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11 páginas Objectives: To evaluate the efficacy and safety of estriol for the treatment of vulvovaginal atrophy in postmenopausal women. Methods: A systematic literature review was performed. We searched the following electronic databases: Medline, Cochrane, Embase, Lilacs, CINHAL and Google Scholar. The studies selected included controlled clinical trials and quasi-experimental studies. Selections were made in pairs and independently, first by title and abstract and then complete texts. Results: We identified 188 studies, 22 of which met the inclusion criteria; 13 were controlled clinical trials and nine were quasi-experimental, and 1217 women were included. These studies confirmed the efficacy of local estrogens to treat symptoms of vulvovaginal atrophy with few adverse effects reported. Following treatment, serum estriol levels rose, peaking at 1 h. At the 6-month follow-up, there was no increase in serum estriol in treated women. Conclusions: The available evidence (of low and moderate quality) shows that, when administered vaginally, estriol preparations appear to be safe for women who have risk factors related to systemic estrogen therapy.

Objective: To assess the estrone (E1), estradiol (E2) and estriol (E3) blood level and its ratio (E2:E1, E2:E3 and E1:E3) between women with and without endometriosis. Method: We performed an analytical cross sectional study with 27 women with endometriosis and 27 women without endometriosis who met the inclusion criteria. The samples were recruited in Dr. Cipto Mangunkusumo hospital and other satellite hospitals from October 2012 to April 2013. The blood level of estrogen metabolites was examined by enzyme-linked immunosorbent assay (ELISA). Comparison between the two groups was analyzed by using Mann- Whitney test. Result: The level of estrone was found to be lower in endometriosis group compared to that in the control group (54.66 pg/ml vs 73.52 pg/ml, p=0.229). Similarly, the levels of estradiol and estriol were lower in endometriosis group (29 pg/ml vs 35 pg/ml, p=0.815 and 1.11 pg/ml vs 1.67 pg/ml, p=0.095, consecutively). The E2:E1 ratio was higher in endometriosis group (0.51 pg/ml vs 0.38 pg/ml, p=0.164), as well as E2:E3 ratio (26.53 pg/ml vs 21.11 pg/ml, p=0.223) and the E1:E3 ratio (58.55 pg/ml vs 50.28 pg/ml, p=0.684). However, all those differences were not statistically significant. Conclusion: The estrone, estradiol and estriol levels in women with endometriosis were lower compared to those in women without endometriosis. The ratio of E2:E1, E2:E3 and E1:E3 were higher in endometriosis group. However, all those differences failed to reach statistical significance. [Indones J Obstet Gynecol 2014; 3: 127-131] Keywords: endometriosis, estradiol, estriol, estrogen, estrone

Objective: To know the difference of salivary estriol level between patients with preterm birth and preterm pregnancy of 32-36 weeks and to determine the correlation between the level of estriol in saliva and the incidence of preterm delivery. Methods: This research was a cross-sectional studies of 80 patients in Dr. Hasan Sadikin Hospital and its networks. The subjects are 40 patients in labor and 40 patients in preterm pregnancy, that met the inclusion criterias during the period September 2011 to November 2011. We took the salivary sample and examine the level of estriol. The data were analyzed by Shapiro-Wilk and Mann Whitney test. Result: The study found that the difference of salivary estriol levels in preterm labor and preterm pregnancy groups was statistically significant (p

A radioimmunoassay for the measurement of estriol in the saliva of pregnant women was developed. The effect of stimulation of saliva flow by citric acid was investigated and found to not affect estriol concentration significantly. Also, estriol levels were not significantly affected by the size of sample collected. Estriol was measured during pregnancy in the saliva of four women. There was an increase in concentration at later gestations although the concentration in saliva was much less than in plasma. This study suggests that assay of salivary estriol will be a convenient method of monitoring material estriol levels during pregnancy.

Among various fetal and placenta/ function tests, the determination of estriol levels in the urine is an indispensable one. In the study presented herein, the basic and clinical aspects of the ESTROTEC kit method for determining estriol levels in the urine of pregnant women which utilizes the HAIR were examined. Estriol levels determined by the use of this kit were very closely correlated with the levels determined by the chemical assay utilizing Amberlite XAD-2, while the kit is simple in procedure, does not need any special laboratory equipment and apparatus, and yields its result in a short time. For these reasons, it is of high clinical value as a prospective method for large scale screening of fetal and placenta/ functions. In order to judge with estriol levels fug/ml) in the urine specimens collect randomly at single micturition that fetal placental functions are within normal range, it will be necessary that the levels remain not lower than 16 ugjml (positive reaction in 160 times dilution of urine) in the 37th week of pregnancy and the stage beyond it. Taking into account the fact that there is a limit of estriol levels determined by this method such as an erroneous reading of the reaction in one test tube yields a considerably large error in terms of estriol level, it is necessary to observe the pattern of the levels in the course that follows, and considering that the cases with estriol levels of lower than 16 ugjml in the urine specimens collected randomly at single micturition are in fetal and placental hypofunction, it is important to perform fetal and placental function tests in further detail.

Objective: The purpose was to establish saliva as a reliable sample for the determination of estriol levels in pregnant women. Study Design: Literature and laboratory analyses were used to develop an assembly system to collect and analyze saliva for estriol level. Results: An enzyme-linked immunoassay for estriol has been developed to use whole saliva samples. Analytic performance characteristics for the assay have been determined to be appropriate for clinical determination of preterm risk assessment. Conclusion: Saliva can serve as a reliable sample for estriol determination when coupled with an appropriate assay method. (Am J Obstet Gynecol 1999;180:S226-31.)

Objective: The objective was to compare the predictive accuracy (percentage of correct vs incorrect predictions) of salivary estriol levels (SalEst; Biex, Inc, Dublin, Calif) with that of the modified Creasy score for predicting preterm labor followed by preterm delivery. Study Design: A triple-blinded prospective trial was conducted at 8 US centers. Results: Among 601 evaluable patients, serial salivary estriol testing correctly predicted the appropriate outcome 91% of the time and the Creasy scoring method correctly predicted the appropriate outcome 75% of the time (McNemar test P < .001). Among subjects with Creasy scores ≥10 (high-risk group, n = 152), use of salivary estriol testing correctly predicted the end point 87% of the time, compared with only 7.2% correctly predicted by modified Creasy scoring (McNemar test P < .001). Conclusion: Salivary estriol assessment was more accurate in predicting outcome than was modified Creasy scoring. (Am J Obstet Gynecol 1999;180:S214-8)

In this study we report a new triple test that combines serum AFP, urine beta-core fragment of hCG, total urine estriol, and maternal age for calculating individual Down syndrome odds in the second trimester. The urine beta-core fragment/estriol ratio was used as a single screening variable. Analyte levels were measured prospectively in 10 Down syndrome cases and 346 normals. Individual Down syndrome odds were calculated by multiplying the product of the Down syndrome likelihood ratios of serum AFP and urine beta-core/estriol levels by the age-related midtrimester risk. The screening efficiency of an algorithm that combines urine beta-core/estriol with maternal age was compared to one that included serum AFP data. A 90% detection rate for Down syndrome was obtained at a 4.65% false positive rate. This was superior to the 75% sensitivity at 5% false positive rate observed when beta-core/estriol and age alone were used. This new triple test has a higher screening efficiency than that generally reported for the traditional serum triple screen and other urine tests, and it also provides information on the risk of neural tube defects. If confirmed in larger trials, the new algorithm could be used as an alternative to the traditional serum triple screen.

Hormone-mediated quiescence involves the maintenance of a decreased inflammatory responsiveness. However, no study has investigated whether labor induction with prostanoids is associated with changes in the levels of maternal serum hormones. The objective of this study was to determine whether labor induction with dinoprostone is associated with changes in maternal serum progesterone, estradiol, and estriol levels. Blood samples were obtained from 81 pregnant women at term. Sixteen patients had vaginal birth after spontaneous labor, 12 required cesarean section after spontaneous labor and 16 underwent elective cesarean. Thirty-seven patients had labor induction with dinoprostone. Eligible patients received a vaginal insert of dinoprostone (10 mg) and were followed until delivery. Serum progesterone (P4), estradiol (E2) and estriol (E3) levels and changes in P4/E2, P4/E3 and E3/E2 ratios were monitored from admission to immediately before birth, and the association of these measures with the resulting clinical classification outcome (route of delivery and induction responsiveness) was assessed. Progesterone levels decreased from admission to birth in patients who underwent successful labor induction with dinoprostone [vaginal and cesarean birth after induced labor: 23% (P < 0.001) and 18% (P < 0.025) decrease, respectively], but not in those whose induction failed (6.4% decrease, P > 0.05). Estriol and estradiol levels, P4/E2, P4/E3 and E3/E2 ratios did not differ between groups. Successful dinoprostone-induced labor was associated with reduced maternal progesterone levels from induction to birth. While a causal relationship between progesterone decrease and effective dinoprostone-induced labor cannot be established, it is tempting to propose that dinoprostone may contribute to progesterone withdrawal and favor labor induction in humans.

This retrospective analysis of the use of serum estriol levels for antenatal assessment was performed in an effort to determine if routine, late third-trimester, daily serum estriol monitoring of insulin-dependent pregnant diabetic women can still be justified. Estriol profiles of 170 diabetic pregnancies, managed under a consistent protocol of weekly contraction stress tests and daily serum estriol assessments, were reviewed. A total of 4612 estriol determinations were performed. Nearly 4% of the estriol determinations showed a 35% fall from the mean of the previous three highest consecutive values. Forty-seven percent of the patients had at least one fall of this magnitude. Eighty-five percent of the fetal heart rate tests performed in association with an estriol fall were normal. A fall in estriol was not found to be associated with a higher risk of having a positive contraction stress test, either at the time the estriol fall was recognized or at any time during the patient's antepartum course. Although use of this strict protocol combining the use of weekly contraction stress tests and daily serum estriol determinations provided a safe method of antepartum assessment, there is little evidence to support the routine use of daily serum estriol monitoring in insulin-dependent pregnant diabetic women.

Specimens of saliva were obtained from 106 women with normal pregnancies and from 42 women, whose children turned out to small for dates (birthweight below the 10th centile). Saliva estriol was highly significantly (P less than 0.0001) decreased in the group with a newborn with a birthweight below the 10th centile (500 +/- 340 ng/ml, mean +/- SD) when compared with the group with infants whose birthweight was over the 10th centile (813 +/- 449 ng/ml). Estriol determination in saliva seems to be a simple, non invasive method of aiding the detection of fetal growth retardation.

Estriol serum levels, neonatal vitality and stromal villous edema were studied in diabetic pregnancies. The average serum estriol levels in diabetic patients whose placentas had villous edema was 26.45 +/- 9.16 ng/ml. This value was significantly lower than that of the diabetic patients without villous edema (59.26 +/- 12.06 ng/ml). The average serum estriol levels in diabetic patients who gave birth to depressed newborns was 25.68 +/- 9.73 ng/ml. In diabetic women who gave birth to vigorous newborns this value was 56.57 +/- 14.10 ng/ml. The difference was statistically significant. These results and similar findings from other authors are discussed.

A new method of radioimmunoassay (RIA) for serum estriol (E3) which utilizes125I-estriol as a tracer has been developed. This steroid was radioiodinated with chloramine T and purified by Sephadex LH-20 column chromatography. Two hundred and sixty-two samples from 130 normal pregnant patients at different stages of gestation were analysed. From 5 women, blood samples were drawn at 15 min intervals for 1 h. An increase in the circulating levels of E3 was observed throughout normal pregnancy and the results were widely distributed. The episodic fluctuations of E3 showed a variation of 13–20 ng/ml during the same 1-h sampling period. The quality control results showed the viability of this RIA in the determination of serum E3 utilizing the iodinated steroid as a tracer.

Diurnal variations in plasma unconjugated estriol and urinary estriol were assessed in 12 pregnant women during the 3rd trimester of uncomplicated pregnancies. Commercially available 125I-labelled radioimmunoassay kits were used. The preliminary data presented here support the hypothesis that there is no circadian rhythm of unconjugated plasma estriol in normal late pregnancy. Total urinary estriol reaches a nadir during the sleep hours (24.00-6.00). A biological carrier 'stick' for estriol measurements might serve as test of choice in the monitoring of high-risk pregnancy as well as for identifying pregnancies complicated by chromosomal abnormalities (e.g., Down's syndrome).

Fetal movements, fetal heart rate patterns, and serum estriol levels were prospectively monitored in 91 high-risk and normal pregnant women. In four women, there was cessation of fetal movements. In three of these cases, there were pathologic changes in fetal heart rate patterns, with one neonatal death. Of the 87 women who did not demonstrate cessation of fetal movements, one had changes in fetal heart rate patterns. The difference between the two groups was statistically significant (Z test: p less than 0.001). No correlation was found between fetal movements and serum estriol levels in this study. Daily recording of fetal movements can be used as an effective screening test, with high sensitivity and specificity for the fetus in utero. Cessation of fetal movement places the fetus in a high-risk category and should alert the physician to the need for non-stress tests.

Three perinatal health indicators (serum human placental lactogen [hPL] levels, serum free estriol [E3] levels, and OCT) were simultaneously completed in 149 high-risk women who were more than 34 weeks pregnant. There was a significant correlation between the hPL and E3 results (r = 0.28, p less than 0.01). There was a 15.4% positive OCT result rate and the blood hormone values for the negative and positive OCT groups were compared. There was a significantly lower hPL value in the positive OCT group (4.7 +/- S.E.M. 0.4 vs. 6.2 +/- S.E.M. 0.2 micrograms/ml for positive and negative groups, respectively), whereas the free E3 levels were not different in these two OCT groups (14.8 +/- S.E.M. 1.5 vs. 16.3 +/- S.E.M. 0.7 ng/ml for positive and negative groups, respectively). The free E3 value did not help in predicting the OCT result as the low free E3 subgroup had the same frequency of positive OCT result as did the over-all group. There was a highly significant increase in the positive OCT results (42.9%) in women with a low hPL value (p less than 0.01). In those women with an hPL value of 6.0 microgram/ml or more there were only 8% positive OCT's. It is concluded that on hPL test at about 34 weeks of gestation could be used to screen pregnant women, and if the value were low (less than 4.0 microgram/ml) an OCT evaluation test would be indicated, for there is a very high frequency of positive results in that subgroup of women.

The DHEA-S loading test was used to evaluate fetoplacental function in 105 pregnant women. The test gave 84% correct results in the 43 cases of fetoplacental deficiency. However, in the control group of 62 subjects it gave only 42% correct results. Measurement of estriol excretion in maternal urine is one of the biochemical tests routinely carried out on pregnancies at risk. The prognostic value of the test is, however, restricted by the big daily fluctuations in estriol excretion. Fluctuations of between 60% and 140% have been reported (12). In addition to the routine determination of estriol levels, the following tests are of importance for the biochemical evaluation of fetoplacental function: 15α-hydroxyestriol (7), pregnanediol (8), placen-tal lactogen (8), heat-stable alkaline phosphatase (8, 14), and finally, the test discussed in this publication, the dehydroepiandrosterone sulphate (DHEA-S) loading test (4). The present investigation evaluated the usefulness of this test in the early detection of ...

To determine the relationship of plasma estriol and retarded intrauterine fetal growth, 14 primiparous and 4 multiparous pregnant women with suspected intrauterine growth retardation were studied by radioimmunoassay of weekly blood samples, and compared with 25 normal pregnant women as controls. The plasma estriol levels in all 4 hypertensive mothers who gave birth to infants of low birthweight were all much less than the normal averages. Estriol levels were also less than average, though not as significantly, in 7 of the 9 normotensive patients with low birthweight infants, and in the 5 patients with low weight gain but normal-weight infants. Thus, a dramatic reduction in estriol concentration occurs in hypertensive patients with intrauterine fetal growth retardation. No correlation was found between predelivery plasma estriol concentration and infant birthweight or incidence of fetal distress. Though both have growth retardation, hypertensive patients have a much higher incidence of fetal distress (75%) than normotensive patients (29%). Further research is being conducted on the relationship of plasma estriol and blood pressure in this regard.

Twenty-one patients classified as “high-risk” problems were observed to assess fetal well-being, size, and growth with repeated plasma estriol and ultrasonographic measurements. Estriol levels were of value in the estimation of the fetal condition if fetal size and age were known. When serial plasma estriol measurements and ultrasonographic cephalometry are used together, the fetal well-being, size, and growth may be more accurately assessed and the risk of prematurity greatly reduced. Further combined studies are needed to clarify the relative values of estriol levels and ultrasonography in the assessment of fetal status. The cirteria of normal fetal growth and welfare in high-risk situations must be established in an effort to decrease high perinatal loss rates.

Serial plasma estriol determinations were conducted in the third trimester of human pregnancy on 22 normal, 25 diabetic, and 16 toxemic patients. In addition, 10 cases of suspected fetal death were evaluated. In normal pregnancy the levels rise in a generally regular fashion as pregnancy proceeds, increasing about fivefold in the last trimester. However, the individual curves vary considerably. The average plasma estriol level at term is about 27 μg per 100 ml. with a range between 10 and 55. The plasma estriol levels of the diabetic patients (Classes A, B, and C) in good control, were not statistically different from those of the normal patients. The toxemic patients could be classified into three groups according to their estriol levels. Those with severe symptoms and small fetuses had correspondingly low levels. The patients under good control had normal values while three patients with renal involvement superimposed on toxemia had surprisingly high levels. The values for patients with dead fetuses were extremely low. Although a larger number of cases involving fetal jeopardy must be studied before the contribution of plasma estriol determinations toward the improvement of fetal salvage rates can be assessed, the potential advantages of plasma assays over urine assays in this regard are discussed.

Plasma estriol levels during normal labor and labor induced by oxytocin infusion were determined by a method developed in this laboratory and the results were compared. In the first category of 18 women who delivered spontaneously the plasma estriol concentrations remained constant in 15 cases, rose in 2 and decreased in 1. In the second category of 14 women in whom labor was induced electively by intravenous oxytocin infusion, the plasma estriol levels rose significantly (average rise =71%) in 8 cases, remained unchanged in 5 cases and decreased in 1 case. The difference between the 2 categories is significant at the 5% level. The origin of the increased plasma estriol in labor is not known but some theoretical possibilities relating oxytocin to estriol are discussed.

Serial plasma estriol levels were determined in 51 uncomplicated and 58 complicated pregnancies. Additionally, in 13 uncomplicated, 16 toxemic, and 4 diabetic pregnancies, urinary estriol levels were also collated with plasma estriol values. Highly significant correlation was observed between plasma and urinary estriol levels in both uncomplicated and complicated pregnancies. In 5 of 37 toxemic patients, unusually high plasma estriol levels were found, though no definite correlation could be established between estriol levels and the severity of toxemia. From the thirty-fourth week of gestation, plasma estriol levels in diabetic and pre-eclamptic patients were essentially the same as those found in uncomplicated pregnancies; however, the levels in hypertensive pregnant patients were significantly lower. Broad guidelines have been postulated to correlate plasma estriol levels with fetal status from the thirty-sixth week of gestation to term. Levels of less than 5 μg per 100 ml. of plasma in this period are not compatible with a living fetus; values of less than 10 μg per 100 ml. with a dropping estriol pattern are indicative of fetal distress.

This presentation relates to multiple facets of amniotic fluid changes associated with fetal life. The composition of amniotic fluid is contrasted with that of fetal urine and the implications with respect to the origin of amniotic fluid are discussed. Amniography, fetal radiography, and angiography are presented with respect to recent developments and the role that these modalities have in assessing the fetal status. Amniotic fluid analyses are presented with respect to (1) management of Rh sensitization, (2) fetal maturity, and (3) esterase levels. A correlation is made between the presence of meconium in amniotic fluid and the fetal outcome. Maternal urinary estriol levels appear to be more closely correlated with the fetal status than previously reported in connection with erythroblastosis fetalis.

Urinary estrogen excretion patterns were determined by means of gas chromatograpby during early, middle and late pregnancy in the rhesus monkey (Macaca mulatta). Estrone, estradiol-17β and estriol levels increased from early to late pregnancy. Average increases were: estrone, 2.6 fold; estradiol-17β 4.7 fold; and estriol 4.5 fold.

The results of 24 hour urinary estriol determinations in 47 prolonged gestations, 25 pre-eclamptic or chronically hypertensive gravidas, and 9 diabetic pregnancies are presented. The use of urinary estriol levels in determining the method and timing of delivery in these 81 complicated pregnancies is discussed. The fetal outcome, including case reports of 4 perinatal deaths, is provided. A brief critical evaluation of the usefulness of urinary estriols is included. "Serial urinary estriol determinations … offer promise of a useful laboratory aid and the only objective method thus far available to supplement clinical judgment." 1

Urinary estriol levels were obtained from 31 normal pregnant women and from 186 women attending the prenatal/diabetic clinic. The latter included 137 Class A (studied in three groups according to the degree of carbohydrate intolerance present), 32 Class B, 7 Class C, and 10 Class D patients. The results were not used to influence the clinical management. Mean values for the entire abnormal group were calculated weekly from 28 weeks until term. These values were used as the basis for comparison of the different classes studied. Only Classes C and D demonstrated depressed levels of excretion. Sixteen perinatal deaths occurred and 9 were considered avoidable had the estriol results been taken into consideration. The “estriol-preventable deaths” are described in detail. It is concluded that the assay presents a potentially valuable adjunct to the clinical management of the pregnant patient with disordered carbohydrate metabolism.

A method has been developed for the determination of plasma estriol in the second half of pregnancy. Only 1 ml of plasma per analysis is required and 5 determinations in duplicate can be completed in 5–6 hr. Besides passing the usual tests of precision, sensitivity, reproducibility and specificity, accurate values are attainable because each determination is corrected for methodological losses by the isotope technique. Values at term in 34 normal pregnancies ranged from 9.3 to 56 μg/100 ml with a mean of 27 and a median of 25. In normal pregnancy the estriol levels rise regularly as pregnancy progresses, increasing about 5-fold in the third trimester. A rapid fall off in the early post-partum period (1–2 hr) to values one half those obtained just prior to delivery was observed. Glucose, up to 600 mg/100 ml, does not interfere with the analysis.

mately 35 to 36 weeks’ gestation. Biweekly urinary estriol levels were reported as normal. An oxytocin challenge test on November 28, 1975, was positive and suggestive of a loss of uteroplacental oxygen transferring capacity. A cesarean section was performed on November 28, 1975. A viable male infant of 9 pounds, 4 ounces, was delivered. The mother and baby did very well following the delivery. Following delivery, the patient had menstrual periods about every 35 days. An endometrial biopsy specimen was taken on August 24, 1976, the 20th day of the cycle. The tissue was reported as early secretory endometrium, free of any tumor. Another endometrial biopsy specimen was taken in January, 1977. Again the pathology report stated the tissue was free of tumor. She has expressed a wish to become pregnant again.

To study the biologic effects of estriol, 14 hypogonadal patients received either vaginal or oral estriol. The vaginal administration of 0.5 mg of estriol to five patients resulted in increases of serum unconjugated and conjugated estriol levels which were maximal at 1 and 2 hours following treatment (161 ± 59 [SE] pg/ml and 762 ± 146 pg/ml, respectively). Significant suppression of luteinizing hormone (LH) to 84% and 81% of base line levels was observed at 2 and 3 hours following treatment, respectively (P Estriol is a weak estrogen. Rapid conjugation of the orally administered estriol renders it a weakly potent estrogen. Estriol administered vaginally is conjugated less rapidly than orally administered estriol, thus rendering it more biologically potent.

Summary We compared here the correlation between the colorimetric method and some other precise testing methods. The results are summarized as follows. 1 A good correlation was observed between the colorimetric method and the LAIR (Neoest, New Estrotec) and HAIR (Estrotec) methods estimating E3 in the urine. The calculated correlation coefficients between the E3 kit and the Neoest, New Estrotec and Estrotec kits were 0.865, 0.729 and 0.788, respectively. Compared to the E3 kit, the LAIR methods tended to give somewhat lower E3 levels. 2 Among 15 samples with below 10μg/ml E3 in the urine by the E3 kit, 13 samples(86.7%) also showed coincident results by the LAIR method (Neoest). 3 A good correlation between serum E3 level and urine E3 level was observed at the low levels. Eight patients with a low serum E3 level of below 10ng/ml revealed low urine E3 levels of below 5μg/ml. Among 14 patients with low serum E3 levels of below 20ng/ml, 12 showed E3 levels in the urine of 5μg/ml, and the other 2 had urine levels below 10μg/ml. 4 It is concluded that the LAIR methods are useful in the mass screening of dysfunction of the feto-placental unit in pregnancy in their rapidity and simplicity, although the E3 levels so obtained tend to be somewhat lower than those obtained by the colorimetric method.

Serum estriol levels have been investigated in patients receiving short-term (2 h) intravenous prophylactic (8 women) or therapeutic (8 women) Β-receptor agonist treatment. None of the patient groups responded with a change in unconjugated estriol or in total serum estriol. This was the case whether isoxsuprine or terbutaline was used. The importance of future studies on estriol metabolism during long-term Β-receptor agonist therapy is emphasized.

Seventeen postmenopausal women were given a bolus of conjugated estrogens (USP, Premarin®), 17β-estradiol and estriol orally, intravenously or by pellet implantation, and circulating levels of estrone, estradiol and/or estriol were measured by radioimmunoassay at various intervals during a 48–72-h period. Oral administration resulted in a marked rise in serum estrone; parenteral administration resulted in a marked increase in serum estradiol. There was no significant fall in serum gonadotropins during this period. Following estriol administration orally, there was a decided elevation in estriol levels but minimal change in estrone and estradiol.

Estriol excretion patterns were studied in normal pregnancies and pregnancies complicated by hypertension and diabetes mellitus. The data reveal a significant correlation between estriol levels and fetal weight. Three distinct excretion patterns of significant prognostic value were found in the diabetic pregnancies. In this laboratory, urinary estriol determinations have been found to be a useful adjunct in the management of complicated gestations.

A simple and specific method for determination of estriol in amniotic fluid is decribed. Results from 80 normal pregnancies at different stages of gestation are presented. Estriol levels rise as pregnancy progresses, and a sudden fivefold elevation in the mean value occurs around the thirty-sixth week of gestation. The differences in the rate of transfer from amniotic fluid of the free and conjugated forms of estriol are discussed as possible mechanisms responsible for the sudden increase during the late phase of pregnancy.

Two placental steroid synthesizing enzymes are non-competitively inhibited by steroids normally present in the placenta. The conversion of 4- 14 C-3β -hydroxy-5-pregnene-20-one to progesterone by Δ 5 -3β -hydroxysteroid dehydrogenase is inhibited by 20α-hydroxy-4-pregnene-3-one. The K i of the inhibition is of the same order of magnitude as is placental inhibitor concentration. The 20α-reduction of 4- 14 C-progesterone is inhibited by estriol. The K i of this inhibition is higher than normal placental estriol levels. We propose that these inhibitions constitute part of the control mechanism for placental steroid synthesis.

Plasma estriol levels were determined in the latter part of nine pregnancies complicated by Class D diabetes. In 5 of the 9 cases, abnormally high values were obtained. Two neonates died as a result of congenital anomalies. In one of these cases, the plasma estriol levels were extremely high, whereas in the other, they were in the low normal range. Thus far, these preliminary data indicate that there is a poor correlation between estriol levels and fetal-placental well-being in patients with Class D diabetes.

A case of pre-eclampsia is described where suspicion of placental insufficiency arose due to low estriol levels and a positive oxytocin challenge test (OCT). The cause, however, of these findings was later proven to be strictly fetal. It is concluded that low estriol levels and a positive OCT may be caused by a decreased placental capacity but specific tests of placental function, as for instance estimations of HPL in plasma and/or a DHAS-test, should be used to verify or rule out a suspicion of placental insufficiency.

Variation in the use of diagnostic procedures may be due to characteristics of patients, physicians, or their environment. Testing rates for 24-hour urinary estriol levels (EST), diagnostic ultrasound, and antepartum fetal heart rate testing (AFHRT) were examined in 8,527 deliveries from 1975 through 1978. Over the period, utilization of EST remained constant at about 7% of deliveries, while ultrasound increased from 20% to 35% and AFHRT, from 7% to 12%. This increase persisted after stratifying patients on a multivariate confounder score using 45 items of clinical information. Those receiving antenatal care in a hospital-based group practice or a resident-staffed community clinic were more likely to be tested than patients seen in private offices or a prepaid group practice. ( JAMA 1983;249:1605-1609)