.ORPLIHQ 6LWUDW LOH 2YXODV\RQ øQGNVL\RQXQGD (NVRMHQ gVWURMHQ
.XOODQÕPÕQÕQ2YDULDQ)ROOLNXORPHWUL%XOJXODUÕh]HULQH(WNLVL
Dr. Özcan Balat1,
8OWUDVRQ
Dr. Arif Kökçü2,
RYXODV\RQ
LQGNVL\RQX
2
'U ùNU dRNúHQLP
\DSÕODQ
KDVWDODUGD
IROOLNO
Dr. Cazip Üstün2
,
JHOLúLPLQL
L]OHPHN
]HUH
\D\JÕQ
RODUDN
NXOODQÕOPDNWDGÕU .ORPLIHQ VLWUDWÕQ && GRPLQDQW IROOLNO JHOLúLPL ]HULQH HWNLVL VSRQWDQ VLNOXVODUD J|UH
EHOLUJLQGLU %X oDOÕúPD RYXODWXDU GLVIRQNVL\RQX RODQ KDVWDGD \DSÕOGÕ KDVWDQÕQ QH \DOQÕ]FD &&
GL÷HU KDVWD\D LVH && NRQMXJH |VWURMHQ YHULOGL dDOÕúPD YH NRQWURO JUXSODUÕ DUDVÕQGD JQ |OoOHQ
VHUXP ( VHUXP 7 G]H\L YH GRPLQDQW IROOLNO oDSODUÕ HVDV DOÕQGÕ÷ÕQGD LVWDWLVWLNVHO RODUDN DQODPOÕ IDUN
gözlendi (p<
.ORPLIHQ VLWUDW LOH HNVRMHQ |VWURMHQ YHULOHQ VLNOXVODUGD EHOLUJLQ RODUDN DUWPÕú GRPLQDQW
IROOLNO oDSÕQ QHGHQLQL WDP RODUDN DoÕNOD\DPDGÕN DQFDN J|UQHQ R NL EX VLNOXVODUGD D]DOPÕú VHUXP 7
G]H\OHUL YDUGÕ YH ELU RODVÕOÕNOD EX VRUXPOX IDNW|U RODELOLUGL $QFDN EX NRQXGD GDKD VD÷OÕNOÕ ELOJLOHULQ HOGH
HGLOHELOPHVL
LoLQ
GDKD
JHQLú
VHULOHUGH
|]HOOLNOH
DQGURMHQ
VHULVLQL
GH
LoHUHQ
KRUPRQDO
YH
JHOLúPLú
J|UQWOHPH WHNQLNOHULQLQ NXOODQÕOGÕ÷Õ D\UÕQWÕOÕ oDOÕúPDODUD JHUHNVLQLP YDUGÕU >-RXUQDO RI 7XUJXW g]DO
Medical Center 1996;3(3):191-194]
Anahtar Kelimeler: Klomifen sitrat, ultrasound, anovulasyon, konjuge östrojen.
The effect of exogenous estrogen on ovarian folliculometric findings in ovulation induction
with clomiphene citrate
Ultrasound is commonly used to asses growth of the dominant follicle in patients underwent ovulation
induction. Accelerated growth has also been found in clomiphene citrate cycles. This study was performed in
48 patients with ovulatory dysfunction. Twenty-four patients received only clomiphene citrate (CC) while the
other 24 patients received CC and conjugated estrogen. Based on the levels of serum E2, T, and the
diameters of dominant follicle on 14th day, there was significant difference between study and control groups
(p< 0.05). We could not explain the reason of increased dominant follicle diameter, but there were the low
levels of serum T in these cycles, and may be this could be a responsible reason. However, to have the exact
data, the further hormonal investigation including androgens series and the developed imaging techniques
should be used in larger studies. [Journal of Turgut Özal Medical Center 1996;3(3):191-194]
Key Words: Clomiphene citrate, ultrasound monitoring, anovulation, conjugated estrogen
8OWUDVRQ
RYXODV\RQ
LQGNVL\RQX
\DSÕODQ
KDVWDODUGD IROOLNO JHOLúLPLQL L]OHPHN ]HUH \D\JÕQ
RODUDN
NXOODQÕOPDNWDGÕU
.ORPLIHQ
VLWUDWÕQ
&&
GRPLQDQW
IROOLNO
JHOLúLPL
1
øQ|Q hQLYHUVLWHVL 7ÕS )DNOWHVL .DGÕQ +DVWDOÕNODUÕ YH 'R÷XP $QDELOLP 'DOÕ 0DODW\D
2
0D\ÕV hQLYHUVLWHVL 7ÕS )DNOWHVL .DGÕQ +DVWDOÕNODUÕ YH 'R÷XP $QDELOLP 'DOÕ 6DPVXQ
Journal of Turgut Özal Medical Center 3(3):1996
]HULQH
HWNLVL
spontan sikluslara göre daha belirgindir (2,4,6,7).
Klomifen sitrat ile indüklenen sikluslarda dominant
191
Ö. Balat ve ark.
Klomifen sitrat ile ovulasyon indüksiyonu
IROOLNO oDSÕ VSRQWDQ VLNOXVODUD J|UH GDKD E\NWU
0HYFXW oDOÕúPDODUGD NORPLIHQ VLWUDWÕQ EX HWNLVL
LQGNOHQPLú
VLNOXVODUOD
NDUúÕODúWÕUÕOPDVÕ
ELOJLOHULPL]H
LOH
J|UH
VSRQWDQ
RUWD\D
HNVRMHQ
VLNOXVODUÕQ
NRQPXúWXU
|VWURMHQ
$QFDN
NXODQÕPÕQÕQ
IROOLNO JHOLúLPL |]HOOLNOH GRPLQDQW IROOLNO oDSÕ
]HULQH HWNLVL LOH LOJLOL \DSÕOPÕú oDOÕúPD \RNWXU %L]
EX
oDOÕúPDGD
LQGNVL\RQX
NORPLIHQ
\DSÕODQ
VLWUDW
KDVWDODUD
LOH
RYXODV\RQ
NRQMXJH
|VWURMHQ
serum E2 düzeyleri ve ovarian follikülometri
EXOJXODUÕ DUDVÕQGDNL LOLúNL LQFHOHQGL dDOÕúPD YH
NRQWURO JUXSODUÕQGD HOGH HGLOHQ VRQXoODU LVWDWLVWLNVHO
veriler, ortalama ± VWDQGDUW KDWD úHNOLQGH EHOLUWLOGL
dDOÕúPD YH NRQWURO JUXSODUÕQÕQ YHULOHUL DUDVÕQGDNL
IDUNOÕOÕNODU VWXGHQW W WHVWL LOH LQFHOHQGL 9HULOHULQ
ELUELUOHUL LOH RODQ ED÷ODQWÕODUÕ NRUHODV\RQ DQDOL]L
NXOODQÕODUDN GH÷HUOHQGLULOGL YHUHUHN GRPLQDQW IROOLNO JHOLúLPL ]HULQH RODQ
HWNLVLQL DUDúWÕUGÕN
BULGULAR
MATERYAL VE METOD
0D\ÕV hQLYHUVLWHVL 7ÕS )DNOWHVL .DGÕQ
+DVWDOÕNODUÕ $QDELOLP 'DOÕ WDUDIÕQGDQ L]OHQHQ DQRYXODV\RQOX ROJXGD \DSWÕ÷ÕPÕ] oDOÕúPDGD
%X oDOÕúPD 0D\ÕV hQLYHUVLWHVL 7ÕS )DNOWHVL
.DGÕQ
+DVWDOÕNODUÕ
YH
'R÷XP
$QDELOLP
'DOÕ
WDUDIÕQGDQ L]OHQPHNWH RODQ RYXODWXDU GLVIRQNVL\RQX
RODQ KDVWDGD \DSÕOGÕ %X KDVWDQÕQ  SULPHU
LQIHUWLOLWH KDVWD LVH VHNRQGHU LQIHUWLOLWH WDQÕVÕ
DOPÕú YH EXQODUÕQ LQGH DQRYXODV\RQ XQGD
ROLJRRYXODV\RQ VDSWDQPÕúWÕU KDVWDGD && LOH
RYXODV\RQ LQGXNVL\RQX SODQODQGÕ YH RYXODV\RQ
LQGNVL\RQXQGDQ |QFH WP KDVWDODUÕQ ODERUDWXYDU YH
IL]LN PXD\HQH LúOHPOHUL WDPDPODQGÕ /DERUDWXYDU
WHWNLNOHULQGHQ +E +FW EL\RNLP\D GH÷HUOHUL UXWLQ
ODERUDWXYDU WHWNLNOHUL\OH |OoOG 7P KDVWDODUÕQ
WHGDYLGHQ |QFH KRUPRQ SURIÕOL oÕNDUÕOGÕ 6HUXP
follikül stimulan hormon (FSH), luteinizan hormon
(LH), östradiol (E2), progesteron (P), prolaktin (Pr),
dehidroepiandrosteronsulfat (DHEAS), testosteron
(T) düzeyleri menstruel siklusun 21. gününde
VDSWDQGÕ
7LURLG
GLVIRQNVL\RQX
YH
hiperprolaktinemisi olan anovulatuar hastalar
oDOÕúPD\D DOÕQPDGÕ dDOÕúPD\D DOÕQDQ KDVWDODU
VDGHFH ELU VLNOXV LoLQ GH÷HUOHQGLULOGL KDVWDQÕQ
QH \DOQÕ]FD && 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 PJ NRQMXJH |VWURMHQ 3UHPDULQ
YHULOGL 2YXODV\RQ LQGNVL\RQX \DSÕODQ WP
KDVWDODU JQ DúÕUÕ RYDULDQ IROOLNORPHWUL YH VHUXP
E2 düzeyi, 14. gün serum E2 düzeyi, dominant
IROOLNO oDSÕ YH VHUXP 7 G]H\L Tablo1.
ölçümleri ile moniterize edildi.
7P KDVWDODUÕQ IROOLNORPHWUL
ölçümleri
abdominal
ultrason
NXOODQÕODUDN \DSÕOGÕ $\UÕFD 14. gün E2 (pg/ml)
1. Klomifen sitrat ile ovulasyon indüksiyonu
±
± 33.2 pg/ml
\DSÕODQ KDVWDGD \Dú RUWDODPDVÕ \ÕO
ED]DO ( GH÷HUOHULQLQ RUWDODPDVÕ idi
2. Klomifen sitrat + konjuge östrojen tedavisi
DODQ DQRYXODV\RQOX KDVWDGD \Dú RUWDODPDVÕ ± \ÕO ED]DO ( GH÷HUOHULQLQ RUWDODPDVÕ ±
19.2 pg/ml idi.
dDOÕúPD JUXEX LOH NRQWURO JUXEX DUDVÕQGD \Dú YH
ED]DO ( GH÷HUOHUL DUDVÕQGD IDUNOÕOÕN ROPDGÕ÷Õ
görüldü (p>0.05)
dDOÕúPD JUXEXQGD YDNDODUÕQ ¶VLQGH
RYXODV\RQ VDSWDQÕUNHQ NRQWURO JUXEXQGD YDNDODUÕQ
¶VLQGH RYXODV\RQ VDSWDQGÕ %X IDUN
LVWDWLVWLNVHO RODUDN DQODPOÕ\GÕ S< 0.05)
dDOÕúPD YH NRQWURO JUXSODUÕ DUDVÕQGD JQ
ölçülen serum E2, serum T düzeyi, ve dominant
IROOLNO oDSODUÕ HVDV DOÕQGÕ÷ÕQGD LVWDWLVWLNVHO RODUDN
DQODPOÕ IDUN J|]OHQGL S< 0.05) (Tablo1).
Eksojen östrojen verilen verilen grupta 14. gün
VHUXP 7 G]H\OHUL NRQWURO JUXEXQD J|UH DQODPOÕ
RODUDN GúN VDSWDQÕUNHQ ( G]H\OHUL \NVHN
VDSWDQGÕ
dDOÕúPD YH NRQWURO JUXSODUÕ DUDVÕQGD JQ
serum T düzeyi ile 14. gün E2 ve dominant follikül
oDSÕ DUDVÕQGDNL LOLúNL LQFHOHQGL÷LQGH IDUN LVWDWLVWLNVHO
dDOÕúPD YH NRQWURO JUXSODUÕQÕQ JQ ( 7 'RPLQDQW IROOLNO
oDSODUÕQÕQ RUWDODPD GH÷HUOHUL
gün serum T düzeyleri ile 14. gün
192
JQ 'RPLQDQW IROOOLNO oDSÕ PP
14. gün T (ng/dl )
CC grubu (n:24)
403,2±67,2
16,1±1,7
68,7±27,1
CC+E grubu (n:24)
624,3±51,4
19,8±1,9
41,3±19,7
7XUJXW g]DO 7ÕS 0HUNH]L 'HUJLVL Balat Ö, et al.
Induction of ovulation with clomiphen citrate
RODUDN DQODPOÕ\GÕ S< ùHNLO DUWPÕú GRPLQDQW IROOLNO oDSÕ J|]OHQGL S<0.05).
dDOÕúPD JUXEXQGD GúN VHUXP 7 YH \NVHN
VHUXP ( G]H\OHUL
LOH ELUOLNWH
DQODPOÕ RODUDN
<LQH WRWDO ROJXODU LQFHOHQGL÷LQGH JQ VHUXP
7
G]H\OHUL
LOH
GRPLQDQW
IROOLNO
oDSÕ
DUDVÕQGD
DQODPOÕ LOLúNL VDSWDQGÕ %X ROJXODUGD GúN VHUXP 7
G]H\OHUL
LOH
RUDQWÕOÕ
RODUDN
GRPLQDQW
oDSODUÕ \NVHN VDSWDQGÕ S< ùHNLO IROOLNO
T$57,ù0$
2YXODV\RQ
LQGNVL\RQX
XOWUDVRQRJUDILQLQ
JHOLúLPLQL
\DSÕODQ
NXOODQÕOPDVÕ
KDVWDODUGD
RYDULDQ
LQFHOHPHN
IROOLNO
KLSHUVWLPXODV\RQ
VHQGURPXQXQ JHOLúLPLQL |QOHPHN
YH JHUHNWL÷LQGH
human koryonik gonadotropin hormon (HCG)
YHULOPH ]DPDQÕQÕ VDSWDPDN EDNÕPÕQGDQ VRQ GHUHFH
Testosteron düzeyi (ng/ml)
ùHNLO 1. CC grubunda 14. gün serum T ve E2 düzeyleri
DUDVÕQGDNL LOLúNL
|QHPOLGLU YH \D\JÕQ RODUDN NXOODQÕOPDNWDGÕU Klomifen sitrat ile indüklenen sikluslarda spontan
VLNOXVODUD J|UH GDKD oRN VD\ÕGD IROONO JHOLúLPL
YDUGÕU
.ORPLIHQ
VLWUDW
LOH
LQGNVL\RQ
\DSÕODQ KDVWDODUGD IROOLNOHU E\PH RUDQÕ VSRQWDQ
VLNOXVODUGDNL IROOLNOHU E\PH RUDQÕQD EHQ]HUOLN
gösterir (3,5). Ancak, klomifen sitrat ile indüklenen
VLNOXVODUGD IROOLNOHU E\PH GDKD KÕ]OÕ YH OLQHHU
JHOLúPH J|VWHULU /XWHLQL]DQ KRUPRQ /+
VDOÕQÕPÕ\OH ELUOLNWH |OoOHQ GRPLQDQW IROOLNO oDSODUÕ
DUVÕQGD VSRQWDQ YH && LOH LQGNOHQHQ VLNOXVODUGD
IDUNOÕOÕN J|]OHQPHPLúWLU .ORPLIHQ VLWUDW LOH
LQGNOHQHQ
VLNOXVODUGD
DUWPÕú
GRPLQDQW
IROOLNO
oDSÕQ QHGHQL DoÕN GH÷LOGLU $QFDN NORPLIHQ VLWUDW LOH
LQGNOHQHQ VLNOXVODUGD DUWPÕú PDNVLPXP IROOLNOHU
Testosteron düzeyi (ng/ml)
ùHNLO 2. CC+E grubunda 14. gün serum T düzeyi ile E2 düzeyleri
DUDVÕQGDNL LOLúNL
oDSÕQ
QHGHQL
EX
VLNOXVODUGD
J|]OHQHQ
X]DPÕú
IROOLNOHU ID] NL EX G|QHP X]DPÕú E\PH SHU\RGX
VD÷ODU
VRUXPOX
IDNW|U
RODELOLU
/DQJHU
YH
DUNDGDúODUÕ NORPLIHQ VLWUDW LOH HNVRMHQ |VWURMHQ
verilen sikluslarda, östrojen verilmeyen sikluslara
J|UH EHOLUJLQ RODUDN GúN VHUXP 7 YH /+ G]H\OHUL
VDSWDPÕúODUGÕU %L] GH EHQ]HU RODUDN NORPLIHQ VLWUDW
verilen sikluslarda 14. gün serum T düzeylerinde
EHOLUJLQ D]DOPD VDSWDGÕN 6HUXP 7 G]H\OHUL LOH
GRPLQDQW
eksojen
IROOLNO
konjuge
GRPLQDQW
IROOLNO
oDSODUÕQÕ
östrojen
oDSÕQ
NDUúÕODúWÕUGÕ÷ÕPÕ]GD
verilen
DQODPOÕ
sikluslarda
RODUDN
DUWPÕú
ROGX÷XQX J|]OHGLN <LQH HNVRMHQ |VWURMHQ YHULOHQ
ROJXODUÕPÕ]GD DUWPÕú VHUXP ( G]H\OHUL VDSWDGÕN
$QFDN
QHGHQLQL
NHVLQ
RODUDN
DoÕNOD\DPDPDNOD
ELUOLNWH EX VLNOXVODUGD DUWPÕú RODQ GRPLQDQW IROOLNXO
Testosteron düzeyi (ng/ml)
ùHNLO 3. Total olgularda 14. gün serum T düzeyi ile 14. gün
GRPLQDQW IROOLNO oDSÕ DUDVÕQGDNL LOLúNL
oDSÕ
\NVHN
NDOLWHOL
IROOLNO
YH
RYXPXQ
ELU
göstergesi olarak sorumlu faktör olabilir. Klomifen
sitrat ile eksojen östrojen verilen sikluslarda belirgin
RODUDN DUWPÕú GRPLQDQW IROOLNO oDSÕQ QHGHQLQL WDP
Journal of Turgut Özal Medical Center 3(3):1996
193
Ö. Balat ve ark.
Klomifen sitrat ile ovulasyon indüksiyonu
RODUDN
DoÕNOD\DPDGÕN
DQFDN
J|UQHQ
R
NL
EX
6.
Lemay A, Bastide A, Lambert R et al. Prediction of human
ovulation
by
rapid
luteinizing
hormone
(LH)
radioimmunassay and ovarian ultrasonography. Fertil Steril
1982;38:194.
7.
Vargyas JM, Marrs RP, Kletzky OA et al. Correlation of
ultrasonic measurement of ovarian follicle size and serum
estradiol levels in ovulatory patients following clomiphene
citrate for in vitro fertilization. Am J Obstet Gynecol
1982;144: 569.
8.
g]GDPDU
VLNOXVODUGD D]DOPÕú VHUXP 7 G]H\OHUL YDUGÕ YH ELU
RODVÕOÕNOD
EX
VRUXPOX
IDNW|U
RODELOLUGL
$QFDN
EX
NRQXGD GDKD VD÷OÕNOÕ ELOJLOHULQ HOGH HGLOHELOPHVL LoLQ
GDKD JHQLú VHULOHUGH |]HOOLNOH DQGURMHQ VHULVLQL GH
LoHUHQ
KRUPRQDO
WHNQLNOHULQLQ
YH
NXOODQÕOGÕ÷Õ
JHOLúPLú
D\UÕQWÕOÕ
J|UQWOHPH
oDOÕúPDODUD
JHUHNVLQLP YDUGÕU
.
%L\RLVWDWLVWLN
øVDWDQEXO
%LOLP
7HNQLN
<D\ÕQHYL KAYNAKLAR
9.
1.
Queenon JT, O'Brien GD, Bains LM, et al. Ultrasound
scanning of ovaries to detect ovulation in women. Fertil
Steril 1980;34:99.
10. Speroff L, Glas RH, Kase NG. Clinical Gynecologic
Endocrinology and Infertility (4th Ed). Baltimore, Williams
and Wilkins, 1989:213-31.
2.
Leerentveld RA, vanGent I, vanderStoep M, et al.
Ultrasonographic assesment of graaphian follicle growth
under monofollicular and multifollicular conditions in
clomiphen citrate stimulated cycles. Fertil Steril
1985;43:565.
11. Hull HE, Moghissi KS, Magyer DM, et al. Correlation of
serum estradiol levels and ultrasound monitoring to asses
follicular maturation. Fertil Steril 1986;46:42.
3.
Templeton A, Messinis IE, Baird DT. Charecteristics of
ovarian follicles in spontanenous and stimulated cycles in
which there was an endogenous lutenizing hormone surge.
Fertil Steril 1986;46:1113.
4.
Vermesh M, Kletzky OA, Davajan V, et al. Monitoring
techniques to predict and detect ovulation. Fertil Steril
1987;47:259.
5.
Randall JM, Templeton A. Transvaginal sonographic
assesment of follicular and endometrial growth in
spontaneous and clomiphen citrate cycles. Fertil Steril
1991;56:208.
6PEOR÷OX . %L\RLVWDWLVWLN $QNDUD +DWLSR÷OX <D\ÕQHYL
1989:150-66.
12. Messinis IE, Templeton A. Superovulation induction in
women supresses luteinizing hormone secretion at the
pituitary level. Clin Endocrinol 1990;32:107.
13. Langer R, Golan A, Ron-El R. Hormonal changes related to
impairment of cervical mucus in cycles stimulated by
clomiphene citrate. Aust NZ J Obstet Gynecol 1990;30:254,
<D]ÕúPD DGUHVL : Yrd.Doç.Dr. Özcan BALAT
øQ|Q hQLYHUVLWHVL 7ÕS )DNOWHVL
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44020
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Klomifen Sitrat ile Ovulasyon İndüksiyonunda Eksojen Östrojen