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Changes in plasma estriol and progesterone during labor induced with prostaglandin F2α or oxytocin
CHANGES IN PLASMA ESTRIOL AND PROGESTERONE DURING LABOR INDUCED WITH PROSTAGLANDIN F2d OR OKYTOCIN
William J. LeMaire, William N. Spellacy, Allen B. Shevach* and Stanley A. Gall
Department of Obstetrics and Gynecology and the Endocrine Laboratory University of Miami School of Medicine Miami, Florida 33152
*Present address: Department of Obstetrics and Gynecology, University of Florida, Gainesville, Florida
ABSTRACT In a double blind study, 12 women received oxytocin for the induction of labor at term and 20 subjects received prostaglandin F2,, (PGFzI). During the infusions, plasma progesterone and estriol levels were measured, and compared with pre-infusion levels of these steroids. From the analysis of the data, it is concluded that neither the infusion of oxytocin or PGF2dper se alters the plasma levels of either progesterone or estriol in term pregnant subjects.
ACKNOWLEGMENTS: This work was supported in part by NIH Contract 71-2238, and Ford Foundation Grant 700-0338. We thank Mrs. K. Holsinger, H. Lopez and A. Loynaz for their assistance in these studies. We also thank Mrs. J. Cassady for the statistical analysis of these data. We are grateful to Guy Abraham, M.D. for the gift of antiserum for the measurement of Progesterone and for sending us the manuscript describing the method of Progesterone-Radioimmunoassay prior to publication.
Accepted August 1, 1972.
AUGUST
1972
VOL. 2 NO. 2
93
PROSTAGLANDINS
INTRODUCTION Oxytocin has been the drug of choice for the induction of labor in the last trimester of pregnancy. More recently, it has been shown that some prostaglandins would induce contractions of the pregnant uterus (1). Earim used an infusion of prostaglandin F2c%(PGF2a ) to induce labor in term pregnancy (2). Large controlled studies of the use of prostaglandins for the initiation of labor have been undertaken in different centers &id r~.,,orisare now beginning to appear as to the efficacy and safety of these compounds (3). The study presented here was begun to determine the effect of PGF2d on the levels of estriol and progesterone in the peripheral venous blood during term pregnancy, and to compare the effect of PGF2q with that produced by oxytocin. MATERIALS AND METHODS Thirty-two multiparous volunteer subjects in the last four weeks of pregnancy were selected for this study. All women attended the prenatal clinic at Jackson Memorial Hospital and were admitted for an elective induction of labor. On the morning of induction, an indwelling catheter was placed in an antecubital vein. The subjects were assigned at random The first group to one of two groups using a double blind study design. of 12 women received oxytocin for induction of labor and the second group of 20 women received PGF2u . During the first hour following the placement of the catheter, only physiologic saline was infused. This Tv‘asthen followed after one hour by an infusion of increasing graded doses of either oxytocin or PGF2d (Table I). Infusions were regulated by means of a continuous infusion pump. A catheter in an antecubital vein of the opposite arm was used for blood sampling and was kept open with a heparinPlasma samples were obtained before the infusion and saline solution. hourly afterwards, until either the infusion was stopped or delivery occurred.
TABLE I Graded doses of PGF2d and Oxytocin for Induction of Labor at Term
Time in hours o-1 l-l% l&2 2-3 3-5 5-end
PGF2 d ng/min 0 2.5 5.0 10.0 20.0 40.0
Oxytocin mU/min 0 0.5 1.0 2.0 4.0 8.0
An aliquot of plasma was analyzed in duplicate for progesterone content, using a radioimmunoassay described by Abraham, et al. (4). In another aliquot of plasma, the total estriol level was measured using the method described by Nachtigall, et al. (5).
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The data analysis was carried out by computer and for each time interval, the means, standard error of the means and mean differences were calculated for each steroid. The post-infusion values were compared with the initial preinfusion control levels. A matched pair t test between groups was done to determine statistical significance and only probability values of less than 0.05 were considered significant. RESULTS The 12 women in the oxytocin group and the 20 women in the PGF2o, group were of comparable age, parity and weight. In the oxytocin group, only three inductions failed, but in the PGF2g group eight inductions failed. Because the process of delivery itself may alter plasma steroid levels, both groups were sub-divided into those subjects who delivered and those who did not deliver. Plasma Progesterone
Levels
The statistical data for the plasma progesterone Oxytocin Infusion: levels in the undelivered and delivered subjects receiving the oxytocin infusion are listed in Table II and the mean values for the two subgroups are plotted in Figure 1. Although the undelivered group (Fig.1) consisted only of three individuals and no meaningful statistical analysis is possible, it appears that there is no change in plasma progesterone levels throughout the infusion. In the group of subjects who delivered during the oxytocin infusion (Fig.l), only the mean value of plasma progesterone at four hours of infusion was significantly lower than the mean value before the infusion. The values at other times were not significantly different although a slight trend towards decreasing progesterone values throughout the infusion of oxytocin is apparent in Figure 1. E,o. Infusion: Table III lists the statistical data for plasma progesterone in the undelivered and delivered women receiving an infusion of PGF20(. The mean values are plotted in Figure 1. In the undelivered groups, the mean progesterone values throughout the infusion of PGF2o do not appear to change from the pre-infusion control value. In the group of subjects who delivered during the PGF2o infusion, however, plasma progesterone values decreased. This decrease was statistically significant at 3, 4, and 5 hours of infusion. At later times, too few subjects remained in this delivered group to allow meaningful statistical analysis. Plasma Estriol Levels The statistical data for the plasma estriol Oxytocin Infusion: levels in undelivered and delivered subjects receiving the oxytocin infusion are listed in Table IV and the mean values for these subjects are plotted in Figure 1. Although there are only a few women in the undelivered group, (Fig.l), there appears to be no change in the estriol values at the different times. Likewise, in the delivered group, estriol levels do not change until the sixth hour of infusion when the values appear to increase slightly (Fig.1).
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TABLE II: PLASMA PROGESTERONELEVELS @g/ml) IN PATIENTS RECEIVING OXYTOCIN INFUSIONS
Time in hours*
0
1
2
3 4 5 6 7 UNDELIVERED Number of subjects 3 3 3 3 2 3 3 2 Mean Progesterone 224 208 228 213 230 212 239 223 SEW* 77.0 27.0 54.7 44.7 27.5 40.6 51.2 25.0 t 1.31 1.83 1.65 1.15 1.68 .661 1.20 pa** NS NS NS NS NS NS NS
a
lJUAlV,LK&lJ
Number of subiects 9 9 9 9 Mean ProgesteGone 245 252 223 238 SE@* 27.8 36.0 39.0 41.8 t .535 1.43 .407 p*** NS NS NS
9 a 3 3 2 176 209 235 224 la9 18.5 35.3 45.8 44.1 26.5 2.54 1.62 0.68 ,336 4.77 4.05 NS NS NS NS
TABLE III: PLASMA PROGESTERONELEVELS (mng/ml) IN PATIENTS RECEIVING PGF2d INFUSIONS
Time in hours*
0
12 a
3 a
a
4 5 6 UNDELIVERED a
7
8
910
Number of subjects a Mean Progesterone 177 SEWk* 34.2 t p***
174 164 173 159 31.2 37.3 45.9 35.7 .538 1.27 .208 1.55 NS NS NS NS
Number of subjects 12 Mean Progesterone 238 SEM'k* 38.4 t p***
DELIVERED 12 12 1074322 240 214 166 140 139 109 124 158 120 49.5 44.5 20.0 21.6 34.8 62.9 23.3 55.0 24.5 ,109 1.96 4.21 2.80 3.40 1.62 .135 .224 1.40 NS <.Ol <.05 <.05 NS NS NS NS NS
7 7 5 155 169 173 33.6 40.5 49.6 1.39 1.88 2.90 NS NS NS
4 169 54.3 2.12 NS
3 143 64.3 2.71 NS
3 142 73.6 1.78 NS
( *
0 is the control sample prior to the infusion of oxytocin or PGF2d after one hour of saline infusion. 1,2,3, etc. refer to blood samples obtained. 1,2,3, etc. hour after the oxytocin or PGF2d infusion was started.
**
SEM means
standard error of the mean
*** NS means not significant
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TABLE IV: PLASMA ESTRIOL LEVELS +g/lOOml) IN PATIENTS RECEIVING OXYTOCIN INFUSIONS
Time
in hours*
0
1
2
3
4
5
6
7
8
UNDELIVERED Number of subjects 3 3 3 3 2 3 3 2 Mean Estriol 23.3 21.6 20.0 23.3 16.5 22.3 22.0 17.0 SEW* 2.4 1.6 2.5 4.5 0.5 6.3 5.5 2.0 t .507 .887 0.0 1.66 .135 .192 1.16 p*";: NS NS NS NS NS NS NS DELIVERED Number of subjects 9 9 9 9 9 8 3 3 2 Mean Estriol 35.7 36.4 36.4 37.6 39.1 41.7 50.6 56.3 53.0 SEW* 7.9 6.7 7.4 7.5 7.6 9.4 12.4 17.6 27.0 t .160 .135 .422 .660 .998 .377 .146 1.00 p;\** NS NS NS NS NS NS NS NS
TABLE V: PLASMA ESTRIOL LEVELS (pg/LOOml) IN PATIENTS RECEIVING PGF2+,INFUSIONS
Time in hours"
0
12
3
4 5 6 DNDELIVERED Number of subjects 8 8 8 8 8 7 7 Mean Estriol 25.1 26.7 24.3 28.2 28.8 33.1 31.2 SEW"< 3.9 5.2 4.5 5.4 5.0 6.1 6.2 t .831 1.34 1.50 1.18 1.78 1.33 pw
7 4 37.2 7.6 1.47 NS
8
910
4 3 3 29.5 29.3 33.0 5.1 5.2 7.5 ,859 -453 .834 NS NS NS
LJ~LL”mcr.JJ
Number of subjects 12 Mean Estriol 26.7 SE&W 5.2 t *>:f lp
12 12 10 26.0 29.0 30.8 4.9 5.4 5.9 .514 1.14 2.15 NS NS NS
7 6 30.7 34.3 6.3 8.0 1.23 1.40 NS NS
5 3 2 34.8 56.6 67.5 6.9 5.7 1.5 .791 .125 1.00 NS NS NS
2 68.0 7.0 .400 NS
*
0 is the control sample prior to the infusion of oxytocin or PGF~,A after one hour of saline infusion. 1,2,3, etc. refer to blood samples obtained. 1,2,3, etc. hour after the oxytocin or PGF2,ainfusionwas started.
**
SEM means standard error of the mean
fXf
NS means not significant
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E3
k_%
-c/
&_&L.
TIME (hours)
DRUG DOSAGE
6,L.H
ESTRIOL
,0--o
PROGESTERONE
PGF2 o( UNDELIVERED
0123456789
100 -
150
-\-\
200 f
250
300
01234567
(pg/min)
v<
UNDELIVERED
PROGESTERONE
OXYTOCIN
-
-
,
0123456789
r
TIME
i
___O--0 I
8
(hours)
PGF2 o( DELIVERED
I
4
(mU/min]
DELIVERED
DRUG DOSAGE
ESTRIOL
OXYTOCIN
012345678
t
r
i
10
- 30
-40
- 50
-60
-10
30
-I 60
f z
ii
0 z
_z
c
g
Fig. 1 Plasma Progesterone and Estriol levels during oxytocin (top) and PGFZa infusions (bottom) for the induction of labor in patients who did deliver (right) and did not deliver (left). The statistical analysis of the data is represented in Tables II through V.
“i
f
c
8
in
ii
CL
300 [
PROSTAGLANDINS
pGF2a Infusion: The statistical data for plasma estriol in the undelivered and delivered subjects receiving the infusions of PGF2o are shown in Table V , and the mean values are plotted in Figure 1. From these data, it is clear that plasma estriol values do not change significantly during the infusion of PGF2&in the undelivered subjects. In the delivered group, there is again no significant change in the plasma estriol levels until six hours when there appears to be an appreciable increase in estriol levels although the numbers of subjects are too small for meaningful statistical analysis. DISCUSSION Conflicting reports have appeared regarding the peripheral plasma progesterone levels during spontaneous labor. A slight decrease has been reported by some investigators as labor progresses (6-12), while other workers have not detected such a decrease (13-15). Antes and co-workers have found a decline in peripheral plasma progesterone levels in early labor induced with oxytocin (16). In the study reported here, peripheral plasma progesterone levels show a slight trend towards decline during the induction with oxytocin, but only in those subjects who eventually delivered. In the subjects who delivered during the infusion with PGF2,, a marked and sustained decline in the peripheral plasma progesterone levels was found, This observed decrease may possibly be attributed to a disturbance of placental function as labor progresses. In this respect it is noted, however, that during the infusion of high levels of PGF2d in early pregnancy for the induction of abortion, no significant change was observed in peripheral plasma progesterone prior to abortion performed as late as 16 to 20 weeks of gestation (17). When the oxytocin or PGF2n infusion did not lead to delivery in the study reported here, no change in progesterone levels were noted. Although the number of observations in the undelivered group is small, especially those receiving oxytocin, it can be concluded that neither oxytocin nor PGF2d itself affects plasma progesterone levels. The measurement of peripheral plasma estriol during spontaneous labor has also led to conflicting reports, indicating either a decrease during labor (18) or no change (19,20). During the induction of labor at term with oxytocin, Jewelewicz, et al reported an increase in estriol (19). The increase in plasma estriol found by these investigators was explained on the basis of a reduction of renal clearance for estriol in oxytocin induced labor (19,21). Speroff et al have reported that the infusion of PGF23, for the induction of abortion in early pregnancy produced a marked decline in plasma estriol. The present data indicate that an increase in plasma estriol may occur during the infusion of either oxytocin or PGF2,, 1 in subjects who go on to deliver, while in the women who do not deliver there is no change in the plasma estriol. It appears therefore, that neither oxytocin nor PGF2u,affect the plasma estriol levels per se and that the increase observed in those subjects who delivered may be attributed to the process of labor. In conclusion, the present data suggest that neither oxytocin nor PGF2tx given intravenously to term pregnant women for the induction of labor, significantly alters the plasma levels of estriol or progesterone. Changes do occur in these steroids when the induction progresses towards
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delivery and these changes are probably due to factors other than the administration of oxytocin or PGF2a. At this point, it appears unclear what these factors might be, but it seems likely that they result in some functional alteration of the placenta and fetus, as suggested by Cantor, et al for midtrimester abortions (22). REFERENCES 1.
Embrey, M.P. and D.L. Morrison. The effect of prostaglandins on human pregnant myometrium _in vitro. J. Obstet. Gynec. Brit. Cwlth. 75:829, 1968.
2.
Karim, S.M.M., R.R. Trussell, R.C. Pate1 and K. Hillier, Response of pregnant human uterus to prostaglandin-F2u -induction of labour. Brit. Med. J. 4:621, 1968.
3.
Intravenous prostaAnderson, G.O., J.C. Hobbins and L. Speroff. glandins E, and F,a( for the induction of term labor. Amer. J. Obstet. Gynec. 112f382, 1572.
4.
Abraham, G.E., R. Swerdloff, D. Tulchinsky and W.D. Odell. Radioiannunoassay of plasma progesterone. J. Clin. Endo. Metab. 32:619, 1971.
5.
Nachtigall, L., M. Bassett, U. Hogsander, S. Slagle and M. Levitz. A rapid method for the assay of plasma estriol in pregnancy. J. Clin. Endo. 26:941, 1966.
6.
PeriCsapo, A.I., E. Knobil, H.J. Van der Molen and W.G. Wiest. pheral plasma progesterone levels during human pregnancy and labor. Amer. J. Obstet. Gynec. 110:630, 1971.
7.
Progesterone in human Llauro, J.L., B. Runnebaum and J. Zander. peripheral blood before, during and after labor. Amer. J. Obstet. Gynec. 101:867, 1968.
9.
Simmer, H. and J. Simmer. Progesterone in peripheren venemblut von Schwangeren mit Spatgestosen. Klin. Wchnsch. 37:971, 1959.
10.
Zander, J. In Barnes A.C. editor: "Progesterone" Augusta, Michigan,
11.
Proc. First International Congress Woolever, C.A. and A. Goldfien. on Hormonal Steroids. New York 1965 Academic Press, Inc. Vol. II p 253.
12.
The role of the fetus and Lurie, A.O., D.E. Reid and C.A. Villee. placenta in maintenance of plasma progesterone. Amer. J. Obstet. Gynec. 96:670, 1966.
100
Brook Lodge Symposium. 1961. Brook Lodge Press, p 7?.
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13.
Deshpande, G.N., A.K. Turner and I.F. Sommerville. Plasma progesterone and pregnandediol in human pregnancy, during labor and postpartum. J. Obstet. Gynec. Brit. Empire 67:954, 1960.
14.
Kumar, D., E.F. Ward and B.C. Barnes. Serial plasma progesterone levels in normal pregnancy, labor and the puerperium. Amer. J. Obstet. Gynec. 101:1058, 1968.
16.
Studies on the level Antes, I.G., J.C. Hisley and A.L. Haskins. of blood progesterone throughout the course of labor. Amer. J. Obstet. Gynec. 109:36, 1971.
17.
Speroff, L., B.V. Caldwell, W.A. Brock, G.G. Anderson and J.C. Hormone levels during prostaglandin F2d infusions for Hobbins. therapeutic abortion. J. Clin. Endo. Metabl. 34:531, 1972.
18.
Smith, O.W. Free and conjugated estrogens in blood and urine before and during parturition in normal human pregnancy. Acta Endocr. (supp. 104), 1966.
19.
Jewelewicz, R. and M. Levitz. Plasma estriol levels during normal spontaneous labor and labor induced by oxytocin unfusion. J. Clin. Endocr. Metab. 27~648, 1967.
20.
Concentration of estrogens Rado, A., C.D. Crystle and J.D. Townsley. in maternal peripheral plasma in late pregnancy, during labor and postpartum. J. Clin. Endocr. Metab. 30:497, 1970.
21.
Jewelewicz, R., M. Bassett and M. Levitz. Estriol "clearance" and creatinine clearance during normal spontaneous labor and labor induced by oxytocin infusion. J, Clin. Endocr. Metab. 29:1539, 1969.
22.
Cantor, B., et al. Hormonal changes during induction of midtrimester abortion by Prostaglandin F2Q . Amer. J. Obstet. Gynec. 113:607, 1972.
AUGUST
1972
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William J. LeMaire, William N. Spellacy, Allen B. Shevach* and Stanley A. Gall
Department of Obstetrics and Gynecology and the Endocrine Laboratory University of Miami School of Medicine Miami, Florida 33152
*Present address: Department of Obstetrics and Gynecology, University of Florida, Gainesville, Florida
ABSTRACT In a double blind study, 12 women received oxytocin for the induction of labor at term and 20 subjects received prostaglandin F2,, (PGFzI). During the infusions, plasma progesterone and estriol levels were measured, and compared with pre-infusion levels of these steroids. From the analysis of the data, it is concluded that neither the infusion of oxytocin or PGF2dper se alters the plasma levels of either progesterone or estriol in term pregnant subjects.
ACKNOWLEGMENTS: This work was supported in part by NIH Contract 71-2238, and Ford Foundation Grant 700-0338. We thank Mrs. K. Holsinger, H. Lopez and A. Loynaz for their assistance in these studies. We also thank Mrs. J. Cassady for the statistical analysis of these data. We are grateful to Guy Abraham, M.D. for the gift of antiserum for the measurement of Progesterone and for sending us the manuscript describing the method of Progesterone-Radioimmunoassay prior to publication.
Accepted August 1, 1972.
AUGUST
1972
VOL. 2 NO. 2
93
PROSTAGLANDINS
INTRODUCTION Oxytocin has been the drug of choice for the induction of labor in the last trimester of pregnancy. More recently, it has been shown that some prostaglandins would induce contractions of the pregnant uterus (1). Earim used an infusion of prostaglandin F2c%(PGF2a ) to induce labor in term pregnancy (2). Large controlled studies of the use of prostaglandins for the initiation of labor have been undertaken in different centers &id r~.,,orisare now beginning to appear as to the efficacy and safety of these compounds (3). The study presented here was begun to determine the effect of PGF2d on the levels of estriol and progesterone in the peripheral venous blood during term pregnancy, and to compare the effect of PGF2q with that produced by oxytocin. MATERIALS AND METHODS Thirty-two multiparous volunteer subjects in the last four weeks of pregnancy were selected for this study. All women attended the prenatal clinic at Jackson Memorial Hospital and were admitted for an elective induction of labor. On the morning of induction, an indwelling catheter was placed in an antecubital vein. The subjects were assigned at random The first group to one of two groups using a double blind study design. of 12 women received oxytocin for induction of labor and the second group of 20 women received PGF2u . During the first hour following the placement of the catheter, only physiologic saline was infused. This Tv‘asthen followed after one hour by an infusion of increasing graded doses of either oxytocin or PGF2d (Table I). Infusions were regulated by means of a continuous infusion pump. A catheter in an antecubital vein of the opposite arm was used for blood sampling and was kept open with a heparinPlasma samples were obtained before the infusion and saline solution. hourly afterwards, until either the infusion was stopped or delivery occurred.
TABLE I Graded doses of PGF2d and Oxytocin for Induction of Labor at Term
Time in hours o-1 l-l% l&2 2-3 3-5 5-end
PGF2 d ng/min 0 2.5 5.0 10.0 20.0 40.0
Oxytocin mU/min 0 0.5 1.0 2.0 4.0 8.0
An aliquot of plasma was analyzed in duplicate for progesterone content, using a radioimmunoassay described by Abraham, et al. (4). In another aliquot of plasma, the total estriol level was measured using the method described by Nachtigall, et al. (5).
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The data analysis was carried out by computer and for each time interval, the means, standard error of the means and mean differences were calculated for each steroid. The post-infusion values were compared with the initial preinfusion control levels. A matched pair t test between groups was done to determine statistical significance and only probability values of less than 0.05 were considered significant. RESULTS The 12 women in the oxytocin group and the 20 women in the PGF2o, group were of comparable age, parity and weight. In the oxytocin group, only three inductions failed, but in the PGF2g group eight inductions failed. Because the process of delivery itself may alter plasma steroid levels, both groups were sub-divided into those subjects who delivered and those who did not deliver. Plasma Progesterone
Levels
The statistical data for the plasma progesterone Oxytocin Infusion: levels in the undelivered and delivered subjects receiving the oxytocin infusion are listed in Table II and the mean values for the two subgroups are plotted in Figure 1. Although the undelivered group (Fig.1) consisted only of three individuals and no meaningful statistical analysis is possible, it appears that there is no change in plasma progesterone levels throughout the infusion. In the group of subjects who delivered during the oxytocin infusion (Fig.l), only the mean value of plasma progesterone at four hours of infusion was significantly lower than the mean value before the infusion. The values at other times were not significantly different although a slight trend towards decreasing progesterone values throughout the infusion of oxytocin is apparent in Figure 1. E,o. Infusion: Table III lists the statistical data for plasma progesterone in the undelivered and delivered women receiving an infusion of PGF20(. The mean values are plotted in Figure 1. In the undelivered groups, the mean progesterone values throughout the infusion of PGF2o do not appear to change from the pre-infusion control value. In the group of subjects who delivered during the PGF2o infusion, however, plasma progesterone values decreased. This decrease was statistically significant at 3, 4, and 5 hours of infusion. At later times, too few subjects remained in this delivered group to allow meaningful statistical analysis. Plasma Estriol Levels The statistical data for the plasma estriol Oxytocin Infusion: levels in undelivered and delivered subjects receiving the oxytocin infusion are listed in Table IV and the mean values for these subjects are plotted in Figure 1. Although there are only a few women in the undelivered group, (Fig.l), there appears to be no change in the estriol values at the different times. Likewise, in the delivered group, estriol levels do not change until the sixth hour of infusion when the values appear to increase slightly (Fig.1).
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PROSTAGLANDINS
TABLE II: PLASMA PROGESTERONELEVELS @g/ml) IN PATIENTS RECEIVING OXYTOCIN INFUSIONS
Time in hours*
0
1
2
3 4 5 6 7 UNDELIVERED Number of subjects 3 3 3 3 2 3 3 2 Mean Progesterone 224 208 228 213 230 212 239 223 SEW* 77.0 27.0 54.7 44.7 27.5 40.6 51.2 25.0 t 1.31 1.83 1.65 1.15 1.68 .661 1.20 pa** NS NS NS NS NS NS NS
a
lJUAlV,LK&lJ
Number of subiects 9 9 9 9 Mean ProgesteGone 245 252 223 238 SE@* 27.8 36.0 39.0 41.8 t .535 1.43 .407 p*** NS NS NS
9 a 3 3 2 176 209 235 224 la9 18.5 35.3 45.8 44.1 26.5 2.54 1.62 0.68 ,336 4.77 4.05 NS NS NS NS
TABLE III: PLASMA PROGESTERONELEVELS (mng/ml) IN PATIENTS RECEIVING PGF2d INFUSIONS
Time in hours*
0
12 a
3 a
a
4 5 6 UNDELIVERED a
7
8
910
Number of subjects a Mean Progesterone 177 SEWk* 34.2 t p***
174 164 173 159 31.2 37.3 45.9 35.7 .538 1.27 .208 1.55 NS NS NS NS
Number of subjects 12 Mean Progesterone 238 SEM'k* 38.4 t p***
DELIVERED 12 12 1074322 240 214 166 140 139 109 124 158 120 49.5 44.5 20.0 21.6 34.8 62.9 23.3 55.0 24.5 ,109 1.96 4.21 2.80 3.40 1.62 .135 .224 1.40 NS <.Ol <.05 <.05 NS NS NS NS NS
7 7 5 155 169 173 33.6 40.5 49.6 1.39 1.88 2.90 NS NS NS
4 169 54.3 2.12 NS
3 143 64.3 2.71 NS
3 142 73.6 1.78 NS
( *
0 is the control sample prior to the infusion of oxytocin or PGF2d after one hour of saline infusion. 1,2,3, etc. refer to blood samples obtained. 1,2,3, etc. hour after the oxytocin or PGF2d infusion was started.
**
SEM means
standard error of the mean
*** NS means not significant
96
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TABLE IV: PLASMA ESTRIOL LEVELS +g/lOOml) IN PATIENTS RECEIVING OXYTOCIN INFUSIONS
Time
in hours*
0
1
2
3
4
5
6
7
8
UNDELIVERED Number of subjects 3 3 3 3 2 3 3 2 Mean Estriol 23.3 21.6 20.0 23.3 16.5 22.3 22.0 17.0 SEW* 2.4 1.6 2.5 4.5 0.5 6.3 5.5 2.0 t .507 .887 0.0 1.66 .135 .192 1.16 p*";: NS NS NS NS NS NS NS DELIVERED Number of subjects 9 9 9 9 9 8 3 3 2 Mean Estriol 35.7 36.4 36.4 37.6 39.1 41.7 50.6 56.3 53.0 SEW* 7.9 6.7 7.4 7.5 7.6 9.4 12.4 17.6 27.0 t .160 .135 .422 .660 .998 .377 .146 1.00 p;\** NS NS NS NS NS NS NS NS
TABLE V: PLASMA ESTRIOL LEVELS (pg/LOOml) IN PATIENTS RECEIVING PGF2+,INFUSIONS
Time in hours"
0
12
3
4 5 6 DNDELIVERED Number of subjects 8 8 8 8 8 7 7 Mean Estriol 25.1 26.7 24.3 28.2 28.8 33.1 31.2 SEW"< 3.9 5.2 4.5 5.4 5.0 6.1 6.2 t .831 1.34 1.50 1.18 1.78 1.33 pw
7 4 37.2 7.6 1.47 NS
8
910
4 3 3 29.5 29.3 33.0 5.1 5.2 7.5 ,859 -453 .834 NS NS NS
LJ~LL”mcr.JJ
Number of subjects 12 Mean Estriol 26.7 SE&W 5.2 t *>:f lp
12 12 10 26.0 29.0 30.8 4.9 5.4 5.9 .514 1.14 2.15 NS NS NS
7 6 30.7 34.3 6.3 8.0 1.23 1.40 NS NS
5 3 2 34.8 56.6 67.5 6.9 5.7 1.5 .791 .125 1.00 NS NS NS
2 68.0 7.0 .400 NS
*
0 is the control sample prior to the infusion of oxytocin or PGF~,A after one hour of saline infusion. 1,2,3, etc. refer to blood samples obtained. 1,2,3, etc. hour after the oxytocin or PGF2,ainfusionwas started.
**
SEM means standard error of the mean
fXf
NS means not significant
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E3
k_%
-c/
&_&L.
TIME (hours)
DRUG DOSAGE
6,L.H
ESTRIOL
,0--o
PROGESTERONE
PGF2 o( UNDELIVERED
0123456789
100 -
150
-\-\
200 f
250
300
01234567
(pg/min)
v<
UNDELIVERED
PROGESTERONE
OXYTOCIN
-
-
,
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r
TIME
i
___O--0 I
8
(hours)
PGF2 o( DELIVERED
I
4
(mU/min]
DELIVERED
DRUG DOSAGE
ESTRIOL
OXYTOCIN
012345678
t
r
i
10
- 30
-40
- 50
-60
-10
30
-I 60
f z
ii
0 z
_z
c
g
Fig. 1 Plasma Progesterone and Estriol levels during oxytocin (top) and PGFZa infusions (bottom) for the induction of labor in patients who did deliver (right) and did not deliver (left). The statistical analysis of the data is represented in Tables II through V.
“i
f
c
8
in
ii
CL
300 [
PROSTAGLANDINS
pGF2a Infusion: The statistical data for plasma estriol in the undelivered and delivered subjects receiving the infusions of PGF2o are shown in Table V , and the mean values are plotted in Figure 1. From these data, it is clear that plasma estriol values do not change significantly during the infusion of PGF2&in the undelivered subjects. In the delivered group, there is again no significant change in the plasma estriol levels until six hours when there appears to be an appreciable increase in estriol levels although the numbers of subjects are too small for meaningful statistical analysis. DISCUSSION Conflicting reports have appeared regarding the peripheral plasma progesterone levels during spontaneous labor. A slight decrease has been reported by some investigators as labor progresses (6-12), while other workers have not detected such a decrease (13-15). Antes and co-workers have found a decline in peripheral plasma progesterone levels in early labor induced with oxytocin (16). In the study reported here, peripheral plasma progesterone levels show a slight trend towards decline during the induction with oxytocin, but only in those subjects who eventually delivered. In the subjects who delivered during the infusion with PGF2,, a marked and sustained decline in the peripheral plasma progesterone levels was found, This observed decrease may possibly be attributed to a disturbance of placental function as labor progresses. In this respect it is noted, however, that during the infusion of high levels of PGF2d in early pregnancy for the induction of abortion, no significant change was observed in peripheral plasma progesterone prior to abortion performed as late as 16 to 20 weeks of gestation (17). When the oxytocin or PGF2n infusion did not lead to delivery in the study reported here, no change in progesterone levels were noted. Although the number of observations in the undelivered group is small, especially those receiving oxytocin, it can be concluded that neither oxytocin nor PGF2d itself affects plasma progesterone levels. The measurement of peripheral plasma estriol during spontaneous labor has also led to conflicting reports, indicating either a decrease during labor (18) or no change (19,20). During the induction of labor at term with oxytocin, Jewelewicz, et al reported an increase in estriol (19). The increase in plasma estriol found by these investigators was explained on the basis of a reduction of renal clearance for estriol in oxytocin induced labor (19,21). Speroff et al have reported that the infusion of PGF23, for the induction of abortion in early pregnancy produced a marked decline in plasma estriol. The present data indicate that an increase in plasma estriol may occur during the infusion of either oxytocin or PGF2,, 1 in subjects who go on to deliver, while in the women who do not deliver there is no change in the plasma estriol. It appears therefore, that neither oxytocin nor PGF2u,affect the plasma estriol levels per se and that the increase observed in those subjects who delivered may be attributed to the process of labor. In conclusion, the present data suggest that neither oxytocin nor PGF2tx given intravenously to term pregnant women for the induction of labor, significantly alters the plasma levels of estriol or progesterone. Changes do occur in these steroids when the induction progresses towards
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delivery and these changes are probably due to factors other than the administration of oxytocin or PGF2a. At this point, it appears unclear what these factors might be, but it seems likely that they result in some functional alteration of the placenta and fetus, as suggested by Cantor, et al for midtrimester abortions (22). REFERENCES 1.
Embrey, M.P. and D.L. Morrison. The effect of prostaglandins on human pregnant myometrium _in vitro. J. Obstet. Gynec. Brit. Cwlth. 75:829, 1968.
2.
Karim, S.M.M., R.R. Trussell, R.C. Pate1 and K. Hillier, Response of pregnant human uterus to prostaglandin-F2u -induction of labour. Brit. Med. J. 4:621, 1968.
3.
Intravenous prostaAnderson, G.O., J.C. Hobbins and L. Speroff. glandins E, and F,a( for the induction of term labor. Amer. J. Obstet. Gynec. 112f382, 1572.
4.
Abraham, G.E., R. Swerdloff, D. Tulchinsky and W.D. Odell. Radioiannunoassay of plasma progesterone. J. Clin. Endo. Metab. 32:619, 1971.
5.
Nachtigall, L., M. Bassett, U. Hogsander, S. Slagle and M. Levitz. A rapid method for the assay of plasma estriol in pregnancy. J. Clin. Endo. 26:941, 1966.
6.
PeriCsapo, A.I., E. Knobil, H.J. Van der Molen and W.G. Wiest. pheral plasma progesterone levels during human pregnancy and labor. Amer. J. Obstet. Gynec. 110:630, 1971.
7.
Progesterone in human Llauro, J.L., B. Runnebaum and J. Zander. peripheral blood before, during and after labor. Amer. J. Obstet. Gynec. 101:867, 1968.
9.
Simmer, H. and J. Simmer. Progesterone in peripheren venemblut von Schwangeren mit Spatgestosen. Klin. Wchnsch. 37:971, 1959.
10.
Zander, J. In Barnes A.C. editor: "Progesterone" Augusta, Michigan,
11.
Proc. First International Congress Woolever, C.A. and A. Goldfien. on Hormonal Steroids. New York 1965 Academic Press, Inc. Vol. II p 253.
12.
The role of the fetus and Lurie, A.O., D.E. Reid and C.A. Villee. placenta in maintenance of plasma progesterone. Amer. J. Obstet. Gynec. 96:670, 1966.
100
Brook Lodge Symposium. 1961. Brook Lodge Press, p 7?.
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13.
Deshpande, G.N., A.K. Turner and I.F. Sommerville. Plasma progesterone and pregnandediol in human pregnancy, during labor and postpartum. J. Obstet. Gynec. Brit. Empire 67:954, 1960.
14.
Kumar, D., E.F. Ward and B.C. Barnes. Serial plasma progesterone levels in normal pregnancy, labor and the puerperium. Amer. J. Obstet. Gynec. 101:1058, 1968.
16.
Studies on the level Antes, I.G., J.C. Hisley and A.L. Haskins. of blood progesterone throughout the course of labor. Amer. J. Obstet. Gynec. 109:36, 1971.
17.
Speroff, L., B.V. Caldwell, W.A. Brock, G.G. Anderson and J.C. Hormone levels during prostaglandin F2d infusions for Hobbins. therapeutic abortion. J. Clin. Endo. Metabl. 34:531, 1972.
18.
Smith, O.W. Free and conjugated estrogens in blood and urine before and during parturition in normal human pregnancy. Acta Endocr. (supp. 104), 1966.
19.
Jewelewicz, R. and M. Levitz. Plasma estriol levels during normal spontaneous labor and labor induced by oxytocin unfusion. J. Clin. Endocr. Metab. 27~648, 1967.
20.
Concentration of estrogens Rado, A., C.D. Crystle and J.D. Townsley. in maternal peripheral plasma in late pregnancy, during labor and postpartum. J. Clin. Endocr. Metab. 30:497, 1970.
21.
Jewelewicz, R., M. Bassett and M. Levitz. Estriol "clearance" and creatinine clearance during normal spontaneous labor and labor induced by oxytocin infusion. J, Clin. Endocr. Metab. 29:1539, 1969.
22.
Cantor, B., et al. Hormonal changes during induction of midtrimester abortion by Prostaglandin F2Q . Amer. J. Obstet. Gynec. 113:607, 1972.
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