Serum Estriol Levels Research Articles

Evaluation of estriol levels in women with preeclampsia in Nnewi, South-East Nigeria

Preeclampsia is a life-threatening pregnancy-induced disorder characterized by the presence of hypertension and proteinuria occurring after 20 weeks of gestation in a previously normotensive and aproteinuric woman. This study is aimed at investigating the maternal serum levels of estriol in pregnant women with preeclampsia. This is an analytical cross-sectional study including a total of 90 pregnant women aged 18-41years at 26-40 weeks of gestation, according to the last date of menstruation and ultrasonographic measurements. Forty five of these were preeclamptic while the other forty five were apparently healthy individuals. Preeclampsia was determined by proteinuria ≥30mg/dl or ≥1+ using a urine dipstick and sphygmomanometer blood pressure reading of ≥ 140/90 mmHg using ausculatory method. BMI was calculated from weight and height measurements of each participant. Estriol (E3) levels were determined utilizing the double-antibody sandwich enzyme linked immunosorbent assay technique. Hypothesis testing was done using the student’s t-test for continuous variables, Chi-square test for categorical variables and Pearson’s correlation for the tests of association. Statistical significance was set at p<0.05. The mean serum values of E3 were significantly lower in women with preeclampsia (124.18±22.40) compared with the apparently healthy control counterparts (141.41±20.68, p<0.001). A moderate negative correlation was observed between maternal serum estriol level and BMI in the preeclamptic group (r = -0.589; p<0.001). There existed a strong negative correlation between maternal serum estriol level and systolic (r = -0.738; p<0.001) as well as diastolic (r = -0.711; p<0.001) blood pressures in women with preeclampsia. Preeclampsia is associated with lower maternal serum levels of estriol which may play a significant role in the pathogenesis of the disorder.

Neuroprotection in Cerebral Cortex Induced by the Pregnancy Hormone Estriol

In multiple sclerosis (MS), demyelination occurs in the cerebral cortex, and cerebral cortex atrophy correlates with clinical disabilities. Treatments are needed in MS to induce remyelination. Pregnancy is protective in MS. Estriol is made by the fetoplacental unit, and maternal serum estriol levels temporally align with fetal myelination. Here, we determined the effect of estriol treatment on the cerebral cortex in the preclinical model of MS, experimental autoimmune encephalomyelitis (EAE). Estriol treatment initiated after disease onset decreased cerebral cortex atrophy. Neuropathology of the cerebral cortex showed increased cholesterol synthesis proteins in oligodendrocytes, more newly formed remyelinating oligodendrocytes, and increased myelin in estriol-treated EAE mice. Estriol treatment also decreased the loss of cortical layer V pyramidal neurons and their apical dendrites and preserved synapses. Together, estriol treatment after EAE onset reduced atrophy and was neuroprotective in the cerebral cortex.

Effect of perchlorate on ovarian morphology and histology, estrous cyclicity, steroidogenic enzyme activities and hormonal profiles in adult female rats

Perchlorate contamination is widespread for its industrial uses and natural occurrence. It is also used as an antithyroid drug. Perchlorate competitively inhibits iodide transport at the level of sodium-iodide symporter (NIS) in the thyroid gland, affecting thyroid hormone synthesis, resulting in alteration of thyroid gland structure and functions. Thyroid hormones are vital for proper functioning of the female reproductive system, since they modulate the metabolism and development of ovary and uterus. This study investigates the effect of perchlorate exposure for consecutive four weeks on the morphological and functional status of reproductive organs in adult female rats following parameters as the estrous cyclicity, histology of ovary and uterus, activities of steroidogenic enzymes, serum estradiol and estriol levels. Results revel irregular estrous cyclicity that ultimately ceased presenting a persistent estrous stage, hypertrophied ovary with corpora lutea of different sizes, large and inflated uterine lumen with proliferated endometrium comprising numerous secretory glands in the perchlorate exposed reproductive organs. The activities of steroidogenic enzymes (Δ⁵ 3β HSD and 17β HSD) were augmented that have heightened serum estriol level while the estradiol level was weakened. Therefore, an apparent hypertrophied and hyperfunctioning condition of ovary and uterus developed resembling pseudopregnancy on exposure of this iodide blocker

Differential Disrupting Effects of Prolonged Low-Dose Exposure to Dichlorodiphenyltrichloroethane on Androgen and Estrogen Production in Males.

Dichlorodiphenyltrichloroethane (DDT) is the most widespread, persistent pollutant and endocrine disruptor on the planet. Although DDT has been found to block androgen receptors, the effects of its low-dose exposure in different periods of ontogeny on the male reproductive system remain unclear. We evaluate sex steroid hormone production in the pubertal period and after maturation in male Wistar rats exposed to low doses of o,p’-DDT, either during prenatal and postnatal development or postnatal development alone. Prenatally and postnatally exposed rats exhibit lower testosterone production and increased estradiol and estriol serum levels after maturation, associated with the delayed growth of gonads. Postnatally exposed rats demonstrate accelerated growth of gonads and higher testosterone production in the pubertal period. In contrast to the previous group, they do not present raised estradiol production. All of the exposed animals exhibit a reduced conversion of progesterone to 17OH-progesterone after sexual maturation, which indicates putative attenuation of sex steroid production. Thus, the study reveals age-dependent outcomes of low-dose exposure to DDT. Prenatal onset of exposure results in the later onset of androgen production and the enhanced conversion of androgens to estrogens after puberty, while postnatal exposure induces the earlier onset of androgen secretion.

Estriol serum levels in new and chronic users of vaginal estriol cream: A prospective observational study.

To quantify estriol serum concentrations in "new" and "chronic users" of topical estriol cream using quantitative liquid chromatography tandem mass spectrometry. In this singlecentre prospective observational study, postmenopausal women with urogynaecological complaints were enrolled: 40 had not used topical estriol previously ("new users") and 50 had been applying estriol cream for more than 12 weeks ("chronic users"). In "new users," serum estriol levels were measured at baseline and after 12 weeks use. Estriol cream 1 mg/g was used daily for 3 weeks, then twice weekly with applicator (group 1A) or digitally (group 1B) or three times per week digitally (group 1C). "Chronic users" applied the cream twice (n = 7) or three (n = 43) times per week. Serum samples were taken in the morning after using cream the previous night. The main outcome measures were estriol serum concentrations in "new" and "chronic users" of estriol cream. Baseline serum estriol concentrations were less than 5 pmol/L in all 40 "new users." At 12 weeks, the 12-hour serum estriol levels ranged from less than 5 to 494 pmol/L (median 22.8; Interquartile range [IQR] 9.2-108.5). Seven "new users" had levels more than 100 pmol/L. Most of the 50 "chronic users" also had 12-hour levels less than 100 pmol/L (median 15.1 pmol/L [IQR 2.7-33.9]: three had levels more than 100 pmol/L. This study reports serum estriol concentrations in a large number of "new" and "chronic users" of vaginal estriol cream, employing a novel highly sensitive and specific technique. Overall, the results are reassuring: 87% had 12-hour estriol levels less than 100 pmol/L.

First and Second Trimester Biochemical Markers in Maternal Epilepsy: A Case-Control Study

Background: Our aim is to investigate whether the maternal serum levels of first and second trimester serum analytes are altered in women with epilepsy in pregnancy. Methods: Maternal serum biochemical markers (estriol, alpha-fetoprotein [AFP], human chorionic gonadotrophin [hCG], free β hCG, pregnancy-associated plasma protein-A) were compared in a series of 122 pregnant women with epilepsy and in a cohort of 122 normal pregnant women. The serum samples were obtained between 11–13 6/7 weeks and 16–18 weeks gestation. Results: Second trimester serum estriol levels, expressed as multiples of the median (MoM), in the epileptic group (1.55 ± 0.77 MoM) were significantly higher than those in the control patients (1.13 ± 0.40 MoM) (p < 0.001). Of the women with epilepsy, 66.3% (n = 81) were exposed to antiepileptic drugs. Conclusion: Our study revealed that otherwise uncomplicated pregnant epileptic women had higher second trimester (18–20 weeks of gestation) estriol levels compared to non-epileptic pregnant women.

Association between serum estradiol levels and carotid atherosclerosis in middle-aged and elderly men with type 2 diabetes

Objective To investigate the association between serum estradiol levels and macrovascular complication of atherosclerosis in mid-aged and elderly male patients with type 2 diabetes mellitus (T2DM). Methods One hundred and twenty nine male diabetic patients aged over 45 years were recruited in this study. Serum estriol (E2), testosterone (T) and lipid levels were detected using chemiluminescent immunoassay. Carotid ultrasonography was taken to evaluate macrovascular complication of atherosclerosis. The demographic characteristics, clinical features including duration of diabetes and prevalence of carotid atherosclerosis and biochemical features were compared among patients with different serum E2 levels. Correlation analysis was also performed using binary logistic analysis. Results There were 43 patients with low serum E2 level ( 198.2 pmol/L). Among 129 patients the carotid artery lesions were detected in 64 cases. There were significant differences in body weight [(61.0±10.4), (67.4±13.0)and(76.8±10.5)kg, t=3.40, P=0.00], waist circumference [(81.5±7.9), (86.6±10.7)and(90.0±8.0)cm, t=3.57, P=0.00], body mass index (BMI) [(21.6±3.2), (23.5±3.8)and(26.2±3.0)kg/m2,t=3.72, P=0.00], systolic pressure [(140.2±14.8), (143.9±18.1)and (155.0±13.1)mmHg(1 mmHg=0.133 kPa), t=3.18, P=0.04] and TG [(1.46±0.88), (2.23±1.08)and(3.35±0.9)mmol/L, t=2.66, P=0.04] among patients with low, intermediate and high serum E2 levels. The age-adjusted incidence of carotid atherosclerotic plaque in patients with low, intermediate and high E2 levels were 25.6%(11/43), 56.8%(25/44) and 66.7%(28/42), respectively (χ2=15.73, P=0.00). Compared to low E2 level, the risk ratio of carotid atherosclerosis in intermediate and high E2 levels was 1.60 (95%CI: 1.04-2.46, P<0.05) and 1.80 (95%CI: 1.17-2.76, P<0.05), respectively. Conclusion Serum E2 level is closely associated with carotid atherosclerotic plaque in middle-aged and elderly male type 2 diabetic patients. Key words: Arteriosclorosis, carotid arteries; Testosterone; Diabetes mellitus, type 2; Meddle aged; Aged

Correlation of Estradiol and Estriol Serum Levels to Melasma Severity in Pregnant Women

Combination of hormonal change, ultraviolet radiation and genetics are the most responsible factors in melasma. One of pigmentation change caused by pregnancy is melasma. The critical key to describe hyperpigmentation process is increased levels of estradiol and estriol. This study is aimed to determined correlation of serum levels of estradiol and estriol to melasma severity in pregnant women. This cross-sectional study was conducted with consecutive sampling in pregnant women with melasma. This study was conducted from June to July 2017 at Dr. Saiful Anwar Regional Hospital, Malang, East Java, Indonesia. Pregnant woman with melasma (15-49 years) was included and pregnant women with the history of melasma not caused by pregnancy, which used hormonal contraception or oral hormone therapy containing estrogen and took oral phototoxic drugs, were excluded. Anamnesis, physical examination, Wood Lamp, MASI (Melasma Area and Severity Index) Score and blood was drawn to measure serum levels of estradiol and estriol by using ELISA to 25 pregnant women with melasma. Data analysis was done with Pearson correlation test and multiple linear regressions. The result showed serum levels of estradiol was significantly positive correlated with MASI Score (r=0.462; p 0.05). Multiple linear regression revealed R2=0.244 (p<0.05), which means that serum levels of estradiol and estriol had 24.4% effects to MASI Score, while the rest 75.6% was influenced by others variables that were not included in this study. The conclusion is that there is a positive correlation between serum levels of estradiol with melasma severity in pregnant women, but serum levels of estriol are not correlated with melasma severity. Another factor besides serum levels estradiol and estriol might influence melasma severity.

Morphological and functional alterations of female reproduction after regular exposure of bamboo shoots of North East India

Objective: To evaluate the effect of daily consumption of bamboo shoots (BS) on the morphological features and functional status of the female reproductive system in adult with respect to thyroid. Methods: Adult female rats were divided into control and experimental groups of six each. Control group was given normal diet while experimental group was fed BS by 1/3rd replacement of 180 g of their food i.e. 60 g of BS containing 35 g of goitrogens of cyanogenic origin such that each rat likely consumed 6 mg/100 g of body weight per day for a period of 45 d. Morphological features like changes in body weight and organ weight were noted. Key steroidogenic enzyme levels viz Δ5 3 β hydroxysteroid dehydrogenase (HSD) and 17 β HSD along with serum estradiol, estriol and progesterone levels were measured. Estrous cyclicity of the animals monitored regularly followed by histological analysis of thyroid, ovary and uterus at the end of experimentation. Results: Increase in body weight, thyroid gland weight and thyroid stimulating hormone, decrease in serum triiodothyronine and thyroxine, a decrease in ovarian as well as uterine weight and the activity of steroidogenic enzymes Δ5 3 β HSD and β 17 β HSD along with diminished serum estradiol, estriol and progesterone levels were noted; while histological plates showed prominent degenerative changes in both the ovary and uterus. Estrous cyclicity of the treated animals were irregular and almost stopped at diestrous stage of the cycle in the latter stage of the treatment as compared to control. Conclusions: Overall results indicates that BS rich in cyanogenic constituents induces biochemical hypothyroidism in the experimental animals that acts in corroboration to cause morphological and functional alteration of reproductive organs indicating its likely impact in fertility on continued use.

Prediction of Gestational Diabetes Mellitus by Unconjugated Estriol Levels in Maternal Serum.

The aim of this study was to evaluate the association between maternal serum estriol levels, which are routinely measured in the first trimester of pregnancy, and adverse pregnancy outcomes including gestational diabetes. We performed a retrospective chart analysis of women who delivered between July 1, 2007, and December 31, 2009, at Kangnam CHA Medical Center in Seoul, Korea. Only patients with available estriol measurements during their pregnancies and complete follow-up data were included in the study. The effect of estriol on the incidence of adverse pregnancy outcomes was examined using multinomial logistic regression analysis with age and pre-pregnancy body mass index (BMI) as covariates. The total number of subjects was 1,553, the mean age was 32.9 ± 3.7 years, and the mean pre-pregnancy BMI was 21.2 ± 3.0 kg/m2. Unconjugated estriol > 95th percentile of the screened population or unconjugated estriol ≥ 2.0 MoM (Multiple of the Median) was significantly associated with an increased risk for developing gestational diabetes mellitus (GDM), after adjusting for age and pre-pregnancy maternal weight. High levels of unconjugated estriol in the maternal serum during the early second trimester of pregnancy are a useful predictor of GDM development.

Vaginal estriol to overcome side-effects of aromatase inhibitors in breast cancer patients

Objective Aromatase inhibitors are essential as endocrine treatment for hormone receptor-positive postmenopausal breast cancer patients. Menopausal symptoms are often aggravated during endocrine treatment. We investigated whether vaginal estriol is a safe therapeutic option to overcome the urogenital side-effects of aromatase inhibitors. Serum hormone levels were used as the surrogate parameter for safety.Methods Fasting serum hormone levels of ten postmenopausal breast cancer patients receiving aromatase inhibitors were prospectively measured by electro-chemiluminescence immunoassays and gas chromatography/mass spectrometry before and 2 weeks after daily application of 0.5 mg vaginal estriol (Ovestin® ovula), respectively.Results Two weeks of daily vaginal estriol treatment did not change serum estradiol or estriol levels. However, significant decreases in levels of serum follicle stimulating hormone (p = 0.01) and luteinizing hormone (p = 0.02) were observed. Five out of six breast cancer patients noticed an improvement in vaginal dryness and/or dyspareunia.Conclusions The significant decline in gonadotropin levels, indicating systemic effects, has to be kept in mind when offering vaginal estriol to breast cancer patients receiving an aromatase inhibitor.

Topical estrogen protects against SIV vaginal transmission without evidence of systemic effect.

Accumulating data suggest that the state of the vaginal epithelium affects a woman's risk of HIV vaginal transmission and several human and non-human primate studies have shown that the rate of HIV or SIV vaginal transmission is decreased when estrogen is dominant. Systemic estrogen can protect against SIV vaginal transmission. To determine the safety and efficacy of topical estrogen in preventing SIV vaginal transmission. The non-human primate model of HIV vaginal transmission was used to assess vaginal estriol cream in ovariectomized macaques. Twelve macaques were treated intravaginally with estriol and eight with placebo cream twice a week. The vaginal and systemic effects of estriol were determined by colposcopy and serum luteinizing hormone, levels of which would decline in the presence of systemic estrogen. After 5 weeks of therapy, the animals were challenged vaginally with pathogenic SIVmac251. Vaginal estriol resulted in minimal serum estriol levels and had no effect on serum luteinizing hormone levels. Vaginal epithelia cornified and thickened significantly in response to estriol therapy. One of the estriol-treated animals became infected after this single challenge, while six of the control animals became infected (P = 0.0044). These data demonstrate that topical vaginal estriol can strongly protect against SIV vaginal transmission, while having no detectable systemic effect. These results support the study of topical vaginal estriol in preventing HIV vaginal transmission in at-risk women.

Plasma surgery and topical estriol: effects on the nasal mucosa and long-term results in patients with Osler's disease

Objective The study goal was to report on the long-term results and effect of argon plasma coagulation (APC) surgery and topical estriol in patients with Osler's disease who had recurrent epistaxis. Study design In a prospective clinical study, 52 patients underwent APC and estriol application and were followed for 18 months regarding their bleeding frequency and intensity. Patient blood samples were obtained to determine the serum estriol levels. Scanning electron microscopy of the nasal mucosa enabled a better understanding concerning the effect of estriol on the nasal mucosa. Results Eighteen months after treatment, 96% of the patients stated a significantly reduced bleeding frequency and intensity. Under estriol influence, former berry-like telangiectasia of the nasal mucosa was flatter. The serum estriol levels did not increase significantly in any of the patients. No side effects from the use of topical estriol were observed. Conclusion The combined treatment approach with APC and topical estriol significantly reduces epistaxis in Osler's disease. Significance APC and topical estriol have proved to be a promising alternative in the treatment of Osler's disease.

Corticotropin-releasing hormone, corticotropin-releasing hormone–binding protein, and activin A in maternal serum: Prediction of preterm delivery and response to glucocorticoids in women with symptoms of preterm labor

Objective: The aim of this study was to determine prospectively whether serum concentrations of corticotropin-releasing hormone, corticotropin-releasing hormone–binding protein, and activin A (1) predict preterm birth within 10 days of hospital admission or at <37 weeks’ gestation among women with symptoms of preterm labor and (2) are affected by glucocorticoid therapy. Study Design: Serum concentrations of corticotropin-releasing hormone and activin A were measured in 94 women with symptoms of preterm labor between 24 and 34 weeks’ gestation, and delivery outcomes were monitored. Corticotropin-releasing hormone–binding protein concentrations were measured in 71 of these women. In a subgroup of 15 women the serum analytes were assayed in conjunction with estriol before and 12 to 24 hours after administration of dexamethasone. Results: Forty-six percent (6/13) of the women who were delivered within 10 days of hospital admission had a raised serum corticotropin-releasing hormone level, but the predictive relationship was not significant (χ2 = 1.7; P =.2). Among the 31 women (including the 6 previously mentioned) who were delivered at <37 weeks’ gestation, 39% (12/31) had a raised corticotropin-releasing hormone level. Although a raised corticotropin-releasing hormone concentration was positively associated with delivery at <37 weeks’ gestation (χ2 = 9; P =.003), the predictive diagnostic value was poor, with sensitivity, specificity, and positive and negative predictive values of 39%, 90%, 67%, and 75%, respectively. The serum concentrations of corticotropin-releasing hormone–binding protein and activin A were unrelated to gestational age at delivery. Dexamethasone markedly lowered the serum estriol level (P <.001) but had no effect on concentrations of corticotropinreleasing hormone, corticotropin-releasing hormone–binding protein, and activin A. Conclusion: Serum concentrations of corticotropin-releasing hormone, corticotropin-releasing hormone–binding protein, and activin A are not clinically useful for the prediction of preterm delivery among women with symptoms of preterm labor and are not affected by administration of glucocorticoids. (Am J Obstet Gynecol 2000;183:643-8.)

Clinical study on effect of Chinese herbal medicine for supplementing kidney and Qi and activating blood circulation in treating intrauterine growth retardation of fetus

To explore the therapeutic effect and its possible mechanism on using Chinese herbal medicine (CHM) for supplementing Kidney and Qi, and activating blood circulation in treating intrauterine growth retardation of fetus (IUGR). Fifty-five cases of IUGR were observed, 30 of them were treated with CHM and 25 treated with amino acid for control. The neonatal birth weight in the CHM group was markedly greater than that in the control group. Not only the maternal fundal height and abdominal circumference, but also the fetal growth parameters, including biparietal diameter, head circumference, abdominal circumference, femur length in the CHM group increased much faster than those in the control group. After CHM treatment, the maternal serum levels of estriol (E3) and human placental lactogen (hPL) were close to the normal pregnancy group, but the levels in the control group were significantly different from the normal range. The umbilical venous plasma concentration of essential amino acids was markedly improved after treatment, however, the improvement in the CHM group was more significant than that in the control group. No adverse effect of CHM was found both in mother and fetus. CHM for supplementing Kidney and Qi, and activating blood circulation was more effective in the improvement of placental function and amino acid transportation than those of amino acid.

Low maternal serum estriol as a marker for steroid sulfatase deficiency

Maternal serum screening began in the early 1980's with the evaluation of alpha-feto-protein (AFP) levels to identify pregnancies at an increased risk for neural tube defects and later for Down syndrome. Elevated levels of AFP have been found to be markers for other conditions like gastroschisis, kidney abnormalities and placental bleeding. Maternal serum screening now includes hCG and estriol to increase aneuploidy detection, with estriol being added in the mid 1990's. Since that time many screening tests have shown abnormally low levels of estriol (≤0.10 MoM). These low values have been reported in association with anencephaly, Smith-Lemli-Opitz, fetal adrenal hypoplasia, high-dose corticosteroid therapy and steroid sulfatase deficiency. We report on 4 cases of very low estriol levels detected through maternal serum screening and referred to our center. The values were 0.02 MoM, <0.03 MoM, 0.06 MoM and 0.10 MoM. In all cases the mothers were found to be carriers of a microdeletion in the steroid sulfatase (STS) region at Xp22.3 by FISH analysis. All had affected sons. Three were detected by amniocentesis and one was tested after delivery. Three cases had a family history of very dry skin consistent with an X-linked recessive inheritance pattern. STS deficiency should be considered when counseling patients presenting with very low maternal serum estriol levels. STS deficiency or X-linked ichthyosis is characterized by dark scaly skin most prominent on the back, neck, face and extremities. Approximately 25% of affected males may develop mild comeal opacities. Carrier females may have mild symptoms. In an estimated 5% of cases, a more severe phenotype may be present resulting from a larger deletion and leading to a contiguous gene syndrome. Other conditions mapped to Xp22.3 include short statue, chondrodysplasia punctata, mental retardation. Kallmann syndrome and ocular albinism Carrier testing and prenatal diagnosis are available. Testing can help elucidate the reason for low estriol levels and identify women at risk for prolonged labor and failure to dilate due to placental sulfatase deficiency. A detailed family history may assist in determining the risk of STS deficiency or a more severe contiguous gene syndrome.

Estriol ameliorates autoimmune demyelinating disease: implications for multiple sclerosis.

To evaluate the use of estriol in the treatment of experimental autoimmune encephalomyelitis (EAE) and other cell mediated autoimmune diseases. Experimental autoimmune encephalomyelitis is a T helper 1 (Th1)-mediated autoimmune demyelinating disease that is a useful model for the study of immune responses in MS. Interestingly, both EAE and MS have been shown to be ameliorated during late pregnancy. Estriol, progesterone, and placebo pellets were implanted in mice during the effector phase of adoptive EAE. Disease scores were compared between treatment groups, and autoantigen-specific humoral and cellular responses were examined. Estriol treatment reduced the severity of EAE significantly compared with placebo treatment whereas progesterone treatment had no effect. Estriol doses that induced serum estriol levels that approximated estriol levels during late pregnancy were capable of ameliorating disease. Estriol-treated EAE mice had significantly higher levels of serum antibodies of the immunoglobulin (Ig) G1 isotype specific for the autoantigen myelin basic protein (MBP). Further, MBP-specific T-lymphocyte responses from estriol-treated EAE mice were characterized by significantly increased production of the Th2 cytokine interleukin 10 (IL-10). T lymphocytes were shown to be the primary source of IL-10 within antigen-stimulated splenocyte populations. Estriol as a hormone involved in immune changes during pregnancy may provide a basis for the novel therapeutic use of estriol for MS and other putative Th1-mediated autoimmune diseases that improve during late pregnancy.

Five years' experience of cholesterol treatment for the Smith-Lemli-Opitz Syndrome (SLOS): What have we learned, where are we going?

Since January of 1994, following the discovery of the defect in cholesterol metabolism now known to cause SLOS, we have been treating SLOS patients with a concentrated suspension of cholesterol in soybean oil. Eighteen patients with SLOS, ranging in age from birth to mid teens, and ranging in pretreatment cholesterol levels from 8-90 mg/dl have been followed by us every 1-3 months for up to five years while on treatment.We will present data to show benefits of treatment in this cohort of patients. No adverse reactions to therapy have been noted. Benefits of therapy include improved growth and nutritional status, better tolerance of infection, and improvement in behavioral disturbances. Adrenal function and neutrophil function have been investigated, and both are normal. Ongoing studies are documenting neuropsychological course, CNS myelinization on MRI, and hearing status with ABR.We have discovered problems in our patients which were not previously known to occur in SLOS. These include photosensitivity, which we are now studying both in vitro in skin fibroblasts, and in vivo using timed exposure to UV light. We have also documented abnormal red cell shape (acanthocytosis), and the development of hypersplenism with thrombocytopenia in some patients. We are now accumulating experience in the management of profoundly ill neonates using fresh frozen plasma, and in prenatal diagnosis, by assessing low maternal serum estriol levels. Future plans include studies of cholesterol absorption, and the use of MR spectroscopy to assess CNS cholesterol metabolism. Our close follow-up of this patient cohort has allowed us to appreciate the complexities of issues seen in children with severe cholesterol deficiency, and to develop a greater understanding of the natural course of SLOS.

Maternal Serum Levels of Estriol, Prolactin, Human Placental Lactogen and Chorionic Gonadotrophin Related to Fetal Sex in Normal and Abnormal Pregnancies

A total of 222 pregnant women had repeated hormone assays of prolactin, estriol, human chorionic gonadotrophin and placental lactogen between week 20 and delivery. The aim of this study was to investigate whether maternal serum levels of the above-mentioned hormones differed between normal and abnormal pregnancies, that is preterm, preterm small-for-date (SFD), SFD at-term and normal at-term deliveries, with special regard to fetal sex. The results of the present study indicated differences related to preterm deliveries and intrauterine growth retardation. This finding was reflected in the estriol levels when mothers of both boys and girls were included, suggesting a primary involvement of fetoplacental factors in these pathological pregnancies. However, when only mothers of girls were investigated, the development of growth retardation was mainly seen in maternal serum hPL differences, thus suggesting a placental involvement.

Feto-placental steroid metabolism in growth retarded human fetuses.

The goal of the study was the determination of the relative roles of the placenta and the fetus in causing low serum estriol (E3) levels in women bearing fetuses with intrauterine growth retardation (IUGR). Umbilical venous levels of E3 and dehydroepiandrosterone sulfate (DHAS) were measured in 31 samples from fetuses with IUGR, 21 of whom were vaginally delivered and 10 who were delivered by cesarean section. In addition, estrone (E1) and estradiol (E2) were measured in 11 of the samples. The results were compared with 11 samples from cesarean section delivered control term infants and 54 samples from vaginally delivered control infants. The vaginally delivered IUGR group had a significantly lower mean umbilical venous DHAS level than did their control group (2128 +/- 158 ng/ml SEM versus 2645 +/- 130, p less than 0.05). Both the vaginally delivered and cesarean section delivered IUGR infants had umbilical venous E3 levels significantly lower than in their control groups (70 +/- 10 ng/ml SEM versus 144 +/- 10, p less than 0.001, and 46 +/- 11 ng/ml SEM versus 136 +/- 23, p less than .01, respectively). Umbilical venous E1 and E2 levels were not different from the control values. E1, E2, E3, and DHAS were measured in eight maternal venous samples obtained from mothers bearing fetuses with IUGR. In comparison with 11 control mothers, only E3 was significantly different (10.7 +/- 3.0 ng/ml SEM in mothers with IUGR fetuses versus 25.0 +/- 4.9 in control mothers p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)