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PubMed2006

The effects of estrone, estradiol and estriol on platelet aggregation induced by adrenaline and adenosine diphosphate.

The impact of estrogens on the cardiovascular system and their ability to regulate platelet functions remains controversial. Changes in platelet functions could contribute to thrombotic risk associated with estrogen treatments. Here, we investigated the effects of various forms of estrogen, including estrone (E1), estradiol (E2) and estriol (E3), on platelet aggregation induced by standard agonists (adrenaline and adenosine diphosphate). Platelet-rich plasma (PRP) was prepared from citrated blood donated by 25 normal volunteers. The study on platelet aggregation was carried out in 96-well flat-bottom microtitre plates and assessed using a microplate reader. For studying the effects of each estrogen, PRP was preincubated with 1, 10 and 100 nM of E1, E2 and E3 at 37 degrees C for 20 min, and then coincubated with normal saline (control untreated PRP), adrenaline (ADR) or adenosine diphosphate (ADP) in the microplate. Platelet aggregation was then measured every minute for 8 min. None of the estrogens (E1, E2 and E3) affected platelet aggregation in untreated PRP. Interestingly, only E1 and E3 can synergize the increased platelet aggregation by either ADR or ADP, while the effects of E2 on the increased platelet aggregation by either ADR or ADP depended on internal factors such as endogenous estradiol and platelet aggregated state. Thus, for the rational use of these internal factors for estrogen use, especially E2, in clinical applications, such as hormone replacement therapy, may need evaluation of thrombotic risk.

Adenosine Diphosphate↗

PubMed2004

Preliminary estimate for the second-trimester maternal serum screening detection rate of the 45,X karyotype using alpha-fetoprotein, unconjugated estriol and human chorionic gonadotropin.

OBJECTIVE: To estimate the detection rate for 45,X pregnancies through second-trimester screening using maternal serum alpha-fetoprotein, human chorionic gonadotropin and unconjugated estriol. METHODS: Twenty-two cases of 45,X were ascertained through a cytogenetics database and an additional 51 cases were identified through publications. Serum analyte concentrations were reviewed for cases with fetal hydrops, cystic hygroma alone, and no evidence of edema. Using the statistical characteristics of this sample of affected pregnancies, computer simulations were carried out to determine the proportion of 45,X pregnancies that should be screen-positive for Down syndrome and trisomy 18. The extent to which additional cases of 45,X might be identified using a protocol specifically designed to detect 45,X pregnancies was also estimated. RESULTS: Approximately 54% of all 45,X pregnancies should be identifiable through screening for Down syndrome and trisomy 18. The detection rate for cases with hydrops and/or cystic hygroma was 60%, and without edema 33%. If offered with screening for Down syndrome and trisomy 18, 45,X screening could identify approximately 7% more of the affected pregnancies with an incremental rise of 0.2% in the false-positive rate. CONCLUSIONS: A screening algorithm for 45,X could be developed. However, the number of additional affected pregnancies identified would appear to be too small to justify this screening.

Algorithms↗

PubMed1995

Low maternal serum unconjugated estriol during prenatal screening as an indication of placental steroid sulfatase deficiency and X-linked ichthyosis.

Placental sulfatase deficiency is an X-linked metabolic defect that occurs in about 1 in 2,000 to 5,000 males. It is associated with congenital ichthyosis. In this report, the authors document a case of placental sulfatase deficiency detected during routine prenatal screening of maternal serum by the triple test: serum alpha-fetoprotein (AFP), unconjugated estriol (uE3), and human chorionic gonadotropin (hCG). At 16-weeks gestation, her AFP was 20.9 IU/mL (multiple of the median [MOM] 0.83), hCG was 14.4 mIU/L (MOM 0.42) and her uE3 was 0.01 nmol/L (MOM 0.01). The extremely low uE3 indicated a possible placental sulfatase deficiency, congenital adrenal hypoplasia, or other unknown abnormality. On receiving this information, the obstetrician obtained a family history that was consistent with ichthyosis in the maternal grandfather and his siblings. Biochemical analysis of placenta documented the lack of sulfatase activity. This case illustrates that an extremely low level of maternal uE3 should prompt investigation of the family for evidence of X-linked ichthyosis associated with placental sulfatase deficiency.

Adult↗

PubMed1986

Gonadotropin-releasing hormone effects on placental hormones during gestation: II. Progesterone, estrone, estradiol and estriol.

The release of progesterone (P), estrone (E1), estradiol (E2) and estriol (E3) from human placental tissue in vitro was found to be related to the gestational age of the placenta. The basal release of P, E1 and E2 on Day 1 of culture was highest from placentas of early gestation (9-13 wk). The release of P then declined, reaching a nadir by 15 wk, and continued at that level. The release of E1 and E2, reached a nadir at 17 weeks, and then again increased by term. In contrast, the basal release of E3 increased with increasing gestational age of the placenta. Thus, it appears that differing factors may influence placental P, E1, E2 and E3 production. In addition, the effect of synthetic gonadotropin-releasing hormone (GnRH) on these hormonal releases was studied. The stimulation of P by GnRH was greatest in placentas of 16 and 17 wk of gestation after extended culture when the basal release of P had declined. As much as a 240-fold increase was observed on the eighth day of culture. A large stimulation of P (32-fold) was also observed in the term placental cultures. A stimulation of E1 and E2 by GnRH was observed during the initial days of culture and in mid-gestational placental cultures (16-17 wk). A stimulation of E2 only was also observed at 13-15 wk and at term. A stimulation of E3 was observed in certain individual placentas. A correlation of the P and human chorionic gonadotropin (hCG) response to GnRH stimulation was noted, as well as an inverse relation of estrogens and hCG stimulation by GnRH. These data demonstrate that steroidogenic competence of the placenta differs with gestational age and that GnRH can influence steroid release. The degree and pattern of response to GnRH varied with the gestational age of the placenta and its endocrine milieu.

Estradiol↗

PubMed2005

Screening for pre-eclampsia by using maternal serum inhibin A, activin A, human chorionic gonadotropin, unconjugated estriol, and alpha-fetoprotein levels and uterine artery Doppler in the second trimester of pregnancy.

AIMS: To analyse the predictive power of maternal serum inhibin A, activin A, human chorionic gonadotropin (hCG), unconjugated estriol (uE(3)), alpha-fetoprotein (AFP) levels and uterine artery Doppler in the second trimester of pregnancy in screening for pre-eclampsia. METHODS: Maternal serum inhibin A, activin A, hCG, uE(3), and AFP levels and uterine artery Doppler were determined in 178 healthy, pregnant women in the second trimester of pregnancy. Serum samples were collected between the 16th and 18th weeks of gestation, and Doppler investigation was performed between the 24th and 26th weeks of gestation. Receiver operating characteristic curves were created to analyse the predictive powers of the above parameters in screening for pre-eclampsia. Different combinations also were analysed. RESULTS: The rate of pre-eclampsia was 7.9% (14/178). Maternal serum inhibin A, activin A, hCG, AFP levels, the rate of presence of the prediastolic notch and uterine artery resistance index (RI) values in pre-eclamptic pregnancies were significantly higher than those in healthy pregnancies. Presence of the prediastolic notch, uterine artery RI, maternal serum activin A and inhibin A levels had high predictive efficacy, and each had a sensitivity between 70 and 93% and a specificity between 87% and 98%. The addition of inhibin A or activin A measurement to the Doppler velocimetry improved the specificity to 99-100%. CONCLUSIONS: Maternal serum inhibin A and activin A levels and uterine artery Doppler appear to be useful screening tests during the second trimester for pre-eclampsia. However, addition of these hormonal markers to Doppler velocimetry only slightly improves the predictive efficacy, which appears clinically insignificant.

Activins↗

PubMedDate not supplied

Association of undetectable unconjugated estriol on multiple marker screening with steroid sulfatase deficiency.

OBJECTIVE: To determine whether all patients with undetectable unconjugated estriol (uE3) on multiple marker screening (MMS) are carriers for steroid sulfatase (STS) deficiency. METHODS: This is a retrospective review of 65 pregnancies with undetectable uE3 on MMS. RESULTS: Of the 65 pregnancies, there were 21 that continued, 40 spontaneous losses, 2 lost to follow-up and 2 elective terminations. Of the 21 continuing pregnancies, 15 were determined to be carriers of the STS deletion. Twenty-seven of the 40 pregnancy losses were associated with elevated alpha-fetoprotein (AFP); about half of the losses were shown to have occurred prior to sampling. CONCLUSION: Patients with undetectable uE3 are likely to be carriers of the STS deletion, except those with associated elevated AFP. Elevated AFP with undetectable uE3 on MMS is a marker of preexisting or impending fetal demise.

Abortion, Spontaneous↗

PubMed1994

Changes in the concentrations of dehydroepiandrosterone sulfate and estriol in maternal plasma during pregnancy: a longitudinal study in healthy women throughout gestation and at term.

In a longitudinal study, the changes in plasma concentrations of dehydroepiandrosterone sulfate (DHAS) and total estriol (E3) were followed in 10 normal pregnant women throughout gestation at 8-10, 14-17, 21-24, 28-32, and 38 weeks as well as at the time of admission to the delivery room. The mean plasma concentration of DHAS decreased from 325 +/- 38.2 micrograms/dl in early gestation to minimum levels of 120 +/- 15.9 micrograms/dl at week 38. At delivery there was a 2-fold increase in plasma DHAS (205.3 +/- 17.7 micrograms/dl). The mean total E3 plasma concentration increased from 6.53 +/- 2.5 ng/ml at week 8-10 to 198.6 +/- 30.3 ng/ml prior to delivery. The decrease in the DHAS plasma levels is caused by the elevated metabolic clearance rate throughout pregnancy. The increasing E3 plasma levels are caused by increasing steroid production by the fetoplacental unit and reflect fetal well-being. The peak levels of DHAS and E3 as well as of other steroids of adrenal or placental origin at admission to the delivery room reflect increased maternal and fetal stress with the onset of labor. These longitudinal reference data determined by modern radioimmunoassay methodology are helpful for the prenatal diagnosis of congenital disorders with insufficient or absent fetoplacental function, and in the control of suppression of the fetal pituitary-adrenal axis during dexamethasone treatment in pregnancies with a female fetus affected with congenital adrenal hyperplasia.

Adult↗

PubMedDate not supplied

Very low maternal serum unconjugated estriol and prenatal diagnosis of steroid sulfatase deficiency.

Twenty-four women out of 7,875 pregnant women who enrolled in a prenatal screening program showed extremely low levels of unconjugated estriol (< 0.15 MOM). In 19 cases, intrauterine fetal death was reported. In 1 case anencephalus was detected. In the remaining 4 cases apparently normal healthy babies (1 female and 3 males) were born following uneventful pregnancies. Physical examination of the 3 boys at 4-6 weeks revealed mild ichthyosis compatible with the X-linked type. Two of them had a positive family history of X-linked ichthyosis. The examination of the girl did not reveal any significant findings. In both cases in which amniocentesis was performed, low levels of steroid sulfatase and arylsulfatase C were found. The prevalence of X-linked ichthyosis in this study is higher than previously reported, i.e. 1:1,300 males. Our results suggest that the prenatal screening program for neural tube defects and for Down's syndrome is useful for the prenatal detection of X-linked ichthyosis as well. These results are in accordance with two recent reports. The implications regarding genetic counseling are discussed.

Adult↗

PubMedDate not supplied

Unconjugated estriol as maternal serum marker for the detection of Down syndrome pregnancies.

The effectiveness of unconjugated estriol (uE3) as a serum marker for the detection of Down syndrome (DS) during the 2nd trimester of pregnancy was evaluated. A population of 18,764 normal singleton pregnancies was screened for alpha-feto-protein and human chorionic gonadotropin. In 9,311 women, uE3 was added. Using a risk of 1:250 at term as a cutoff value, the false-positive rates were 4.1 and 4.3% without and with uE3, respectively. The detection rates in 47 DS serum samples, some of which were studied retrospectively, were 66% without uE3 and 57% with uE3. In 12 of 25 younger women and in 19 of 22 older women, DS was detected without uE3. The uE3 contributed to the detection of 4 additional DS pregnancies (1 in the young and 3 in older women). On the other hand, 8 DS pregnancies (3 in younger women and 5 in older women) escaped detection. In our sample the addition of uE3 lowered the detection rate of DS pregnancies with only a small and insignificant effect on the false-positive rate. Our results call for special caution in the addition of markers for risk calculations. We suggest that pregnancies with a calculated risk of > 1:250 following maternal serum alpha-fetoprotein and human chorionic gonadotropin markers tests should be regarded as high-risk pregnancies, even in cases in whom the addition of uE3 lowers the risk beneath the cutoff value.

Adult↗

PubMed1992

[Effectiveness of estriol depot vaginal suppositories in postmenopausal women with urogenital climacteric manifestations].

In this study, 43 postmenopausal patients with urogenital complaints such as vaginal dryness, incontinence, or bleeding with intercourse were treated with weekly applications of Orthogynest vaginal estriol suppositories in a new depot form. A marked increase in the vaginal epithelium (A. Schmitt score) and a significant decrease in symptoms due to vaginal atrophy were noted. The depot form allows for decreased dosing frequency, leading to improved compliance. Systemic symptoms, such as hot flashes and emotional lability, were also noted to respond to the Orthogynest suppositories.

Administration, Intravaginal↗

PubMed1985

Surveillance of the diabetic pregnancy with antepartum fetal nonstress testing and urinary estriol excretion.

The value of daily fetal heart rate (FHR) nonstress test (NST) and 24-hour urinary excretion of estriol (E3) were compared in a consecutive series of 76 diabetic pregnancies. The NST scoring system (0-10 points) employed included monitoring of fetal movements in addition to evaluation of FHR decelerations, accelerations as well as frequency and amplitude of oscillations. Patients were delivered electively after 38 weeks of gestation unless spontaneous labor began earlier or if delivery was indicated for either maternal reasons or presumed fetal distress. Fetal distress was believed to be present if two consecutive NST scores were 6 points or less. Seven patients had a day-to-day E3 fall of 50% or more at least once. Six of these patients had normal NST scores and 5 of the infants showed no signs of asphyxia at delivery. Forty-two patients had E3 drops of 30-50% and 27 patients had E3 drops of less than 30%; in contrast, the NST scores were 6 or less in 15 patients but were normal the next day. These data indicate that measurements of urinary excretion of E3 give many false alarms of fetal jeopardy and that daily NST can replace measurement of urinary excretion of E3 and reduce unwarranted intervention and unnecessary prematurity.

Estriol↗

PubMed1984

Retrograde time-scale analysis of human placental lactogen, beta human chorionic gonadotropin, and unconjugated estriol levels in human maternal serum from the onset of spontaneous labor.

We analyzed on a retrograde time scale which calculated in maternal serum, from the onset of spontaneous labor, human placental lactogen (hPL), beta human chorionic gonadotropin (beta-hCG), unconjugated estriol (E3) levels, and the ratios among these hormones in the normal late pregnancy. Maternal serum hPL, beta-hCG, and unconjugated E3 levels were measured simultaneously and serially in regular menstrual sera from 27 women in late pregnancy (total 155 samples) by radioimmunoassay. The peak level of hPL was found at 2 weeks before labor, and the peak of beta-hCG was found during 2-4 weeks before the onset of spontaneous labor. On the other hand, the mean level of E3 rose slightly with advancing gestational age. The hormonal ratios of hPL to E3 and beta-hCG to E3 decreased gradually toward the onset of labor, but the ratios of hPL to beta-hCG did not change. From these data, it is possible to conclude that the onset of spontaneous labor can be predicted by measuring the levels of hPL and unconjugated E3 in maternal peripheral serum.

Chorionic Gonadotropin↗

PubMed1977

Studies on phenolic steriods in human subjects. XXI. renal metabolism, conjugation and excretion of four androgens: a comparison with estriol.

The present study was conducted in order to ascertain whether the human kidney can conjugate androgens to an extent similar to that of estriol (E3). Differently labeled androgens (testosterone, DHT and androstenedione) were injected simultaneously into a peripheral vein and the renal artery. The excretion of the radioactivity in the early urine collections served as an index of the ability of the kidney to conjugate and/or metabolize the various steroids administered. It was shown that the human kidney can conjugate testosterone to some extent as the 17-glucuronide of DHT, but to a much lesser degree that E3. Androstenedione was not conjugated by the kidney and the excretion DHT was paradoxically lower following its renal artery administration than following its peripheral injection. We interpret the latter to indicate that some kidney cells may contain receptors with very high affinity for DHT, thus leading to the lower excretion observed. The administration of androstenediol (into the renal artery) and E3 (peripherally) indicated that the diol was not conjugated as readily as E3. The results point to the ability of the kidney to conjugate testosterone to some extent; however, in no case was it able to conjugate an androgen with the same facility as it does E3.

Androgens↗

PubMed1979

Interrelationships of circulating maternal steroid concentrations in third trimester pregnancies. II. C18 and C19 steroids: estradiol, estriol, dehydroepiandrosterone, dehydroepiandrosterone sulfate, delta 5-androstenediol, delta 4-androstenedione, testosterone, and dihydrotestosterone.

This report describes aggregate time trend effects of advancing gestational age on circulating maternal concentrations of 17beta-estradiol (E2), estriol (E3), dehydroepiandrosterone (D), dehydroepiandrosterone sulfate (D-S), delta 5-androstenediol (delta 5 diol), delta 4-androstenedione (delta 4 A), testosterone (T), and dihydrotestosterone (DHT) in a sequential series of 155 blood samples obtained from 19 normal pregnant women ranging from 26-40 weeks gestational age. Only E2, E3, and D-S show aggregate time trend effects. Log (E2) plots as a linear positive sloping curve from 26-40 weeks. Log (E3) plots as a positive sloping curve that is significantly steeper than log (E2) (P less than 0.05). Log (D-S) plots into a negative sloping curve which mirrors the pattern for log (E2) but cannot be statistically associated with log (E2) except for the opposite sign of their slopes, which are both significantly different from a zero slope (P less than 0.05). delta 4 A, T, DHT, delta 5 diol, and D show no aggregate time trends; however wide, comoving undulations for delta 4 A, T, DHT, and delta 5 diol between 26-28 and 38-40 weeks are confirmed in time by comparison of log mean plots and in magnitude by regressing the C19 steroids on one another. D shows virtually no association with the other C19 steroids. All C19 steroids, except for T, circulate at nonpregnant concentrations, implying that there is little placental secretion of these steroids into the maternal circulation.

Androgens↗

PubMed1979

Renal clearance of estriol and its conjugates in normal and abnormal pregnancies.

Renal clearance of estriol (E3), E3-3-sulfate (E3S), E3-16-glucuronide (E316G), E3-3-glucuronide (E33G), and E3-3-sulfate-16-glucuronide (E3SG) has been measured in 13 normal and 17 abnormal pregnancies between the 33rd and 40th weeks of gestation. The methodology involved a chromatographic separation on a celite column in the presence of tritiated tracers, enzymic hydrolysis of the conjugates, and measurement of the E3 moiety by a specific RIA. Preeclampsia (eight patients) was characterized by a significant decrease of renal clearance for all conjugates except E33G. In contrast to that pattern, a patient with cholestatic icterus had normal clearances except for E33G, which was reduced to less than 15% of its normal mean value. Administration of ampicillin to a pregnant woman induced an important decrease of all E3 clearances, especially for E33G which decreased to nearly 1% of its initial value; normal clearances were resumed within a week after the end of the treatment. In a small number of complicated pregnancies, E3 clearances were normal. A significant correlation between the renal clearance of E316G and that of urea and creatinine has been demonstrated.

Estriol↗

PubMed1984

Variation in the fractional conversion of plasma estrone to estriol among women and men.

In the present investigation, we determined the transfer constant of conversion of plasma estrone to estriol (E3) ( [rho] E1- E3BU ) in men, postmenopausal women, and premenopausal parous and premenopausal nulliparous women. We found no significant difference in [rho] E1- E3BU among men, postmenopausal women, premenopausal parous or nulliparous women (whether the latter were studied during the midfollicular or midluteal phase of the ovarian cycle), or in women who were ingesting oral contraceptives. On the other hand, there was a striking variation in the [rho]E1- E3BU among individuals, viz. 0.02-0.27, whereas in a given individual, the variation in [rho] E1- E3BU , evaluated on separate occasions, was small. In addition, we found a negative correlation between age at first fullterm pregnancy and [rho] E1- E3BU .

Adult↗

PubMed1992

Relationship between the concentrations of estriol sulfate and estrone sulfate in human breast cyst fluid.

Estriol-3-sulfate (E3S) is present in human breast cyst fluid (BCF) in median levels of 8.7-10.4 nmol/L, yet is barely detectable in the serum (less than 0.034 nmol/L). The source of this huge concentration of E3S is unknown. It may accumulate from blood by active transport or be synthesized and concentrated within the cyst. Since estrone sulfate (E1S) and its possible precursor, dehydroepiandrosterone sulfate (DHEAS) are elevated in BCF, E3S may originate via 16 alpha-hydroxylation of E1S. The present study examined the correlations between the levels of DHEAS and E1S with those of E3S in BCF. The sodium and potassium ions were also quantified and related to the steroid concentrations. By linear regression analysis of log-normalized data there was a highly significant correlation between the concentrations of E1S and E3S (n = 355, r = 0.690, P less than 0.001) and between DHEAS and E3S (n = 361, r = 0.577, P less than 0.001). The BCF were classified according to their K/Na ion ratios: type 1, greater than 1.0, type II, less than 0.25, and type III, 0.25-1.0. By Student's t test, the concentrations of E3S differed between each BCF Type (P less than 0.002). This was also true for E1S and DHEAS. Type 1 cysts were associated with the highest estrogen sulfate levels and type II with the lowest levels. The possible physiological importance of this observation resides in reports that the BCF type expressing the highest steroid concentrations has been related to an aporcine-like epithelial lining of the cyst wall and a somewhat higher risk for developing breast cancer. The results suggest that E3S in BCF may originate from E1S, but alternate mechanisms are not precluded.

Aryl Hydrocarbon Hydroxylases↗

PubMed1994

Maternal plasma progesterone levels fall after rectal administration of estriol.

Maternal plasma unconjugated estriol (E3), progesterone (P), and estradiol (E2) levels were measured at 30-min intervals for 6 h after the rectal administration of a 100-mg E3 or placebo suppository to 28 pregnant women at term. Mean plasma unconjugated E3 levels showed a sustained rise approximately 50% above baseline levels 2 h after rectal E3 administration (P < 0.003). There was a simultaneous sustained fall of approximately 20% in mean plasma P levels (P < 0.05); the fall in mean P levels was greatest in the women who delivered within 48 h of E3 suppository administration (P < 0.05). There was no change in mean plasma E2 levels. This study demonstrates that a significant rapid increase in maternal circulating E3 levels can be obtained by the rectal administration of E3, and that this increase in maternal E3 levels is associated with a decrease in circulating P levels.

Adult↗