P R A C E O R Y G I N A L N E ginekolog i a

Ginekol Pol. 2013, 84, 922-929

Markers of insulin resistance in perimenopausal women with endometrial pathology Wskaźniki insulinooporności u kobiet z patologią endometrium w wieku okołomenopauzalnym 2OJD.DFDOVND-DQVVHQ$JQLHV]ND5DMWDU&LRVHN$QGU]HM=PDF]\ĔVNL-DNXE:\URED Tomasz Milewicz, Magdalena Krzyczkowska-Sendrakowska, Józef Krzysiek Department of Gynecological Endocrinology, Jagiellonian University Medical College, Kraków, Poland

Abstract Objectives: To determine and compare the prevalence of insulin resistance and carbohydrate metabolism parameters in women with endometrial pathology. Material and Methods: 100 perimenopausal women with abnormal uterine bleeding and/or abnormal endometrium were included into the study. Hysteroscopy with biopsy was performed. The study population was divided into four groups according to histopathological results of the endometrium: non-atypical endometrial hyperplasia, endometrial polyp, endometrial cancer, and controls. Fasting glucose and insulin levels and OGTT, IR indexes, occurrence of diabetes, pre-diabetic state, overweight, obesity, and hypertension were assessed. Results: Insulin resistance was diagnosed in 41.0% of the patients. The prevalence of markers of insulin resistance increased to 57.1% in cases with confirmed endometrial pathology, compared to 31.8% in histologically normal endometrium (p57 μU/ml in case of hyperplasia and >61 μU/ml in endometrial polyps). Conclusion: Insulin resistance and carbohydrate metabolism disturbances are common in women with endometrial pathologies. In these patients there is clinical basis for recommending lifestyle modification (change of diet, more physical activity), or for introduction of pharmaceutical insulin-sensitizing agents.

Key words: HQGRPHWULDOSRO\S/ QRQDW\SLFDO HQGRPHWULDO K\SHUSODVLD / / HQGRPHWULDO FDQFHU / LQVXOLQ UHVLVWDQFH /

Corresponding author: Olga Kacalska-Janssen Department of Gynecological Endocrinology, Jagiellonian University Medical College, Kraków, Poland 31-501 Kraków, ul. Kopernika 23 tel. 12 4248570 / fax 12 4248571 e-mail: [email protected]

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Otrzymano: 11.06.2012 Zaakceptowano do druku: 30.09.2013

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Ginekol Pol. 2013, 84, 922-929

O R Y G I N A L N E g i n e kol og i a

Olga Kacalska-Janssen et al. Markers of insulin resistance in perimenopausal women with endometrial pathology.

Streszczenie Cel pracy: Ocena częstości występowania insulinooporności oraz zaburzeń węglowodanowych u kobiet z patologią endometrium. Materiał i metody: 100 pacjentek w wieku okołomenopauzalnym z patologicznymi krwawieniami z dróg rodnych i/lub poszerzonym endometrium w badaniu USG TV. U każdej pacjentki przeprowadzono badanie histeroskopowe z biopsją endometrium. Na podstawie oceny histopatologicznej endometrium badaną populację podzielono na 4 grupy pacjentek (rozrost endometrium bez atypii, polip endometrialny, rak endometrium, grupa kontrolna). U pacjentek oznaczono stężenia glukozy i insuliny na czczo oraz wykonano OGTT, określono wskaźniki insulinooporności, oceniono występowanie cukrzycy, stanu przedcukrzycowego, nadwagi, otyłości, nadciśnienia tętniczego. Wyniki: Insulinooporność stwierdzono u 41,0% pacjentek. Częstość nieprawidłowych markerów insulinooporności wzrasta do 57,1% w przypadkach histopatologicznie potwierdzonej patologii endometrium w porównaniu do 31,8% z prawidłowym endometrium (p@ ,W is esWimaWed WKaW - of endomeWrial cancers deYeloS dXe Wo endocrine-meWaEolic disorders >, @ TKere is accXmXlaWing eYidence WKaW KySerinsXlinemia is associaWed wiWK carcinogenesis >@ and WKaW KySerinsXlinemia and insXlin resisWance are associaWed wiWK a more aggressiYe coXrse of endomeWrial cancer >, @ MaMor modi¿aEle deWerminanWs of insXlin resisWance, sXcK as oEesiWy and SKysical inacWiYiWy, KaYe also Eeen sKown Wo consWiWXWe risk facWors for endomeWrial cancer >-@ ([cessiYe faW consXmSWion and oYerweigKW are imSorWanW risk facWors SresenW in almosW  of women wiWK endomeWrial cancer risk ,n SremenoSaXsal women, oYerweigKW may lead Wo insXlin resisWance, oYarian androgen e[cess, anoYXlaWion and cKronic SrogesWerone de¿ciency +oweYer, in SosWmenoSaXsal women iW caXses KigKer circXlaWing concenWraWions of EioaYailaEle esWrogens from e[WraglandXlar conYersion of androgens +igKer leYels of esWrogens sWimXlaWe endomeWrial-cell SroliferaWion, inKiEiW iWs aSoSWosis and SromoWe angiogenesis >@ $ %M, aEoYe  kgmð doXEles a woman¶s risk of endomeWrial cancer, and a %M, aEoYe  kgmð WriSles WKe risk >@ SXcK endomeWrial lesions as aWySical KySerSlasia are sWrongly relaWed Wo cancer deYeloSmenW, wKereas oWKers like endomeWrial SolySs or non-aWySical KySerSlasia are raWKer of Eenign naWXre wiWK carcinogenesis noW e[ceeding - 1eYerWKeless, all WKese endomeWrial cKanges reSresenW differenW forms of endomeWrial SroliferaWion >@

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MXcK Kas Eeen said aEoXW WKe relaWionsKiS EeWween carEoKydraWe meWaEolism and endomeWrial cancer risk in Seriand SosWmenoSaXsal women, EXW mXcK less aEoXW WKe correlaWion EeWween insXlin resisWance and endomeWrial SolySs >, , @

Objectives To deWermine and comSare WKe SreYalence of insXlin resisWance and carEoKydraWe meWaEolism SarameWers in Seri- and SosWmenoSaXsal women sXEmiWWed Wo KysWeroscoSic e[aminaWion wiWK endomeWrial EioSsy dXe Wo sXsSecWed endomeWrial SaWKology

Material and methods  Seri- and SosWmenoSaXsal women wiWK aEnormal XWerine Eleedings andor aEnormal endomeWriXm on WransYaginal XlWrasoXnd !mm in SosWmenoSaXsal women and in sWill mensWrXaWing SaWienWs EeWween - day of WKe cycle , admiWWed Wo WKe 'eSarWmenW of *ynecological (ndocrinology, Medical &ollege, Jagiellonian 8niYersiWy, &racow, 3oland EeWween $Sril  and $Sril , XnderwenW a KysWeroscoSic e[aminaWion 'iagnosWic KysWeroscoSy was Serformed in eacK SaWienW Xsing a µsize ¶ KysWeroscoSe Eased on a  mm WelescoSe Karl SWorz, *ermany  TKe KysWeroscoSe is cKaracWerized Ey conWinXoXs-Àow sKeaWK wiWK an oYal Sro¿le and a WoWal diameWer of  mm 1o anesWKesia was reTXired owing Wo WKe YaginoscoSic aSSroacK wiWKoXW sSecXlXm or WenacXlXm Ey %eWWoccKi meWKod $  saline was used as distention medium. 3atients witK endometrial SolySs diagnosed Ey KysteroscoSy were referred for KysteroscoSic SolyS resection witK suEseTuent curettage in a surgical setting under general anesthesia. The remaining Satients without endometrial SolyS were Tuali¿ed for

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Olga Kacalska-Janssen et al. Markers of insulin resistance in perimenopausal women with endometrial pathology.

suEseTuent dilation curettage under general anesthesia in order to oEtain sSecimens for histoSathological e[amination. The material from Eoth Srocedures was sent to the 'eSartment of 3athomorShology of Medical &ollege, Jagiellonian 8niYersity, &racow, for histoSathological e[amination. ,n each Satient the oral glucose tolerance test 2*TT was assessed ± glucose and insulin leYels fasting,  and  minutes after a g glucose load . 'emograShic characteristics and data on diaEetes, hySertension and menoSausal status were collected, and anthroSometric Sarameters were analyzed. :omen were considered SostmenoSausal when there had Eeen at least  consecutiYe months of amenorrhea >@. 2Yerweight was de¿ned as %M, Eetween ., oEesity when %M, • >@. 'iaEetes was diagnosed according to the $merican 'iaEetes $ssociation recommendations fasting glucose • . mmoll  measurements andor ¶ Sost-load glucose in 2*TT • . mmoll >@. 3rediaEetes was de¿ned as imSaired fasting glucose ,)* ± fasting glucose .-. mmoll andor imSaired glucose tolerance ,*T ± ¶ Sost-load glucose in 2*TT .. mmoll >@. The formula descriEed Ey Matthews et al. fasting glucose >mmol/@ î fasting insulin >ȝ8m/@ . was used for +2M$ inde[ >@. /ocal ethical committee aSSroYal was oEtained for the trial. ,n the SaSer seYeral statistical tests were used. 3roSortion tests were used to check the signi¿cance of differences Eetween the freTuency of symStoms oEserYed in the grouSs of Satients. The strength of the relationshiS Eetween the YariaEles like glucose leYels, insulin leYels, +2M$ inde[ and age was estimated Ey non-Sarametric correlation analysis SSearman . Mann-:hitney and Kruskal-:allis tests were used to inYestigate the differences of mean Yalues Eetween the grouSs of Satients. 52& curYes were used to determine the cut-off Soints of the e[amined Sarameters for sSeci¿c endometrial Sathology and S  . was considered as statistically signi¿cant. The statistical analysis was Serformed with the use of a commercial software Srogram ± StatSoft, ,nc.  ST$T,ST,&$ data analysis software system , Yersion .. www.statsoft.com.

Results 2ut of  women included into the study, four grouSs of Satients were selected according to the result of the histoSathological e[amination ± non-atySical endometrial hySerSlasia 1$+ ± n   hySerSlasia simSle[,  hySerSlasia comSle[ , ± endometrial SolySs (3 ± n , ± endometrioid endometrial cancer (& ± n , ± histoSathologically normal endometrium ± the control grouS & ± n . TaEles , and ,, show Satient characteristics with regard to the measured Sarameters. 3atients with endometrial SolySs and endometrial cancer were signi¿cantly older than Satients with endometrial hySerSlasia and controls resSectiYely, .“. yrs and .“. yrs Ys. . “. yrs and . “. yrs TaEle , . 3atients in all  grouSs did not differ in weight and %M, Eut, imSortantly, the maMority of Satients in each grouS . ±  were classi¿ed either as oEese or oYerweight TaEle ,, TaEle ,, .

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There was no signi¿cant difference in the occurrence of hySertension, SrediaEetes, SrediaEetes  diaEetes, oEesity, oYerweight, oEesity  oYerweight Eetween the grouSs. TySe  diaEetes occurred more freTuently in Satients with (&  and (3 . than in controls . . 1eYertheless, it is necessary to mention that although these results were statistically signi¿cant, the numEer of the Satients with tySe  'M was Yery small  Satients in the (3 and  in the (& grouSs TaEle ,, . 2*TT test results demonstrated differences in mean serum fasting glucose leYels Eetween the (3 .“. or (& .“. and the control grouS .“. TaE. ,,, . These differences were SroEaEly related to the age difference Eetween the grouSs due to the signi¿cant correlation Eetween age and glucose leYels r . S. in the e[amined SoSulation TaE. ,9 . Signi¿cant differences in mean insulin leYels at  minutes after the glucose load Eetween 1$+, (3 and the control grouS .“. and .“. Ys. . “. were found TaE.,,, . ,mSortantly, no correlation Eetween insulin leYels and Satient age was found TaEle ,9 . +2M$ inde[ was higher in the (3 grouS when comSared to the control grouS .“. Ys. .“. TaEle 9 . 'ue to the fact that Satients with (3 were older than controls, the correlation Eetween age and +2M$ in the e[amined SoSulation was checked. 1o correlation Eetween the Sarameters was found TaEle ,9 . 3reYalence of at least one of insulin resistance markers insulin ¶ ! —8ml, insulin ¶ ! —8ml, +2M$ • ., was seen more often in Satients with (& and (3 comSaring to the control grouS  and ., resSectiYely Ys. . . 3reYalence of one of these markers was oEserYed in . of the women with endometrial hySerSlasia, Eut in that case the difference did not reach statistical signi¿cance. ,ncreased fasting insulin leYels ! —8ml occurred signi¿cantly more often in the (& Satients when comSared to the control grouS  Ys.  . ,ncreased insulin leYels at  minutes after a g glucose load aEoYe —8ml occurred more freTuently in 1$+ Satients than in controls . Ys. . . +2M$ inde[ • . was oEserYed more often in (& and (3 Satients comSared to the control grouS resSectiYely,  and . Ys. . TaEle 9, . 52& curYes were imSlemented to check if there were any cut-off Soints, aEoYe which the endometrial Sathology can Ee seen more often. ,n case of insulin leYels  minutes after the glucose load, 52& curYe showed discrimination aEility Eetween the 1$+ grouS and the control grouS for Yalue . —8ml with sensitiYity . and sSeci¿city  )ig.  . . of controls and . of the 1$+ Satients had serum insulin ¶ leYels . —8ml S . . ,n case of insulin leYels at  minutes after the glucose load, the 52& curYe showed discrimination aEility Eetween the 1$+ grouS and the control grouS for Yalue . —8ml with sensitiYity . and sSeci¿city . )ig.  . . of controls and . of the 1$+ Satients had serum insulin ¶ leYels . —8ml S , . MoreoYer, in case of insulin leYels at  minutes after the glucose load, the 52& curYe showed discrimination aEility Eetween the (3 grouS and the control grouS for Yalue . —8 ml with sensitiYity . and sSeci¿city . )ig. . . of controls and . of the (3 Satients had serum insulin ¶ leYels . —8ml S . .

© Polskie Towarzystwo Ginekologiczne

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P R A C E

Ginekol Pol. 2013, 84, 922-929

O R Y G I N A L N E g i n e kol og i a

Olga Kacalska-Janssen et al. Markers of insulin resistance in perimenopausal women with endometrial pathology.

Table I. Group characteristics (mean values with standard deviations) . &RQWUROV Q 

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© Polskie Towarzystwo Ginekologiczne

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P R A C E O R Y G I N A L N E ginekolog i a

Ginekol Pol. 2013, 84, 922-929

Olga Kacalska-Janssen et al. Markers of insulin resistance in perimenopausal women with endometrial pathology.

Table IV. Correlation between age and examined parameters within examined population. Współzależność wieku z wybranymi parametrami w całym materiale.

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Table V. Mean HOMA and QUICKI in examined groups of patients (mean values with standard deviations). Średnie wartości HOMA i QUICKI w poszczególnych grupach pacjentek (średnie wartości oznaczeń z odchyleniami standardowymi) &oQtroOV Q 

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There is eYidence suggesting that endometrial neoSlasia Eefore menoSause is related esSecially to Srogesterone de¿ciency, as we can oEserYe in women with chronic anoYulatory cycles like in the Solycystic oYary syndrome, while after the menoSause the cancer risk is directly related to estrogen leYels >, @. (ndometrial hySerSlasia, an oYergrowth or thickening of the uterine lining, can Ee the ¿rst warning sign of a Sathological Srocess, eYentually leading to endometrial carcinoma >@. The maMority of endometrial hySerSlasia cases regress sSontaneously >@. ,n the case of non-atySical simSle endometrial hySerSlasia, only  Srogresses to carcinoma. $tySical comSle[ endometrial hySerSlasia, the lesion with the highest neoSlastic Sotential,

© Polskie Towarzystwo Ginekologiczne

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Ginekol Pol. 2013, 84, 922-929

O R Y G I N A L N E g i n e kol og i a

Olga Kacalska-Janssen et al. Markers of insulin resistance in perimenopausal women with endometrial pathology.

Srogresses to carcinoma in  of Satients >@. 5isk factors for endometrial hySerSlasia are similar to those found to Ee associated with endometrial cancer. 2Eesity is a Sredominant risk factor for endometrial hySerSlasia in younger women >@. $ recent study concluded that high education, oEesity, diaEetes and hormone reSlacement theraSy increase the risk of endometrial hySerSlasia >@. (ndometrial SolySs are Eenign oYergrowths of endometrial tissue containing endometrial glands in a ¿Erous stroma >@. (ndometrial SolySs are Yery common. Studies reSorted that they can Ee found in aSSro[imately - of the general female SoSulation >@. 3olySs occur most commonly in women Eetween the ages of  and  years >, @. ,ncreasing age is associated with an increased risk that SolySs are Sremalignant or malignant >@. Studies reSort an incidence of malignancy from . to . within endometrial SolySs, with most studies recording an incidence around  >, @. The etiology of endometrial SolySs remains unclear. Three central causes of endometrial SolySs haYe Eeen suggested ‡ 3olySs are local outgrowths of the Easalis endometrium ± Eecause Easalis cells resSond to estrogen, Eut not Srogesterone, SolySs are stimulated to undergo hySerSlasia, Eut could Ee resistant to the antiSroliferatiYe effects of Srogesterone. ‡ 3olySs form in resSonse to an imEalance of estrogen and Srogesterone receStors. ‡ 3olySs are a Sroduct of genetic mutations that increase mitosis and decrease aSoStosis >@. SeYeral risk factors SredisSose women to deYeloSing endometrial SolySs. $ge, oEesity, hySertension, tamo[ifen, hormone reSlacement theraSy, anoYulation, endometriosis and age at menoSause haYe all Eeen associated with SolyS occurrence. Many of these risk factors are associated with eleYated estrogen leYels. ,t was hySothesized that estrogens lead to the Sroduction of certain growth factors, which may Sromote SolyS growth >@. Some studies haYe tried to ¿nd an association Eetween diaEetes mellitus and endometrial SolySs growth, Eut so far they haYe not con¿rmed the inÀuence >, @. $ clinically imSortant fact is that - of women with aEnormal uterine Eleedings haYe SolySs >@. 3olySs account for aSSro[imately  of SostmenoSausal Eleeding >@. $lthough the chance of malignancy in case of non-atySical endometrial hySerSlasia or endometrial SolySs is Yery low, eYaluation of these Sathologies is still imSortant as they are freTuent ¿ndings in gynecological Sractice and reTuire further diagnostic steSs. :hen aEnormal uterine Eleeding is Sresent, the older the Satient, the higher the susSicion for endometrial Sathology. :hile SremenoSausal Eleedings can Ee managed conserYatiYely, any uterine Eleeding after menoSause must Ee inYestigated e[Seditiously as the risk of endometrial cancer is higher in that age grouS >@. Endometrial cancer has high incidence rates in the Western, industrially deYeloSed societies. ,n these countries, oEesity has Eeen associated with -to -fold increase in endometrial cancer risk in Eoth Sre- and SostmenoSausal women and has Eeen estimated to account for aEout  of endometrial cancer cases. $Sart from e[cess weight, eSidemiological eYidence suggests that lack of regular Shysical actiYity may also Ee a risk factor. $ maMor metaEolic link Eetween oEesity, lack of Shysical

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Figure 1. ROC curve for insulin 60’ – NAH vs Controls.

Figure 2. ROC curve for insulin 120’ – NAH vs Controls.

Figure 3. ROC curve for insulin 120’ – Polyp vs Controls.

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Ginekol Pol. 2013, 84, 922-929

Olga Kacalska-Janssen et al. Markers of insulin resistance in perimenopausal women with endometrial pathology.

actiYity and deYeloSment of oYarian androgen e[cess is chronic hySerinsulinemia. 2Eesity and Shysical inactiYity lead to insulin resistance, and increased fasting and non-fasting insulin leYels >,@. 2ther conditions characterized Ey insulin resistance and hySerinsulinemia, such as noninsulin-deSendent diaEetes mellitus and Solycystic oYary syndrome 3&2S , haYe also Eeen related to an increased endometrial cancer risk >, @. ,nsulin has Eeen shown to Sromote the growth of cancer cell lines in Yitro, including endometrial cancer cells >@. $lso, the role of insulin in Sathogenesis of endometrial cancer was shown in seYeral case-control studies. ,t has Eeen oEserYed that eleYated leYels of &-SeStide a marker of Sancreatic insulin secretion were related to an increase in endometrial cancer risk >, @. 2ther studies showed higher fasting and Sost-glucose challenge insulin in endometrial cancer Satients than in control grouSs >-@. ,nsulin, as the agent Slaying a role in Sathogenesis of endometrial cancer, may act through Yarious mechanisms ± ,nsulin can act as a growth factor, it can stimulate cell Sroliferation and inhiEit aSoStosis directly through insulin receStors >@. ± ,nsulin may increase ,*)-, EioactiYity in many tissues, including the endometrium, Ey down-regulating the synthesis of ,*)%3- >, @. ± ,n SostmenoSausal women insulin induces inhiEition of heSatic synthesis of se[ hormone-Einding gloEulin S+%* , which results in an increase in the free estradiol leYels >-@. ± ,n SremenoSausal women chronically eleYated insulin concentrations contriEute to oYarian androgen e[cess, which may cause chronic anoYulation and Srogesterone de¿ciency >@. ,n the Sresent study aEnormal markers of insulin resistance fasting insulin leYels ! —8ml, insulin at  minutes of 2*TT ! —8ml, +2M$ inde[ •. were found in . of women with histoSathologically con¿rmed endometrial Sathology when comSared to . with histologically normal endometrium S. . The freTuency of aEnormal markers of insulin resistance in women with non-atySical hySerSlasia was . S . comSared to the control grouS , whereas in case of Satients with endometrial SolySs it was . S . comSared to the control grouS . ,nterestingly, in the Sresented study there is relatiYely high Sercentage of insulin resistance in women with histoSathologically normal endometrium . . $ccording to data of the EuroSean *rouS for the study of ,nsulin 5esistance from , the SreYalence of insulin resistance in EuroSean &aucasian SoSulation was estimated at  >@. +igher SroSortion oEserYed in the conducted study is most SroEaEly the result of Srior selection of women, characterized Ey aEnormal uterine Eleedings andor aEnormal transYaginal ultrasound image. EleYated fasting insulin leYels ! —8ml were noticed in aSSro[.  of Satients with SolySs and  of Satients with hySerSlasia, Eut these results were not signi¿cant comSaring to the control grouS  . EleYated leYels of insulin at  minutes of 2*TT ! —8ml were noticed in aSSro[.  of Satients with hySerSlasia, which reached statistical signi¿cance when comSared to the control grouS . . EleYated +2M$ inde[ of •. was noticed in aSSro[. 

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of cases with non-atySical hySerSlasia ns and  of cases with endometrial SolySs, and in that last case it reached statistical signi¿cance when comSared to controls . . MoreoYer, mean Yalues of +2M$ inde[ were signi¿cantly higher in case of Satients with endometrial SolySs than in the control grouS. Women with endometrial SolySs were signi¿cantly older than controls, Eut 3earson correlation within the whole e[amined SoSulation did not show correlation of this inde[ with age. MoreoYer, according to one of the recent studies, age Ser se does not inÀuence insulin sensitiYity. ,nsulin resistance, often oEserYed in the elderly, results most SroEaEly from oEesity and lack of Shysical actiYity. 2n the other hand, insulin secretion, which is deSendent on age, decreases . Ser year in SeoSle with normal glucose tolerance, while in SeoSle with imSaired tolerance this Sercentage is twice as high >@. ,n our study,  out of  Satients with non-atySical endometrial hySerSlasia were diagnosed with tySe  diaEetes mellitus. What is interesting, frequent occurrence of this disease was oEserYed not only in Satients with endometrial cancer, Eut also with endometrial SolySs. 1eYertheless, as SreYious studies on large grouSs of Satients did not show a connection Eetween 'M and endometrial SolyS Sathogenesis >,@, and in our study 'M was diagnosed only in  Satients with endometrial SolyS, we should Ee careful when drawing conclusions. We did not oEserYe any signi¿cant differences in the Eody mass inde[ %M, among the four grouSs of Satients, Eut the mean Yalues of %M, in all grouSs corresSonded to e[cessed Eody weight. Mean Slasma glucose leYels were higher in Satients with endometrial cancer and endometrial SolySs, and the highest in the endometrial cancer Satients at  minutes after the glucose load. +oweYer, Eecause of more adYanced age of women in Eoth mentioned grouSs, these results cannot Ee taken into account. The literature reSorts that glucose tolerance decreases with age >@, and in our study weak, Eut SositiYe correlation Eetween glucose concentration and age was indeed oEserYed. ,mSortantly, no correlation Eetween insulin leYels and Satient age was found. Signi¿cant difference in mean serum insulin leYels at  minutes after the glucose load Eetween E3, 1$+ and the control grouS was found. %ased on the 52& curYe, the leYels of insulin at  minutes of 2*TT SroYed to Ee the most useful marker for Sredicting endometrial Sathology. ,n case of leYels e[ceeding - —8ml, we can e[Sect a higher risk of hySerSlasia or endometrial SolySs with sensitiYity of .-.  and sSeci¿city of ., S . and ., resSectiYely . The analysis of the 52& curYes SroYed also that insulin leYels at  minutes of 2*TT can Ee a Sredictor of endometrial hySerSlasia. ,n case of insulin leYels •. —8ml, measured one hour after the glucose intake, a higher risk of this tySe of endometrial Sathology can Ee e[Sected with sensitiYity of . and sSeci¿city of , S . . %ased on the conducted study, as well as the aEoYe mentioned literature, it can Ee concluded that hySerinsulinemia and insulin resistance are commonly found in women with endometrial hySerSlasia. +oweYer, interestingly, in our study insulin resistance markers were seen frequently also in Satients with endometrial SolySs. 2n the Easis of the oEtained results we could hySothesize that insulin can Slay a role not only in the Sathogenesis of endometrial hySerSlasia and endometrial cancer,

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P R A C E

Ginekol Pol. 2013, 84, 922-929

O R Y G I N A L N E g i n e kol og i a

Olga Kacalska-Janssen et al. Markers of insulin resistance in perimenopausal women with endometrial pathology.

Eut also endometrial SolySs. 3ossiEly, the same mechanisms of insulin action which are resSonsiEle for Sromoting the growth of cancer cells Slay a role in the Sathogenesis of endometrial SolySs.

Conclusions ,nsulin resistance and carEohydrate metaEolism disturEances are common in women with endometrial Sathology. ,n case of women with aEnormal insulin resistance markers, who e[Serience Sathological uterine Eleeding andor aEnormal endometrium in transYaginal ultrasound, there is clinical Easis for recommending modi¿cation of life style change of diet, more Shysical actiYity , or introduction of Sharmaceutical insulin-sensitizing agents, which additionally can haYe anti-SroliferatiYe effect on the endometrium. 1eYertheless, more studies on that suEMect are needed.

Oświadczenie autorów: 1. Olga Kacalska-Janssen – uzyskanie funduszy na realizację badań laboratoryjnych, współautor koncepcji i założeń pracy, zebranie materiału, autor tekstu pracy, przygotowanie manuskryptu i piśmiennictwa, analiza i interpretacja wyników, autor zgłaszający i odpowiedzialny za manuskrypt. 2. Agnieszka Rajtar-Ciosek – zebranie materiału, analiza i interpretacja wyników, pomoc w przygotowaniu manuskryptu. 3. Andrzej Zmaczyński – zebranie materiału, aktualizowanie bazy danych. 4. Tomasz Milewicz – zebranie materiału, korekta manuskryptu. 5. Magdalena Krzyczkowska-Sendrakowa – zebranie materiału, analiza i interpretacja wyników. 6. Józef Krzysiek – uzyskanie funduszy na realizację badań laboratoryjnych, współautor koncepcji i protokołu, analiza i interpretacja wyników, korekta i aktualizacja piśmiennictwa, ostateczna weryfikacja i akceptacja manuskryptu. Źródło finansowania: Część projektu finansowanego z grantu KBN nr 2P05C06530. Konflikt interesów: Autorzy nie zgłaszają konfliktu interesów oraz nie otrzymali żadnego wynagrodzenia związanego z powstawaniem pracy.

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