The effect of exogenous estrogen on the luteal and follicular phases in clomiphene citrate stimulated cycles

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2 Balat Ö, et al. The effect of exogenous estogen on the luteal and follicula phases Klomifen sitat oal olaak aktif, östojenik ve antiöstojenik özelliklei olan non-steoidal bi DMDQGÕU (VDV RODUDN NORPLIHQ VLWUDW FLV (zuklomifen) %38 ve tans (enklomifen) %62 gibi LNL D\UÕ L]RPHULQ ELOHúLPLQGHQ ROXúXU.ORPLIHQ VLWUDW RYXODV\RQ LQG NVL\RQX DPDFÕ\OD orn \D\JÕQ RODUDN NXOODQÕOPDVÕQD NDUúÕQ RYXODV\RQ RUDQÕ LOH JHEHOLN RUDQÕ DUDVÕQGD EHOLUJLQ ELU IDUN gözleni. Klomifen sitat ile elde edilen ovulasyon RUDQÕ LOH JHEHOLN RUDQÕ DUDVÕQGDNL beligin fak; klomifen sitat ile indüklenen VLNOXVODUGD VHUYLNDO PXNXV NDOLWHVLQLQ G ú N ROPDVÕQD DUWPÕú OXWHDO \HWPH]OLN RUDQÕ VXENOLQLN JHEHOLN ND\ÕSODUÕ YH LQG NOHQPLú RRVLWOHUGH ROXúDQ NURPR]RPDO DEHUDV\RQODU LOH DoÕNODQPD\D odoõúõoõu.orplihq VLWUDWÕQ VHUXP /+ G ]H\OHULQL IROOLN OHU ID]GD DUWÕUGÕ Õ YH EXQXQ VRQXFX RODUDN seum andojen düzeyleinde göeceli olaak bi DUWÕú ROGX X ELOLQHQ ELU JHUoHNWLU 1RUPDO VLNOXVODUGD IROOLN OHU ID]GD HQGRPHWULDO NDOÕQOÕNGD YH XWHULQ YRO PGH DQODPOÕ ELU DUWÕú J ]OHQLU %X DUWÕúÕQ RYXODV\RQD \DNÕQ G QHPGH EHOLUJLQ ROGX X YH EXQXQ VHUXP VWUDGLRO G ]H\OHUL LOH DQODPOÕ ELU NRUHODV\RQ J VWHUGL L ELOLQPHNWHGLU.ORPLIHQ LOH LQG NOHQPLú VLNOXVODUGD IROOLN OHU ID]GDNL DUWPÕú VHUXP ( G ]H\OHULQH NDUúÕQ HQGRPHWULDO NDOÕQOÕNGD ve utein volumde beligin bi azalma gözleni (12). %X D]DOPD NORPLIHQ VLWUDWÕQ DQWL VWURMHQLN HWNLVL\OH DoÕNODQÕU %HQ]HU ROXPVX] HWNLOHU OXWHDO ID]GD GD J ]OHQLU.ORPLIHQ VLWUDWÕQ IROOLN OHU YH OXWHDO ID]GDNL ROXPVX] HWNLVLQL QOHPHN DPDFÕ\OD eksojen östojen tedavisi öneilmektedi %L] EX odoõúpdpõ]gd NORPLIHQ VLWUDW LOH LQG NOHQPLú VLNOXVODUGD LODYH RODUDN YHULOHQ konjuge östojenin, folliküle ve luteal faz faz etkileini inceleyeek, konjuge östojenlein NORPLIHQ VLWUDW LOH UXWLQ RODUDN NXOODQÕOPDVÕQÕQ EDúDUÕ RUDQÕQÕ DUWÕUÕS DUWÕUPDGÕ ÕQÕ DUDúWÕUGÕN MATERYAL METOD %X odoõúpd 0D\ÕV hqlyhuvlwhvl 7ÕS )DN OWHVL.DGÕQ +DVWDOÕNODUÕ YH 'R XP $QDELOLP 'DOÕ WDUDIÕQGDQ L]OHQPHNWH RODQ RYXODWXDU GLVIRQNVL\RQX RODQ WRSODP KDVWDGD \DSÕOGÕ %X KDVWDQÕQ pime infetilite, 14 hasta ise sekonde infetilite WDQÕVÕ DOPÕú YH EXQODUÕQ LQGH DQRYXODV\RQ XQGD ROLJRRYXOD\RQ VDSWDQPÕúWÕU KDVWDGD && LOH RYXODV\RQ LQG NVL\RQX SODQODQGÕ YH RYXODV\RQ LQG NVL\RQXQGDQ QFH W P KDVWDODUÕQ ODERUDWXYDU YH IL]LN PXD\HQH LúOHPOHUL WDPDPODQGÕ 7 P KDVWDODUÕQ WHGDYLGHQ QFH KRUPRQ SURILOL oõnduõogõ 6HUXP Follikül stimulan homon (FSH), Luteinizan homon (LH), Östadiol (E2), Pogesteon (P), Polaktin (P), Testosteon (T), Dehidoepiandosteonsulfat (DHEAS) düzeylei genelde menstuasyonun 21. J Q QGH VDSWDQGÕ 7URLG GLVIRQNVL\RQX YH hipepolaktinemisi olan anovulatua hastala odoõúpd\d DOÕQPDGÕ ddoõúpd\d DOÕQDQ KDVWDODUÕPÕ] VDGHFH ELU VLNOXV LoLQ GH HUOHQGLULGL KDVWDQÕQ QH \DOQÕ]FD && YHULOGL GL HU KDVWD\D LVH &&NRQMXJH VWURMHQ YHULOGL +DVWDODUÕQ KHUELULQH VSRQWDQ YH\D LQG NVL\RQ VRQUDVÕ ROXúDQ DGHWOHULQLQ J QOHUL DUDVÕ ; PJ && YHULOGL ddoõúpd JUXEXQD LODYH RODUDN VLNOXVXQ J QOHUL DUDVÕ mg konjuge östojen (Pemain) veildi. Klomifen sitat ile ovulasyon indüksiyonu \DSÕODQ KDVWDODU J Q DúÕUÕ VHUXP ( YH RYDULDQ follikülometi, 21. gün seum pogesteon, 14.gün seum T ve E2, ve 26.gün endometial biopsi Oo POHUL\OH L]OHQGL ddoõúpd YH NRQWURO JUXSODUÕQGD elde edilen sonuçla istatistiksel veile, otalama ± VWDQGDUW KDWD úhnolqgh EHOLUWLOGL ddoõúpd YH NRQWURO JUXSODUÕQÕQ YHULOHUL DUDVÕQGDNL IDUNOÕOÕNODU VWXGHQWW testi ile incelendi. Veilein bibiilei ile olan ED ODQWÕODUÕ UHJUHV\RQ NRUHODV\RQ DQDOL]L NXOODQÕODUDN GH HUOHQGLULOGL BULGULAR 0D\ÕV hqlyhuvlwhvl 7ÕS )DN OWHVL.DGÕQ +DVWDOÕNODUÕ YH 'R XP $QDELOLP 'DOÕ WDUDIÕQGDQ L]OHQHQ DQRYXODV\RQOX ROJXGD \DSWÕ ÕPÕ] odoõúpdgd && LOH RYXODV\RQ LQG NVL\RQX \DSÕODQ KDVWDGD \Dú RUWDODPDVÕ ±3.97, bazal E2 GH HUOHULQLQ RUWDODPDVÕ ±33.2 pg/ml bulundu. CC+konjuge östojen tedavisi alan 24 DQRYXODV\RQOX KDVWDGD \Dú RUWDODPDVÕ ±4.37, ED]DO ( GH HUOHULQLQ RUWDODPDVÕ ±19.2 pg/ml VDSWDQGÕ ddoõúpd YH NRQWURO JUXSODUÕ DUDVÕQGD J Q Oo OHQ ( YH 7 VHUXP G ]H\OHUL DUDVÕQGD DQODPOÕ IDUNODU J ]OHQGL S 7DEOR ddoõúpd JUXEXQGD G ú N VHUXP 7 G ]H\OHUL YH \ NVHN VHUXP ( G ]H\OHUL VDSWDQGÕ ddoõúpd YH NRQWURO JUXSODUÕ DUDVÕQGD J Q SURJHVWHURQ G ]H\OHUL DoÕVÕQGDQ J U OHQ IDUN LVWDWLVWNVHO DoÕGDQ DQODPOÕ GH LOGL S! 7DEOR 1). Jounal of Tugut Özal Medical Cente 4(1):

3 .ORPLIHQ VLWUDW LOH LQG NOHQHQ VLNOXVODUGD HNVRMHQ VWURMHQ NXOODQÕPÕQÕQ «Ö. Balat ve ak. J Q HQGRPHWULDO EL\RSVL EXOJXODUÕ NDUúÕODúWÕUÕOGÕ ÕQGD RYXODWXDU ID] DoÕVÕQGDQ EHOLUJLQ ELU IDUNOÕOÕN J ]OHQGL DQFDN OXWHDO \HWPH]OLN RODUDN G ú Q OHQ ROJXODU DUDVÕQGD IDUNOÕOÕN J ]OHQPHGL (Tablo 2). J Q VHUXP 7 G ]H\OHUL LOH GL HU SDUDPHWUHOHU NDUúÕODúWÕUÕOGÕ ÕQGD LNL JUXS DUDVÕQGD LVWDWLVWLNVHO DoÕGDQ DQODPOÕ IDUNODU J ]OHQGL S 7DEOR 7RWDO KDVWD JUXEX LQFHOHQGL LQGH VHUXP 7 G ]H\OHUL LOH GL HU SDUDPHWUHOHU DUDVÕQGDNL NRUHODV\RQ LVWDWLNVHO RODUDN DQODPOÕ\GÕ S 7DEOR 7$57,ù0$ CC gubunda 14. gün seum T ve E2 düzeylei DUDVÕQGDNL LOLúNL gvwudglro IHUWLO \DúDPGD QHPOL ELU KRUPRQ olup, endometiumda gözlenen diekt mitotik etkisi \DQÕQGD SURJHVWHURQXQ DNWLYLWH J VWHUHELOPHVL LoLQ pogesteon eseptöleini indükleyeek indiekt etki J VWHULU.ORPLIHQ VLWUDWÕQ DQWL VWURMHQLN HWNLVL VWURMHQ UHVHSW UOHUL WDúÕ\DQ W P GRNXODUGD RUWD\D oõnpdvõqd NDUúÕQ UHPH IRNVL\RQX DoÕVÕQGDQ QHPOL ROPDVÕ QHGHQL\OH HQGRPHWULXP YH VHUYLNV ]HULQH HWNLVL orn EHOLUJLQGLU.ORPLIHQ VLWUDWÕQ IROOLN OHU faz süesince endometial ve utein büyümeye ROXPVX] HWNLVL ED]Õ odoõúpdodugd J VWHULOPLúWLU.ORPLIHQ VLWUDW LOH LQG NOHQPLú VLNOXVODUGD D]DOPÕú HQGRPHUWLDO NDOÕQOÕN YH XWHULQ YRO P && ÕQ Tablo 1. ddoõúpd YH NRQWURO JUXSODUÕ DUDVÕQGD S GH HUOHUL CC gubu (n:24) CC+E gubu (n:24) p 14. gün E2 (pg/ml) 403,2±67,2 624,3±51,4 < gün T (ng/ml) 68,7±27,1 41,3±19,7 < gün P (ng/ml) 9,6±7,1 13,1±8,4 >0.05 Tablo 2. (QGRPHWULDO EL\RSVL EXOJXODUÕ 26. gün endometial biyopsi CC gubu (n:24) CC+E gubu (n:24) 6D\Õ 6D\Õ Ovulatuva 16 / 66,7 19 / 79,2 Anovulatuva 8 / / 20.8 Tablo 3. && YH &&( JUXSODUÕ DUDVÕQGD J Q 7 GH HUOHUL LOH GL HU SDUDPHWUHOHU DUDVÕQGDNL LOLúNL CC Gubu (n:24) CC + E gubu (n:24) 14. gün E2 (pg/ml) gün P (ng/ml) CC gubunda 14. gün seum T düzeyi ile 21. gün SURJHVWHURQ DUDVÕQGDNL LOLúNL antiöstojenik etkisi ve luteal ganulosa K FUHOHULQGHQ D]DOPÕú SURJHVWHURQ UHWLPLQH ED OÕ RODELOLU %D]Õ odoõúpdodugd J VWHULOGL L JLEL && LOH LQG NOHQPLú VLNOXVODUGD IROOLN OHU ID]GD Tablo 4. 7RWDO ROJXODU LoLQ J Q 7 GH HUL LOH GL HU SDUDPHWUHOHU DUDVÕQGDNL LOLVNL p 14.gün E2 (pg/ml) 0.42 < gün P (ng/ml) 0.56 <0.05 CC+E gubunda 14. gün seum T ile E2 G ]H\OHUL DUDVÕQGDNL LOLúNL 86

4 Balat Ö, et al. The effect of exogenous estogen on the luteal and follicula phases DOÕQDQ HQGRPHWULDO EL\RSVL UQHNOHULQGH J ]OHQHQ HUNHQ VHNUHWXYDU GH LúLNOHU &&ÕQ HQGRPHWULXPGDNL GLUHNW HWNLVLQL J VWHUPHVL EDNÕPÕQGDQ orn QHPOLGLU %X QHGHQOH && LOH LQG NVL\RQ \DSÕODQ KDVWDODUD HNVRMHQ VWURMHQOHUÕQ YHULOPHVL QHULOPHNWHGLU <DJHO YH DUNDGDúODUÕQÕQ \DSWÕ Õ odoõúpdgd HWLQLO VWUDGLRO Q (( HQGRPHWULXP NDOÕQOÕN YH XWHULQ YRO P ]HULQH HWNLVL DUDúWÕUÕOPÕúWÕU %X odoõúpdgd VLNOXVXQ J QOHULQGH ((XQ LODYHVL\OH &&ÕQ IROOLN OHU ID] V UHVLQFH endometium üzeindeki olumsuz etkisinin JLGHULOGL L VDSWDQPÕúWÕU.ORPLIHQ VLWUDW LOH LQG NOHQPLú VLNOXVODUGD IROOLN OHU ID] V UHVLQFH VHUXP 7 YH /+ G ]H\OHULQLQ \ NVHN ROGX X J WHULOPLúWLU $UWPÕú 7 YH /+ GH HUOHUL LOH ELUOLNWH VHUXP VHNV KRUPRQ ED OD\DQ JORE O Q G ]H\LQGH GH DUWÕú J ]OHQPLúWLU $QFDN EX DUWÕúÕQ testosteonun peifeik etkisi, özellikle seviks ve endometium üzeine net etkisi tam olaak otaya NRQDPDPÕúWÕU /DQJHU YH DUNDGDúODUÕQÕQ \DSWÕ Õ odoõúpdgd && LOH LQG NOHQHQ VLNOXVODUGD VHUXP 7 YH /+ G ]H\OHUL \ NVHN VDSWDQPÕú ROXS HNVRMHQ östojen veilen sikluslada T ve LH düzeylei DQODPOÕ RODUDN G ú N EXOXQPXúWXU ddoõúpdpõ]gd benze olaak CC veilen olgulada 14. gün seum T düzeyi yüksek bulunuken, eksojen östojen veilen ROJXODUGD VHUXQ 7 G ]H\L DQODPOÕ RODUDN G ú N EXOXQGX.ORPLIHQ VLWUDWÕQ LQG NOHQPLú VLNOXVODUGD IROOLN OHU ID] ]HULQGHNL ROXPVX] HWNLOHUL \DQÕQGD OXWHDO ID] ]HULQGH GH ROXPVX] HWNLOHUL YDUGÕU <HONR YH DUNDGDúODUÕQÕQ \DSWÕ Õ ELU odoõúpdgd && LOH LQG NOHQHQ VLNOXVODUGD RUDQÕQGD HQGRPHWULXPXQ KLVWRORMLN JHOLúLPLQGH J QGHQ ID]OD JHFLNPH VDSWDQPÕúWÕU %X odoõúpdgd OXWHDO SURJHVWHURQ DUWPÕú ROPDVÕQD NDUúÕQ VDSWDQDQ KLVWRORMLN JHFLNPH &&ÕQ DQWL VWURMHQLN HWNLVL LOH endometiumdaki pogesteon eseptöleinin LQG NVL\RQXQXQ EORNH HGLOPHVLQH ED ODQPÕúWÕU ddoõúpdpõ]gd NORPLIHQ VLWUDW YHULOHQ ROJXODUGD \DSÕODQ J Q HQGRPHWULDO EL\RSVL YH J Q VHUXP SURJHVWHURQ G ]H\OHUL GH HUOHQGLULOGL LQGH ROJXODUÕPÕ]ÕQ VDGHFH QGH OXWHDO \HWPH]OLN G ú Q O UNHQ && LOH HNVRMHQ VWURMHQ YHULOHQ ROJXODUÕQ VDGHFH QGH OXWHDO \HWPH]OLN G ú Q OG 2YXODWXYDU ID] DoÕVÕQGDQ HQGRPHWULDO EL\RSVL EXOJXODUÕ YH J Q VHUXP SURJHVWHURQ G ]H\OHUL GH HUOHQGLULOGL LQGH && YHULOHQ ROJXODUGD DQRYXODV\RQ RUDQÕ RODUDN VDSWDQÕUNHQ eksojen östojen veilen olgulada anovulasyon RUDQÕ RODUDN VDSWDQGÕ /DQJHU && YH && LOH HNVRMHQ RVWURMHQ YHULOHQ KDVWDODU DUDVÕQGD J Q CC+E gubunda 14. gün seum T düzeyi ile 21. gün SURJHVWHURQ G ]H\OHUL DUDVÕQGDNL LOLúNL Total olgulada 14. gün seum T ve E2 düzeylei DUDVÕQGDNL LOLúNL Total olgulada 14. gün seum T düzeyi ile 21. gün SURJHVWHURQ G ]H\L DUDVÕQGDNL LOLúNL seum östadiol ve 21. gün seum P düzeylei DUDVÕQGD IDUNOÕOÕN ROPDGÕ ÕQÕ ELOGLUPLúWLU ddoõúpdpõ]gd && YHULOHQ ROJXODUGD J Q VHUXP östadiol düzeyi konjuge östojen veilen olgulaa J UH DQODPOÕ RODUDN G ú N EXOXQXUNHQ S J Q VHUXP SURJHVWHURQ GH HUOHUL DUDVÕQGD DQODPOÕ ELU IDUN VDSWDQPDGÕ S! %L] EX odoõúpdpõ]gd Jounal of Tugut Özal Medical Cente 4(1):

5 .ORPLIHQ VLWUDW LOH LQG NOHQHQ VLNOXVODUGD HNVRMHQ VWURMHQ NXOODQÕPÕQÕQ «Ö. Balat ve ak. NORPLIHQ VLWUDW LOH LQG NVL\RQ \DSÕODQ VLNOXVODUGD HNVRMHQ NRQMXJH VWURMHQ NXOODQGÕN (NVRMHQ VWURMHQ NXOODQÕOPDVÕQÕQ IROOLN OHU ID]GD GDKD QFH \DSÕOPÕú odoõúpdodugd GD J VWHULOGL L JLEL ROXPOX HWNLOHULQL J ]OHGLN $QFDN OXWHDO ID] IRQNVL\RQODUÕ ]HULQH DQODPOÕ ELU HWNLVLQL J ]OHPHGLN.ORPLIHQ VLWUDW LOH LQG NVL\RQ \DSÕODQ VLNOXVODUGD HNVRMHQ VWURMHQ NXOODQÕOPDVÕQÕQ IROOLN OHU YH OXWHDO ID] IRQNVL\RQODUÕ ]HULQH HWNLVL YH RYXODV\RQ YH JHEHOLN RUDQODUÕ DUDVÕQGDNL LOLúNL\L NHVLQ RODUDN DoÕNOD\DELOPHN LFLQ SURVSHNWLI UDQGRPL]H JHQLú seilede, özellikle andojen seisini de içeen KRUPRQDO odoõúpdoduõq \DSÕOPDVÕ JHUHNWL LQL G ú QPHNWH\L] KAYNAKLAR 1. Speoff L, Glas RH, Kase NG. Clinical Gynecologic Endocinology and Infetility (4 th Ed). Williams and Wilkins, Baltimoe, 1989: Glass RH. Infetility. In: Yen SSC, Jaffe RB (eds). Repoductive Endocinology (2 nd ed). W.B. Saundes Company, Philadephia, 1986: Hammond MG. Induction of ovulasyon with clomiphene citate. In: Sciaa JJ, (edt). Gynecology and Obstetics, J.B. Lippincot Company, Philadelphia, 1987:5; Mikkelson TJ, Koboth PD, Cauneon WJ et al. Single dose phamacokinetikcs of clomiphene citate in nomal voluntes. Fetil Steil 1986;4: Fitz MA, Holmes RT, Keenan EJ. Effect of clomifen citate teatment on endometial estogen and pogesteon ecepto induction in women. Am J Obstet Gynecol 1991;165: Chog AP, Lee JL, Fote CC, et al. Identification and management of clomiphene citate esponses. Fetil Steil 1987;48: Bateman BG, Kolp LA, Felde R, et al. Subclinical pegnancy loss in clomiphene citate-teated women. Fetil Steil 1992;57: Yagel S, Chetit AB, Antey E, et al. The effect of ethynil estadiol on endometial thickness and uteine volume GXULQJ RYXODWÕRQ LQGXFWLRQ E\ FORPLSKHQH FLWUDWH )HUWLO Steil 1992;57: <HNR 75 1LFRVÕD 60 0RURXOLV *% HW DO +LVWRORJ\ RI PLGOXWHDO FRUSXV OXWHXP DQG HQGRPHWUÕXP IURP FORPLSKHQH citate induced cycles. Fetil Steil 1992;57: Randall JM, Templeton A. Cevical mucus scoe and invito spem mucus inteaction in spontaneous and clomiphene citate cycles. Fetil Steil 1991;56: Lange R, Golan A, Ron-El et al. Homonal changes elated to impaiment of cevical mucus in cycles stimulated by clomiphene citate. Aust NZ J Obstet Gynecol 1990;30: Eden JA, Place J, Cate GD et al. The effect of clomiphene citate on follicula phase incease in endometial thickness and uteine volume. Obstet Gynecol 1989;73: Eden JA, Place J, Cate GD et al. What ae the ultasound DQG ELRFKHPLFDO IHDWXUHV RI LPSHQGLQJ RYXODWÕRQ $XVW 1= - Obstet Gynaecol 1988;28: van Hall EV, Mastboom JL. Luteal phase insufficiency in patients teated with clomiphene. Am J Obstet Gynecol 1969;103: Seege JG, Maffezoli RQ, Rose GT. Pathophysiology of epoductive failue afte clomiphen citate induced ovulation. Am J Obstet Gynecol 1970;108: Kokia E, Bide D. Lunenfeld H, et al. Addition of exogenous estogens to impove cevical mucus following FORPLSKHQH FLWUDWH PHGLFDWÕRQ $FWD 2EVWHW *\QHFRO 6FDQ 1990;69: g]gdpdu. %L\RLVWDWLVWLN øvwdqexo %LOLP WHNQLN \D\ÕQHYL PE OR OX. %L\RLVWDWLVWLN $QNDUD +DWLSR OX <D\ÕQHYL Randall JM, Templeton A. Tansvaginal sonogaphic assessment of follicula and endometial gowth in spontaneous and clomiphene citate cycles. Fetil Steil 1991;56: Bikinfeld A, Bei AM, Schenke JG. The effect of clomiphene citate on ealy embyonic development, endometium, and implantation. Hum Repod 1986;1: Bikenfield A, Navot D, Levij IS, at al. Advanced secetoy changes in the polifeative human endometial epithelium following clomiphene citate teatment. Fetil Steil 1986;45:531. <D]ÕúPD DGUHVL Yd.Doç.D. Özcan BALAT øq Q hqlyhuvlwhvl 7ÕS )DN OWHVL.DGÕQ +DVWDOÕNODUÕ YH 'R XP $%' MALATYA Tel ve Fax :