A. B. M. Anderson

SIGNIFICANT FALL IN PROGESTERONE AND RISE IN ŒSTRADIOL LEVELS IN HUMAN PERIPHERAL PLASMA BEFORE ONSET OF LABOUR

Abstract Plasma progesterone and œstradiol17β levels have been measured serially in thirty-three obstetrically normal young primigravidae from the 20th week of pregnancy up to and during spontaneous labour. Hormones were measured by radioimmunoassay using specific antisera. A significant fall in progesterone and rise in œstradiol occurred during the 5 weeks preceding labour. The plasma progesterone and œstradiol concentrations during labour were no different from those found in the week before labour. These changes are consistent with those found in other species and suggest that the onset of labour in human pregnancy occurs after the withdrawal of an inhibitory effect of progesterone on the myometrium and at a time of relative oestrogen dominance.

REDUCTION OF MENSTRUAL BLOOD-LOSS BY PROSTAGLANDIN-SYNTHETASE INHIBITORS

Six patients with menorrhagia due to dysfunctional uterine bleeding and one patient with an intrauterine contraceptive device were treated with prostaglandin-synthetase inhibitors in an attempt to reduce their excessive menstrual blood-loss. Mefenamic acid (six patients) or flufenamic acid (one patient) taken during menstruation for 2-3 cycles reduced menstrual loss in each patient. These preliminary observations suggest a new treatment for a common gynaecological problem and could imply that prostaglandins are involved in the aetiology of excessive menstrual blood-loss in such patients.

Risk of pre-term delivery in patients with previous pre-term delivery and/or abortion.

Patients with a history of two or more pregnancies which ended spontaneously before 37 weeks gestation had an increased risk of spontaneous pre‐term labour and delivery in future pregnancies. This increased risk related mainly to previous second trimester abortions and not to previous first trimester abortions. Patients with one previous spontaneous pre‐term labour and delivery had a 37 per cent risk, and those with two or more pre‐term deliveries a 70 per cent risk of again delivering pre‐term. There appeared to be no beneficial effect of cervical suture on the incidence of pre‐term delivery in these patients.

PROSTAGLANDINS IN THE HUMAN UMBILICAL CIRCULATION AT BIRTH

Prostaglandin E (PGE), prostaglandin F (PGF) and 13, 14‐dihydro‐15‐keto‐prostaglandin F (PGFM) have been measured in umbilical cord plasma obtained immediately after delivery of the baby before clamping of the cord. In general the prostaglandin levels followed the pattern PGFM>PGE>PGF. A significant arterio‐venous difference was demonstrated only for PGE with raised venous levels (P<0.01). In cord blood samples obtained from infants whose mothers had received epidural anaesthesia, no arterio‐venous difference for PGE could be demonstrated although the mean levels were not significantly different from controls. The concentrations of prostaglandins in Umbilical cord plasma proximal to the placenta were found to rise continuously from the time of delivery of the baby with no significant changes after cord clamping or placental delivery. The possible physiological significance of these findings is discussed.

Plasma oxytocin concentrations during the menstrual cycle

Concentrations of oxytocin have been measured in plasma samples obtained daily from 6 women throughout complete menstrual cycles. Measurements of menstrual blood loss and plasma levels of luteinizing hormone (LH), progesterone and 17beta-oestradiol suggested that normal ovulatory cycles were studied. A significant elevation in the circulating concentration of oxytocin was found in association with peak levels of LH. It is suggested that oxytocin may have a role in the process of ovulation in the human female.

MATERNAL URINARY ŒSTROGEN EXCRETION AS EVIDENCE OF A FŒTAL ROLE IN DETERMINING GESTATION AT LABOUR

Abstract Urinary excretion of oestriol, oestrone, and pregnanediol was measured at the 34th and 37th weeks of gestation in 35 healthy young primigravidae having a normal pregnancy and in whom the onset of labour was spontaneous or induced 12 days or more past term. At the 34th week there was a significant correlation between the level of urinary oestriol and oestrone and gestation at the subsequent onset of labour; the higher the oestriol output or the lower the oestrone, the nearer was delivery. At the 37th week the relation between oestriol excretion and gestation at labour was still significant but at a lower level, and there was no correlation between oestrone and the time of delivery. No association was found between pregnanediol excretion at 34 or 37 weeks and the stage of gestation at which delivery eventually took place. These results support the concept of a foetal role in timing the onset of labour in human pregnancy.

RELEASE OF PROSTAGLANDINS AFTER AMNIOTOMY IS NOT MEDIATED OXYTOCIN

The rise in peripheral plasma levels of 13,14‐dihydro‐15‐keto‐prostaglandin F (PGFM) following amniotomy has now been shown to be maximal within five minutes of the procedure, and levels remain elevated for at least 30 minutes. There was no change in plasma oxytocin levels with amniotomy and therefore a local mechanism for prostaglandin release has been postulated.

PLASMA STEROID CHANGES IN PRE‐TERM LABOUR IN ASSOCIATION WITH SALBUTAMOL INFUSION

Serial measurements of peripheral plasma concentrations of progesterone and oestradiol‐17β were made in 23 women with singleton pregnancies who were given intravenous salbutamol in an attempt to inhibit pre‐term labour. Mean levels of both hormones fell significantly during salbutamol infusion but returned to pre‐treatment levels after therapy was stopped. Plasma human placental lactogen concentrations did not change during salbutamol infusion, suggesting that the fall in steroid hormone levels was unlikely to be an effect of altered uterine or placental blood flow.

The influence of spontaneous and induced labour on the rise in prostaglandins at amniotomy

Summary. Maternal peripheral plasma levels of 13, 14‐dihydro‐15‐keto‐prostaglandin F (PGFM) were measured immediately before and 5 min after amniotomy. Three groups of women were studied: women in late pregnancy; women in spontaneous labour; and women who had received intravaginal prostaglandin E2 (PGE2) pessary. There was no significant difference in the magnitude of the rise in PGFM after amniotomy in late pregnancy or during spontaneous labour suggesting that labour has no influence on the release of prostaglandin F2α (PGF2α) induced by artificial rupture of the fetal membranes. However, local administration of PGE2 before amniotomy caused a greater rise in PGFM suggesting that PGE2 can influence the release and/or metabolism of PGF2α.

Oxytocin in the fetal and maternal circulations during induced and spontaneous parturition in sheep

Oxytocin has been measured in fetal and maternal plasma samples obtained serially from 6 sheep during late pregnancy, spontaneous labor and labor induced by intrafetal infusion of Synacthen (ACTH1-24). Fetal plasma contained significantly (P less than 0.001) greater concentrations of oxytocin than maternal plasma. Concentrations of oxytocin rose in maternal plasma during the later stages of spontaneous and induced labor, whereas concentrations in fetal plasma did not exhibit a consistent trend.