complince. renl hemodynmics. Microlbuminuri nd reduced glomerulr filtrtion rte (GFR) re two different spects of renl dysfunction. It is known tht renl hemodynmics ssocited with microlbuminuri nd reduced GFR [6]. We did not investigted to linked with renl hemodynmics nd renl biometry in this study. Potentil limittions of our study should be noted. First, the cross-sectionl study design mkes it difficult to infer cuslity between the PCOS nd risk for chronic kidney disese. Second, study popultion were heterogen in terms of ge, BMI (both obes nd len), hving insulin resistnce. If it is creted ptient subgroup with obesity nd insulin resistnce ptient, It could obtin whether cuses of hemodynmic ltertions re PCOS or insülin resistnce. It ws suggested by Chen tht the metbolic syndrome nd insulin resistnce might be n importnt fctor in the cuse of chronic kidney disese nd microlbuminuri [18]. Third, in our study, it is indeterminte ptient to wht extent period with PCOS. As renl nd vsculr effect consist during long term period, our findings my be wek thn expected relly. Fourth, the disdvntges of renl doppler ultrsound include decresed relibility in ptient who is not fsting nd/ or is obese, high level of opertor dependence, nd poor detil resolution. But, renl doppler ultrsound exmintion ws done by one rdiologist for decrese of these disdvntges. Another limittion of our study is tht we did not investigte the wveform in the inferior ven cv which might likely be ltered nd ffect the intrrenl venous wveform. In conclude, we suggested tht there ws ltertions especilly kidney blood flow in normotensive reproductive ge women with PCOS. This findings my explin to results of long term renl nd vsculr complictions of PCOS. However, further study with wider selected subgroups is required. Competing interests The uthors declre tht they hve no competing interests. References 1. Azziz R, Woods KS, Reyn R, Key TJ, Knochenhuer ES, Yildiz BO. The prevlence nd fetures of the polycystic ovry syndrome in n unselected popultion. 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