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PubMed2006

Estrogen and alpha-fetoprotein levels in maternal and umbilical cord blood samples in relation to birth weight.

Birth weight has been associated with a subsequent risk of breast cancer. The present study examined associations between birth weight and pregnancy estrogens and alpha-fetoprotein (AFP). The concentrations of estradiol, estriol, and AFP were measured in maternal and umbilical cord blood samples from 194 women during pregnancy and at birth. Birth weight was significantly positively correlated with maternal serum estradiol and estriol levels in the 29th week (estradiol: r = 0.16, P = 0.03; estriol: r = 0.29, P = 0.001) and at delivery (estradiol: r = 0.20, P = 0.01; estriol: r = 0.41, P < 0.0001) after controlling for covariates. The umbilical cord estriol level was moderately but significantly correlated with birth weight (r = 0.15, P = 0.049). There was no significant association between umbilical cord serum estradiol and birth weight. There was no significant association between birth weight and maternal serum AFP in any gestational week. Umbilical cord AFP was significantly inversely correlated with birth weight (r = -0.16, P = 0.04). Umbilical cord AFP was unrelated to cord levels of estradiol and estriol. The data suggested a greater exposure to estriol and a lower exposure to AFP among high birth weight babies.

Adolescent↗
PubMed2000

Enterohepatic recycling of estrogen and its relevance with female fertility.

Enterohepatic recycling of estrogen after oral administration of 1 mg non-radioactive estriol was studied in fourteen women selected as the control subjects and ten infertile women in whom the infertility was appearing to be of endocrine origin. The extent of enterohepatic recycling of estriol (E3) during the early follicular phase of menstrual cycle was assessed by monitoring during 48 h the urinary excretion of its two major metabolites i.e; estriol 16 alpha-glucuronide (E3-16 alpha-CG) and estriol-3 glucuronide (E3-3-G). The change in urinary level of E3-3-G with respect to E3-16 alpha-G was considered to reflect the extent of enterohepatic recycling of estriol. Lower values of urinary output of both metabolites in the infertile women as compared with the control subjects and the urinary excretion profile of both metabolites during 48 h after estriol ingestion reveal that the reduced extent of enterohepatic recycling could possibly be one of the factors which contribute towards the incidence of infertility in women.

Adolescent↗
PubMed1975

Impact of betamethasone load given to pregnant women on endocrine balance of fetoplacental unit.

Corticosteroid administration to pregnant women for attempted prevention of the respiratory distress syndrome in infants (IRDS) involves the hazard of seriously altering the endocrine status in the fetoplacental unit. The effect of a betamethasone load (12 mg. daily for three days) to 19 pregnant women in the last trimester was studied, and a comparison was made with 13 control subjects. Amniocentesis was performed twice in most patients. There was a sharp reduction of cortisol in maternal serum and a significant decrease in cortisol concentration in amniotic fluid (p less than 0.05) after betamethasone treatment. Maternal urinary estriol excretion decreased; this was strongly correlated to the basal estriol excretion (r equals 0.945). A residual fraction of estriol excretion, not less than 2 mg. per 24 hour urine specimen, remained despite the high corticosteroid dose. The origin of the nondepressed part of urinary estriol might be multifactorial, e.g., nonadrenal production of estriol precursors and functional inhomogeneity of the fetal adrenal in response to adrenocorticotropic hormone stimulation. The corticosteroid treatment for prevention of IRDS transiently excludes the use of urinary estriol for assessment of fetoplacental integrity but does not influence the plasma level of human chorionic somatomammotropin.

Amniocentesis↗
PubMed1984

Uterine vascular effects of estetrol in nonpregnant ewes.

Estetrol is produced by the fetal liver and has been suggested to be a sensitive indicator of fetal well-being. Although the uterine vascular effects of estrogens (17 beta-estradiol, estriol, and estrone) have been extensively investigated in our laboratory and those of others, the ability of estetrol to dilate the ovine uterine vasculature is not presently known. The present experiment was designed to compare the vasoactivity of estetrol to that of a second pregnancy-associated estrogen, estriol. Five nonpregnant oophorectomized ewes were chronically instrumented with catheters in the femoral artery, femoral vein, uterine arteries, and electromagnetic flow probes on both uterine arteries. Upon recovering from operation, animals received unilateral intra-arterial (uterine) injections of either estriol (0.1, 0.3, 1, and 3 micrograms) or estetrol (1, 3, 10, and 30 micrograms). Ewes received only one dose of either estetrol or estriol daily and all doses were given in a randomized order. Uterine blood flow responses were continuously monitored and the time of onset, peak, and duration were recorded. The time of onset (38 +/- 2 minutes), time of peak response (75 +/- 1 minute), and duration (189 +/- 7 minutes) were approximately equal to those observed for estriol. On the basis of the data obtained in the present study we have determined that estetrol is 15 to 30 times less potent than estriol as a uterine vasodilator.

Animals↗
PubMed1988

Estrogens and phenylpropanolamine in combination for stress urinary incontinence in postmenopausal women.

Thirty-six postmenopausal women with objectively verified stress incontinence were treated with oral estriol (Triovex, 2 mg x 1) and phenylpropanolamine (Kontexin, 50 mg x 2) alone and in combination. After an initial four-week single-blind period with phenylpropanolamine (PPA), either estriol or estriol and PPA were given randomly in four-week periods, in a crossover design. PPA and estriol in combination as well as PPA alone, raised the intraurethral pressure and significantly reduced the urinary loss by 35 per cent in a standardized physical strain test. In women with an initial low urethral pressure estriol also induced pressure increase. The leakage episodes and the assessed leakage amounts were significantly reduced by both estriol and PPA given separately as single treatment (28%) or when given as combined therapy (40%). Most of the women preferred the combined treatment to either drug alone. Additive but no synergistic effects are indicated.

Administration, Oral↗
PubMed1997

Endometrial sonographic and histologic findings in women with and without hormonal replacement therapy suffering from postmenopausal bleeding.

OBJECTIVES: To evaluate, in women with postmenopausal bleeding, the effect of hormonal replacement (HRT) therapy on the endometrial thickness as measured by transvaginal sonography in relation to endometrial histology. METHODS: 1110 women with sequential/progestin treatment (E + P) (n = 202), with Estriol treatment (n = 149) or without HRT (n = 759) and postmenopausal bleeding were examined by transvaginal sonography (TVS) prior to curettage, with special reference to the relation of endometrial thickness to its histopathology. RESULTS: The distribution of endometrial pathology was different in those women with E + P and Estriol compared with those without HRT. Endometrial pathology was found most frequently in women with an endometrium exceeding 8 mm in thickness. Furthermore, the incidence was found to increase with increasing endometrial thickness in all treatment groups. Atrophy was found significantly more often in women without HRT. Hormonal effects on the endometrium were found significantly more often in women with E + P and Estriol. Endometrial hyperplasia was found most commonly in women with Estriol in the thickness group 5 8 mm (P < 0.001) as compared to those with HRT and without HRT. Endometrial cancer occurs most in women without HRT, in those women with an endometrium exceeding 8 mm in thickness as compared both to the E + P (P < 0.001) group and to the Estriol (P < 0.001) group. Endometrial cancer did not occur in any woman (with E + P, Estriol or without HRT) with an endometrial thickness of < or = 4 mm. CONCLUSIONS: TVS is of value for excluding endometrial pathology in women with HRT and postmenopausal bleeding. The distribution of endometrial findings and histopathological diagnosis in women with abnormal postmenopausal bleeding was different in women with E + P than in women without HRT. Furthermore, the cut-off for excluding endometrial abnormalities is the same in both groups i.e. < or = 4 mm.

Endometrium↗
PubMed2001

An immunoassay for small analytes with theoretical detection limits.

A flow-based immunoassay that uses microspheres as the solid phase accomplished the theoretical limit of detectability achievable with the antibody. An equilibrated mixture of anti-estriol monoclonal antibody and estriol was briefly exposed to a bead pack containing immobilized estriol in a flow cell. A small portion of free antibody was separated rapidly from the mixture by binding it to immobilized hormone, but the antibody-hormone complex was kinetically excluded from binding. This rapid separation prevented shift in the equilibrium of the liquid phase binding. Signals were generated by labeling the separated antibodies on the beads with a Cy5-conjugated antispecies secondary antibody. By labeling after the separation step, perturbing the liquid-phase or solid-phase binding was prevented. This assay allowed the reduction of the concentration of primary antibody by continuously accumulating free antibody onto the beads prior to quantification and, thus, offered ideal conditions to achieve theoretical limits of detectability. The optimum achievable dynamic range of this immunoassay was 4-300 pM. Because the proportion of free anti-estriol antibody in the mixture was controlled by the Kd of the antibody-estriol interaction, when the concentration of the antibody was below the Kd, the smallest detectable estriol concentration approached the theoretical limit of detectability achievable with this antibody.

Antibodies, Monoclonal↗
PubMed1979

Mechanism of action of estrogen agonists and antagonists.

The relationship between estrogen agonists and antagonists and the nuclear binding of the estrogen receptor was investigated in the immature rat uterus. Estriol (and other short acting estrogens) are antagonistic when administered as a single injection due to the inability of the receptor-estriol complex to be retained by uterine nuclei for a critical period necessary to stimulate true uterine growth. This failure of the receptor-estriol complex to be retained appears to be due to rapid clearance of estriol from uterine tissue following a single injection of the hormone. When estriol is present in a chronic fashion, it acts as an agonist because receptor estriol complex is retained at nuclear sites for long periods of time. Nonsteroid estrogen antagonists, such as Nafoxidine, also cause long term nuclear retention of the estrogen receptor and act as estrogen agonists after a single injection. However, after multiple injections these drugs are antagonistic and this effect is correlated with decrease availability of cytoplasmic estrogen receptors. In addition, these compounds appear to specifically stimulate the growth of uterine epithelial cells while minimally affecting other cell types which results in hyperestrogenization of the epithelium.

Animals↗
PubMed1979

Sequential radioimmunoassay of unconjugated and conjugated estrogen in male human plasma.

A sequential radioimmunoassay procedure for unconjugated and conjugated estrone, estradiol-17 beta and estriol in male human plasma was developed. The blank values in this assay for unconjugated estrone, estradiol-17 beta, estriol conjugated estrone, estradiol-17 beta and conjugated estriol were 0.36 +/- 1.14 pg, 3.90 +/- 2.75 pg, 2.25 +/- 2.08 pg, 0.92 +/- 1.51 pg, 5.02 +/- 2.86 pg and 3.12 +/- 2.97 pg, respectively. Mean values of unconjugated estrone, estradiol-17 beta, estriol, conjugated estrone, estradiol-17 beta and conjugated estriol in plasma from 28 normal adult males were 38.4 +/- 13.4 pg/ml, 32.6 +/- 9.90 pg/ml, 4.06 +/- 3.68 pg/ml, 34.2 +/- 13.8 pg/ml, 40.4 +/- 12.3 pg/ml and 31.8 +/- 7.41 pg/ml, respectively. Both unconjugated and conjugated estrogen levels in patients with liver cirrhosis were elevated and conjugated estrogen, especially estriol levels, in patients with renal insufficiency were markedly elevated.

Acute Kidney Injury↗
PubMed1978

Estrogen profiles of premenopausal women with breast cancer.

Population surveys have demonstrated an inverse relationship between breast cancer incidence rates and the urine "estriol ratio," the concentration of estriol relative to the sum of the concentrations of estrone and estradiol. In this study, the urine estriol ratio was evaluated in premenopausal breast cancer patients and control women from Boston and San Francisco. Although at least 2 years had passed since last use of oral contraceptives, women with a history or oral contraceptive use for 19 months or longer excreted estrogen in low concentrations compared to nonusers and so were excluded. Among the remaining 73 cases and 55 controls, the cases had lower estriol ratios and higher estrone and estradiol levels than did controls. However, these differences, which averaged about 10%, were not statistically significant. Thus the hypothesis that a low estriol ratio is a cause of breast cancer is given only minimal support. Among women in their 40's, the excretion of estrogens is subject to many influences and is difficult to study. The many determinants of estrogen excretion, including age and oral contraceptive use, should be accommodated in the design of future studies of the estriol ratio.

Adult↗
PubMed1983

Acute and subchronic effects of methadone on the blood hormonal levels of pregnant and nonpregnant Charles River CD-1 mice.

Blood levels of ACTH, FSH, and estriol were measured throughout the estrous cycle and estriol was determined at different stages during pregnancy in Charles River CD-1 mice treated with 10 mg/kg/day of methadone or vehicle (physiological saline). Animals received one dose in a constant volume (10 ml/kg) per day subcutaneously of either methadone or saline. Blood samples of nonpregnant mice were collected 1 hour after the first dose for acute effects and 1 hour after the last dose treatment for subchronic effects. The acute administration of methadone in nonpregnant mice produced an increase in ACTH level throughout the estrous cycle whereas subchronic treatment reduced ACTH level by 51%. Acute treatment did not alter the estriol or FSH levels whereas subchronic treatment significantly lowered estriol by 17% and FSH by 79%. Methadone injected beginning on day 1 of gestation and continued through day 15 did not produce any effect on maternal body weight or food consumption but resulted in an increase in resorption sites and decrease in implantation sites. The estriol levels in control pregnant mice were 19.8, 54.8, and 109.1 ng/ml on days 1, 10, and 15 of gestation, respectively. A significant reduction of 18.8% and 35.2% in estriol was associated with methadone treatment by days 10 and 15 of gestation, respectively. Methadone, by affecting several hormonal levels in both pregnant and nonpregnant CD-1 mice, may be responsible for some of the adverse effects on reproduction encountered in this species.

Adrenocorticotropic Hormone↗
PubMed1978

Relationship between urine and plasma estrogen ratios.

Normal young and postmenopausal women were placed into groups according to the ratio of the estrogens in their urine. Women whose ratio was greater than 1.3 if young and greater than 3.2 if postmenopausal were compared to women whose ratio was less than 0.7 and less than 2.1 for young and postmenopausal, respectively. Between the respective high- and low-ratio groups, there were no significant differences for circulating levels of estriol, metabolic clearance rates of estriol, or blood production rates of estriol, estrone, or estradiol. Women who had had breast cancer were compared to a group of normal controls and were also found to have similar blood production rates for estriol, estrone, and estradiol. The ratios of the blood production rates of estriol to estrone and estradiol were similar for the high and low groups for young and postmenopausal women and also between the breast cancer women and their controls. It appears, therefore, that the difference in urinary estrogen ratios is primarily due to different pathways of metabolism of the free circulating estrogens and not to differences in the production rates of the estrogens. Estriol is produced at only 10% the rate of estrone and estradiol.

Breast Neoplasms↗
PubMed1982

Electrochemical investigation of hapten-antibody interactions by differential pulse polarography.

The binding of electroactively labeled estriol with estrogen-specific antibody and its subsequent displacement by unlabeled estriol have been monitored by differential pulse polarography. Estriol was found to be electro-inactive in the potential range -200 mV to -1000 mV vs a silver/silver chloride electrode. Estriol labeled in the 2 and 4 position with nitro groups was electroactive, giving two reduction waves at -422 mV and -481 mV vs a silver/silver chloride electrode. The peak current was linear with concentration over the range 60 micrograms/L to 3.7 mg/L. The addition of aliquots of estrogen-specific antibody reduced the peak current proportionately, indicating the binding of ligand to specific antibody. Subsequent addition of unlabeled estriol produced incremental increases in peak reduction current, indicating competitive and reversible binding of the two ligands for the antibody. Separation of bound from free labeled hapten was not necessary because reduction of the antibody-bound labeled estriol is attenuated at the electrode.

Antibodies, Monoclonal↗
PubMedDate not supplied

Ultrasound and estradiol plasma levels in threatened abortion.

Ultrasound examination and unconjugated estriol assay were performed in 111 women with threatened abortion between the 6th and the 20th week of pregnancy. In viable pregnancies, fetal echoes and fetal heart movements were always observed by sonar from the 10th week onward and estradiol levels always increased above 30 pg/ml from the 13th week. Both ultrasound and estriol assay showed high percentages of uncertain prognostic indication on pregnancy outcome when examinations were performed during the first weeks of pregnancy. However, in the same period estriol levels higher than 30 pg/ml were always correlated with the favourable outcome of pregnancy, since no abortion occurred in subjects with detectable estriol values. During the second trimester ultrasound and estradiol results were normal in all viable pregnancies, while they were abnormal in 71.4% of pregnancies which failed to continue. Estriol values were always undetectable when fetuses could not be identified by sonar or they were dead. These data seem to demonstrate that both methods have similar prognostic value in patients with threatened abortion. However both sonar examination and estriol levels sometimes failed in predicting subsequent pregnancy interruptions, suggesting that abortions were not related to either fetal or placental alterations.

Abortion, Threatened↗
PubMed1993

Effect of ovarian steroids and diethylstilbestrol on the contractile responses of the human myometrium and intramyometrial arteries.

Estriol, estradiol, progesterone and diethylstilbestrol in the concentration range of 0.2-40 microM inhibited the spontaneous contractions of the myometrium in a dose-dependent manner but the differences in IC50 values obtained with different hormones were not statistically significant. All these hormones caused a concentration-dependent inhibition of the K(+)-induced contraction. The IC50 values were lowest for diethylstilbestrol and highest for estriol. Vasopressin at concentrations of 1.5 x 10(-6) - 1.8 x 10(-3) U/ml stimulated myometrial contractions. These responses were also inhibited by ovarian steroids and diethylstilbestrol. The IC50 values for estriol and progesterone were significantly higher than for estradiol or diethylstilbestrol. The values for estriol and progesterone did not differ significantly. In the uterine arteries, which lacked spontaneous activity, ovarian steroids and diethylstilbestrol inhibited contractions induced by K+ depolarization. As with myometrium, the lowest effect was observed with estriol and the highest with diethylstilbestrol. A dose-dependent inhibition by all four hormones (0.2-40 microM) of vasopressin-induced contractile responses of the uterine arteries was observed. With the lowest concentration of progesterone, however, the arterial response to vasopressin was enhanced. The increases by progesterone (0.02 and 0.2 microM) of responses induced by vasopressin were statistically significant (P < 0.05). The present data strongly suggest that, in human myometrium and uterine arteries, ovarian steroids and diethylstilbestrol cause a more pronounced inhibition of receptor-mediated than of voltage-dependent Ca2+ channels. The increase by a very low (physiological) concentration of progesterone of vasopressin-induced responses in both myometrium and arteries may be of significance in the pathophysiology of dysmenorrhea.

Arteries↗
PubMed2003

Testosterone levels in pregnant women correlate with the insulin response during the glucose tolerance test.

OBJECTIVE: To evaluate the association between insulin/insulin-like growth factor I (IGF-I) systems and androgen levels in pregnancy. DESIGN: Prospective cohort study. SETTING: Yale University School of Medicine. PATIENT(S): Pregnant women undergoing a 100-gram 3-hour glucose tolerance test (GTT). INTERVENTION(S): Serum samples collected during GTT were analyzed for insulin, androgens, free IGF-I, insulin-like growth factor-binding protein (IGFBP) 1, and estriol. MAIN OUTCOME MEASURE(S): Observing the relationship between insulin/IGFs and androgen levels. RESULT(S): The insulin area under the curve (I(AUC)) during GTT correlated positively with total T and free T, but not with dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), or estriol. The peak insulin values (I(max)) during GTT also correlated positively with total T and free T, but not with DHEA, DHEAS, or estriol. There was no statistically significant correlation of T levels with free IGF-I, IGFBP-1, glucose, DHEAS, or estriol. Multiple linear regression analysis modeling showed that I(AUC) and I(max) did have a statistically significant correlation with free T levels. CONCLUSION(S): This study demonstrates for the first time that I(AUC) and I(max) measured in hyperinsulinemic states such as pregnancy correlate with T levels. In view of the lack of correlation between insulin and DHEAS or estriol, insulin-related T production during pregnancy is likely of ovarian origin.

Adult↗
PubMed1996

Endometrial unresponsiveness: a novel approach to assessment and prognosis in in vitro fertilization cycles.

OBJECTIVE: To categorize endometrial responsiveness to orally administered estriol in natural cycles of patients with thin endometrium. The value of endometrial responsiveness in predicting the outcome of subsequent IVF-ET cycles was evaluated. DESIGN: Prospective clinical study. SETTING: Miami IVF-ICSI Center, Alexandria, Egypt, a private center. PATIENTS: Forty-two patients undergoing IVF-ET. All had endometrial thickness < or = 7 mm at the time of maximal follicular diameter in natural cycle. INTERVENTION: Estriol was orally administered in subsequent unstimulated cycle. Patients were categorized into responsive and unresponsive groups (those with improved and unimproved endometrial thickness, respectively). Lastly, controlled ovarian hyperstimulation (COH) with or without estriol was started in the IVF-ET cycles. MAIN OUTCOME MEASURES: The endometrial thickness during COH with or without estriol, fertilization, pregnancy, and abortion rates. RESULTS: The responsive group compared with the unresponsive group had a significantly higher rate of improved endometrial thickness, a similar number of oocytes retrieved, a similar fertilization rate, and a significantly higher pregnancy rate. CONCLUSION: Patients with endometrial unresponsiveness to estriol in their natural cycles rarely improve by COH and have a poor pregnancy rate in IVF cycles.

Adult↗
PubMed2000

The triple-marker test in predicting fetal aneuploidy: a compromise between sensitivity and specificity.

OBJECTIVE: to review the contribution of unconjugated estriol in Down's syndrome detection, and influence of maternal age, cut-off choice, and population specificity on the balance between triple-marker test sensitivity and specificity. STUDY DESIGN: Prenatal karyotyping was performed in 2833 pregnant women, 73% of them over the age of 34. Duration of gestation was determined by ultrasound in 98% of women. Prior to amniocentesis, the serum levels of alpha-fetoprotein, human chorionic gonadotropin and unconjugated estriol were evaluated and corrected for weight. The risk of trisomy 21 was calculated for the first 986 subjects using default medians, and for 1847 by our population-specific medians. The cut-off was initially 1:300 at term, but the 1:100 and 1:200 risks were also tested. Down syndrome risk was calculated with alpha-fetoprotein and human chorionic gonadotropin combination as well. Linear logistic regression model was performed to test the ability of aneuploidy markers to classify patients into normal and trisomic groups. RESULTS: There were twelve cases of Down's syndrome, seven of trisomy 18, four of trisomy 13, and one trisomy 22. Four cases of aneuploidy (16.7%) referred to women younger than 35. With the cut-off risk of 1:300, detection rate was 87.5% and specificity 63.3%, and with 1:100, 66.7% and 79.5%, respectively. The sensitivity for Down's syndrome was from 75% for cut-off=1:100 to 92% for cut-off=1:300, while detection of other trisomies was less successful (58% and 83%, respectively). Exclusion of unconjugated estriol MoM from the risk calculations reduced detection rate by 33% and improved specificity by 4% independently of cut-off choice. Linear logistic regression analysis showed that only unconjugated estriol was able to correctly classify patients between normal and trisomy 21 (p=0.011, odds ratio=1.445), and normal and trisomy 18 (p=0.0023, odds ratio=1.96) groups. CONCLUSIONS: The unconjugated estriol significantly contributes in Down's syndrome detection with cost of slightly reduced specificity. The 1:300 risk caused an unfavorable compromise between sensitivity and specificity. A higher cut-off, 1:100, would indicate performance of amniocentesis in women aged 39 years and older, and in those aged 35-39 only after the screen-positive result.

Adult↗