PROSTAGLANDINS

SERUM HORMONE LEVELS IN WOMEN UNDERGOING ABORTION WITH INTRA-AMNIOTIC, EXTRA-AMNIOTIC OR INTRA-MUSCULAR

ADMINISTRATION OF lS(S)lS-METHYL-PROSTAGLANDIN Fza

CHANDER P. PURI, S.A. RAHMAN, A.K. JAIN, R. BHADURI, C.M. SINGH, V. HINGORANI

AND KESHO R. LAUMAS

Department of Reproductive Biology and the Department of Obstetrics and Gynaecology

All India Institute of Medical Sciences New Delhi-110016, INDIA

ABSTRACT

The serum levels of estradiol-179, progesterone and HPL have been estimated by specific radioimmunoassay in thirty women undergoing abortion with 15-methyl-PGF2o given by intra-amniotic, extra-amniotic or intra- muscular route. A significant decline in the levels of these hormones was observed in 27 cases in which the pregnancy was terminated. However, in the remaining three cases, 15-methyl-PGF2, was found to be unsuccessful, and no significant change in the hormone levels was evident. The decline

in these hormones was more marked by intra-muscular route, than that obser- ved by the other routes. The pattern of estradiol-17fl decline was more consistent when compared with progesterone and HPL. The levels of proges- terone and HPL, in a few cases, rather showed an increase in the initial hours of lS-methyl-PGF2o administration before the decline began and this pattern was more prominent on extra-amniotic administration. In general, the decline in the hormone levels was slower in cases which took longer time for abortion than cases with shorter induction-abortion time (IAT).

The decline in estradiol-179 levels was about 65 percent at six hour of intra-muscular administration of 15-methyl-PGF2,, whereas the corresponding fall with intra-amniotic and extra-amniotic routes was 29 and 22 percent, respectively. However, the net drop in its levels during IAT was not significantly different (range 70 to 80 percent) by the three routes. About 38 percent fall in progesterone levels was observed at six hour of intra-muscular administration whereas, by intra-amniotic the fall was 19 percent. The net decline in progesterone levels, during IAT, was in the range of 46 to 60 percent by the three routes. Similarly, intra- muscular 15-methyl-PGF2o evoked a sharper decline in HPL levels as compared with other routes. The total decline during IAT was 58 to 66 percent. The results, thus indicated that the abortion with lS-methyl-PGF2, was associated with a fall in the serum hormone levels, which could be result- ant effect of alterations in the hormone production by the foeto-placental unit. This along with the uterine contractions may play a significant role in the abortifacient action of 15-methyl-PGF2,.

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INTRODUCTION

The earlier reports on the abortifacient action of naturally occurring prsstaglandins (1,2)-- demanded further improvements in the delivery system, efficacy and potency of these compounds. In pursuit of this, the addition of a methyl group to carbon-15 of the prostaglandin Fzcr (PGFza) molecule resulted in an analogue, lSfS)lS-methyl-prosta- glandin F20, (15-methyl-PGF2,), which has a longer half-life (3) and is ten times more potent than the parent compound (4,s). The relative abortifacient efficacy of this compound, when delivered by intra-amniotic, extra-amniotic or intra-. muscular route, has been evaluated by us (6) and others (4,7). However, the precise mechanism of abortifacient action of 15-methyl-PGF2, thus administered is not fully understood. It is not clear whether its administration by the three routes produces a similar or different pattern of decline in the serum levels of hormones which play a significant role in the funct- ioning of foeto-placental unit. The objective of the present investigation was to evaluate the effect of l5-methyl-PGF2,on the serum levels of estradiol-17b, progesterone and human placental lactogen (HPL) in patients undergoing termination of pregnancy. A preliminary report has been presented (8).

MATERIALS AND METHODS

Sub j ects

Thirty young healthy women, with a gestation of 8 to 20 weeks, seeking medical termination of pregnancy at the All India Institute of Medical Sciences Hospital were selected for the present study. No special criterias were fixed for selection but the patients were put in three groups of different gestational length.

Intra-amniotic administration of 15-methyl-PGF2,

Intra-amniotic route was used in ten cases between 16 to 20 weeks pregnancy. Amniocentesis was done per abdomen and a single dose of 2.5 mg of 15-methyl-PGF2, in 5 ml saline was injected into the amniotic cavity (9).

Extra-amniotic administration of 15-methyl-PGF2,

Extra-amniotic route was used in ten women between 12 to 16 weeks pregnancy. 15-Methyl-PGF2,, 750 pg in 3 ml

906 MAY 1976 VOL. 11 NO. 5

PROSTAGLANDINS

saline, was administered through No. 8 Foley’s catheter into the uterine walls and the foetal membranes (9).

Intra-muscular administration of 15-methyl-PGF2,

This route was used in ten cases between 8 to 14 weeks gestation. An initial intra-muscular injection of 2OOpg 15-methyl-PGF2o (T romethamine salt) was followed by subsequent injections of 300 ug every 3 hours till the patient aborted or for a maximum period of 30 hours.

Collection of blood

Peripheral blood samples were collected from all these subjects immediately before the instillation of the drug, at various time intervals during the IAT and one sample after the expulsion of the foetus. The serum was separated and immediately frozen below -lS’C, in aliquots, for hormone estimations.

Estimation of hormones

Estradiol-17B, progesterone and human placental lactogen levels were estimated in serum using specific radioimmunoassays (9). Estradiol-17s was estimated using antiserum, raised against estradiol-6-(O-carboxy-methyl)- oxime-BSA, at a final dilution of l/3,000 and 2,4,6,7- 3H-estradiol-17B as tracer. The sensitivity of the assay was 5 pg and the coefficient of variation between and within assay was about 6 to 16 percent. To estimate progesterone, antiserum raised against lla-hemisuccinate- BSA at a final dilution of l/15,000 and 1,2,6,7-3H-proges- terone as tracer were used. The values of water and stripped serum were less than 25 pg; the least detectable levels for the linearised standard curve. The separation of free and bound steroid was achieved using dextran coated charcoal, HPL was measured using 125I-HPL as tracer and HPL-NIH as reference oreuaration. Seoaration of free and bound HPL was done by*using anti-rabbit gamma globulin raised in goat. The least detectable levels of HPL for the linearised curve, from 0.5 to 20.0 ng, was 2 ng.

RESULTS

The administration of 15-methyl-PGF2, by intra- amniotic, extra-amniotic or intra-muscular route termi- nated pregnancy in 27 of the 30 cases studied. The

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average gestation length (mean + S.E.) was 18.4 + 0.6, 13.0 + 0.5 and 11.8 + 0.8 weeks-in three erouns.-of 10 cases-each, treated with intra-amniotic, extra-amniotic or intra-muscular route respectively. The mean IAT was 17.9 + 3.4 (10 cases), 17.2 * 1.2 (8 cases) and 13.1 + 1.3 (g cases) hours respectively.

-

Levels of estradiol-178

Intra-amniotic administration of 2.5 mg 15-methyl- PGF2o caused a significant (P <O.OOl) fall in serum estradiol-17B levels during an average IAT of 17.9 + 3.4 hours, in ten subjects. The mean levels declined fFom 7.25 ng/ml to 5.35 ng/ml in the first six hours and by the time of abortion the levels had declined further to 1.87 ng/ml (Table 1). time for abortion, i.e.

In two cases, which took a longer 42.7 and 30; 5 hours respectively,

the decline was comoarativelv slow. being only 8.8 and 6.5 percent during the first’ 6 hours. In these two cases, because of some degree of placental retention, vacuum aspiration was deemed necessary to clear the conceptus contents.

Single extra-amniotic instillation of 750 ~g 15-methyl- PGF2o produced a significant fall (P qO.001) in serum estradiol-176 during IAT of 17.2 + 1.2 hours in 8 cases. The mean levels declined from 2.7T ng/ml (range 1.35 to 6.5 ng/ml) to 2.22 ng/ml (range 0.5 to 6.25 ng/ml) during the first six hours. The decline continued thereafter and the levels dropped down to 1.65 ng/ml and 0.63 ng/ml at 12 hours and at the time of abortion respectively (Table 2). In two cases, terminate pregnancy,

where 15-methyl-PGF2p could not insignificant variations in estradiol-17B

levels were seen upto 24 and 30 hours.

Two different patterns of decline in estradiol-176 levels were observed following intra-muscular injection of 15-methyl-PGF declined in t e first one hour i.e. with one’injection of ?l*

In seven successful cases the levels

200 !lg. In two other cases, an initial spurt in levels was observed at one hour before declining. In the nine success- ful cases, ng/ml.

the mean levels declined from 5.16 ng/ml to 3.50 The detrimental changes continued thereafter and the

levels dropped to 2.53 and 1.95 ng/ml at 3 and 6 hours of treatment respectively (Table 3). The net decline in estradiol-17B levels at the time of abortion was 76.1 + 4.5 percent of pre-instillation values, which is significantly

908 MAY 1976 VOL. 11 NO. 5

PROSTAGLANDINS

different from the pre-treatment levels (P <O.OOl). Interest- ingly , no significant change in serum estradiol-178 levels was observed in the failure case.

A comparison of 15-methyl-PGF different routes suggested that the ~~c~p~fn~~t~:~~~~i”,:_,7, levels was initiated more rapidly by the intra-muscular route (Fig. 1). The average fall at one hour being 37.7 + 6.2 per cent (7 cases). Even at six hours, the decline in Zstradiol-176 levels (65 percent), with intra-muscular route, was significantly (P< 0.05) more than the corresponding fall with intra-amniotic (28.8 + 4.1 percent) and extra-amniotic routes (21.6 + 5.0 percenT). However, during IAT, the net fall by the triree routes was not significantly different.

Levels of progesterone

Following intra-amniotic administration of 15-methyl-PGF2 the mean progesterone levels declined from 60.5 ng/ml to 49.5 ng7 ml serum at 6 hours in 8 cases. In the other two cases an initial increase at 6 and 12 hours respectively was observed before the levels started declining. By the time of abortion, the progesterone levels had declined to 23.39 ng/ml (10 cases) (Table 1). In one case, with a longer IAT of 42.7 hours, although the progesterone levels had declined by about 16.0 percent by the time of abortion erratic. In this case,

, yet the pattern was quite the progesterone levels, evenafter

36 hours of 15-methyl-PGF2, administration, were higher than the pre-instillation values. On the other hand, in another case, with comparatively shorter IAT of 11.7 hours, a rapid fall in progesterone levels was observed. level declined from 75 ng/ml to 14.4 ng/ml.

In this case, the

Extra-amniotic administration of 15-methyl-PGF two patterns of decline in serum progesterone (Table $7.

produced In

four cases, ng/ml

the mean levels declined from 24.75 ng/ml to 17.58 (about 27.1 percent) at 6 hours. The decline continued

thereafter and the levels dropped further to 8.63 ng/ml (about 57.7 + 6.7 percent) at abortion which occurred at 16 + 2.1 hours: In the other four successful cases, however, Zn initial increase, from 23.58 ng/ml to 30.53 ng/ml (about 33.1 + 13.4 percent), was observed at 6 hours. The decline startea there- after and the mean levels dropped to 22.38 ng/ml and 10.18 ng/ ml at 12 hours and at the time of abortion respectively. The mean IAT (18.4 + 1.4hours) in these four cases, was higher as compared with c%.es where an initial fall was observed at 6 hours (16.0 + 2.1). However, this difference in time is not statistically significant. of 10.25 hours,

In one case, with the shortest IAT the drop in progesterone levels (from initial

25.0 ng to 4.2 ng/ml at abortion) was maximum. in two cases who failed to abort,

Interestingly, erratic levels of progesterone

were observed at different time intervals upto 30 hours.

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A significant decline (PC O.OOl), as calculated by the student paired It’ test, in progesterone levels was observed following 15-methyl-PGF administration. In seven cases, the decline was apparen $” at one hour of treatment, whereas in the other two cases, the decline started after 3 or 6 hours of drug administration. In these two cases, an initial spurt was observed at one hour. The mean change in progesterone levels was from 24.56 ng/ml to 20.49 ng/ml at one hour (9 cases) (Table 3). However, the pattern of ,progesterone change was quite variable among aborters after showing an initial drop at one hour. In a few cases, the detrimental changes continued till the patient aborted, whereas in a few cases, the progesterone levels showed a secondary rise at 3 hours before dropping below the pretreatment levels. At six hours, the levels had declined to 16.09 ng/ml which is significantly different from pretreatment values-at the 99 percent confidence limit. A steady decline continued thereafter and during the mean IAT of-13.1 hours, the levels dropped down to 11.66 ng/ml. Interestingly, no significant change in progestqrone levels was observed in one case which failed to expel the foetus.

A comparison of the decline of progesterone levels, following lS:methyl-PGF2, administration by three routes,. revealed a more ranid drop with intra-muscular route (P< 0.05) as compared with ihtra-amniotic or extra-amniotic route (Fig. 2). The pattern of decline was consistent in most of the cases administered by intra-amniotic or intra-muscular route, whereas with extra-amniotic route in half of the successful cases progesterone levels declined at 6 hours while in the other half an initial spurt was observed at 6 hours followed by the decline. These cases, with an initial increase in progesterone levels

The total fall in generally took a longer

abortion time. hormone levels bv the three routes was not statistically different (range.46 to 60 percent) from one another.

Levels of HPL

A significant (PC 0.001) decline in serum HPL levels was observed in ten cases following intra-amniotic adminis- tration of 15-methyl-PGF pre-infusion value of 1. 6

a. The levels declined from mean 6 pg/ml to 0.91 ug/ml in the first

six hours. The decline continued thereafter and by the time of abortion the levels had declined to 0.42 pg/ml (Table 1). In two cases with incomplete abortion, the decline in HPL levels was comparatively very slow. In these two cases a decline of only 3.6 and 318 percent was observed at six hours respectively.

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Two patterns of decline in serum HPL levels were observed following extra-amniotic administration of 15-methyl- PGF (Table 2). In four cases, l.O~e~g/ml to 0.79 ug/ml (22.6

the levels declined from + 1.6 percent) at six hours

and the decline continued till She patients aborted. In the other four successful cases, HPL levels initiallv showed a spurt from 0.78 vg/ml to 0.96 vg/ml at six hours’before drooping down to 0.59 ue/ml at 12 hours. The net decline during iAT was more (6lT3 + 4.8 percent) in cases with a consistent fall than in cases where an initial rise was observed (SO.3 + 7.0 percent). In unsuccessful cases, quite erratic HPL valiies were observed.

Following intra-muscular administration of 15-methyl- PGF2as the HPL patterns were in general similar to those of progesterone and estradiol-178. Seven cases showed a rapid response to drug administration and the mean levels dropped to 0.96 ug/ml from pretreatment levels of 1.15 vg/ml (7 cases). Amongst the other cases, an initial increase was observed in one, while in the other the levels remained unchanged at one hour. The mean HPL level in 9 cases declined from 1.15 pg/ml to 0.96 ug/ml in the first hour. However, in a few cases, HPL levels increased after an initial decline at one hour. The mean values remained apparently stationery at 3 (0.80 + 0.18 ug/ml) and 6 hours (0.81 + 0.21 pg/ml) of treat- ment . After six hours a significant aiid persistant fall was observed which continued till abortion occurred. In the failure case, observed.

no significant change in the HPL levels was

The drop in HPL levels following intra-muscular administration of 15-methyl-PGF2,, even at one hour, was more significant than the corresponding fall at six hours with intra- or extra-amniotic route (Fig. 3). With the intra-amniotic route the decline in levels was consistent, whereas with extra-amniotic route, as in the case of proges- terone, a rise at six hours was observed in a few cases before the levels started declining. In the intra-muscular group p after an initial decline at one hour, in a few cases, the levels recovered at 3 hours before they started declining again. The total fall in HPL levels, by the three routes, was in the range of 58 to 66 percent.

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DISCUSSION

The present investigation precisely demonstrated a significant-decline in serum estradiol-17f3 progesterone and HPL levels. during IAT in 27 cases. in Which pregnancy was successfully terminated with 15-methyl-PGF2,.‘ The decline in the hormone levels, even at one hour, was more marked with intra-muscular route than that at six hours by intra- or extra- amniotic route. However, no change in the hormone levels was observed in three treatment failure cases. The results thus suggested a correlation between the pattern of decline in the hormone levels and the abortifacient action of 15-methyl-PGF2,.

The pattern of estradiol-17d decline was consistent in most of the cases aborted with 15-methyl-PGF2,, administered by different routes. With intra-muscular route, at six hour, about 65 percent decline was observed whereas with intra- amniotic or extra-amniotic route the fall was 29 and 22 percent respectively. A comparable fall in the serum estradiol-17% and estriol levels have been reported during PGF2a(9-ll) and hypertonic saline (9) induced abortions. More recently, Brenner and coworkers (12) have reoorted a significant fall in serum estradiol-17B,‘in_nine preinant women-of 5 to 7 weeks gesta- tion, treated.with intra-muscular 15-methyl-PGF2,. In our earlier studies. we suggested that the decline in estradiol-178 levels following PGF2o -or hypertonic saline administration could be either due to the decreased synthesis of estradiol-176 pre- cursors in the foetal compartments and their subsequent conversion to estradiol-178 in the placenta, or to the impaired foeto-placental function due to increased uterine contractions (9) - Speroff et al (10) suggested that the decrease in estrogen levels, after zeintra-venous infusion of PGF2,, could be either due to the hypoxia produced in the foeto-placental unit, because of strong uterine contractions, or due to the constric- tion of blood supply in the foetus. Similar possibilities could also be considered for the action of lS-methyl-PGF2,. In addition, the decline in estradiol-17B levels in the early pregnancy cases in part could also be due to its action on the ovary. Recently Corson bt al (13) could not demonstrate a signi- ficant change in estradiz Eels during the first eight to ten hours of intra-muscular administration of 15-methyl-PGF a. These authors have suggested that in these cases, proba g ly 15-methyl-PGF2, p reduced a fall in placental production of estra- diol but adrenal stimulation may, by increasting the supply of androgenic precursors (14), maintain the levels.

Administration of 15-methyl-PGF2,, by the three routes, resulted in a decline of progesterone and HPL levels, with a

912 MAY 1976 VOL. 11 NO. 5

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somewhat similar pattern. In the extra-amniotic group, in a few cases, an initial increase in both these hormones was observed before the decline was initiated, whereas in the intra-muscular cases, after an initial decline, the tendency for the hormone levels to recover between the first two doses was more. In general, the decline was comparatively rapid in cases with shorter IAT than the ones with longer IAT. In patients treated with PGFza or PGF2a and urea, the drop in the progesterone levels was faster in cases aborting sooner (15). The tendency for the hormone levels to return towards the pretreatment levels has been suggested to be due to atleast two reasons (13). Firstly, two initial doses of 15-methyl- PGF2,, given intra-muscularly, are not sufficient to irreversi- bly alter the placental biosynthetic-excretory capability and secondly the increase could be due to the alterations in cell permeability or cell lysis. However, these posibilities do not explain the initial rise in these hormones beyond the pre- instillation levels observed after extra-amniotic administration of 15-methyl-PGF2,. Since sufficiently large amount of proges- terone is present in the human myometrium during pregnancy (16), it is possible that direct addition of 15-methyl-PGF2, between the uterine membranes causes sudden release of hormone in the circulation, thus raising the blood levels. The inability to get consistent hormone pattern, in all the cases aborted with extra-amniotic 15-methyl-PGF2,, could be due to the different state of uterine activity. However, the precise reason of getting two patterns of decline in placental hormones needs further investigation.

As described for estradiol-17B, the decline in the serum levels of progesterone and HPL could be due to at least two possibilities. Firstly, since the administration of 15-methyl- PGFZaproduces uterine contractions these may start detaching the placenta thereby affecting the secretion of these hormones in maternal circulation. In this case, the hormonogenesis in the placenta may continue even after its detachment, because, placenta has an inherent capacity to produce amino acids from proteolysis of its own tissue proteins for HPL biosynthesis (17) and is not solely dependent upon the maternal supply of pre- cursors. Secondly, 15-methyl-PGF endocrine function of the I"

may directly affect the

its biosynthetic capacity. foeto-p acental unit by affecting

It has been reported that intra-amniotic injection of 2.5 mg 15-methyl-PGF2, initiated uterine contractions within a few minutes of its administration and the maximum activity was observed only after six hours (18). Lauerson and Wilson(l9)

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have recently observed that the uterine activity was maximum. after one hour and 50 minutes and the frequency of contractions rose to a peak after one hour of intra-amniotic administration of 2.5 mg 15-methyl-PGF2 . Similarly, tration of 250 pg 15-metffyl-PGF

intra-muscular adminis- initiated uterine contract-

ions within 10 to 30 minutes of’?he first injection and the contractions increased further with the subsequent injections (20) * Wiqvist et al (18) have reported that in cases failing to abort there E usually a transient response in uterine activity that subsequently results in inadequate contractions. In our studies, we have observed a significant fall, in hormone levels at one hour of lS-methyl-PGF2, administration. No signi- ficant change in hormone levels was observed in cases which failed to abort. Similarly, Corson et al (13) have reported a _- fall in the serum levels of progesterone and HPL within half-an- hour of intra-muscular injection of 15-methyl-PGF2,. Now it is to be delineated if the contractions produced in one hour of 15-methyl-PGF2, administration are sufficient to affect the secretion of estradiol-17B, progesterone and HPL into the blood stream.

The decline in the hormone levels was generally rapid in cases with shorter IAT as compared to ones taking longer time for abortion. The IAT possibly depends upon the time needed by prostaglandin to provoke effective uterine contract- ions and upset the endocrine function of foeto-placental system. A wide difference in the half-life of prostaglandins in the amniotic fluid, and difference in the metabolic’turnover among different cases (21, 22), may possibly explain the difference in the IAT. The difference in the status of foeto-placental unit, as reflected by the pre-induction base line hormone levels, may also partly contribute to the variations in IAT among different groups.

In our earlier studies (9), a significant decline in the serum progesterone and HPL was observed in cases aborted with intra-amniotic PGF2,. 15-methyl-PGF2

A comparison of the action of PGF2o and cL suggested that the pattern of decline in hormone

levels was quite similar with the two compounds. On the other hand, the decline in the levles of these hormones was slow and. inconsistent in cases treated with intra-amniotic hypertonic saline. Our subsequent studies revealed that in cases aborting with hypertonic saline, the levels of PGF2, increased in the amniotic fluid as the abortion time approached (23). Therefore, it is suggested that even in such cases prostaglandins contri- bute to the abortifacient action of hypertonic saline.

914 MAY 1976 VOL. 11 NO. 5

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Although in the present study a. fall in the serum been established, after the administration by the different routes, yet the mechanism

hormone levels has of 15-methyl-PGF leading to this ia ecline has not been fully resolved. The possibility of direct action of 15-methyl-PGF2, on the bio- synthetic capacity of foeto-placental unit and the role of uterine contractions in hormonogenesis needs further elucidation.

ACKNOWLEDGEMENTS

This work was supported by grants from the Expanded Programme of Research Development and Research Training in Human Reproduction of the World Health Organization, Geneva.

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Wiqvist, N., F. Beguin, M. Bygdeman and M. Toppozada: lS(S)lS-methyl-prostaglandin F ; Myometrial response and abortifacient efficacy. A%. Biosci. 9:831, 1973.

Kirton, K.T. and A.D. Forbes: Activity of 15(S)-methyl- prostaglandin E2 and F as stimulants of uterine con- tractility. ProstaglaQins 1:319, 1972.

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Karim, S.M.M., S.D. Sharma, G.M. Filshie, J.A.Salmon and P.A. Ganesan: Termination of pregnancy with prostaglandin analogs. Adv. Biosci. 9:811, 1973.

Laumas, K.R., S .A. Rahman, C.P. Puri, A.K. Jain, S. Bhadury, C.M. Singh and V. Hingorani: Patterns of decline in serum hormone levels in women undergoing termination of pregnancy with intra-amniotic, extra- amniotic or intra-muscular lS(S)-lS-methyl-prosta- glandin F2a. Int. Conf. on Prostaglandins. 26-30 May 1975, Florence, P. 199.

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Speroff, L., B.V. Caldwell, W.A. Brock, G.G. Anderson and J.C. Hobbins: Hormone levels during prostaglandin

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Brenner, P.F., M.E. Lumkin, C. Ballard and D .R. Mishell Jr.: Termination of early gestation with intramuscular 15(S)15-methyl-prostaglandin F2a. Contraception 11: 279, 1975.

Corson, S.L., T.J. Gilbertson, J.T. Sobota and R.J. Bolognese: Hormone changes occurring during second trimester abortion induced with 15(S)15-methyl-prosta- glandin FZcc. Prostaglandins 9:975, 1975.

Maeyama, M., T. Nakagawa, F. Tuchida and H. Matuoka: The role of human fetal adrenals in steroidogenesis. Effect of adrenocorticosterone on urinary excretion of estrogens in pregnancy. Steroids 13:59, 1969.

Walker, S.M., A.P.F. Flint and A.C. Turnbull: Rate of fall in plasma progesterone and time to abortion following intra-amniotic injection of prostaglandin

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Runnebaum, B. and J. Zander: Progesterone and 20a- dihydroprogesterone and human myometrium during pregnancy. Acta Endocri. (Suppl.) 150:5, 1971.

Suwa, S. and H. Friesen: Biosynthesis of human placental proteins and human placental lactogen (HPL) in vitro. I. Identification of 3H-labelled HPL. Endocrinology 85:1028, 1969.

Wiqvist, N., M. Bygdeman and M. Toppozada: Intra- amniotic prostaglandin administration - a challenge to the currently used methods for induction of mid- trimester abortion. Contraception 8, 113:1973.

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19. Lauersen, N.H. and K.H. Wilson: Midtrimester abortion induced by a single intra-amniotic instillation of two dose schedules of lS(S)lS-methyl prostaglandin F2a. Prostaglandins 9:617, 1975.

20. Lauersen, N.H. and K.H. Wilson: Midtrimester abortion induced by serial intra-muscular injection of lS(S)lS- methyl-prostaglandin FZcr. Am. J. Obstet. Gynecol. 121: 273, 1975.

21. Hingorani, V., N. Baliga, C.P. Puri, V. Laumas, S.A. Rahman and K.R. Laumas: Clinical, hormonal and metabolic studies in patients undergoing second trimester abortion with prostaglandin F hypertonic saline.

lS(S)lS-methyl-PGF2, and 3a'Obstet. Fr Gynaecol. India

(accepted for publication).

22. Salmon, J.A. and S.M.M. Karim: Disappearance of

"f;;;;a~;a;~;~,;$a ,"~"r~~r~~~~~,~~~a~~omp~~~~~~~~nains

10:865, 1975.

23. Puri, C.P., N. Baliga, N. Aggarwal, V. Hingorani and K.R. Laumas: Prostaglandin FzCL disappearance and concentration in amniotic flula and blood of women undergoing abortion with intra-amniotic hypertonic saline. Contraception 12:679, 1975.

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TABLE 1

SERUM ESTRADIOL-17B, PROGESTERONE AND HPL LEVELS OF WOMEN UNDERGOING

TERMINATION OF PREGNANCY WITH SINGLE INTRA-AMNIOTIC ADMINISTRATION

OF 2.5 MG lS(S)lS-METHYL-PROSTAGLANDIN F2"

0 HR

6 HR

ABORTION (Ab)

ESTRADIOL-178

7.25 + 0.88*

5.35 t 0.31

1.87 + 0.30

(ng/ml)

-

-

PROGESTERONE

59.04 + 4.55

51.67 t 4.79

23.39 + 2.77

(ng/ml)

-

-

HP

L (&

ml)

1.06 t 0.88

0.91 + 0.10

0.42 + 0.06

-

SIGNIFICANCE

Estradiol-176 0 Vs 6 Hr N.S., 0 Vs Ab p<O.OOl, 6 Vs Ab p<O.OOl

Progesterone

0 Vs 6 Hr N.S., 0 Vs Ab p<O.OOl, 6 Vs Ab p<O.OOl

HPL

0 Vs 6 Hr N.S., 0 Vs Ab p<O.OOl, 6 Vs Ab p<O.OOl

* Each observation is a mean + SEM of 10 cases

Induction-abortion interval-of these cases is 17.9 + 3.4 hours.

-

TABLE 2

SERUM ESTRADIOL-176, PROGESTERONE AND HPL LEVELS OF WOMEN UNDERGOING TERMINATION OF

PREGNANCY BY EXTRA-AMNIOTIC ADMINISTRATION OF 750 ug lS(S)lS-METHYL-PROSTAGLANDIN Fza

0 HR

6 HR

12 HR

ABORTION

ESTRADIOL-178

2.74 + 0.62(S)

2.22 + 0.62

1.65 + 0.67

(ng/ml)

-

-

0.63 + 1.40

PROGESTERONE

(ng/ml)

;Zs;sh;fth decline

24.75 + 2.77(4)

17.58 + 2.08

14.43 + 2.03

8.63 + 2.71

tZZs;sh;iEh increase 23.58 + 7.97(4)

30.53 + 9.30

22.38 - +10.42

10.18 + 3.45

HPL(pg/ml)

Cases with decline

1.03 + 0.05(4)

0.79 + 0.03

0.72 * 0.03

0.32 + 0.05

at 6 hr@

Cases with increase

0.78 + 0.07(4)

0.96 + 0.14

0.59 + 0.10

0.30 + 0.02

at 6 hr@@

SIGNIFICANCE:

ESTRADIOL-176

0 Vs 6 Hr N.S., 0 Vs 12 Hr p<O.Ol, 0 Vs Ab p<O.OOl

PROGESTERONE

* 0 Vs 6 Hr ~~0.05, 0 Vs 12 Hr p<O.OS, 0 Vs Ab p<O.OOl

**

? Vs 6 Hr N.S., 0 Vs 12 Hr N.S., 0 Vs Ab ~~0.01

HPL @

0 Vs 6 Hr pqO.05, 0 Vs 12 Hr p<O.OS, 0 Vs Ab p<O.OOl

@@

0 Vs 6 Hr N.S.,

0 Vs 12 Hr N.S.

, 0 Vs Ab p<O.Ol

The number in parenthesis indicates the number of observations.

Each observation represents mean + SEM

PROSTAGLANDINS

920 MAY 1976 VOL. 11 NO. 5

PROSTAGLANDINS

Fi

100

1 90

e 80-

d 2 70-

E $ 60-

z SO-

! 4 40- 5

W INTRA-AMNIOTIC Cn =iO)

d-+ EXTRA-AMNIOTIC CA = 8 1

M INTRA-MUSCULARCn=71

-+ 1.2 HRS.

0 3 6 9 I2 IS 18

HOURS

.gure 1. Serum estradiol-17B levels of women undergoing abortion with intra-amniotic, extra-amniotic or intra-muscular administration of lS(S)lS- methyl-prostaglandin F The results are expressed as the mean of individual cases.

-aSEM of percent change

MAY 1976 VOL. 11 NO. 5 921

PROSTAGIANDINS

+ 501 O-4 INTRA-AMNIOTIC tn: 8)

w 70-

P

2 60- v

5 50- w

: aw

40-

30-

1

ti6~0+2.itiRS.

1 I I I

0 3 6 9 12 15 I8 21

HOURS

Figure 2. Serum progesterone levels of women undergoing abortion with intra-amniotic, extra-amniotic or intra-muscular administration of lS(S)lS- methyl-prostaglandin Fzcr . The results are expressed as the mean + SEM of percent change of individual cases.

922 MAY 1976 VOL. 11 NO. 5

PROSTAGLANDINS

M INTRA-AMNIOTIC (n=lO)

+30-

+20_

+10.

100

20

IO

1 ’ \ I’ \ /

/’ \ 1

/’ \ \ \

113.2d.7 HRS.

I 1

0 3 6 9 I2 15 18

HOURS

Figure 3. Serum human placental lactogen levels of women undergqing abortion with intra-amniotic, extra- amniotic or intra-muscular administration of 15(S)15-methyl-prostaglandin Fzu . The results are expressed as the mean + SEM of percent change of individual cases,

MAY 1976 VOL. 11 NO. 5 923