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PubMedDate not supplied

[Estriol reaction test for the diagnosis of fetal distress in the 3d trimester].

In order to perform the estriol reaction test, venous blood samples for two basal estriol values were drawn at 7.30 and 8.00 a.m. from each patient. Subsequently all gravidas received 4 mg dexamethasone i.v. Blood was drawn again 4, 8, 24, 28 and 32 h thereafter for determination of unconjugated serum estriol. The analysis of the estriol response curves in 101 patients revealed that the estriol reaction test is helpful to indicate fetoplacental impairment in pregnancies at risk.

Adult↗

PubMed1984

Improved assay of unconjugated estriol in maternal serum or plasma by adsorption and liquid chromatography with fluorimetric detection.

In this improved assay only a 500-microL sample is needed and a single assay can be done within 30 min, 10 samples within 90 minutes. The sample of serum or plasma is diluted 20-fold with water, and the estriol is adsorbed from it onto graphitized carbon black ( Carbopack B, Supelco ). After two washings the estriol is desorbed with chloroform/methanol (60/40 by vol), which then is evaporated. The residue is redissolved in 50 microL of water/acetonitrile, and 20 microL is injected into the chromatograph. Analytical recovery for estriol-supplemented serum or plasma averaged 98.6%. Day-to-day CVs ranged from 3.9% at 2 micrograms/L to 2.1% at 20 micrograms/L. The limit of sensitivity is 0.3 micrograms/L, which makes this procedure suitable for determination of estriol even in the first half of pregnancy. Our method is inexpensive, and shows that liquid chromatography can be used to determine estriol in pregnancy serum or plasma. It also is more sensitive and precise and requires less sample than other such methods.

Adsorption↗

PubMed1980

Two-hour Sephadex column method for assay of unconjugated estriol in serum.

The column method of Christner and Fetter (Steroids 24: 327, 1974) has been modified to give a simple, rapid assay for unconjugated estriol in serum. Estriol is isolated from serum by being retained on a Sephadex column, while estriol conjugates and serum proteins are eluted. The sample and labeled estriol compete for antibody on the column. Antibody is eluted, removing proportional amounts of sample and labeled estriol. Our modifications include using stable serum-based standards, shortening the incubation to 10 min, complete removal of conjugates, and regeneration of the columns so that they can be used repeatedly. The assay, which can be completed in 2 h, has a mid-range interassay CV of 8.2%.

Chromatography, Gel↗

PubMed1995

Efficacy and safety of estriol replacement therapy for climacteric women.

BACKGROUND: As an estrogen derivative, estriol is rather effective in the relief of climacteric symptoms due to estrogen deficiency. When given one dose a day, it will not provoke endometrial proliferation and shedding. Thus, it is suitable for postmenopausal women who no longer want to have uterine bleeding and for those with comparatively higher risk of endometrial hyperplasia. In the aspect of postmenopausal osteoporosis, the prevention of further bone loss due to estrogen deficiency is also important and to be evaluated. METHODS: We collected 20 patients, aged 44-62 years, who had undergone either natural or surgical menopause and were treated with estriol succinate (Synapause; Organon; Holland 2 mg/tab) 2 mg/day for 2 years, with relief of climacteric symptoms evaluated after the first 3 months of treatment. Bone mineral density (BMD) of lumbar spine was measured using quantitative computed tomography (QCT) after one and two years of treatment, respectively. RESULTS: Estriol was very effective in the improvement of major subjective climacteric complaints in 86% of patients, especially hot flush and insomnia within 3 months. The atrophic genital changes caused by estrogen deficiency were also improved satisfactorily. No subjective symptoms induced by the therapy were seen. The rate of uterine bleeding was low, complained by only one patient. However, our study did not show the preventive effect of estriol against osteoporosis. CONCLUSIONS: Estriol can be a safe and effective alternative in the relief of climacteric symptoms for postmenopausal women, but it cannot prevent the bone loss.

Adult↗

PubMed1998

Estriol: safety and efficacy.

While conventional hormone replacement therapy provides certain benefits, it is not without significant risks. Estriol has been found to provide some of the protection without the risks associated with stronger estrogens. Depending upon the situation, estriol may exert either agonistic or antagonistic effects on estrogen. Estriol appears to be effective at controlling symptoms of menopause, including hot flashes, insomnia, vaginal dryness, and frequent urinary tract infections. Results of research on its bone-density-maintaining effects have been contradictory, with the most promising results coming from Japanese studies. Estriol's effect on cardiac risk factors has also been somewhat equivocal; however, unlike conventional estrogen prescriptions, it does not seem to contribute to hypertension. Although estriol appears to be much safer than estrone or estradiol, its continuous use in high doses may have a stimulatory effect on both breast and endometrial tissue.

Estriol↗

PubMed1998

[Comparison of the antioxidant effect of estriol and estradiol on low density lipoproteins in post-menopausal women].

BACKGROUND: Estradiol (E2) has a potent antioxidant effect on low density lipoproteins (LDL) in vitro and in vivo, which could be important in explaining the cardioprotective effect of hormone replacement therapy (HRT) in post menopausal women. Estriol (E3), on the other hand, is a weak estrogen with low metabolic effects on different tissues, and at present no cardioprotective effect has been attributed to this steroid. AIM: To study the antioxidant effect of E3 on LDL and to compare it with the potent antioxidant action exhibited by E2. SUBJECTS AND METHODS: After LDL was isolated by ultra centrifugation from plasma of 12 healthy untreated post menopausal women, it was divided into aliquots containing 0.5 mg of LDL protein. Estriol and E2 in doses of 0, 1, 5, 15 and 50 microM were incubated with different aliquots of LDL. CuSO4 15 microM was added to each aliquot to induce an oxidative stress. The aliquots were then incubated during 4 hours at 37 degrees C. Malonaldehyde (MDA) was measured as a marker of LDL oxidation, and expressed as nM/mg protein. RESULTS: (mean +/- SD): Estriol induced a dose-dependent decrease in MDA concentration (baseline 62.8 +/- 21.7; 1 microM: 61.5 +/- 23.0; 5 microM: 52.9 +/- 20.3; 15 microM 43.5 +/- 20.1 and 50 microM: 31.0 +/- 17.6 nM/mg protein; F = 92.4; p < 0.0001), reaching a mean decrease of 50.7% at the highest dose tested. Estradiol has a similar dose-dependent decrease in MDA concentration (F = 60.2; p < 0.0001), revealing a more potent effect than E3 (p < 0.05), with a mean decrease of 67.4% at the highest dose tested. CONCLUSIONS: Our results demonstrate that estriol shows an important antioxidant action of LDL in vitro, although its effect is less potent than estradiol. These results raise the possibility that estriol could have a cardioprotective effect in post menopausal women, possibility that has not been yet demonstrated.

Antioxidants↗

PubMed1987

Antimammary carcinogenic activity of 17-alpha-ethinyl estriol.

Both initiation and promotion of dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis were inhibited by prophylactic therapy for 1 to 7 months using 17-alpha-ethinyl-estriol in doses as low as 1.0 microgram/d administered to intact virgin female Sprague-Dawley rats at 35 to 65 days of age. Administration of 638-micrograms single or multiple doses 2 to 3 weeks before DMBA induced a 75% to 85% reduction in cancer incidence after 1 year (P less than 0.001). When treatment was begun 2 weeks after DMBA, 1.0 microgram/d infused for 84 days resulted in a 44% reduction in incidence, with higher-dose, more prolonged therapy achieving a 73% reduction, equal to the reduction in carcinoma incidence observed after ovariectomy. Biopsies of nontumorous mammary glands showed a positive correlation between prelactational lobuloalveolar hyperplasia, hormone dose, and reduction in incidence of mammary carcinoma. Similar treatment with 17-alpha-ethinyl-estradiol-17B and diethylstilbestrol did not inhibit the 90% to 100% incidence of carcinoma observed in DMBA-treated control rats, and induced lactational hyperplasia in mammary gland biopsies. Continuous ethinyl estriol infusion subcutaneous (sc) in 2.5 to 7.5 micrograms daily dosage significantly increased uterine weights by as much as 10% to 46% after 2 to 4 weeks. At the time of mammary neoplasm development when rats were necropsied, no significant difference was observed in uterine weights between rats receiving 638 micrograms/mo in a readily soluble pellet implant, and uterine weights of control rats. Ethinyl estriol given seven times monthly in 638-micrograms bolus doses was more inhibitory of mammary carcinogenesis than estriol after a year (P less than 0.1 greater than 0.05). Short-term intermittent administration of ethinyl estriol to young nulliparous women may offer a method of simulating the differentiating effect of pregnancy on mammary tissues, increasing durable resistance to carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1977

Serum unconjugated estriol levels in the third trimester and their relationship to gestational age. II.

The purpose of this study was to further validate a preliminary report concerning the clinical usefulness of serum unconjugated estriols as a marker of gestational age. Serial estriol values from 50 women with uncertain dates were plotted on semilogarithmic graphs and the gestational age predicted from the timing of the abrupt surge in estriol values which normally occurs between 35 and 36 weeks. The gestational age at birth, as determined by careful neonatal examination, agreed with the age predicted by the estriol surge within +/- 1 week.

Estriol↗

PubMed1981

[The determination of unconjugated estrone, estradiol, estriol and estetrol in serum or amniotic fluid by high performance liquid chromatography with an amperometric detector (author's transl)].

A simultaneous microdetermination of unconjugated estrone, estradiol, estriol and estetrol in serum or amniotic fluid by High Performance Liquid Chromatography with an Amperometric Detector is described. Steroids in serum or amniotic fluid were extracted with 10 volumes of ethyl ether, and then ether extract was evaporated to dryness under N2 gas. After defatting with a mixture of 50% methanol/n-hexane, the methanol phase was evaporated to dryness under N2 gas. The residue was applied to microcolumn packed with 2 ml volume of Sephadex LH-20 in the eluting solvent benzene/methanol (85:15). Fractions contained estrone and estradiol; estriol and estetrol were collected and then evaporated to dryness under N2 gas. The sample solution was applied to HPLC using a reverse phase ODS column and acetonitrile: 0.1M KH2 PO4 47:53 for estrone and estradiol fraction, and 30:70 for estriol and estetrol fraction as a mobile phase, respectively. The fraction of each estrogen was separated completely within a 20 minute period. The limit of detection of estrone, estradiol, estriol and estetrol was 50 pg, respectively.

Amniotic Fluid↗

PubMed1998

Combination of elevated maternal serum alpha-fetoprotein (MSAFP) and low estriol is highly predictive of anencephaly.

Increased levels of second trimester maternal serum alpha-fetoprotein (MSAFP) have long been established as a marker for neural tube defects (NTDs). In addition, decreased levels of maternal estriol in the third trimester have been reported in pregnancies with anencephalic fetuses. The purpose of this study was to evaluate whether early second trimester unconjugated serum estriol (uE3) is an independent predictor of NTDs. The study included 57,031 patients who underwent maternal serum screening with MSAFP at 14-22 weeks gestation. Of these, 23,415 also had uE3 measurements. There were 63 cases of NTD, an overall incidence of 1.1 per 1,000. Elevated MSAFP (> or =2.5 MOM) was detected in 1,346 patients, 48 of which had NTDs. Decreased uE3 (< or =0.5) was detected in 1,437 patients, 17 of which had NTDs. The incidence of NTDs was significantly higher in patients with low uE3, compared to patients with normal/high uE3 (1.15% vs. 0.09%, P < 001). Finally, 51 patients had both increased MSAFP and decreased uE3; 16 of these had NTDs, 14 of which were anencephalics. In conclusion, both elevated MSAFP and low maternal serum estriol are predictive of NTD but have a low sensitivity. The combination of abnormally elevated MSAFP and low estriol is highly predictive of NTD in particular anencephaly.

Anencephaly↗

PubMed2003

Direct determination of estriol 3- and 16-glucuronides in pregnancy urine by column-switching liquid chromatography with electrospray tandem mass spectrometry.

Using column-switching liquid chromatography/tandem mass spectrometry (LC-MS/MS), we developed an improved analytical method of urinary estriol glucuronides. This new method is derived predominantly from maternal and fetal precursors in pregnancy. We used in the following procedure: first, we filtered urine samples with a membrane filter. Next, we directly injected the 50 microL aliquot of urine samples onto a pre-column. Then, after activating the column-switching valve, we backflushed the loaded samples onto the C(18) analytical column. Urine samples can be assayed within 20 min without any sample preparation steps. We monitored separated estriol glucuronides by negative electrospray ionization (ESI) and selected-reaction monitoring (SRM). The calibration range of estriol-3-glucuronide (E3-3G) and estriol-16-glucuronide (E3-16G) was 0.1-20 microg/mL and the linearity of the method was 0.9984 for E3-3G and 0.9987 for E3-16G. The limits of detection at a signal-to-noise (S/N) ratio of 3 were 10 ng/mL (E3-3G) and 5 ng/mL (E3-16G). The analytical recovery was over 85% and, in general, inter-day and intra-day variability for precision and accuracy were less than 10%. When applied to a pregnancy urine sample to biomedical monitoring of the function of the maternal/fetal unit, the proposed method allowed rapid and sensitive screening for the detection of E3-3G and E3-16G.

Adult↗

PubMed1988

Inhibition of imidazole-induced tyrosinase activity by estradiol and estriol in cultured B16/C3 melanoma cells.

The effect of estrogens on tyrosinase (EC 1.14.18.1) activity was studied in B16/C3 melanoma cultures. Estradiol, estriol, and other related steroids failed to influence tyrosinase activity when added to the medium of proliferating cultures. Imidazole (10 mM), on the other hand, induced the activity of that enzyme 3-fold, as reported previously. Estradiol and estriol blocked imidazole induction, however, unlike the other estrogenic compounds. The blockade occurred within 15 min of hormone addition and was reversible. Dose-response studies revealed that the maximal estradiol effect occurred at 0.75 nM and the half-maximal effect occurred at 0.5 nM. Estriol was more potent, with the maximal blockade occurring at approximately 0.5 nM and half-maximal effect at 0.25 nM. The induction of tyrosinase by imidazole and the blockade of this induction by estradiol and estriol could not be demonstrated in broken cell preparations, suggesting that direct enzyme activation-inactivation was not involved. Studies utilizing inhibitors of protein and RNA synthesis suggest that this effect is mediated at a pre-translational level and is independent of mRNA destabilization.

Animals↗

PubMed2006

Differentiation of estriol glucuronide isomers by chemical derivatization and electrospray tandem mass spectrometry.

This paper describes a way of differentiating between the three isomers of estriol glucuronide by the use of chemical derivatization and liquid chromatography/electrospray tandem mass spectrometry (MS/MS). In their native form, these isomers gave rise to almost identical product ion spectra, involving the neutral loss of 176 Da (i.e. monodehydrated glucuronic acid), which made it impossible to determine the position of conjugation by MS/MS alone. In order to change the fragmentation pathways, positive charges were introduced into the analytes by chemical derivatization. The following reagents were tested: 2-chloro-1-methylpyridinium iodide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and 2-picolylamine. Interestingly, derivatization using a combination of all three reagents gave a selective fragmentation pattern that could differentiate between the isomers estriol-16-glucuronide and estriol-17-glucuronide. Estriol-3-glucuronide, which lacks a free phenolic group, could be differentiated through a different type of reaction product when exposed to 2-chloro-1-methylpyridinium iodide. Furthermore, in order to assist structural assignment of the fragments, their accurate masses were determined using a hybrid quadrupole time-of-flight mass spectrometer and fragmentation pathways were elucidated by the use of MS3 on an ion trap mass spectrometer.

Chromatography, Liquid↗

PubMed1996

The relative effectiveness of estrone, estradiol-17 beta, and estriol in sex reversal in the red-eared slider (Trachemys scripta), a turtle with temperature-dependent sex determination.

In many turtles the temperature during the middle of incubation determines the gonadal sex of the hatchling. Sex steroid hormones have been implicated in temperature-dependent sex determination in the red-eared slider turtle, Trachemys scripta; nonaromatizable androgens are involved in male sex determination and estrogens and aromatizable androgens in female sex determination. Administration of exogenous estradiol-17 beta to eggs incubating at a temperature that normally produces only males can overcome the effect of temperature and result in all offspring being female. Further, estradiol-17 beta and incubation temperature synergize to produce a greater feminizing effect at intermediate incubation temperatures that produce mixed sex ratios. This study demonstrates that, in the red-eared slider, there is a complex interaction between incubation temperature, different estrogens, and the dosage effect of each hormone. There are changes in potency of different estrogens with incubation temperature such that estriol is more potent than estrone and estradiol-17 beta at 26 degrees (an all-male producing incubation temperature), estrone and estriol are equipotent to each other and more potent than estradiol-17 beta at 28.8 degrees (an incubation temperature that produced a male-biased sex ratio), and estradiol-17 beta is more potent than estrone and estriol at 29 degrees (an incubation temperature that produced equal numbers of males and females). These changes may be due to differences in synergism between the hormones and incubation temperature. Estriol treatment also resulted in cranially hypertrophied oviducts at all incubation temperatures in a dose-dependent manner, whereas animals treated with estradiol-17 beta and estrone had normal oviducts. These results support the hypothesis that estrogens are involved in the final common pathway of female sex determination in this species.

Animals↗

PubMed1977

Trial of intravenous therapy in women with low urinary estriol excretion.

Estriol excretion in pregnancy is favourably improved following administration of 25% dextrose to patients with persistently low estriol excretion. A double-blind controlled trial was undertaken in 60 patients to assess the efficacy of other regimens of infusion therapy with Hartmann's solution, aminofusin, 10% dextrose, or ritodrine in Hartmann's solution. Estriol excretion rose above the lower limit of normal in 69% of the patients treated. There was no significant difference in success rates between the four solutions studied when subjected to analyses of variance and covariance. Fetal and placental weights were directly related to estriol excretion. Influences of the various therapeutic regimens on metabolic acidosis have been considered and possible reasons for therapeutic success discussed.

Amino Acids↗

PubMed1979

Effect of stress during labor on the concentration of cortisol and estriol in maternal plasma.

The effect of stress during labor on the plasma concentration of cortisol, unconjugated estriol, and human chorionic somatomammotropin was studied in 15 healthy primiparous women. According to the method of pain relief the parturients were divided into two groups. One group was given continuous epidural analgesia and the other group received pethidine, diazepam, and nitrous oxide/oxygen in response to pain. In the most stressed nonepidural group there was a significant rise in the cortisol level during labor and the estriol concentration fell significantly. In the epidural group no significant changes were observed with respect to the concentration of either cortisol or estriol. These results give further support to the hypothesis that severe maternal stress may lead to a reduced concentration of estriol in maternal plasma.

Adult↗

PubMed1979

Fetal growth and placental function assessed by urinary estriol excretion before the onset of pre-eclampsia.

In a series of 1,316 patients with pre-eclampsia 744 had urinary estriol excretion measured before and 366 after the onset of clinical signs of the disease. Low estriol excretion had a highly significant association with fetal growth retardation and perinatal death both before and after the onset of clinical signs (p less than 0.001). As assessed by the incidences of low estriol excretion, fetal growth retardation, and perinatal wastage, pre-eclampsia of early onset (before 37 weeks) was a malignant disease in comparison with pre-eclampsia of late onset (after 37 weeks). Patients destined to develop early-onset pre-eclampsia had a high incidence of subnormal estriol excretion (25.4%; p less than 0.001). Although further deterioration of placental function occurred after the onset of clinical signs (41.3%; p less than 0.01), fetal growth and prognosis were already determined.

Estriol↗

PubMed1980

Rhythmic changes in estriol excretion during pregnancy.

Different biologic rhythms with effect on one and the same parameter may cause a complicated signal pattern in which no regularity can be visually identified. In this study an autocorrelation function approach, well established in the interpretation of electroencephalograms, was shown to be applicable also in the interpretation of processes with few points of observation. This technique, used on the excretion of estriol in urine, reveals several rhythms with wavelengths between 6 and 72 hours. Interference between these signals may explain the irregular visual appearance of plots of subsequent estriol determinations and the considerable rise and fall of urinary estriol excretion during pregnancy. The presence of two independent sources of the rhythms is suggested. It is concluded that the complicated and individual rhythmic changes in urinary excretion of estriol results in a low diagnostic specificity for fetoplacental malfunction of this component.

Circadian Rhythm↗