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PubMed1983

Homogeneous enzyme immunoassay of estriol in picogram amounts.

A homogeneous enzyme immunoassay for estriol has been described using estriol-glucose-6-phosphate dehydrogenase (E3G6PD) as enzyme conjugate. Antisera for estriol were raised by immunising rabbits with two different immunogens, estriol-6-(O-carboxymethyl oxime) bovine serum albumin (E36CMOBSA) and estriol-3-carboxymethyl ether bovine serum albumin (E33CMEBSA). A new method for preparation of estriol 3-O-carboxymethyl ether in high yield (90%) has also been described. Addition of anti-estriol antibodies to E3-G6PD conjugate resulted in inhibition of enzyme activity. In the presence of free estriol, the antibody induced inhibition of enzyme activity was reduced in a concentration dependent manner. The use of the heterologous combination between immunogen and enzyme conjugate, i.e. using anti-E33CMEBSA and E36CMOG6PD improves the sensitivity at the expense of specificity, the cross-reaction with other estrogenic hormone being 10-15%.

Antibody Specificity↗

PubMed1984

Intermediary metabolism of estriol in pregnancy.

Estriol (E3), the most abundant estrogen in pregnancy is produced predominantly in the placenta from androgen precursors of fetal origin. The estriol so formed is secreted efficiently into the maternal circulation where it is converted to 4 conjugates--estriol-3-sulfate (E3-3S), estriol-16-glucosiduronate (E3- 16G ), estriol-3-glucosiduronate (E3- 3G ) and estriol-3-sulfate-16-glucosiduronate (E3-SG). The order of renal clearances is E3- 16G greater than E3- 3G greater than E3-3S approximately E3-SG. Unconjugated E3 and E3- 3G differ from the other forms of estriol in that their removal from the blood compartment is essentially irreversible. E3-3S, E3- 16G and E3-SG undergo interconversions during enterohepatic circulation and eventual partial conversion to E3- 3G . Following delivery of the fetus and placenta, unconjugated E3 is no longer detectable in the maternal serum within 1-2 h, whereas the concentrations of the conjugates decline more slowly, the rates being determined by the rates of renal clearance and enterohepatic interconversions. E3- 3G levels were dramatically elevated in a case of Group C polycystic kidney disease, providing evidence that this conjugate is indeed an end-product of estriol metabolism.

Cholestasis, Intrahepatic↗

PubMedDate not supplied

Estriol induced squamous metaplasia on the nasal mucosa in patients with hereditary hemorrhagic telangiectasia.

BACKGROUND: The aim of this study was to evaluate by light and electron microscopy the effect of topical estriol on the nasal mucosa in patients with hereditary hemorrhagic telangiectasia (HHT). METHODS: Twelve patients were instructed to apply twice daily 0.1% estriol as a nose ointment over a period of 12 months. Written consent was obtained from each patient, allowing biopsy specimens of the nasal mucosa to be taken prior to and 3, 6 and 12 months after estriol application. RESULTS: Metaplastic change of the nasal mucosa was observed 6 months after topical estriol application. The former ciliated columnar epithelium changed into a keratinizing squamous epithelium. The effect was reversible after discontinuation of estriol application. CONCLUSIONS: For the first time, we could outline the effect of topical estriol on the nasal mucosa. These histomorphological findings, and the fact that estriol is a low-potency metabolite of estradiol, make estriol a valuable agent in the treatment of HHT patients.

Administration, Topical↗

PubMed1999

Diurnal variation in saliva estriol level during pregnancy: a pilot study.

OBJECTIVE: The object of the study was to characterize daily values and patterns of salivary estriol levels during normal pregnancy at mid to late gestation. STUDY DESIGN: We measured salivary estriol levels in a clinical research center setting with an established enzyme-linked immunosorbent assay. Fourteen pregnant women (24-36 weeks' gestation) submitted unstimulated saliva samples hourly from 10:00 am until 10:00 pm and at midnight and 2:00, 4:00, 6:00, and 8:00 am. RESULTS: Each subject demonstrated greater salivary estriol levels at night (10:00 pm-6:00 am) than in the daytime (8:00 am-9:00 pm, P <.001). Salivary estriol levels consistently increased at 10:00 pm, peaked at 4:00 am, and returned to daytime levels between 6:00 and 7:00 am. Salivary estriol concentrations were stable during daylight hours. CONCLUSIONS: (1) There was a dramatic diurnal variation in salivary estriol levels (nadir during daylight with nighttime apogee). (2) Diurnal patterns and salivary estriol levels were consistent in each of 14 subjects evaluated in the latter half of pregnancy. Samples for baseline measurements of salivary estriol level should be obtained during daylight hours (8:00 am-8:00 pm).

Adolescent↗

PubMed2003

Effects of estriol on the proliferation and differentiation of human osteoblastic MG-63 cells.

Estriol has been showed to prevent bone loss in osteoporotic rats and postmenopausal women, but the mechanisms remain unclear. In the present study, we evaluated the effect of estriol on osteoblastic MG-63 cells in vitro, and compared its action with 17beta-estradiol (E2). Cell proliferation was determined by measuring total cell numbers and [3H]thymidine incorporation. Cell function was studied by measuring alkaline phosphatase (ALP) activity and secreted osteocalcin. Our data showed that estriol stimulated MG-63 cells proliferation in a dose-dependent manner, but had no influence on ALP activity in MG-63 cells and osteocalcin production. Compared with estriol treatment, E2 showed a stronger proliferation. Estrogen receptor (ER) alpha and beta expression in MG-63 cells can be detected by Western immunoblot analysis, and the proliferative response to E2 and estriol can be all abrogated by ER antagonist ICI 182,780. In conclusion, estriol stimulates osteoblastic MG-63 cells proliferation, but has no effects on differentiation. The proliferative response to estriol is mediated by the ER. These results suggest that estriol has an effect on osteoblastic proliferation, and this may contribute to its actions on prevention of bone loss.

Alkaline Phosphatase↗

PubMed2003

Effectiveness of estriol-containing vaginal pessaries and nitrofurantoin macrocrystal therapy in the prevention of recurrent urinary tract infection in postmenopausal women.

We compared the efficacy and safety of estriol-containing vaginal pessary use with those of oral nitrofurantoin macrocrystal (NM) therapy for preventing urinary tract infection (UTI) in postmenopausal women with recurrent UTI. Over a period of 9 months, 86 women received an estriol-containing vaginal pessary (0.5 mg estriol) twice weekly, and 85 women received NM (100 mg) once daily. We recorded 124 episodes of UTI in women who received estriol-releasing pessaries and 48 episodes of UTI in women treated with NM (P=.0003). Twenty-eight women (32.6%) who received estriol had no episodes of UTI versus 41 women (48.2%) in the NM group. There was a significant increase in the number of superficial cells in women who received estriol, whereas in the NM group, no such changes occurred. However, there was no change in the extent of Lactobacillus colonization and in the vaginal pH in women who received estriol. Use of an estriol-containing pessary is less effective than oral NM therapy in the prevention of bacteriuria in postmenopausal women because of its failure to restore the population of lactobacilli and to reduce the vaginal pH in these women.

Aged↗

PubMed2006

Urodynamic and morphologic changes in the lower portion of the urogenital tract after administration of estriol alone and in combination with phenylpropanolamine in sexually intact and spayed female dogs.

OBJECTIVE: To compare the urodynamic and morphologic effects of the administration of estriol alone and in combination with phenylpropanolamine on the lower portion of the urogenital tract in female dogs. ANIMALS: 3 sexually intact and 3 spayed female Beagles without urinary incontinence. PROCEDURE: Dogs received estriol (2 mg, PO) once daily for 7 days followed by estriol (2 mg, PO) and phenylpropanolamine (1.5 mg/kg, PO) once daily for 7 days. Urethral pressure profilometry, diuresis cystometry, and vaginourethrography were performed before treatment (day 0) and at days 7 and 14. The maximum urethral pressure (MUP) and closure pressure (MUCP), urethral functional and anatomic profile lengths, integrated pressure (IP), plateau, distance before MUP, maximum meatus pressure, threshold pressure, threshold volume, compliance, urethral length, and vaginal length and width were measured. RESULTS: Before treatment, no urodynamic differences were observed between the 2 groups; however, vaginal length and width were significantly shorter in spayed dogs. Compared with day 0 values, estriol treatment significantly increased MUP, MUCP, and IP values at day 7, but at day 14, this effect decreased despite phenylpropanolamine administration. No morphologic changes from baseline were detected after either treatment in any dog. CONCLUSIONS AND CLINICAL RELEVANCE: Data suggest that estriol mainly acts on the urethral sphincter mechanism by increasing urethral resistance in sexually intact and spayed female dogs without urinary incontinence. Administration of estriol and phenylpropanolamine did not increase the urethral resistance more than estriol alone. The urodynamic effects of estriol in female dogs with urinary incontinence remain to be elucidated.

Animals↗

PubMed1999

Comparative measurements of serum estriol, estradiol, and estrone in non-pregnant, premenopausal women; a preliminary investigation.

Little to no data exists in the literature for serum estriol values in non-pregnant, premenopausal women. The current medical community opinion holds that estriol has no significant role in non-pregnant women relative to the other estrogens. It is a possibility that estriol's primary function has yet to be discovered. Accordingly, the first step is to understand cycle-dependent serum estriol concentrations. We have made a preliminary investigation for serum estriol concentration of 26 women during the known cycle peaks of estrone and estradiol. Five of the women were also tested for serum estriol on various days throughout the cycle in order to develop a cycle-dependent concentration profile. The result of these experiments show that serum estriol was always significantly higher than the sum of estrone and estradiol and less fluctuating. We conclude that estriol is probably a significant estrogen component.

Adult↗

PubMed1976

Direct radioimmunoassay for serum estriol during pregnancy.

I describe an assay for serum estriol during pregnancy, which does not require prior extraction or chromatography of the serum. Fifty microliters of 20-fold diluted serum can be assayed to detect as little as 20 pg of estriol. For a 20 mug/liter serum estriol concentration the CV was 16%; for 100 mug/liter concentration it was 5%. There was no significant interference by serum "binding" proteins. The assay measures unconjugated estriol, estriol conjugated with either sulfate or glucuronide at the 3' position, and a portion of the estriol 16 alpha (beta-D-glucuronide). Serum estriol concentrations increase during gestation from a low at 20 weeks of less than 10 mug/liter to a high of 100-150 mug/liter at term. Serum estriol values correlate well with those for urinary total estrogens and with values for human placental lactogen in serum at various gestational ages.

Estriol↗

PubMed1980

Ratio of unconjugated to total estriol in uncomplicated third-trimester pregnancy.

The serum unconjugated estriol, as a percent of total estriol, has been determined in third-trimester pregnancies studied longitudinally. The unconjugated fraction in any specific sample ranged from 4.1% to 21.6% of the total. The mean percent unconjugated estriol in 34 patients sampled 7 to 15 times each between 32 and 40 weeks of gestation ranged from 5.3% to 13.6%. Higher serum total estriol concentration correlates with a lower percent of unconjugated. The mean percent unconjugated decreases during the last eight weeks of gestation from 11.4% to 8.4%, with a calculated regression line of Y = 23.323--0.368X. Thus, the concentration of serum unconjugated estriol is relatively more constant. The majority of patients demonstrate a narrow range of percent serum unconjugated estriol. These circumstances, combined with ease of assay, support the use of serum unconjugated estriol in pregnancy estriol monitoring.

Estriol↗

PubMedDate not supplied

[Critical analysis of fetal risk recognition by serum estriol determination].

In 901 pregnancies between 1978-1981 a total of 5281 serum estriol determinations were performed. 596 gravidas were high-risk patients (diabetes mell., toxemia, IUGR, premature labour, prolonged pregnancy, Rh incompatibility). In 142 of these high-risk pregnancies the estriol values were below the 10th percentile or the estriol decrease extended 40%. These cases were analysed individually, in order to answer the question, how often serum estriol values were decisive for active obstetrical management. Our data show that a drop of estriol over 40% was very rare (0.53%). For the newborn such an estriol-drop does not mean higher perinatal morbidity or mortality in any case. The endocrine parameters were not very often decisive for an active obstetrical intervention. Probably because of the large fluctuations and day-to-day-variations of the estriol values mainly due to drugs which were widely used in risk pregnancies. These exogenous factors had a negative effect on the clinical value of the serum estriol determinations.

Estriol↗

PubMed1980

Variability in unconjugated and total estriol in serum during normal third trimester pregnancy.

We determined unconjugated and total estriol concentrations in serum during the third trimester in 34 normal gestations. Data were obtained weekly for 13 women for as long as nine weeks; 21 others were studied daily for up to 15 days. No correlation between birth weight and either estriol fraction was demonstrated. Between-patient variability was less for unconjugated estriol and was similar for weekly and daily data. Within-patient variability was also less for unconjugated estriol and, as expected, was less for daily than for weekly data. The CV for daily samples, within patient, averaged 13.0% for unconjugated estriol and 20.3% for total estriol. Our data support the daily determination of unconjugated estriol in serum, evaluated for percent changes from single or mean preceding values, as the preferred method of monitoring estriol during pregnancy.

Estriol↗

PubMed2002

Treatment of multiple sclerosis with the pregnancy hormone estriol.

Multiple sclerosis patients who become pregnant experience a significant decrease in relapses that may be mediated by a shift in immune responses from T helper 1 to T helper 2. Animal models of multiple sclerosis have shown that the pregnancy hormone, estriol, can ameliorate disease and can cause an immune shift. We treated nonpregnant female multiple sclerosis patients with the pregnancy hormone estriol in an attempt to recapitulate the beneficial effect of pregnancy. As compared with pretreatment baseline, relapsing remitting patients treated with oral estriol (8 mg/day) demonstrated significant decreases in delayed type hypersensitivity responses to tetanus, interferon-gamma levels in peripheral blood mononuclear cells, and gadolinium enhancing lesion numbers and volumes on monthly cerebral magnetic resonance images. When estriol treatment was stopped, enhancing lesions increased to pretreatment levels. When estriol treatment was reinstituted, enhancing lesions again were significantly decreased. Based on these results, a larger, placebo-controlled trial of estriol is warranted in women with relapsing remitting multiple sclerosis. This novel treatment strategy of using pregnancy doses of estriol in multiple sclerosis has relevance to other autoimmune diseases that also improve during pregnancy.

Adolescent↗

PubMed1996

Estriol: a potent regulator of TNF and IL-6 expression in a murine model of endotoxemia.

The increased incidence of autoimmune disease in premenopausal women suggests the involvement of sex steroids in the pathogenesis of these disease processes. The effects of estrogen on autoimmunity and inflammation may involve changes in the secretion of inflammatory mediators by mononuclear phagocytes. Estradiol, for example, has been reported to regulate TNF, IL-6, IL-1 and JE expression. In the present study the effects of the estrogen agonist, estriol, on cytokine expression have been investigated in mice administered a sublethal lipopolysaccharide, LPS, challenge. Pretreatment of mice with pharmacologic doses of estriol, 0.4-2 mg/kg, resulted in a significant increase in serum TNF levels in both control and autoimmune MRL/lpr mice, following LPS challenge. This increase in TNF over the placebo group was blocked by the estrogen antagonist tamoxifen. Estriol treated mice also exhibited a rapid elevation in serum IL-6 levels following LPS challenge with the peak increase occurring 1 hr post LPS. This contrasted with the placebo group in which maximal serum IL-6 levels were detected at 3 hrs post challenge. This shift in the kinetics of IL-6 increase by estriol was inhibited by tamoxifen. The estriol mediated effects of TNF and IL-6 serum levels were consistent with the changes in TNF and IL-6 mRNA observed ex vivo in elicited peritoneal macrophages. Macrophage cultures from estriol treated animals however, did not demonstrate significant differences from the placebo group for TNF or NO secretion following in vitro LPS challenge. These results suggest that the estrogen agonist estriol can have significant quantitative, TNF, and kinetic, IL-6, effects on inflammatory monokines produced in response to an endotoxin challenge.

Animals↗

PubMed2003

[Argon plasma coagulation and topically applied estriol. Long-term results in the treatment of hereditary hemorrhagic telangiectasia of the nasal mucosa].

BACKGROUND AND OBJECTIVE: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant fibrovascular dysplasia with the main symptom of recurrent epistaxis. At present, only limited data are available on long-term results in the treatment of epistaxis. A part from the surgical treatment of the bleeding telangiectasia with argon plasma, an additional postoperative long-term treatment with estriol nose-ointment was performed and the results were analysed. PATIENTS AND METHODS: 69 patients with HHT were treated with APC and estriol nose ointment. 43 patients could be examined over a follow-up period of more than 20 months. The bleeding frequency and intensity as well as the patient's satisfaction with the treatment result were evaluated and the serum estriol level determined. RESULTS: After more than 20 months, the bleeding frequency and intensity were reduced in 95% of the patients compared to their preoperative findings. Under the influence of estriol, former berry-like telangiectasias became flatter and more even. Neither systemic side effects under topically applied estriol nor a relevant increase of serum estriol levels were observed. CONCLUSION: The combined treatment regimen with APC and topically applied estriol provides a new treatment concept of epistaxis in HHT.

Administration, Topical↗

PubMed1979

Estriol determinations in diabetic pregnancies complicated by nephropathy.

In order to study the effect of renal disease on urinary estriol clearance rate, we have measured the concentrations of plasma and urinary estriol (E3) in pregnancies of 69 diabetic patients, 25 of whom had nephropathy. No correlation was found between endogenous creatinine clearance (CCr) and estriol clearance (CE3) rates (r = 0.07), and mean CE3 of diabetic patients with diminished CCr (less than 100 ml/min) was not significantly different from that of patients with normal CCr (greater than or equal to 100 ml/min). The ratios between total, unconjugated estriol and urinary estriol concentrations in patients with diminished CCr were not different from those patients with normal CCr. Cases where high plasma estriol and low urinary estriol concentrations coexisted were not found. It is concluded that in this group of diabetic patients, diminished CCr had no discernible effect on urinary CE3 possibly because renal tubular function remained intact. In patients with diabetic nephropathy either urinary or plasma E3 could be used to assess fetoplacental function.

Creatinine↗

PubMed1975

Estriol concentrations in plasma of normal, non-pregnant women.

Using a rabbit antisera directed against estriol-3-0-carboxy methyl ether complexed to BSA, an immunoassay for estriol (1) was developed. The mean plus or minus SE concentration of estriol in 18 women in days 5-7 of their cycle was 7.9 plus or minus 0.6 pg/ml which was significantly (P less than 0.01) less than the mean value of 11.1 plus or minus 0.8 pg/ml in 15 women in days 20-22 of the cycle. In 3 of 6 women in whom plasma samples were drawn frequently during their cycle, an estriol peak occurred coincident with the estradiol peak. In 3 women from whom plasma was obtained several times during the course of a day estriol levels did not appear to vary significantly. In 8 women who were on oral contraceptives the mean level of estriol was 7.6 plus or minus 1.5 pg/ml. In 8 post-menopausal women the mean level was 6.0 plus or minus 1.2 pg/ml which is significantly (P less than 0.01) less than the mean luteal phase value but not less (P greater than 0.1) than the follicular phase or oral contraceptive user values. We conclude that some of the circulating estriol is directly secreted by the ovary of normal women.

Adult↗

PubMed1985

A simple radioimmunoassay for estriol 3-sulfate in pregnancy plasma without deconjugation.

A highly specific anti-estriol 3-sulfate antiserum was treated with 50% ammonium sulfate, and the crude globulin fraction was coupled to CNBr-activated Sepharose-4B. Addition of 0.1M Tris-HC1 buffer (pH 8.3) containing 0.1M glutamine to the solution of antigen-antibody enabled assaying without solvent-extraction or chromatography to remove endogenous interference. Subsequently, a direct radioimmunoassay using [6,7-3H]-estriol 3-sulfate as a radioactive ligand without deconjugation has been established and applied to the determination of estriol 3-sulfate levels in pregnancy plasma. The increasing plasma levels of estriol 3-sulfate are correlated with estriol levels over the period of gestation. The mean values of sulfated estriol concentration (A) in late pregnancy plasma were approximately 7 times as high as unconjugated estriol (B), but individual ratios of A to B showed considerable variability.

Estriol↗