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[Progesterone and pregnandiol levels in the pripheral blood and urinary pregnandiol level in pregnant women before and after delivery].

Determinations of progesterone and pregnandiol in blood and pregnandiol in urine of 18 women in the last 9 days of pregnancy, in labour and in the first 7 days of puerperium were performed. The results were conformable to the data of other authors except the levels of progesterone in blood after labour. It was established that the levels of progesterone and pregnandiol in blood are increasing till the moment of labour. The levels of pregnandiol in urine have a tendency to decrease from the 5-th day before labour. The results are discussed in the aspect of Csapo's theory of placental block.

Female↗

An endocrine model for the diagnosis of intrauterine growth retardation as demonstrated by the determination of total estrogen and pregnandiol 24-hour urinary excretion in 222 at risk pregnancies.

A reliable method for surveillance of chronic impairment of nutritive placental function is described. The techniques are simple, tested for their reliability, without need for isotopes or special apparatus and hence inexpensive. Using 222 pregnancies at risk it is shown that the simultaneous determination of a fetal (estrogen) and a placental (pregnandiol) parameter makes the early diagnosis of intrauterine growth retardation possible. Estrogen diagnosis alone has a reliability of 90.1% with 1.8% falsely pathological and 8.1% falsely normal findings (Tab. I). Simultaneous pregnandiol determinations increase the number of falsely pathological findings to 8.1% but reduce that of falsely normal ones to 2.7%. No small for date (SGA) infants are found here. It consists of 5 cases of imminent (3 times actual) premature delivery and one postmature one. Hence our technique indicates the risk of intrauterine growth retardation in all cases but not the risk of premature or postmature delivery. Early diagnosis (from week 20) indicates that impairment of placental function as indicated by decreased pregnandiol excretion, occurs weeks or months earlier than decreased estrogen excretion (Fig. 1). This can be explained only by assuming that the rate of estrogen excretion is usually not dependent on the placenta but on the capacity of the fetal adrenals and liver. Thus our results indirectly confirm those of others who claim that the fetus can synthetize estrogen precursors without the need for placental pregnenolon by using acetate. Thus it appears that the synthetic pathway is independent of the placenta at the beginning plays a quantitative role also. Since the placenta can form aromatic compounds even when its nutritive function is severely impaired, our finding is further proof that estrogen excretion reflects fetal and not fetoplacental well-being. It follows that pathological estrogen excretion indicates fetal injury that has already occurred. The requirement that a sensitive parameter of placental function be hence determined in time is met by pregnandiol assays. Low pregnandiol excretion often precedes low estrogen excretion which leads to a SGA infant, indicating that pregnandiol excretion is closely correlated to placental nutritive function. Synthetic reactions in the fetus require energy and hence depend on the placenta. Normal estrogen excretion frequently observed in the presence of prolonged decreased pregnandiol excretion must hence indicate that the fetus can compensate for placental insufficiency. In the placenta this can be demonstrated by hyperplasia of the capillaries. This is reflected in the undulating excretion of pregnandiol (Fig. 1), where compensation (new vessel formation) and depression (lesion of vessels) make these contradictory placental processes "visible". The functional unity of the fetus and the placenta is finally also demonstrated by the fact that each prolonged compensatory phase of the placenta is reponded to by the fetus with a clearly compensatory excretion of estrogen (Fig. 1)...

Adult↗

Effect of pregnandiol on caffeine metabolism in female rats.

Three groups of six 5-week-old Sprague Dawley female rats received i.p. injections of pregnandiol, 1.25, 2.50 or 5 mg/kg, respectively, in triolein daily for 7 days. Caffeine metabolism was studied in liver slices on day 8 by HPLC. Only primary metabolites were formed. N-1 demethylation was the most important pathway (theobromine represented 51% of total dimethylxanthines). Unlike in human in vitro or in vivo, 1,3,7-DAU (6-amino-5-(N-formylmethylamino)-1,3-dimethyluracil) was an important metabolite (9.7% of total caffeine metabolites). Pregnandiol inhibited N-1, N-3 and N-7 demethylation in vitro (-33%, -33% and -28%, respectively, at 5 mg/kg/day), but it had no effect on N-1 demethylation at 1.25 or 2.50 mg/kg/day. Pregnandiol at all doses had no effect on 1,3,7-trimethyluric acid and 1,3,7-DAU formation. These results are consistent with the hypothesis that C-8 hydroxylation and demethylation of caffeine are mediated by different isoenzymes. They indicate that pregnandiol is a potent inhibitor of microsomal drug metabolism, specifically of cytochrome P450 IA, which could explain the immaturity of some metabolic pathways of caffeine in neonates.

Animals↗

Progesterone and human chorionic gonadotrophin in serum and pregnandiol in urine in threatened abortion.

Progesterone and human chorionic gonadotrophin (HCG) in serum and pregnandiol in urine were measured in 64 patients admitted to hospital because of threatened abortion. Blood samples were taken and urine specimens collected at regular intervals during admission and after discharge during the rest of the pregnancy. A reference range was worked out for each hormone based on the hormone values obtained from the pregnancies proceeding to term. The predictive significance of values within and below the reference range was determined, for the initial sample and for serial samples. An association between hormone levels and outcome of pregnancy was observed but it is concluded that both single and serial determinations of progesterone and pregnandiol and serial determinations of HCG are unsatisfactory for the evaluation of threatened abortion. However, an initial progesterones value below the reference range and HCG values below 10,000 mIU/ml between the 8th and 15th week of pregnancy was in every case always followed by spontaneous abortion. A hormonal test of fetoplacental origin is recommended for monitoring threatened abortion.

Abortion, Threatened↗

Urinary oestrogens and pregnandiol in breast cancer patients.

Urinary E1, E2, E3 and pregnandiol were determined in 60 premenopausal and 12 postmenopausal breast cancer patients before and after mastectomy, as well as in 30 normal females. Data obtained showed great individual variation. The general findings were low oestrogens in young patients, normal in old premenopausal patients and high in postmenopausal patients. The ratio E3/E1 + E2 showed comparatively high values in premenopausal patients. Pregnandiol excretion was low in almost all premenopausal patients with the exception of few cases in the different age groups. The changes in the hormonal pattern in premenopausal breast cancer patients, before and after mastectomy, and of postmenopausal patients were discussed in view of the current literature.

Adult↗

[Pregnandiol and progesterone in the umbilical cord blood in comparison with the level of both hormones in the maternal peripheral blood].

The levels of pregnandiol and progesterone in venous and arterial umbilical blood in 18 neonates were determined. The statistical analysis has shown that the values of both hormones were higher in venous blood. The comparison of the results with the levels of these hormones in maternal peripheral blood was performed. No correlation was found.

Female↗

Urinary pregnandiol-3-glucuronide and estrone conjugates to creatinine ratios in early pregnancies complicated by vaginal bleeding.

There is no simple and rapid test available to predict the outcome of an early pregnancy complicated by vaginal bleeding. In this prospective study, 15 women with normal pregnancies collected a weekly urine sample between 6 and 13 weeks' gestation. A single random urine sample was obtained from 15 women with bleeding who continued to carry their child and 50 women who proceeded to have a spontaneous abortion (SAB). Pregnandiol-3-glucuronide (PDG) was determined with the use of enzyme-multiplied immunoassay technique (EMIT) and estrone conjugates (E1C) were measured by radioimmunoassay (RIA). The ratios of these metabolites to creatinine (C) were calculated. PDG/C ratios in normal women rose gradually from 6 weeks on. All women with bleeding during a normal pregnancy had ratios in the normal range, but 94% of women with a SAB had ratios below the normal range. The E1C/C ratio remained unchanged from 6 to 11 weeks and then rose rapidly. Until 11 weeks, there was no clear separation between the E1C/C ratios of the women with a SAB and the women with bleeding who continued their pregnancies. The prognosis of threatened abortion can be made by a urinary PDG/C ratio but not by an E1C/C ratio. EMIT is simple and quick and uses technology present in many laboratories.

Abortion, Threatened↗