Effect of Oestrogens on Myometrial Contractions

Abstract

Some observations by Jeffcoate (1938) (Reynolds, 1949).The work of Csapo (1956) shows that during pregnancy progesterone reduces myometrial contractility. Short and Moore (1959) have shown that at the onset of labour there is no fall in blood progesterone, nor according to Shearman (1959) does the output of urinary pregnanediol decline in the weeks before the onset of labour. It is possible that toward the end of pregnancy some endocrine factor which overcomes the progesterone block on myometrial contractility comes into play. During pregnancy large amounts of oestriol are excreted, and in a recent study it was shown that a sharp rise in oestriol excretion occurs toward the end of pregnancy (Klopper et al., 1961). It seemed possible, therefore, that this oestrogen in particular is concerned in bringing about an endocrine milieu in which the myometrium will respond to the mechanical stimuli which bring about labour.In all the literature on the effects of oestrogen in labour we have been unable to find records of a trial controlled in accordance with modern statistical criteria. We therefore set out to test the efficacy of oestriol in such a trial. When the figures of this " double-blind " trial were analysed it became of interest to determine whether the results were peculiar to oestriol or would occur with other oestrogens also. This was therefore followed by a second, larger, trial in which the effects of oestriol were compared with those of a synthetic oestrogen, stilboestrol. MethodsFor the first trial a small homogeneous group of subjects who would show minimal variation in their obstetric performance was used. Women who were to be subjected to artificial rupture of membranes for clinical reasons were selected, but those with twins, hydramnios, antepartum haemorrhage, intrauterine foetal death, or previous caesarean section were excluded. The trial was limited to primigravidae under 30 years old who were within 21 days of their expected date of delivery. Messrs. Organon kindly supplied us with tablets containing 10 mg. of oestriol and a set of identical placebo tablets. The tablets for each patient were dispensed in advance by our statis;tical section and none of the observers knew whether oestriol or placebo tablets had been given. Oral administration was started 24 hours before the rupture of membranes and continued until delivery. The dosage was two tablets (20 mg.) initially, followed by one tablet (10 mg.) six-hourly thereafter. A record of possible side-elfects such as vomiting or flushing was kept for each patient, but such occasional phenomena were equally distributed and it proved impossible to tell from the patient's clinical behaviour whether she was having oestrogen or not. The trial was discontinued and the code broken when 44 patients had been treated.For the second trial a larger variety of patients was included and a greater number were studied in order to exclude chance concentrations of aberrant cases. The subjects in this trial were divided into four groups; (I) primigravidae 29 years old ...

Effect of Intra-amniotic Oestriol Sulphate on Uterine Contractions

“…Our attention was first directed to a possible specific role of oestriol by the finding of Klopper and Billiewicz (1963) that women with a higher urinary oestriol excretion tended to go into labour before those with a lower output. Klopper and Dennis (1962), however, failed to find any effect from oestriol or stilboestrol given by mouth on the induction-delivery interval or on the length of labour following artificial rupture of the membranes. Thus in the light of subsequent findings the absence of any demonstrable effect following oestriol by mouth was probably due to two reasons.…”

Urinary oestriol after intra-amniotic injection of oestriol sulphate.

“…It would be a therapeutic advance if the onset of labour could be influenced by the administration of such a physiological compound. In our previous trial (Klopper and Dennis, 1962), we were concerned with the effect of oral administration of free oestriol on the onset of labour. It may be that the failure of oestriol to have any effect on that occasion was due to the fact that insufficient steroid or an inactive combination reached the myometrium and that manipulations of the endocrine environment of the myometrium from within the uterus may be more successful in imitating the natural course of events.…”

Oestrogens alone or with amniotomy for cervical ripening or induction of labour

“…The oestrogen preparations used varied. One study (Klopper 1962) used oral tablets, one used intravenous infusion (Pinto 1967), two used extra-amniotic oestrogen (Peedicayil 1990, Quinn 1981) and three used intravaginal oestrogen cream (Larmon 2002, Magann 1995, Tromans 1981 Five studies compared oestrogen with placebo. The oestrogen was delivered as oral tablets in one trial (Klopper 1962), as an intravenous infusion in another (Peedicayil 1990), as an extraamniotic formulation in two studies (Pinto 1967;Quinn 1981) and a vaginal oestrogen cream in one study (Larmon 2002).…”

“…One study using intravaginal cream in the intervention arm (Larmon 2002 with 87 women) was undertaken in an outpatient setting. Three studies did not state if the study had been conducted in an inpatient or outpatient setting, the first used oral oestradiol tablets (Klopper 1962), the second (Magann 1995) used vaginal cream, and the third (Peedicayil 1990) used extra-amniotic oestrogen.…”