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PubMed1977

The use of equilin as an internal standard to quantitate estriol in pregnancy urine.

The assay of pregnancy urine estriol by gas chromatography is most often carried out by adding cholesterol as an internal standard at the end of the extraction procedure. The reason for this is that cholesterol does not contain a phenolic ring, and would be lost during the extraction procedure for estriol. This does not allow for corrections of recovery loss, which would be the case if the internal standard was a phenolic steroid. This paper describes the utilization of equilin (delta 1,3,5,7-estratetraen-3-01-17-one) as the internal standard. The sample is hydrolyzed to remove sulfate and glucuronide groups and then the equilin is added. If equilin is added before hydrolysis, variable destruction takes place. Derivative studies indicate that room temperature silylation can be used with bis (trimethylsilyl)-trifluoroacetamide/trichlorosilane/trimethylsilylimidazole, 3:3:2 by weight. Results on control material containing a low, critical pregnancy concentration of estriol were as follows--listed value 5.0 mg/1, found 5.3 mg/1, co-efficient of variation %, 8.9% for 17 runs on different days.

17-Ketosteroids↗

PubMed1998

Bridge-heterologous chemiluminescence enzyme-linked immunosorbent assay of estriol 3-sulfate in pregnancy plasma.

A facile and sensitive chemiluminescence enzyme-linked immunosorbent assay (ELISA) of estriol 3-sulfate using a bridge-heterologous system was established. 6 alpha-Hydroxyestriol 3-sulfate 6-hemisuccinate was synthesized as a novel hapten. Antisera were raised in male guinea-pigs against 6 alpha-hydroxyestriol 3-sulfate 6-hemisuccinate-bovine serum albumin (BSA) and 6-oxoestriol 3-sulfate O-carboxymethyloxime-BSA conjugates. Both haptens were coupled to horseradish peroxidase as an enzyme-label reagent. For separation of free and estriol 3-sulfate bound to the antibody, the crude globulin fractions of these antisera were immobilized to CNBr-activated Sepharose-4B. The enzyme activity was measured by chemiluminescent reaction using amino-butylethylisoluminol and hydrogen peroxide as a substrate. The immobilized antibody raised against 6 alpha-hydroxyestriol 3-sulfate 6-hemisuccinate-BSA exhibited a high affinity and an excellent specificity for estriol 3-sulfate. The two bridge-heterologous ELISAs were more sensitive than the homologous systems. The specificity and sensitivity (10 pg) of the bridge-heterologous chemiluminescence ELISAs was comparable to those of the radioimmunoassays (RIAs). Results obtained by the ELISA and the RIA in pregnancy plasmas, showed excellent correlation between ELISA and RIA (r = 0.96).

Animals↗

PubMed2003

Biochemical predictors of preterm labor: fetal fibronectin and salivary estriol.

Preterm birth is a major complication of pregnancy and remains a leading cause of neonatal morbidity and mortality worldwide. Improvements in the authors' understanding of the pathophysiology of preterm labor have led to the development of novel diagnostic tools of use to identify women at greatest risk for preterm birth. Currently two FDA-approved biochemical tests are available in the United States: (1) fetal fibronectin and (2) salivary estriol. The presence of a positive fetal fibronectin test in the midtrimester of pregnancy is strongly associated with early spontaneous preterm birth. In contrast, a positive salivary estriol test is associated with late preterm birth, thus limiting its clinical use. Both tests have low test sensitivity and are currently used clinically for their negative predictive values. That is, women who screen negative are at very low risk for preterm birth and, thus, no interventions are indicated to prevent preterm birth. Women with a positive test are at increased risk and would be candidates for intervention. One of the main limitations of fetal fibronectin and salivary estriol, and an array of other proposed markers, is the fact that while these markers may aid in identification of women at increased risk for preterm birth, the authors currently have no clearly effective obstetric interventions for preterm-birth prevention in these high-risk women. Use of tocolytics, antimicrobials, or progesterone therapy currently has limited or unproven benefit in the management of women deemed at increased risk using these markers. Thus, until effective targeted obstetric interventions are available, the use of biochemical markers to identify women at increase risk for preterm birth remains largely research tools.

Biomarkers↗

PubMed1997

Continuous low dose estradiol released from a vaginal ring versus estriol vaginal cream for urogenital atrophy.

OBJECTIVES: To determine if the efficacy of continuous low dose estradiol released from a vaginal ring is equivalent to estriol vaginal cream regarding improvement of the patient's subjective feeling of vaginal dryness and to determine if there is a preference for either of the two study treatments. METHODS: Open-label randomized parallel group trial with active control with a blind evaluation of vaginal cytology and with a cross-over (change-over) phase for preference comparison. One hundred and sixty five postmenopausal women with symptoms of vaginal dryness and signs of vaginal atrophy were randomized to an estradiol ring (Estring) or estriol cream (Synapause). The duration of each treatment period was 12 weeks. RESULTS: Both study treatments were equally effective regarding the ability to alleviate the symptom feeling of vaginal dryness and the signs of vaginal atrophy. Both treatments were efficient in restoring the vaginal mucosa, recorded as higher maturation values and as decreased vaginal pH. Estring was superior to estriol cream regarding preference of treatment. Both treatments were equivalent for the occurrence of adverse events, including bleeding. CONCLUSION: data from this change-over study confirm efficacy and safety of both the vaginal ring and cream in the treatment of postmenopausal women with urogenital atrophy symptoms and signs. The patients had a strong preference for the vaginal ring.

Administration, Intravaginal↗

PubMed1983

Rapid simultaneous assay of serum estrone, estradiol, and estriol in pregnant women using methyl ether acetate derivatives by capillary gas chromatography and electron-impact mass spectrometry.

A simple gas chromatographic--mass spectrometric method capable of measuring estrone, estradiol, and estriol simultaneously with a sensitivity close to that of radioimmunoassay has been developed. The estrogens in serum were extracted with diethyl ether, and internal standards (3-O-C2H3-estrone, 3-O-C2H3-estradiol, and 3-O-C2H3-estriol) were added, followed by converting to methyl ether compounds with an extractive alkylation procedure. The methyl ethers were then acetylated. Analyses were performed using a SP-2250 capillary column gas chromatograph coupled with an electron-impact mass spectrometer. The estrogen methyl ether acetate derivatives were more stable chemically and gave less fragmentation upon electron impact than the conventional trimethylsilyl derivatives. The use of selected ion monitoring of molecular ions and that of the corresponding internal standards (M + 3) provides a sensitivity down to 10 pg for estrone and estradiol and to 200 pg for estriol. The time required for the preparation of multiple samples is within 4 hours.

Dehydroepiandrosterone↗

PubMed1997

Direct determination of estriol 3- and 16-glucuronides in pregnancy urine by column-switching high-performance liquid chromatography with fluorescence detection.

An HPLC method for the direct and simultaneous determination of estriol 3- and 16-glucuronides in pregnancy urine is described. The method is based on direct derivatization of the glucuronic acid moiety in estriol glucuronides in urine with 6,7-dimethoxy-1-methyl-2(1H)-quinoxalinone-3-propionylcarboxylic acid hydrazide. The derivatization reaction proceeds in aqueous solution (or urine sample) in the presence of pyridine and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide at 37 degrees C. The resulting fluorescent derivatives were separated by column-switching chromatography using a first column (YMC-Pack C4) for clean-up of the derivatives and a second column (YMC Pack Ph) for the complete separation of the derivatives. The derivatives were detected spectrofluorimetrically at 445 nm with excitation at 367 nm. The detection limits (signal-to-noise ratio=3) for estriol 3- and 16-glucuronides were 150 and 180 fmol in a 5 microl of urine (14 and 17 ng ml(-1) urine), respectively. The present method is highly sensitive and simple without any clean-up such as conventional solid-phase extraction.

Chromatography, High Pressure Liquid↗

PubMed2003

Quantitative trace analysis of estriol in human plasma by negative ion chemical ionization gas chromatography-mass spectrometry using a deuterated internal standard.

A stable isotope dilution gas chromatography-mass spectrometry (GC-MS) assay for the trace level determination of estriol in human plasma is described. Negative ion chemical ionization (NICI) MS is used for highly specific detection. The method involves derivatization of the phenolic hydroxyl to the pentafluorobenzyl ether derivative and subsequent reaction of the remaining hydroxyls with heptafluorobutyric anhydride. This derivative allows detection of the strikingly abundant phenolate ion under NICI conditions. [2,4,17beta]-2H(3)-labeled estriol was used as an internal standard. For high-level measurements (>313 ng/l) plasma was directly derivatized by extractive alkylation followed by heptafluorobutylation prior to analysis. A rapid and simple sample work up procedure was elaborated for trace level determinations (>5 ng/l plasma) using solid-phase extraction on C(18) with an absolute recovery of 92.9%. For low-level measurements, the calibration curve was linear in the range of 5 to 625 ng/l (r=0.99993). Inter-assay analytical precisions (RSDs) were 1.29, 2.30 and 2.89% at 39, 156 and 650 ng/l plasma, respectively. For high-level measurements, calibration curve linearity was observed in the range of 0.313 to 20 microg/l (r=0.99998). Inter-assay analytical precisions (RSDs) were 5.17, 1.92, 2.57 and 2.74% at 0.313, 0.625, 2.5 and 10 microg/l plasma, respectively. Postmenopausal plasma was used for spiked plasma samples. Sensitivity and specificity of the presented method allows adequate determination of estriol in human plasma samples.

Calibration↗

PubMed1976

RNA polymerase activity and uterine growth: Differential stimulation by estradiol, estriol, and nafoxidine.

We have shown previously that estradiol, estriol, and Nafoxidine (Upjohn 11, 100A) have differential effects on uterine growth and that these effects are associated with the retention of the estrogen receptor by the nucleus. In order to examine these relationships further, we have studied the effect of these hormones on endogenous nuclear RNA polymerase I and II in the immature rat uterus. All three compounds caused a rapid elevation in polymerase II activity that reached a peak by the first hour and declined to almost control levels by 2 h after the injection. This transient peak in polymerase II activity was followed by a second elevation by the fourth hour in estradiol- and Nafoxidine-treated animals which was not observed in estriol-treated rats. The activity of polymerase I increased monotonically to very high levels by 4 h and was maintained 12 h or longer in estradiol- and Nafoxidine-treated animals. A similar elevation was observed in estriol-treated rats but the activity declined very rapidly to control levels by 12 h. The second elevation in polymerase II activity and the sustained stimulation of polymerase I activity were correlated with the stimulation of true uterine growth. These data confirm our previous suggestion that long-term nuclear retention of the receptor is a requirement for true uterine growth and suggest that an obligatory response in the production of true growth is the stimulation of a second rise in polymerase II activity and an elevated and sustained activity of polymerase I.

Aging↗

PubMed1981

[Human placental lactogen and free estriol in maternal blood before and after external version of the fetus from breech to vertex presentation near to term (author's transl)].

In 51 patients with 53 external versions of the child from breech presentation to vertex presentation near to term under tocolysis, the maternal serum-level of human placental lactogen (HPL) and free estriol (E3) was examined immediately before attempting the version and also 30 minutes and 60 minutes after the version, in order to find out whether these two parameters vary according to stress made on the placenta and fetus. In the whole group these were no significant differences in the HPL and estriol levels 30 and 60 minutes after the version compared with the levels before the version. Furthermore comparisons made with attempted versions with heavier stress on the placenta, such as anterior wall placenta, small volume of amniotic fluid, longer duration of the version, and placenta insufficiency did not lead to any significant HPL or estriol decrease in these groups.

Breech Presentation↗

PubMed1980

Oxytocin challenge tests and urinary estriols in the management of high-risk pregnancies.

Three hundred sixty-two pregnant patients at risk for placental insufficiency were evaluated with the oxytocin challenge test (OCT) and urinary estriol determinations. The perinatal mortality in patients with positive tests was 6 times higher than the perinatal mortality in patients with negative tests. Expectant treatment of patients with a positive OCT was associated with a perinatal mortality 6 times higher than if immediate delivery was accomplished. A negative stress test was reassuring, as the risk of death in utero within a week of a negative test was only 0.3%. The combination of low estriol levels and positive OCT was quite ominous, while the presence of normal estriol levels provided reassurance of good perinatal outcome when expectant treatment of a patient with a positive OCT was undertaken. The overall perinatal mortality of the patients in this study was not different from that in the general obstetric population.

Cesarean Section↗

PubMedDate not supplied

Efficacy of low-dose intravaginal estriol on urogenital aging in postmenopausal women.

OBJECTIVE: To assess the efficacy and safety of intravaginal estriol administration on urinary incontinence, urogenital atrophy, and recurrent urinary tract infections in postmenopausal women. DESIGN: Eighty-eight postmenopausal women with urogenital aging symptoms were enrolled in this prospective, randomized, placebo-controlled study. Participants were randomly divided into two groups, with each group consisting of 44 women. Women in the treatment group received intravaginal estriol ovules: 1 ovule (1 mg) once daily for 2 weeks and then 2 ovules once weekly for a total of 6 months as maintenance therapy. Women in the control group received inert placebo vaginal suppositories in a similar regimen. We evaluated urogenital symptomatology, urine cultures, colposcopic findings, urethral cytologic findings, urethral pressure profiles, and urethrocystometry before as well as after 6 months of treatment. RESULTS: After therapy, the symptoms and signs of urogenital atrophy significantly improved in the treatment group in comparison with the control group. Thirty (68%) of the treated participants, and only seven (16%) of the control participants registered a subjective improvement of their incontinence. In the treated participants, we observed significant improvements of colposcopic findings, and there were statistically significant increases in mean maximum urethral pressure, in mean urethral closure pressure as well as in the abdominal pressure transmission ratio to the proximal urethra. Urethrocystometry showed positive but not statistically significant modifications. CONCLUSIONS: Our results show that intravaginal administration of estriol may represent a satisfactory therapeutic choice for those postmenopausal women with urogenital tract disturbances who have contraindications or refuse to undergo standard hormone therapy.

Administration, Intravaginal↗

PubMed1995

New treatment of atrophic acne scars by iontophoresis with estriol and tretinoin.

BACKGROUND: Common treatment of atrophic acne scars consists of invasive methods such as dermabrasion, chemopeeling, or implantation of bovine collagen. In our study a new noninvasive treatment method consisting of local iontophoresis is demonstrated. Local iontophoresis was performed with either estriol--a mainly topically active estrogen--or with tretinoin. PATIENTS AND METHODS: Eighteen women were treated with estriol iontophoresis twice weekly for a period of 3 months. In addition to photographic and clinical documentation of the skin, venous blood for determination of serum levels of prolactin and estradiol according to standard radioimmunoassay methods was obtained monthly. Tretinoin iontophoresis was performed according to the same time schedule in 28 patients (19 women and 9 men) with atrophic acne scars. RESULTS: Improvement of acne scars was observed in 93% of patients treated with tretinoin iontophoresis and in 100% of the group treated with estriol iontophoresis. No hormonal changes were noted in the estrogen group. Side effects involving the skin appeared in the tretinoin group in 4 cases and consisted of increased dryness and of retinoid dermatitis. CONCLUSION: Both treatments were shown to be clinically effective in decreasing acne scars and persistence of effects. This promising new therapeutic approach may thus replace invasive treatment methods in many patients.

Acne Vulgaris↗

PubMed1996

Effect of estriol on bone loss in postmenopausal Japanese women: a multicenter prospective open study.

OBJECTIVES: To assess the effects of oral estriol on the bone mineral density (BMD) and bone metabolism in postmenopausal women. METHODS: Seventy-five natural postmenopausal women with a BMD of more than 10% below the peak bone density were treated for 50 weeks with 2 mg/day estriol (E3) cyclically and 0.8 g/day of calcium lactate continuously. BMDs at L2-L4 were measured by dual energy X-ray absorptiometry (DXA). RESULTS: The BMD increased 1.79% (p < 0.01 vs. pretreatment) after 50 weeks, accompanied with decrease of biochemical markers of bone turnover. With regard to climacteric symptoms, Kupperman's menopausal index improved (p < 0.01 vs. pretreatment) after 5 weeks of treatment. As to the incidence of adverse events genital bleeding was observed in only 8.0% of the subjects. Endometrial histology and cytology showed neither abnormalities nor hyperplasia during and after the treatment. CONCLUSIONS: Estriol prevented postmenopausal bone loss and improved climacteric symptoms effectively with low incidence of genital bleeding.

Bone Density↗

PubMed1989

Estriol reduces the reactivity of the human umbilical artery to mechanical stimuli.

The effect of estriol on the reactivity of the human umbilical artery to mechanical stimulation was studied using an in vitro perfusion method. The mechanical stimuli were produced by force applied to the outer surface of the vessel through a system consisting of a lever with equal length arms which was activated by small weights of known mass placed on one of the arms. The contractions of the preparations were proportional to the weights applied. When a 0.5-gram stimulus was applied, the mean contractile response of seven preparations was 46.7 +/- 2.72 mm Hg (mean +/- SEM). The addition of 10 micrograms/ml estriol to the nutrient fluid (Tyrode) caused a (mean 6.8 +/- 1.32 mm Hg) reduction of the response to the mechanical stimuli. We suggest that estrogens, and estriol in particular, play an important role in the modulation of the reactivity of the human umbilical artery during pregnancy in the presence of the mechanical stimulation caused by intrauterine fetal movements.

Estriol↗

PubMed1987

Diurnal variation in the excretion of 6 beta-hydroxycortisol and estriol at 32 weeks gestation.

We have previously shown a marked diurnal variation in the excretion of cortisol and 6 beta-hydroxycortisol at 36-38 weeks pregnancy with no variation in estrogen excretion. Since others have shown a reciprocal relationship between plasma levels of estriol and cortisol at 30-35 weeks of pregnancy, we decided to determine whether a similar relationship was present in urinary concentrations of cortisol, 6 beta-hydroxycortisol and estriol at this gestational age. A significant variation in excretion of both cortisol and 6 beta-hydroxycortisol was found. The variation in urinary levels of estriol was less than that of the corticosteroids but followed the same pattern.

Circadian Rhythm↗

PubMed1984

Estriol and cholic acid in maternal serum in induced labor.

Prostaglandin E2 (PGE2), but not oxytocin, treatment to induce parturition brought about an increase (p less than 0.001) in maternal serum levels of total estrogens (conjugated and nonconjugated estriol). There was no increase in nonconjugated estriol. To explore if the changes were related to an altered enterohepatic circulation, cholic acid assay in maternal serum was used. There were no changes in cholic acid which parallelled those in total estrogens. It is concluded that PGE2 does not appear to affect enterohepatic circulation of steroids, and it is suggested that the increase in total estrogens may be caused by changes in the kidney excretion of estriol.

Adolescent↗

PubMed1984

Effect of estradiol and estriol treatment on vaginal estrogen receptors in the ovariectomized rabbit.

Wet weight of the vagina increased by more than two-fold following treatment of the ovariectomized rabbits daily for 7 days with 100 micrograms/kg estradiol-17 beta or estriol. The concentration of estrogen receptors expressed on the basis of milligrams of protein in both the cytosolic and nuclear fractions decreased significantly after treatment with estradiol or estriol. The data reinforce the view that estriol given in low doses over a long period of time has as good an effect as estradiol on the vagina, and its use might be safer with respect to the effect on endometrial proliferation.

Animals↗

PubMed1983

Relation between diurnal changes in peripheral plasma progesterone, cortisol, and estriol in normal women at 30-31, 34-35, and 38-39 weeks of gestation.

To determine the relation of diurnal changes in plasma progesterone to those in cortisol and estriol we measured the concentrations of progesterone, cortisol and estriol in samples of plasma taken at 30- to 60-min intervals throughout 24 h from women at 30-31, 34-35, and 38-39 weeks of gestation. Plasma progesterone showed a significant diurnal rhythm at 30-31 and at 34-35 weeks of pregnancy, with troughs at 04.30-10.00 h. Major peaks occurred between 15.30 and 02.30 h. There was no diurnal rhythm in progesterone at 38-39 weeks. Plasma progesterone showed a significant negative correlation with plasma cortisol at 30-31 and 34-35 but not at 38-39 weeks. Plasma progesterone showed a significant positive correlation with estriol at 34-35 and at 38-39 weeks. We suggest that daily fluctuations in plasma progesterone may be related to the concentration of plasma cortisol, either directly by competition for binding sites on transcortin, or indirectly after modulation of fetal pituitary-adrenal function by maternally derived glucocorticoid.

Circadian Rhythm↗