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PubMed2003

Multiple-marker screening in human immunodeficiency virus-positive pregnant women: Screen positivity rates with the triple and quad screens.

OBJECTIVE: The study was undertaken to determine the screen-positive rates of multiple-marker screening tests in pregnant women who are positive for human immunodeficiency virus (HIV) at our institution for open neural tube defects and aneuploidy, for both triple (alpha-fetoprotein, human chorionic gonadotropin [hCG], unconjugated estriol) and quad (alpha-fetoprotein, hCG, unconjugated estriol, inhibin A) screens, and to compare these rates with a matched control group. STUDY DESIGN: A 1:1 matched case-control study was performed comparing multiple marker screening test results in 34 HIV-positive women with age- and race-matched HIV-negative controls. Individual serum markers and screen positive rates for both the triple and quad screens were compared among the cases and controls. RESULTS: In each group, there were 19 women with triple screens and 15 with quad screens. Serum hCG multiples of the median were significantly higher in the HIV-positive compared with the HIV-negative women (P=.033). There was no difference in screen positive rates between the cases and controls using the triple screen, but there was a significantly higher overall screen positive rate in the HIV-positive group when the quad screen was used (33% vs 7%, P=.046). CONCLUSION: There is a significantly higher rate of overall quad screen positivity on multiple-marker screening among HIV-positive women compared with a matched control group.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Effect of leptin on the regulation of placental hormone secretion in cultured human placental cells.

Placenta is an important source of leptin during pregnancy that contributes to the high plasma leptin levels in pregnant women. Leptin and its functional receptors are synthesized in trophoblast cells that, in turn, secrete gestational hormones supporting a paracrine or autocrine role for leptin in the endocrine activity of the placenta. In the present study we examined the effect of leptin on in vitro release of gestational hormones (human chorionic gonadotropin (hCG), human placental lactogen (hPL), progesterone, estrogens and testosterone) by human term placental cells in culture. Placentas at term were obtained immediately after delivery from mothers with uncomplicated pregnancies. Progesterone, hCG, hPL, estradiol, estrone, estriol and testosterone levels were measured by different assays in culture media of cells maintained in monolayer culture after incubation for 12, 24, 48 or 72 h with leptin or placebo. Incubation with leptin did not modify hCG, hPL, progesterone, estriol and estrone secretion for any of the doses and times assayed. However, leptin led to a dose-dependent decrease in estradiol release. This effect was observed when treatment with recombinant human leptin spanned from 12 to 72 h. At this time an increase in testosterone levels was observed in leptin-treated cells versus placebo. These results indicate that leptin can be considered a gestational hormone implied in the endocrine function of the placenta, with an important role in control of the production of steroid reproductive hormones in placental cells in vitro.

Cells, Cultured↗
PubMed2002

Extreme second-trimester serum analyte values in down syndrome pregnancies with hydrops fetalis.

OBJECTIVE: To compare second-trimester maternal serum analyte values in Down syndrome pregnancies with, and without, hydrops fetalis. METHODS: Seven hydropic and 85 non-hydropic Down syndrome pregnancies were identified among women with positive second-trimester maternal serum screening results. Values for maternal serum alpha-fetoprotein (MSAFP), human chorionic gonadotropin (hCG), unconjugated estriol and inhibin-A, and risks for Down syndrome were compared using the non-parametric Mann-Whitney statistical test. RESULTS: Hydropic Down syndrome pregnancies had significantly lower MSAFP and estriol concentrations, while hCG levels were higher. For subgroups of five hydropic and 42 non-hydropic cases, no statistically significant difference in the inhibin-A levels could be demonstrated. CONCLUSION: Second-trimester Down syndrome screening risks are significantly higher in affected pregnancies that are complicated by fetal hydrops.

Adult↗
PubMed1977

Relationship between steroid excretion patterns and breast cancer incidence in Israeli women of various origins.

A nationwide study of the steroid excretion patterns in postmenopausal Israeli migrant women demonstrated differences between high- and low-risk groups for breast cancer in the following variables: age at first parturition, number of pregnancies, number of live births, height, and weight. The direction of the differnces was in line with those observed for breast cancer patients. The groups also differed in the exretion of estriol, 17-ketosteroids, and allotetrahydrocortisol. Multiple regression analysis revealed that the exretion of estriol was significantly lower in population groups in whom breast cancer incidence was high. Possibly this trend--which has also been observed in adolescent and premenopausal women--reflected environmental influences on peripheral estrogen metabolism.

17-Ketosteroids↗
PubMed1977

Comparison of urinary and plasma hormone levels in daughters of breast cancer patients and controls.

Plasma and urinary levels of estrogens and progesterone were studied on days 11 and 22 of the menstrual cycle in 27 teenage daughters of breast cancer patients and 25 teenage daughters of controls. Plasma and urinary values correlated well, which implied that most previous findings based on urinary levels of these hormones were applicable to their plasma levels. The "estriol ratio" (urinary estriol:urinary estrone plus estradiol) hypothesis was not supported by this study, the ratio having been no lower in the daughters of breast cancer patients than in daughters of controls. The day-11 results showed elevated plasma prolactin-estrogen values in daughters of breast cancer patients; the day-22 results did not.

Adolescent↗
PubMed2006

Breast cancer risk in postmenopausal women using estrogen-only therapy.

OBJECTIVE: To evaluate whether the risk of estrogen-only therapy on breast cancer varies by dose, constituent, and route of administration. METHODS: All Finnish women older than age 50 years using oral or transdermal estradiol (n=84,729), oral estriol (n=7,941), or vaginal estrogens (n=18,314) for at least 6 months during 1994-2001 were identified from the national medical reimbursement register. They were followed for breast cancer with the aid of the Finnish Cancer Registry to the end of 2002. RESULTS: Altogether, 2,171 women with breast cancer were identified. The standardized incidence ratio of breast cancer with systemic estradiol for less than 5 years was 0.93 (95% confidence interval 0.80-1.04), and for estradiol use for 5 years or more, 1.44 (1.29-1.59). Oral and transdermal estradiol was accompanied by a similar risk of breast cancer. The risk was most prominent with the dose greater than 1.9 mg/d orally; whereas the risk associated with transdermal route was not dose-dependent. The standardized incidence ratio for the lobular type of breast cancer (1.58) was slightly higher than that for the ductal type (1.36). The use of estradiol was associated with both localized breast cancer (1.45; 1.26-1.66) and cancer spread to regional nodes (1.35; 1.09-1.65). The incidence of carcinoma in situ (n=32) was increased (2.43; 1.66-3.42) among estradiol users. CONCLUSION: Estradiol for 5 years or more, either orally or transdermally, means 2-3 extra cases of breast cancer per 1,000 women who are followed for 10 years. Oral estradiol use for less than 5 years, oral estriol, or vaginal estrogens were not associated with a risk of breast cancer. LEVEL OF EVIDENCE: II-2.

Administration, Cutaneous↗
PubMed2004

A systematic review of the effects of estrogens for symptoms suggestive of overactive bladder.

OBJECTIVE: To perform a systematic review of the effects of estrogen therapy on symptoms suggestive of overactive bladder (OAB) in postmenopausal women. MATERIALS AND METHODS: This analysis involved a literature review of Medline, Excerpta Medica, and the Science Citation Index and a manual search of popular urology, gynecology, gerontology, and primary care medicine journals from January 1969 to December 1999. Articles had to include estrogen and placebo treatment groups, published or original data presented at a scientific meeting and report symptoms suggestive of OAB. This search identified 11 randomized trials and included a total of 430 subjects. Thirty-six subjects who participated in two crossover studies received both estrogen and placebo and thus are counted twice, therefore 236 received estrogen therapy and 230 were placebo controls. Estrogen was administered systemically or locally as estriol, estradiol, conjugated estrogen, or estradiol and estriol. A meta-analysis of these studies was performed for all estrogen therapies and then separately for systemic and local therapies. RESULTS: Overall, estrogen therapies were associated with statistically significant improvements in all outcome variables: diurnal frequency (P = 0.0011), nocturnal frequency (P = 0.0371), urgency (P = 0.0425), number of incontinence episodes (P = 0.0002), first sensation to void (P = 0.0001), and bladder capacity (P = 0.0018). Local therapies had statistically significant beneficial effects on all outcome variables. However, systemic therapies were only associated with significant improvements in incontinence episodes and first sensation to void while nocturnal frequency actually worsened. CONCLUSION: Estrogen therapy may be effective in alleviating the symptoms suggestive of OAB. Local administration may be the most beneficial route of administration.

Cross-Over Studies↗
PubMed2003

Prenatal diagnosis for placental steroid salfatase deficiency with fluorescence in situ hybridization: a case of X-linked ichthyosis.

X-linked ichthyosis (XLI) is a relatively common genetic disorder that occurs in about one in every 2000-6000 male births. Clinically, XLI is characterized by a generalized scaling of the skin, with large, polygonal, dark brown scale, and more prominent on the extensor aspects of the limbs. It is known that an undetectable maternal serum, unconjugated estriol, associated with placental steroid sulfatase (STS) deficiency, may be the cause of cause of XLI. In most case, STS deficiency is caused by a complete or partial deletion of the STS gene mapped on chromosome Xp22.3. We describe here the prenatal detection of a male fetus affected with STS deficiency as a result of an undetectable unconjugated estriol in the second-trimester maternal serum screening. Microdeletion of the STS gene was confirmed by fluorescence in situ hybridization analysis of cultured amniotic fluid.

Adult↗
PubMed1996

Treatment of skin aging with topical estrogens.

BACKGROUND: The coincidence of climacteric symptoms and the beginning of skin aging suggests that estrogen deficiency may be a common and important factor in the perimenopausal woman. Often hormones have been considered important in endogenous aging of the skin, but their role has not been clearly defined. Therefore, we investigated, whether topical treatment of the skin with estrogen could reverse some of the changes in the aging skin. MATERIAL AND METHODS: The effects of 0.01% estradiol and 0.3% estriol compounds were compared in 59 preclimacteric women with skim aging symptoms. Monthly determinations of estrodiol (E2), follicle-stimulating hormone (FSH), and prolactin (PRL) were done and the monthly clinical monitoring was supplemented by measurements of skin hydration by corneometry and profilometry. In 10 patients, skin biopsies were taken for immunohistochemical determination of collagen types I and III. RESULTS: After treatment for 6 months, elasticity and firmness of the skin had markedly improved and the wrinkle depth and pore sizes had decreased by 61 to 100% in both groups. Furthermore, skin moisture had increased and the measurement of wrinkles using skin profilometry, revealed significant, or even highly significant, decreases of wrinkle depth in the estradiol and the estriol groups, respectively. On immunohistochemistry, significant increases of Type III collagen labeling were combined with increased numbers of collagen fibers at the end of the treatment period. As to hormone levels, only those of PRL had increased significantly and no systemic hormonal side effects were noted.

Administration, Topical↗
PubMedDate not supplied

2nd-trimester maternal serum marker results are not altered by delayed analysis.

OBJECTIVE: The goal of the study was to evaluate the significance of delayed laboratory analysis of maternal serum alpha-fetoprotein, beta-subunit of human chorionic gonadotropin, and unconjugated estriol for prenatal screening. METHODS: Biochemical analysis of 30 consecutive biochemical screening specimens of maternal serum alpha-fetoprotein, beta-subunit of human chorionic gonadotropin, and unconjugated estriol was performed immediately upon arrival to the laboratory, 7 days later, and again 14 days after maternal blood was drawn. Differences among the results of the three sets of biochemical studies were evaluated by one-way analysis of variance for repeated measures. RESULTS: No significant differences were found among the results of immediate assays as compared with those at a 7- or a 14-day delay for all three biochemical markers. CONCLUSIONS: Our data suggest that up to a 14-day delay in the performance of the 2nd-trimester maternal serum biochemical screening assays will not alter the results significantly. The results of maternal serum screening are, thus, clinically valid even if the laboratory assays were performed several days after maternal blood was drawn.

Adolescent↗
PubMed1979

Effect of steroid hormones and diethylstilbestrol on adrenomedullary catecholamine secretion.

Acetylcholine-induced catecholamine secretion from isolated, perfused bovine adrenal medulla was strongly inhibited by hydrocortisone (30 micro M), estradiol (30 micro M), and estriol (30 micro M). Diethylistilbestrol (DES) (10 and 30 micro M) inhibited acetylcholine-induced secretion, and the effect of the higher dose was prolonged. Inhibition of high potassium-induced secretion by DES (30 micro M) indicated that hormonal inhibition of evoked secretion was not by competition for acetylcholine-sensitive receptor sites. Dehydrotestosterone (30 micro M) was ineffective in inhibiting acetylcholine-induced secrection. Hydrocortisone, estradiol, and estriol treatments enhanced nonstimulated release. It is suggested that incorporation of certain steroid into plasma and granule membranes, thereby modifying membrane function, enhances nonstimulated release and may also block evoked release of secretoy material.

Acetylcholine↗
PubMedDate not supplied

Maternal serum triple analyte screening and adverse pregnancy outcome.

The prognostic value of maternal serum triple analyte screening with AFP, hCG and uE3 (unconjugated estriol) was studied early in the second trimester of pregnancy. In this case-control study of 38 women and 76 matched controls derived from a consecutive screened population of 28,897, case selection was based upon elevated MSAFP and MShCG (> or = 2 MOM) and low MSuE3 (< or = 0.6 MOM). Adverse pregnancy outcome was found in 65.8% of cases and 2.6% of controls (RR 25, 95% CI 6.3-100.0). When increased odds (> or = 1 in 270) for Down's syndrome were considered with the abnormal analyte screen, fetal/congenital defects, fetal neonatal loss or low birth weight were noted in 17/26 cases (65.4%). Elevated MSAFP and MShCG with low values for estriol, with or without increased odds for Down's syndrome, imply an unfavorable prognosis for both the fetus and the child.

Case-Control Studies↗
PubMedDate not supplied

Effect of Hispanic ethnicity on interpretation of maternal serum screening.

Maternal serum concentrations of alpha-fetoprotein (MSAFP), unconjugated estriol (uE3) and human chorionic gonadotropin (hCG) were measured in the sera of 3,046 Hispanic women and of 15,154 Caucasian women from gestational weeks 14 through 20 between January 1990 and December 1995. Median values for analytes were calculated for each gestational week and the two ethnic groups compared. Our findings indicate that the median values for Hispanics are lower for MSAFP and hCG, but higher for estriol. These differences are not accounted for by differences in median weights of the two ethnic groups. Although these results would suggest that Hispanic women at risk for a fetus with a neural tube defect (NTD) may be missed when cut-offs derived from a Caucasian population are used, in fact, that was not the case in our screening population. However, a disproportionate number of Hispanic women may be identified with an abnormal serum screening test unrelated to a risk for neural tube defects. This does not infer that detection rates are different across different ethnic groups since other factors are involved. Adjustment of medians for Hispanic ethnicity may have a small but significant effect, especially with regard to low values.

Adult↗
PubMed1984

Hormone levels in amniotic fluid and maternal serum in women who undergo spontaneous abortion after second trimester amniocentesis.

Second trimester spontaneous abortion occurring on the average 1.5 weeks after amniocentesis in 15 symptom-free women has been studied. Thus, hormone (total estriol, hCG, prolactin, and hPL) levels in amniotic fluid and maternal serum were compared to those in 60 women who also underwent second trimester amniocentesis but went to term without complications. The abortion group had significantly (p less than 0.01) elevated levels of total estriol in maternal serum and in amniotic fluid, significantly (p less than 0.01) increased prolactin concentration in amniotic fluid, and decreased (p less than 0.05) hCG levels in maternal serum. It is suggested that these differences may relate to fetal adrenal stress response in the subsequent abortion group indicating an abnormality which may or may not be aggravated by amniocentesis.

Abortion, Spontaneous↗
PubMed2003

Maternal asthma is associated with reduced female fetal growth.

Asthma during pregnancy is associated with a low birth weight, although the mechanisms contributing to this outcome remain unknown. The relationship between maternal asthma and its treatment, placental function, fetal sex, and low birth weight was examined to establish the effect of asthma on fetal growth. Glucocorticoid intake by women with asthma was assessed throughout pregnancy. The placenta was collected after delivery, and 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity was measured. Fetal cortisol and estriol were measured in the umbilical vein plasma at delivery. Those with asthma were compared with a nonasthmatic control group. In women with asthma who did not use inhaled steroids and were pregnant with a female fetus, we observed significantly reduced birth weights, whereas male birth weights were unaffected. The presence of a female fetus was associated with significantly increased maternal circulating monocytes, significantly reduced placental 11beta-HSD2 activity and fetal estriol, and a trend toward elevated fetal plasma cortisol. This study provides evidence that in pregnancies complicated by asthma there is a fetal sex-specific effect on the maternal immune system with adverse effects on placental function and female fetal growth.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2002

Topical estrogens combined with argon plasma coagulation in the management of epistaxis in hereditary hemorrhagic telangiectasia.

The aim of this study was to assess the value of topically applied estrogens in patients with hereditary hemorrhagic telangiectasia. Twenty-six patients with this disorder were treated with argon plasma coagulation and randomized into 2 groups: group A, which had postoperative application of estriol ointment (n = 14), and group B, which had postoperative application of dexpanthenol ointment (n = 12). Over a period of 12 months, the frequency and intensity of bleeding, the patient's satisfaction, and the success of the treatment were evaluated with a questionnaire. Before the operation, more than 90% of the patients in both groups complained of daily episodes of epistaxis. Twelve months after treatment, the frequency and intensity of bleeding had significantly decreased in group A as compared to group B. Of the patients in group A, 93% were satisfied with the treatment. Of the patients in group B, only 42% were satisfied with the treatment. In both groups, more than 90% of the patients were willing to undergo the same treatment again. The combined treatment approach with argon plasma coagulation and topical estriol enables us to significantly prolong the hemorrhage-free interval.

Administration, Intranasal↗
PubMed2006

Quantitative structure-activity relationship of various endogenous estrogen metabolites for human estrogen receptor alpha and beta subtypes: Insights into the structural determinants favoring a differential subtype binding.

To search for endogenous estrogens that may have preferential binding affinity for human estrogen receptor (ER) alpha or beta subtype and also to gain insights into the structural determinants favoring differential subtype binding, we studied the binding affinities of 74 natural or synthetic estrogens, including more than 50 steroidal analogs of estradiol-17beta (E2) and estrone (E1) for human ER alpha and ER beta. Many of the endogenous estrogen metabolites retained varying degrees of similar binding affinity for ER alpha and ER beta, but some of them retained differential binding affinity for the two subtypes. For instance, several of the D-ring metabolites, such as 16 alpha-hydroxyestradiol (estriol), 16 beta-hydroxyestradiol-17 alpha, and 16-ketoestrone, had distinct preferential binding affinity for human ER beta over ER alpha (difference up to 18-fold). Notably, although E2 has nearly the highest and equal binding affinity for ER alpha and ER beta, E1 and 2-hydroxyestrone (two quantitatively predominant endogenous estrogens in nonpregnant woman) have preferential binding affinity for ER alpha over ER beta, whereas 16 alpha-hydroxyestradiol (estriol) and other D-ring metabolites (quantitatively predominant endogenous estrogens formed during pregnancy) have preferential binding affinity for ER beta over ER alpha. Hence, facile metabolic conversion of parent hormone E2 to various metabolites under different physiological conditions may serve unique functions by providing differential activation of the ER alpha or ER beta signaling system. Lastly, our computational three-dimensional quantitative structure-activity relationship/comparative molecular field analysis of 47 steroidal estrogen analogs for human ER alpha and ER beta yielded useful information on the structural features that determine the preferential activation of the ER alpha and ER beta subtypes, which may aid in the rational design of selective ligands for each human ER subtype.

Diethylstilbestrol↗
PubMed1981

Characterization of a cytosolic estrogen-binding protein in lung tissue of fetal rats.

An estrogen-binding macromolecule was identified in cytosolic fractions prepared from fetal rat lung tissue. This component sedimented at 4.5S on sucrose gradients and was heat labile and proteinaceous in nature. This estrogen-binding protein bound 17 beta-estradiol (Ka = 10(8) M-1) and estrone but had little or no affinity for estriol. Diethylstilbestrol bound to the cytosolic estrogen binding protein, but with lower affinity than for 17 beta-estradiol or estrone. The estrogen binding capacity of the cytosolic fraction of rat fetal lung tissue was high during late gestation (10-12 pmol/mg protein) but declined after birth (0.6 pmol/mg protein on day 5). Since fetal rat plasma contains alpha-fetoprotein, a substance that binds 17 beta-estradiol with relatively high affinity, the characteristics of the lung cytosolic estrogen binding protein were compared to those of fetal rat plasma, employing various physicochemical criteria. The affinities of fetal rat lung and plasma estrogen binding proteins for 17 beta-estradiol were similar, as were the sedimentation coefficients estimated by sucrose density gradient centrifugation analysis. However, the estrogen-binding protein in plasma differed from that in the cytosolic fraction of fetal lung tissue in that the plasma protein bound radiolabeled estriol, had higher mobility on polyacrylamide gel electrophoresis, and the estrogen binding capacity of plasma remained high for at least 6 days after birth. An estrogen-binding macromolecule (4.5S) was also present in high concentration in cytosolic fractions of fetal rat kidney and heart tissues, whereas a relatively small amount of estrogen binding was detected in fetal liver tissue.

Animals↗