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PubMed1981

Determination of serum unconjugated estrone, estradiol-17 beta and estriol during pregnancy by selected ion monitoring.

A simple, rapid and highly specific method by selected ion monitoring (SIM), using 9 alpha, 11 alpha-[2H2]estrone, [2,4-2H2]estradiol-17 beta and 2,4-[2H2]estriol as internal standards, was developed for the determination of serum estrogens during pregnancy. Serum samples were submitted to a simple extraction procedure and were analysed after formation of the trifluoroacetic anhydride derivative. The inter-assay coefficients of variation for estrone, estradiol-17 beta and estriol were 3.73%, 3.42% and 3.49%, respectively. The results obtained by SIM were compared with analysis performed using radioimmunoassay.

Estradiol↗

PubMed2000

Comparison of the long-term effects of oral estriol with the effects of conjugated estrogen on serum lipid profile in early menopausal women.

OBJECTIVE: We investigated the long-term effects of oral estriol (E(3)) on serum levels of total cholesterol (t-Cho), high-density lipoprotein cholesterol (HDL-Cho), low-density lipoprotein cholesterol (LDL-Cho), and triglycerides in early menopausal women. METHODS: We studied 67 healthy early menopausal women who were treated for 48 months with 2.0 mg of E(3) plus 2.5 mg of medroxyprogesterone acetate daily (E(3) group, n=21), 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate daily (CE group, n=19), or 1.0 microg of 1alpha-hydroxyvitamin D(3) daily or 1.8 g of calcium lactate containing 250 mg of elemental calcium daily (control group, n=27). The serum levels of t-Cho, HDL-Cho, LDL-Cho, and triglycerides were evaluated at baseline and every 6 months. RESULTS: After 48 months of treatment, the t-Cho decreased significantly by 4.3+/-2.1% (mean+/-SE) from baseline in the E(3) group, did not change in the CE group (-1.9+/-2.1%), and significantly increased (5.4+/-3.4%) in the control group. The HDL-Cho significantly increased in the CE group (10.7+/-2.4%), but not in the E(3) group (3.8+/-3.3%) or in the control group (-3.6+/-3. 0%). The LDL-Cho significantly decreased in the CE group (-11.4+/-4. 0%), did not change in the E(3) group (-5.2+/-3.6%), and significantly increased in the control group (11.8+/-6.3%). The triglyceride level decreased significantly in the E(3) group (-6. 7+/-4.9%), whereas it significantly increased in the CE group (17. 6+/-11.4%), and did not change in the control group (6.1+/-6.4%). CONCLUSIONS: Oral E(3) prevented a postmenopausal rise in the t-Cho. Oral estriol did not induce the hypertriglyceridemia that was seen after treatment with conjugated estrogen. Oral E(3) may be a useful alternative therapy in women with hypertriglyceridemia and in women who are reluctant to continue conventional hormone replacement therapy because of uterine bleeding.

Administration, Oral↗

PubMed2001

The physiological role of estriol during human fetal development is to act as antioxidant at lipophilic milieus of the central nervous system.

Estriol is the most abundant estrogen during human pregnancy, it has a low estrogenic effect and its physiological role is not known. Recently it has been shown that estrogens have antioxidant and free-radical scavenging activity; in free form estrogens are lipophilic, here it is proposed that the role of estriol is to act as antioxidant at level of the developing fetal central nervous system, whose tissues are substantially lipid in nature.

Antioxidants↗

PubMed2000

Estriol (E3) replacement improves endothelial function and bone mineral density in very elderly women.

We investigated the effects of estriol (E3) on endothelial function and bone mineral density (BMD) in very elderly women. Twenty-four very elderly women (80 +/- 3.5 years old) were administered CaCl2 with or without estriol treatment (2 mg/day) for 30 weeks (hormone replacement treatment [HRT] group vs control group). Endothelium-dependent flow-mediated dilatation (FMD), endothelium-independent dilatation by nitroglycerin of the brachial artery, and BMD were assessed. Levels of plasma lipids and apoproteins were not changed; however, both plasma E3 and E2 were substantially increased (E2, 4.6 to 31.3 +/- 8.1; E3, <5 to 45.3 +/- 7.9 pg/mL) by HRT. The FMD value was also increased by HRT, as were the plasma nitrite/nitrate and cGMP values. The response to nitroglycerin was not changed. The BMD was increased by HRT, but decreased in the control group. There were significant differences between the HRT group and control group after 30 weeks' treatment in the levels of osteocalcin, P1CP, and urinary deoxypiridinoridine. E3 significantly improved BMD by inhibiting bone resorption. Endothelial function was improved in line with the antiatherosclerotic effects. E3 might be effective for use in HRT in elderly patients.

Aged↗

PubMed1996

Differential diagnosis and management of very low second trimester maternal serum unconjugated estriol levels, with special emphasis on the diagnosis of X-linked ichthyosis.

Incorporation of maternal serum unconjugated estriol into the calculation of risk may increase the yield of serum screening performed during pregnancy for detection of fetal chromosomal and structural anomalies. The differential diagnosis of very low and undetectable levels of unconjugated estriol in maternal serum is discussed, with special emphasis on the prenatal diagnosis of X-linked ichthyosis. The prenatal detection of these findings dictates skilled genetic counseling, targeted sonographic evaluation and examination of fetal karyotype and fetal cDNA for Xp 22.32 with amniotic fluid levels of cortisol, STS, and ASC.

Adult↗

PubMed1977

Urinary estriol for assessment of fetoplacental function.

A total of 1,607 urinary estriol determinations were performed in 447 patients with normal and complicated pregnancies. In general, the test provided reliable information concerning fetal status, particularly in pregnancies complicated by toxemia, diabetes, and postmaturity. When measured consecutively, a drop of 50% or more in estriol level usually should be considered a significant index of fetal distress. Limitations of the test and several compensatory measures aimed at minimizing inaccuracy are discussed.

Adolescent↗

PubMed1979

Low urinary estriol during pregnancy caused by isolated fetal ACTH-deficiency.

In a 34-year-old pregnant woman, serum HPL and urinary HCG were normal, but urinary estriol was repeatedly low. A normal boy was delivered after 38 week gestation. During the neonatal period, he had hypoglycemia, muscular hypotonia and transient hyperbilirubinemia. The ACTH-test was normal, but the THS-response to metyrapone was low. Serum ACTH did not respond to insulin and metyrapone. Growth hormone, TSH and gonadotropin responses to stimuli were normal. Treatment with hydrocortisone resulted in disappearance of the symptoms. It is concluded that fetal ACTH-deficiency is one of the specific endocrine causes of low maternal estriol.

Adrenocorticotropic Hormone↗

PubMed1991

Relationships of serum estriol, cortisol and albumin concentrations with pig weight at 110 days of gestation and at birth.

In polytocous species, animals with reduced birth weights are associated with reduced neonatal survival, which may be related to substandard placental function. At 110 days of gestation (n = 84) and at birth (approximately 114 days, n = 193), fetal pigs were bled and weighed, so that indexes of placental function (estriol), fetal stress (cortisol), and fetal growth (albumin) could be related to fetal development. Concentration of estriol at birth or 110 days of gestation was not linearly related to weight of pig. Pig serum albumin was linearly related to pig weight and increased as body weight increased (p less than 0.05). In blood from pigs sampled at birth, cortisol concentrations significantly decreased as body weight increased (p less than 0.05).

Animals↗

PubMed1990

Maternal serum levels of estriol, prolactin, human placental lactogen and chorionic gonadotrophin related to fetal sex in normal and abnormal pregnancies.

A total of 222 pregnant women had repeated hormone assays of prolactin, estriol, human chorionic gonadotrophin and placental lactogen between week 20 and delivery. The aim of this study was to investigate whether maternal serum levels of the above-mentioned hormones differed between normal and abnormal pregnancies, that is preterm, preterm small-for-date (SFD), SFD at-term and normal at-term deliveries, with special regard to fetal sex. The results of the present study indicated differences related to preterm deliveries and intrauterine growth retardation. This finding was reflected in the estriol levels when mothers of both boys and girls were included, suggesting a primary involvement of fetoplacental factors in these pathological pregnancies. However, when only mothers of girls were investigated, the development of growth retardation was mainly seen in maternal serum hPL differences, thus suggesting a placental involvement.

Chorionic Gonadotropin↗

PubMed1980

HPL and estriol serum levels of placental perfusion as indexes of placental function in EPH gestosis and placental insufficiency.

62 patients with EPH gestosis and 64 subjects suffering from placental insufficiency were monitored with estimation of placental perfusion and determination of radioimmunoassayable serum levels of human placental lactogen (HPL) and estriol. The utero-placental blood flow was measured by quick intravenous administration of 0.25-1.0 mCi of (113m)In, and the radioactivity uptake curve was evaluated by a computer program. Good correlation between perfusion type of serum levels of HPL and estriol was recorded. The present data combine to suggest that the recording of utero-placental blood flow is valuable aid in the diagnostic and prognostic evaluation of high-risk pregnancies.

Blood Circulation↗

PubMed1969

Studies on phenolic steroids in human subjects. 8. Metabolism of estriol-16 alpha-glucosiduronate.

6,7-(3)H-Estriol-16alpha-glucosiduronate-(14)C was administered to eight women (nine studies) by several routes: both injection and infusion (300 min) into the cubital vein, injection into the portal vein system, ingestion and instillation into the duodenum, jejunum, and ileum. Urine, collected from 0-2, 2-4, 4-8, 8-12, and 12-24 hr, was analyzed by countercurrent distribution for its content of radioactive 3- and 16-glucosiduronate (E(3)-3Gl,E(3)-16Gl) and sulfoglucosiduronate (E(3)-3S,16Gl) of estriol as well as for (3)H/(14)C ratio of each conjugate. After peripheral injection 50-60% of the injected E(3)-16Gl was excreted unchanged along with about 5% as E(3)-3S,16Gl with an unchanged (3)H/(14)C ratio, indicating direct sulfation of the injected E(3)-16Gl. During a 300 min infusion, urinary excretion closely resembled that following injection. But 2-4 hr after the end of the infusion excretion of E(3)-3S, 16Gl stopped, excretion of E(3)-3Gl (17%/24 hr) with an elevated (3)H/(14)C ratio started, and excretion of E(3)-16Gl continued (70%/24 hr), but with a rapidly increasing (3)H/(14)C ratio. This indicated sequestration in a sluggishly metabolizing compartment where two processes occurred: (a) extensive hydrolysis of E(3)-16Gl followed by reconjugation at either C3 or C16 with unlabeled uridine diphosphate glucuronic acid (UDPGA), thereby increasing the (3)H/(14)C ratio; and (b) transconjugation from C16 to C3, thereby producing E(3)-3Gl with finite (3)H/(14)C ratios. Instillation into various segments of the small intestine produced results qualitatively similar to those after intravenous infusion, whereas ingestion and intraportal injection resembled peripheral intravenous injection. Therefore, we have postulated the possibility of an enteric circulation (in addition to an enterohepatic circulation) in which the steroid or its conjugates are transported into the small intestine in the succus entericus, modified, and then reabsorbed and excreted in the urine-a process which requires several hours.

Adolescent↗

PubMed1978

Studies on human sexual development. VI. Concentrations of unconjugated dehydroepiandrosterone, estradiol, and estriol in amniotic fluid throughout gestation.

Concentrations of unconjugated dehydroepiandrosterone, estradiol, and estriol were measured in samples of amniotic fluid from uneventful pregnancies of 9-40 weeks conceptual age. There was no apparent influence of fetal sex upon the levels of these steroids. Dehydroepiandrosterone concentrations rose slightly from 9-20 weeks, and then showed little further change. Estradiol concentrations declined slightly from 9-20 weeks; after 32 weeks gestation, there was a 2-fold rise to term. Estriol levels rose in almost exponential fashion throughout gestation.

Amniotic Fluid↗

PubMed1979

Interrelationships of circulating maternal steroid concentrations in third trimester pregnancies. III. Effect of intravenous cortisol infusion on maternal concentrations of estriol, 16 alpha-hydroxyprogesterone, 17 alpha-hydroxyprogesterone, progesterone, 20 alpha-dihydroprogesterone, delta 5-pregnenolone, delta5-pregnenolone sulfate, dehydroepiandrosterone sulfate, and cortisol.

The effect of a large dose (1000 mg) of iv cortisol-hemisuccinate on circulating steroid concentrations in five women, 28--34 weeks, gestational age, is reported. Maternal concentrations of estriol, 16 alpha-hydroxyprogesterone, 17 alpha-hydroxyprogesterone, progesterone, 20 alpha-dihydroprogesterone, delta 5-pregnenolone, delta 5-pregnenolone sulfate, dehydroepiandrosterone sulfate, and cortisol were measured by RIA before and at 8 and 12 h after iv cortisol infusions at 0 and 8 h. Data were evaluated by repeated measure analysis of variance. Estriol and 17 alpha-hydroxyprogesterone suppressed initially (P less than 0.05) and suppressed further with retreatment and increased treatment time (P less than 0.05). Dehydroepiandrosterone sulfate and progesterone suppressed initially (P less than 0.05) but did not suppress further with retreatment and increased treatment time (P greater than 0.05). delta 5-Pregnenolone and delta5-pregnenolone sulfate increased initially (P less than 0.05) but did not increase further (P greater than 0.05). Concentrations of 16 alpha-hydroxyprogesterone and 20 alpha-dihydroprogesterone were unchanged by cortisol infusion initially (P greater than 0.1) and with retreatment and increased treatment time (P greater than 0.1).

20-alpha-Dihydroprogesterone↗

PubMed1986

Competitive studies with dehydroepiandrosterone sulfate and 16 alpha-hydroxydehydroepiandrosterone sulfate in cultured human choriocarcinoma JEG-3 cells: effect on estrone, 17 beta-estradiol, and estriol secretion.

The estradiol (E2) to estriol (E3) ratio during human pregnancy depends on fetal liver hydroxylation of fetal adrenal dehydroepiandrosterone sulfate (DHEAS) and conversion by the trophoblast of DHEAS and 16 alpha-hydroxy-DHEAS (16 OH-DHEAS) to estrone (E1), estradiol (E2), and estriol (E3), respectively. It is not known whether the conversion of DHEAS into E1 and E2 influence the conversion of 16OH-DHEAS into E3 and vice versa. To examine this question, we studied these interactions in human choriocarcinoma JEG-3 cells. In serum-free medium (Dulbecco's Modified Eagle's Medium), JEG-3 cells secreted hCG [27 +/- 3 (+/- SEM) ng/mg cellular protein X 24 h] and progesterone (22 +/- 2.5), but neither C-19 nor C-18 steroids. The addition of DHEAS resulted in secretion of E1 and E2; at a concentration of 500 ng DHEAS/ml, the secretion of E1 (1 +/- 0.16) and E2 (11 +/- 3.1) was maximal, while E3 remained undetectable. The addition of 1000 ng 16 OH-DHEAS/ml resulted in maximum E3 secretion (13 +/- 1.8), while E1 and E2 remained undetectable. The addition of increasing concentrations of DHEAS to cultures exposed to 1000 ng 16OH-DHEAS/ml caused a decrease in E3 secretion and increased secretion of E1 and E2. Conversely, addition of increasing concentrations of 16OH-DHEAS in cultures exposed to 500 ng DHEAS/ml resulted in inhibition of E1 and E2 secretion and increased E3 secretion. A concentration of 16OH-DHEAS that inhibited the conversion of DHEAS into E1 and E2 neither altered the intracellular to extracellular steroid ratios (approximately 0.1) nor reduced the secretion of DHEA, androstenedione, and testosterone. The inhibitory effect of 16OH-DHEAS was minimal at low DHEAS concentrations (favoring the secretion of E1 and E2) and was greatly enhanced at concentrations of DHEAS that induced maximum E1 and E2 secretions. The results indicate that in trophoblastic cells, the metabolism of DHEAS can modulate E3 secretion, and the metabolism of 16OH-DHEAS can modulate the secretion of E1 and E2; and this regulatory mechanism appears to take place at the level of the aromatase system.

Cells, Cultured↗

PubMed1987

Estradiol, estriol, progesterone, prolactin, and human chorionic gonadotropin in pregnant women with alcohol abuse.

Serum estradiol, estriol, progesterone, PRL, and hCG concentrations were measured at 4-week intervals in 40 pregnant women who chronically abused alcohol and in 20 abstinent pregnant women. Sixteen alcohol users gave birth to infants with the fetal alcohol syndrome (FAS), whereas the remaining 24 infants of alcohol users and all infants of the abstinent women were healthy. The women whose infants had the FAS had decreased estradiol and estriol levels throughout pregnancy. Progesterone levels also tended to be low. In contrast, the alcohol users had increased PRL levels during the 16-24th weeks of pregnancy compared with those in the abstinent women, but this rise was not related to the FAS. The concentrations of hCG fluctuated widely, without any consistent difference between alcohol users and abstinent women. Thus, heavy maternal abuse of alcohol resulting in FAS is accompanied, primarily or secondarily, by reduced estrogen concentrations throughout pregnancy and increased PRL levels during the 16-24th weeks of pregnancy.

Adult↗

PubMed1983

Antigenic properties of estriol 3-glucuronide-[C-6]-bovine serum albumin conjugates having oxime bridges.

The preparation and antigenic properties of estriol 3-glucuronide-bovine serum albumin (BSA) conjugate in which the hapten is linked to the carrier protein through an (O-3-carboxypropylcarbamoylmethyl)oxime bridge at the C-6 position on the steroid nucleus, has been described. 16,17-Di-O-acetyl-6-oxoestriol 6-(O-carboxymethyl)oxime 3-glucuronide acetate-methyl ester was condensed with gamma-amino-n-butyric acid by the mixed anhydride method. Subsequent coupling with BSA followed by removal of the protecting groups with alkali gave the desired hapten-BSA conjugate. The antisera elicited in the rabbit with the conjugate were highly specific to estriol 3-glucuronide, discriminating from other 3-substituted compounds. The specificity of antisera improved by elongation of the 6-(O-carboxymethyl)oxime bridge has been discussed.

Animals↗

PubMed1981

Oxytocinase versus estriol for the assessment of fetal well-being.

In a group of 26 primiparae, 48 hours after cesarean section, we have examined the urinary estriol (E3) and serum cystine aminopeptidase (CAP). 13 patients received ampicillin treatment, and 13 patients did not. In the group of patients without antibiotic treatment the urinary estriol after 48 h reached an average value of 5.55 mg/24 h. in the group of treated patients the drastic decrease of E3 reached a mean value of 1.62 mg/24 h. This fact may be explained by the arrest of the feto-placental inflow after delivery, and the blocking effect of the antibiotic on the enterohepatic circulation, compartment which afford for 50% of the maternal circulating estrogen. From the present work it results that the determination of the serum CAP activity, which is not affected by antibiotic treatment, is an appropriate test for the assessment of the fetoplacental unit activity. It must be mentioned that all the biochemical tests complete one another and may have a decisive role in taking immediate obstetrical decisions, together with the additional fetal heart rate monitoring and oxytocin challenge test.

Adult↗

PubMed1985

Rapid and simultaneous measurement of estrone, estradiol, estriol and estetrol in serum by high performance liquid chromatography with electrochemical detection.

A high performance liquid chromatographic (HPLC) method with electrochemical detection (ECD) was developed for the simultaneous measurement of estrone, estradiol, estriol and estetrol in serum. These hormones were extracted with diethylether, chromatographed on an silica-octadecyl silane (ODS) column with an eluent of phosphate buffer solution-acetonitrile-methanol (volume ratio 152:85:40), and detected by ECD at +1.0V vs. Ag/AgCl. In comparisons between the values measured by this method and radioimmunoassay, significant correlations were noted for estrone (r = 0.759, p less than 0.01), estradiol (r = 0.816, p less than 0.001) and estriol (r = 0.830, p less than 0.001). In clinical applications of this method, differences between cases of the normal and the anencephalic pregnancy in the thirty-eighth week of gestation were distinct not only in the individual estrogen, but also in the profile analysis of estrogens. With this method, all 4 serum estrogens above approximately 500 pg/ml could be measured within 2 h, and the method seemed to be clinically applicable.

Chromatography, High Pressure Liquid↗