Serial estimations of maternal urinary oestriol, serum cystine aminopeptidase (S-CAP), and human chorionic somatomammotrophin (S-HCS) were studied prospectively in 29 pregnancies complicated by intrauterine growth retardation. The newborn growth-retarded infants were examined by neurological and behavioural techniques. Growth variables and neurological and developmental findings were compared with those in 18 healthy controls at 5, 10 and 18 months of age. The growth-retarded infants caught up with regard to body size from 5 months of age, although the severely retarded infants (birth weight less than or equal to -2 SD) differed from the controls with regard to weight and head circumference at 18 months of age. Abnormal maternal oestriol excretions were negatively correlated to weight and length during the follow-up period. Infants who had been severely growth-retarded at birth were neurologically below optimal level at 10 months of age, compared to the controls. There were no significant differences between the growth-retarded infants and the controls with regard to psychomotor development, as assessed by a screening test and by Griffiths' method. Significant correlations were found between abnormal biochemical placental tests (especially urinary oestriol and S-CAP) and psychomotor development. Significant correlations also appeared between neonatal orientation and motor behaviour and some Griffiths' scales at 18 months of age. No relationship was found between the neurological condition in the neonatal period and the neurological findings and development at follow-up.

Serial estimations of maternal urinary oestriol, serum cystine aminopeptidase (S-CAP), and human chorionic somatomammotrophin (S-HCS) were done in a prospective study on 29 pregnancies in which intrauterine growth retardation was diagnosed in the third trimester by the gravidogram method and/or serial ultrasound measurements of the fetal biparietal diameter. The series was divided into 2 growth-retarded groups: (i) severe growth retardation with birth weight less than -2 SD from the mean for gestational age (N = 14); (ii) moderate growth retardation with birth weight between -1 and -2 SD from the mean for gestational age (N = 15). These were compared with a control group of 18 normal pregnancies and infants. A modified Prechtl neurological examination and the Brazelton Neonatal Behavioural Assessment Scale (NBAS) were done in the neonatal period at full-term age. Both categories of growth-retarded infants showed lower muscle tonus than the controls. The severely growth-retarded infants showed fewer optimal items in the neurological examination; they also showed poorer capacity for orientation to external stimuli, inferior motor function, and less physiological stability in NBAS than the controls. The abnormal biochemical placental tests were significantly correlated to low Apgar scores (urinary oestriol), to low excitability (S-CAP) and to poor motor function (S-HCS). The neurological and behavioural condition of the neonate seemed to be more closely associated to the extent of growth retardation than to the occurrence of abnormal biochemical placental tests.

Radioimmunoassay of sex steroids and prostaglandins was performed on plasma obtained from 10 uncomplicated primigravid subjects at a stated time of the day at varying stages of gestation. Prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha), oestrone and oestriol concentrations reached a peak a few weeks before term and then declined. Progesterine, 17-hydroxyprogesterone and oestradiol increased during pregnancy particularly after 32 weeks. In two normal patients repeated blood samples were taken throughout the day at weekly intervals in late pregnancy for sex steroid assays to evaluate the variation of concentrations with the time of sampling and the significance of changes in mean concentrations of different steroids with approaching parturition. Marked variability was found in the levels of different steroids during the day. Plasma oestriol values were lowest at 8.00 a.m. in one patient sampled frequently. A marked decrease in oestriol, oestrone, oestradiol and 17-hydroxyprogesterone was found in one patient prior to the onset of spontaneous labour. In another subject there was no decrease in concentrations of oestrogens or progestogens prior to induction of labour at term.

Taking Solid-Phase Extraction (SPE) as pre-treatment process, a laboratory experiment was conducted by adopting the technology of High Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MSMS) to develop a method to determine the concentrations of 13 steroids in feedlot wastewater. Atmospheric Press Chemical ionization (APCI) source was applied and operated in negative ion model, with the parameters of Chromatography and Spectrometry being optimized. Quasi-molecular ion peak [M + H]+ appeared in the full scan of the first quadrupole of mass spectrometer (Q1) of Testosterone propionate and other 6 steroid compounds, while quasi-molecular ion peak [M + H-H2O]+ appeared in the full scan of Q1 of rest 6 steroid compounds. The linear range of the 9 points calibration curve for the 13 target compounds was determined to be from 1 to 1000 ng x ml(-1), and the calibration curve regression correlation coefficients (R) were always above 0.9990 for all sample batches. The average recovery rate of all target compounds was 83.75%-111.50%, and the methodological stability was determined to be acceptable, with the relative standard deviations between 2.02%-14.21% (n=6). Except that the limit of detection (LOD) of Mestradiol and Oestriol was higher than 15 ng x ml(-1), all the other target compounds had a LOD lower than 5 ng x ml(-1). In the determination of real samples from feedlot wastewater, the developed method represented a good profile to all target compounds at different concentrations in each stage of treatment.

A limited numbers of published studies evaluate the referral reasons for genetic counseling services in the literature. These studies are focused on prenatal genetic counseling services, in particular, prenatal diagnosis. In order to provide the most effective and helpful genetic counseling services, genetics professionals need adequate knowledge about the profile of individuals referred for these services. In addition, physicians need increased awareness of the nature of genetic issues in order to make appropriate referrals. This study was intended to provide a descriptive analysis of the referral reasons of patients that received genetic counseling at a genetics center in Izmir, Turkey during an 11-year period. A total of 8965 records generated between 1998 and 2008 from one genetic center (which consists of The Department of Medical Genetics and Division of Pediatric Genetics) were evaluated retrospectively. Of these, 6,258 involved referrals for prenatal reasons, and 2,707 involved referrals for postnatal reasons. Both prenatal and postnatal records were further classified into more specific categories of referral reasons. The most common reason for genetic counseling among the prenatal patients was advanced maternal age (42.0%), followed by high risk results on prenatal biochemical screening tests such as second trimester double test [(serum concentration of alphafetoprotein (AFP), beta-human chorionic gonadotropin (beta-HCG)], triple test (serum concentration of AFP, beta-HCG, oestriol) and integrated test (26.5%). The most common indications for postnatal patients were recurrent miscarriages (28.2%) and infertility (19.7%). A significant increase in number of specific categories of referrals for genetic counseling was observed for the last 3 years after the establishment of the Medical Genetics Department. These data provide useful information about the frequency of referrals to the genetics department, and the feasibility of genetic services. Organization of genetic services and systematic procedures for genetic counseling and genetic testing may improve the public's awareness of genetics and ensure a high standard of patient care.

Previously in world literature there have been reports of 40 pregnancies in women with untreated Cushing's syndrome. The perinatal mortality in these series has been 12.9%. This paper reports on a case in which low serum oestriol excretion was the first abnormal laboratory value in a patient with only a few signs of Cushing's syndrome habitus and adrenal adenoma.

This prospective study investigates the relationship between insulin-dependent diabetes and maternal serum levels of alpha-fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotropin (hCG). It also examines the potential impact on screening for Down syndrome. The population-based cohort included 20,321 pregnant women in Maine who underwent routine serum screening for Down syndrome in the second trimester. The cohort included 52 women with insulin-dependent diabetes. Maternal serum AFP levels are now routinely adjusted for insulin-dependent diabetes. These adjustments, therefore, were made routinely in the diabetic women, but no equivalent adjustments were made for uE3 and hCG values. The initial false-positive rate (using all three markers) among the women with diabetes was not significantly different from that in the non-diabetic population (7.7 and 5.4 per cent, respectively). Prior to adjustment for insulin-dependent diabetes, the median AFP level in the 52 women was 0.73 multiples of the median (MOM); the median levels of uE3 and hCG were 0.93 and 0.98 MOM, respectively. When the uE3 and hCG levels were adjusted, the initial false-positive rate was unchanged. Median serum levels of uE3 were significantly higher in the 33 women whose onset of diabetes was prior to 19 years of age (0.99 MOM) than in the 19 women whose onset of diabetes was at age 19 or older (0.84 MOM). This is the first population-based study to investigate the relationship between diabetes and serum levels of AFP, uE3, and hCG, and confirms earlier observations from a case-control study that found only slightly lower uE3 and hCG levels.

Equimolar concentrations of [4-14C]oestriol and [6,9-3H]oestriol 16 alpha-monoglucuronide were simultaneously perfused through isolated rat livers. Oestriol was hydroxylated to 2-hydroxyoestriol and 6 xi-hydroxyoestriol; 2-hydroxyoestriol was further methylated to 2-methoxyoestriol. Oxidoreduction of oestriol led to the formation of 16 alpha-hydroxyoestrone, 16-0xooestradio-17 beta and 16-epioestriol. In addition, two dehydroxylation products, namely oestrone and oestradiol-17 beta were found. The metabolites formed from oestriol were partly conjugated to monoglucuronides, monosulphates and sulphoglucuronides. About 80% of the oestriol perfused was hydroxylated at C-atom 2. Most of the 2-hydroxyoestriol formed was either methylated (about 37%) or sulphated (about 55%). Only small amounts (less than 2%) of the catecholoestrogens formed were methylated as well as sulphated. The 2-hydroxyoestriol monosulphates accumulated in the liver. After their conjugation with glucuronic acid, the double conjugates formed were immediately excreted into the bile. In fact, 2-hydroxyoestriol 16 alpha-monoglucuronide 2(3?)-monosulphate comprised by far the main biliary metabolite of [4-14C]oestriol, followed by oestriol 16 alpha-monoglucuronide and 2-methoxyoestriol 16 alpha-monoglucuronide. No triated sulphoglucuronides were detected, thus indicating that the monosulphates are the immediate precursors of the double conjugates. [6,9-3H2]Oestriol 16 alpha-monoglucuronide was metabolised only to a small extent. After its uptake into the liver more than 90% of this conjugate was secreted unchanged into the bile. The remaining part was hydrolysed; the oestriol liberated followed the same metabolic reactions as those found for [4-14C]oestriol. This indicates that the 16 alpha-glucuronide of oestriol is not metabolised to any appreciable extent.

Oestrone, oestradiol-17 beta and oestriol were detected in the urine of menstruating and pregnant langur monkeys. More oestrone than the other two oestrogens was excreted during the cycle and oestradiol-17 beta and oestriol could not be detected during the luteal phase. There was an increase in the amount of all the three oestrogens excreted during pregnancy when compared with the menstruating animals and oestriol was the major oestrogen excreted in the urine of pregnant langurs. Normal cyclic levels were reached 2 days after parturition. Most of the oestrogens (95%) were conjugated with glucuronic acid and little with sulphuric acid or in any other form.

Detergent must be added to the strongly acidic Kober reagent to obtain reproducible and well separated peaks in continuous flow analytical methods for oestriol in pregnancy urine. Brij 35 and other polyether detergents are not satisfactory because they or their impurities interfere in the reaction causing high blank response in colorimetric reactions and diminished fluorescence responses. In a single phase fluorometric method these detergents also caused turbidity or phase separation in the solution which passed through the fluorometer. Some anionic sulphate and sulphonate detergents were also unsatisfactory being immiscible with Kober reagent. Selected cationic and betaine detergents are shown to be possible alternatives, although one which is satisfactory in the kober reagent may be unsuitable for a dilution reagent. The betaine Empigen BB was found to be suitable for inclusion in both of these reagents.

The gas-chromatographic method is confronted with the amply used colorimetric method in the determination of the urinary oestriol. The two methods give practically the some results, even so the gas-chromatographic is to be preferred for its specificity, for salvaging accuracy, and for the possibility to receive hormonal profiles with only one determination.

A new fluorescent derivatization reagent, 10-ethyl-9-oxo-9, 10-dihydroacridine-2-sulfonyl chloride (EASC), was synthesized. A pre-column derivatization with EASC and reversed-phase high performance liquid chromatographic (RP-HPLC) method with fluorescence (FL) detection and mass spectrometry (MS) identification was performed for the trace analysis of oestradiol (E2) and oestriol (E3) in urine. This reagent shows higher sensitivities in ultraviolet (UV), FL and MS detection than those of dansyl chloride (DNS-Cl), and the fluorescence intensity of EASC is 1000 times higher than that of DNS-Cl. The results of derivatization indic ted that the derivatives can be obtained by the labeling reaction of EASC with estradiol (E2 and estriol (E3) in the presence of NaHCO3 buffer (pH 10.5) at 60 degrees C for 3 min. The excitation wavelength (lamda ex) and emission wavelength (lamda em) were 270 nm and 430 nm, respectively. The established method exhibited excellent reproducibility and recovery. The calibration curve were linear with regression coefficients over 0.9990, and the detection limits (S/N = 3) w 40, 31 fmol for the studied compounds. The practical applicability of the method was demonstrated by analyzing trace of free oestradiol and oestriol in the urine of root voles.

In 40 pregnant women in the pregnancy period from 16 to 28 weeks with threatened preterm labor diagnosed after clinical investigations and recording of cardiotocogram the values of oestriol in 24-hour urine and placental lactogen in the serum was measured. These values were compared to analogous determinations in a group 40 healthy women with similar duration of pregnancy. Statistically significantly lower values of placental lactogen were found in the serum of pregnant women with threatened preterm labor. The values of oestriol in 24-hour urine were also lower, but the differences were not statistically significant. In conclusion the authors state that enzymatically determined placental lactogen in the serum is a useful method of monitoring of pregnancy with threatened preterm labor. Determination of oestriol was without any greater diagnostic significance in the case of threatened preterm labor.

The authors studied 60 pregnant women in the pregnancy period from 29-37 weeks with threatened preterm labor. The control group formed 40 healthy pregnant women in the same pregnancy period. In all pregnant women the values of oestriol in 24-hour urine and placental lactogen in the serum was measured. Statistically significantly lower values of placental lactogen were found in the serum of pregnant women with threatened preterm labor. The values of oestriol in 24-hour urine were also lower, but the differences were not statistically significant. In 40 pregnant women in the pregnancy period from 16 to 28 weeks with threatened in the serum is a useful method of monitoring of pregnancy with threatened preterm labor. Determination of oestriol was without any greater diagnostic significance in the case threatened preterm labor.

Maternal serum alpha-fetoprotein (MSAFP), human chorionic gonadotropin (hCG) and unconjugated oestriol (uE3) concentrations were measured in maternal serum samples from 21 pregnancies with neural-tube defects, 4 pregnancies with ventral wall defects (VWD) and 1662 unaffected pregnancies in women. These congenital malformations were confirmed by ultrasound scanning. The mean multiplate of the median (MoM) for AFP and uE3 was significantly different from the control values in cases of open NTD (AFP median MoM = 5.95, p < 0.001, uE3 median MoM = 0.2, p < 0.001), while hCG values did not differ from those of matched controls (hCG median MoM = 0.9). The biological basis of altered levels of uE3 in pregnancies with fetal NTDs is unclear.

The authors studied 50 at-risk pregnancies to decide how useful fetal movements were prognostically. They compared this method with electronic measurements of fetal cardiac rhythm. The results show that it is both sensitive and specific. The levels of total oestriols and of plasma placental lactogen hormone when compared with the fetal heart rhythm are just as specific and sensitive.

It is possible to estimate the daily rate of oestriol production by the fetoplacental unit to monitor pregnancy by radio-immunoassay of the concentrations of unconjugated and total oestriol in the serum. The usefulness of these two parameters was compared by comparing variations from day to day in the same individuals and between them and other individuals, as well as over 24 hours. We think the best choice of test for biochemical monitoring of at-risk pregnancies is the estimation of unconjugated oestriol because there is a lower day to day variation in the same individual as well as throughout the 24 hours.

The levels of oestriol in urine of 30 healthy pregnant women in the last 22 to 25 days of pregnancy were determined and the statistical analysis was performed. It was found that the levels of oestriol in urine were the highest in 19-th and 9-th days before labour. This form of curve of oestriol levels was found to be characteristic for pregnant women before normal labour.

The level of oestriol in amniotic fluid was estimated in 17 women in pregnancy and in labour. The correlation between level of oestriol and the time of labour was found. However no influence of foetal sex and weight on the level of oestriol was observed. There was also no correlation between the level of oestriol and placenta weight and the type of employment of these women.

A population of 39 women (average age 64.5 years) suffering from presenile or senile vulvovaginitis was subjected to topical treatment with oestriol-based vaginal cream (daily applications of 0.50 mg of oestriol corresponding to 4 g of cream for 14 days and three times a week in the three following weeks). The results of treatment were assessed on the basis of the clear-cut improvement in symptomatology and the noteworthy increase in the index and volume of maturation of the vaginal epithelium. The effectiveness of topical treatment of postmenopausal vulvovaginitis with oestriol in the absence of unwanted side-effects is confirmed.

Local intravaginal application of oestriol is part of the therapeutical programme of sensory urge-incontinence. The effectiveness of a new method--intravesical administration of 1 mg oestriol versus a placebo--has been proved in a prospective randomised study. 21 patients each were treated over a period of three weeks with oestriol or with the placebo-substance intravesically. The effectiveness of the administered therapy was checked with clinical and urodynamic parameters. The intravesical administration of 1 mg oestriol proved to be efficient and free of side effects in respect of the parameters such as imperative micturition, bladder capacity, of the maximum urethral closure pressure as well as the number of micturitions per diem. The intravesical administration of oestriol may be considered as additional method of therapy for treatment of sensory urge-incontinence.

Much greater quantities of 16 alpha-hydroxyoestrogens (e.g. oestriol) than of 16-deoxyoestrogens (e.g. oestradiol-17 beta) are formed in human pregnancy than might be expected from the relative availability to the placenta of the 16 alpha-hydroxy- and 16-deoxy-C19 precursors. To investigate this further, 16 alpha-hydroxyandrostenedione (16 alpha-OH-A4) and androstenedione (A4) were tested in vitro as substrates and mutual inhibitors of human placental aromatase. It was found that the Km for aromatisation of A4 (mean = 0.26 mumol/l) was very similar to Ki (0.30, 0.35 mumol/l) for the inhibition by A4 of the aromatisation of 16 alpha-OH-A4. Similarly, Km for aromatisation of 16 alpha-OH-A4 (mean = 1.21 mumol/l) had the same value as the Ki (1.0, 1.2 mumol/l) for the inhibition by 16 alpha-OH-A4 of the aromatisation of A4. From graphical analysis of Lineweaver-Burk plots, both inhibitions were characterised as noncompetitive. Hence, it was concluded that the two 16-deoxy- and 16-hydroxy-C19 substrates bind at separate, but interactive, sites and that each substrate on binding inhibits the aromatisation of the other. Additional evidence for the separate but interactive substrate binding sites for the 16-deoxy- and 16-hydroxy-C19 steroids was obtained by use of the suicide inhibitor 4-hydroxyandrostenedione (4-OH-A4), which is recognised as binding to the aromatisation site for A4. Aromatisation of 16 alpha-OH-A4 was found to be inhibited by pre-incubation of the microsomes with 4-OH-A4 (0.1 mumol/l). The presence of A4 (4.6 mumol/l), but not of 16 alpha-OH-A4 (4.0 mumol/l) during the pre-incubation successfully protected the subsequent aromatisation of 16 alpha-OH-A4 from this inhibition. In addition, the Km values, reported here, suggest also that the 16-deoxyandrogens are preferred to the 16 alpha-hydroxyandrogens as oestrogen precursors. In consequence, factors other than substrate affinity and plasma concentrations must be presumed to be involved in the overwhelming production of 16 alpha-hydroxyoestrogens in human pregnancy.