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PubMed1986

Mitotic inhibition and aneuploidy induction by naturally occurring and synthetic estrogens in Chinese hamster cells in vitro.

We used a predominantly diploid Chinese hamster cell line to test a number of naturally occurring and synthetic estrogens for their ability to arrest cells at metaphase, their potential for allowing anaphase recovery, and their capability of inducing aneuploid progeny. The chemicals employed included diethylstilbestrol, dienestrol, hexestrol, beta-estradiol, ethynylestradiol and estriol. We also tested progesterone, estrone and testosterone in this regard. Only estrogens and their synthetic analogs caused mitotic arrest and aneuploidy, while progesterone, estrone and testosterone did not cause mitotic disturbances. Among the estrogens, DES was the most effective arrestant on a comparative molar basis, whereas dienestrol was most potent over a wide range of concentrations. Estriol was the least potent as an arrestant but was an effective inducer of aneuploidy. The addition of a metabolic activator (S9) did not alter the ability of DES to arrest mitosis. Following the removal of the drugs, cells were able to quickly reorganize a spindle apparatus and enter anaphase. Diethylstilbestrol, dienestrol, hexestrol, beta-estradiol, ethynylestradiol and estriol caused significant increase in aneuploidy within a narrow range of high concentrations in recovering cell populations. Aneuploidy was induced in a non-random manner. Immunofluorescence studies with anti-tubulin antibody indicate that estrogens may have a mechanism of mitotic arrest similar to that of colchicine and colcemid, viz inhibiting the polymerization of tubulin to form microtubules. These data suggest that the interaction between estrogens and microtubules may mediate the induction of aneuploidy in somatic cells. Aneuploidy induction by DES and similar compounds may be related to their carcinogenic potential.

Anaphase↗
PubMed2004

Identification of UGT2B9*2 and UGT2B33 isolated from female rhesus monkey liver.

Two UDP-glucuronosyltransferases (UGT2B9(*)2 and UGT2B33) have been isolated from female rhesus monkey liver. Microsomal preparations of the cell lines expressing the UGTs catalyzed the glucuronidation of the general substrate 7-hydroxy-4-(trifluoromethyl)coumarin in addition to selected estrogens (beta-estradiol and estriol) and opioids (morphine, naloxone, and naltrexone). UGT2B9(*)2 displayed highest efficiency for beta-estradiol-17-glucuronide production and did not catalyze the glucuronidation of naltrexone. UGT2B33 displayed highest efficiency for estriol and did not catalyze the glucuronidation of beta-estradiol. UGT2B9(*)2 was found also to catalyze the glucuronidation of 4-hydroxyestrone, 16-epiestriol, and hyodeoxycholic acid, while UGT2B33 was capable of conjugating 4-hydroxyestrone, androsterone, diclofenac, and hyodeoxycholic acid. Three glucocorticoids (cortisone, cortisol, and corticosterone) were not substrates for glucuronidation by liver or kidney microsomes or any expressed UGTs. Our current data suggest the use of beta-estradiol-3-glucuronidation, beta-estradiol-17-glucuronidation, and estriol-17-glucuronidation to assay UGT1A01, UGT2B9(*)2, and UGT2B33 activity in rhesus liver microsomes, respectively.

Amino Acid Sequence↗
PubMed2006

A sensitive determination of estrogens with a Pt nano-clusters/multi-walled carbon nanotubes modified glassy carbon electrode.

On the top of a multi-walled carbon nanotubes (MWNTs) modified glassy carbon electrode (MWNTs/GCE), Pt nanoclusters were electrochemically deposited, fabricating a Pt/MWNTs composite modified electrode, Pt/MWNTs/GCE. X-ray photoelectron spectroscopy, powder X-ray diffraction and field emission scanning electron microscope were used for the surface characterization of the electrode, and demonstrated the formation and distribution of Pt clusters of Pt nanoparticles of 8.4 nm in averaged size in the MWNTs matrix. The preliminary study found that this composite modified electrode has strong electrocatalytic activity toward the oxidation of estrogens involving estradiol, estrone and estriol. The voltammetric behavior of estrogens on this electrode was investigated by cyclic voltammetry, linear sweep voltammetry and square-wave voltammetry. In comparison with the MWNTs/GCE or a Pt nanoparticles modified GCE prepared in the similar way, this composite modified electrode exhibited much higher current sensitivity and catalytic activity. This electrode is also stable. The linear range of square-wave voltammetric determination was 5.0 x 10(-7)-1.5 x 10(-5)mol/L for estradiol, 2.0 x 10(-6)-5.0 x 10(-5)mol/L for estrone, and 1.0 x 10(-6)-7.5 x 10(-5)mol/L for estriol. Under an assumption that the concentration ratio of estradiol:estrone:estriol is 2:2:1, the real sample of blood serums was tested for the determination using this electrode. Satisfactory result was obtained with averaged recovery of 105%.

Adsorption↗
PubMed2005

Fully automated analysis of estrogens in environmental waters by in-tube solid-phase microextraction coupled with liquid chromatography-tandem mass spectrometry.

A simple, rapid and sensitive method for the determination of five estrogens, estrone, 17beta-estradiol, estriol, ethynyl estradiol, and diethylstilbestrol, was developed using a fully automated method consisting of in-tube solid-phase microextraction (SPME) coupled with liquid chromatography-tandem mass spectrometry (LC/MS/MS). These estrogens were separated within 8 min by HPLC using an XDB-C8 column and 0.01% ammonia/acetonitrile (60/40, v/v) at a flow rate of 0.2 mL/min. Electrospray ionization conditions in the negative ion mode were optimized for MS/MS detection of the estrogens. The optimum in-tube SPME conditions were 20 draw/eject cycles of 40 microL of sample using a Supel-Q PLOT capillary column as an extraction device. The extracted compounds were easily desorbed from the capillary by passage of the mobile phase, and no carryover was observed. Using the in-tube SPME LC/MS/MS method, good linearity of the calibration curve (r > or = 0.9996) was obtained in the concentration range from 10 to 200 pg/mL for all compounds examined. The limits of detection (S/N= 3) of the five estrogens examined ranged from 2.7 to 11.7 pg/mL. The in-tube SPME method showed 34-90-fold higher sensitivity than the direct injection method (5 microL injection). This method was applied successfully to the analysis of environmental water samples without any other pretreatment and interference peaks. Several surface water and wastewater samples were collected from the area around Asahi River, and estriol was detected at 35.7 pg/mL in the effluent of a sewage treatment plant. The recoveries of estrogens spiked into river waters were above 86%, except for estriol, and the relative standard deviations were below 0.9-8.8%.

Automation↗
PubMed1997

Elevated second-trimester dimeric inhibin A levels identify Down syndrome pregnancies.

OBJECTIVE: Our purpose was to determine whether second-trimester dimeric inhibin A levels distinguish Down syndrome pregnancies from euploid pregnancies. STUDY DESIGN: With use of a commercially available enzyme-linked immunosorbent assay (Serotec, Oxford) inhibin A medians were established in stored sera from 40 to 50 euploid pregnancies at each week of gestation from 14 to 20 weeks and from 33 Down syndrome pregnancies. Maternal serum alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin levels measured in each sample before storage were retrieved. The performance of inhibin A in the multiple-marker screening test was evaluated. RESULTS: The mean inhibin A multiple of the median was significantly higher in the Down syndrome group than in the euploid group (2.84 +/- 2.0 vs 1.22 +/- 1.0, p = 0.0001). An inhibin A level > or = 1.6 multiples of the median identified 70% of all Down syndrome pregnancies at a false-positive rate of 22%. Replacing estriol with inhibin A in the multiple-marker screening test resulted in a higher Down syndrome detection rate at a lower screen-positive rate. CONCLUSION: Elevated second-trimester maternal serum inhibin A levels identify Down syndrome pregnancies; replacing estriol with inhibin A in the multiple-marker screening test improves test performance.

Adult↗
PubMed2002

Prediction of the bioaccumulation factors and body burden of natural and synthetic estrogens in aquatic organisms in the river systems.

This study undertakes an initial prediction of the bioaccumulation factors and body burden of the steroid estrogens, estrone, estradiol, estriol and ethinylestradiol in a range of aquatic organisms (plankton, benthic and free-living invertebrates and fish) in river systems using a food-web model. These data are compared to that derived from less complex predictions based on octanol-water partition coefficient and molecular connectivity index. The model predicted that bioaccumulation of steroid estrogens occurred in all organisms, however, the values were small, and the maximum and minimum bioaccumulation factors in this study were found in the fish at the lowest trophic level with ethinylestradiol (332) and the fish at the highest trophic level with estriol (1.8), respectively. Moreover, the bioaccumulation factors were sensitive to the metabolic rates of the estrogens in the free living organisms, while the concentration of estrogens in sediment was a significant factor in determining these values in benthic invertebrates. Biomagnification contributed little to the overall bioaccumulation, but the importance increased in fish exposed to ethinylestradiol. The predicted bioaccumulation factors from the food web model were generally smaller than the calculated bioconcentration factors from the simpler octanol-water partition coefficient/molecular connectivity index based estimates. Compared to literature measured data, the predicted values for fish were approximately 1000 times less than the values observed in laboratory tests, while for invertebrates, the modeled values were less than two orders of magnitude below laboratory results. However, the model predicted a similar bioconcentration factor for plankton in relation to experimental data for Chlorella vulgaris for estrone and estriol.

Animals↗
PubMed2000

[Basic principles of hormone replacement therapy in the postmenopause].

17 beta-estradiol, conjugated equine estrogens, esterified estrogens, and estriol constitute postmenopausal replacement therapy, all of which are in clinical use as oral preparations. Non-oral routes--matrix and reservoir patches, gel--were developed for estradiol, as was the intravaginal administration of estriol and estradiol. Daily doses of 1 mg estradiol(valerate) or 25 micrograms estradiol delivered via a patch or 0.5 mg gel or 0.3 mg conjugated equine estrogens are often sufficient to alleviate climacteric symptoms. Bone resorption may be effectively reduced and bone mineral density maintained by 1 mg estradiol or 25 micrograms transdermal estradiol. Maximal bone sparing dosages are 2 mg estradiol, 50 micrograms transdermal estradiol, 0.625 mg conjugated equine estrogens, and 1.25 mg estrone Estriol, predominantly used for the prevention and or treatment of urogenital symptoms, has no bone sparing effect at the doses in clinical use. Non-oral administration of estradiol may be superior in diabetic women and those with hypertriglyceridemia due to the different metabolism which does not mainly involve the hepatic first pass effect. Epidemiological data do not support any preference of oral versus non-oral routes of administration regarding side-effects such as venous thromboembolism. Progestogens--natural progesterone, derivatives structurally related to progesterone and testosterone, respectively--are necessary for endometrial protection. Sequential use of a progestogen for at least 10 days per month, preferably 12-14 days abolishes the increased incidence of endometrial hyperplasia which is likely to develop with unopposed use of estrogen. Observational studies do not suggest any superiority of a given progestogen regarding cardiovascular risk, prevention of osteoporosis, and cognitive function in postmenopausal women on estrogen replacement therapy. Tibolone, a derivative of norethindrone, is yet another option for replacement therapy. The recommended dose for treatment of climacteric symptoms and prevention of bone loss is 2.5 mg. Controlled clinical studies do not suggest that this compound is superior in achieving amenorrhea compared with continuous combined estrogen progestogen replacement therapy, as available data are inconsistent. In early postmenopause the sequential use of a progestogen in conjunction with an estrogen is the preferred treatment option. With advancing postmenopausal age either continuous combined replacement or tibolone may be choices in case withdrawal bleeding is no longer acceptable for women. However, there are no rigid age limit when to change treatments, the selection of which is largely influenced by the preference of the individual's acceptance of withdrawal bleeding.

Administration, Cutaneous↗
PubMed1992

Substrate and endocrine responses during exercise at selected stages of pregnancy.

To determine whether the concomitant effects of pregnancy and exercise yield substrate and endocrine patterns different from those expected during exercise alone, we compared the responses of glucose, lactate, free fatty acids, insulin, epinephrine (EP), norepinephrine (NE), human chorionic gonadotropin (HCG), human placental lactogen (HPL), estriol, and progesterone (P) in nonpregnant women (NP; n = 7) and pregnant women in the second (TR2; n = 6) and third trimester (TR3; n = 8) of pregnancy, before, during, and after 30 min of bicycle ergometer exercise at heart rates of 130-140 beats/min. In general, all substrates and hormone concentrations increased with exercise (P less than 0.05), except insulin, which decreased (P less than 0.05), and HCG, which did not change (P = 0.08). Differences in selected hormone concentrations (P, estriol, HCG, and HPL) among groups were already present at rest because of the different stages of pregnancy. Differences among groups at rest were also found in insulin and NE (P less than 0.05). Significantly different responses to exercise (i.e., group x time interactions) were as follows. NP vs. TR2:P, estriol, HCG, HPL, EP, and NE (P less than 0.05); NP vs. TR3: glucose, EP, and NE (P less than 0.05); TR2 vs. TR3: lactate, EP, and NE (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Uterine estrogen receptor interaction with estrogen-responsive DNA sequences in vitro: effects of ligand binding on receptor-DNA complexes.

Interaction between the mouse estrogen receptor (ER) and its responsive element (ERE) were examined in vitro using tissue extracts and an oligonucleotide containing a Vitellogenin A2 ERE (VRE) in a gel retardation assay. Three specific complexes were formed when nuclear extracts were prepared from estrogen agonist-treated uteri or when ligand-free ER from cytosol was used. ER protein was associated with the three complexes, as demonstrated by their ability to bind anti-ER antibody H222. Specific complexes were formed only when double stranded nonheat-denatured VRE was used. Mutation of the ERE in VRE abolished specific binding. The complexes formed by nuclear extracts were qualitatively identical when obtained from mice treated with a variety of estrogenic compounds with different potencies. Nuclear extracts obtained from mice treated with an estrogen antagonist LY117018 formed complexes that migrated slower than the complexes formed by the other estrogenic compounds examined. The dissociation rates (k-1) and equilibrium dissociation constants (Kd) of the ER-VRE complexes formed by estradiol- or estriol-bound ER or ligand-free ER were measured and were found to be very similar, although the ligand-free specific ER complexes associate and dissociate less rapidly than those of estradiol- or estriol-bound ER. In addition, one of the specific complexes formed by the estriol nuclear extract dissociated more slowly than the equivalent estradiol complex. Heat activating ligand-free ER did not increase its binding to VRE. It appears that the ligand-binding domain of the ER does not exert its regulatory effects at the level of sequence-specific DNA binding, since its occupancy does not alter binding to the ERE. The subtle differences we observed in association and dissociation of multiple complexes when unoccupied ER and ER bound to ligands of varying potencies are compared may reflect differences in ER association with other protein factors that govern transcriptional activity.

Animals↗
PubMedDate not supplied

An assessment of endocrine disrupting activity changes during wastewater treatment through the use of bioassays and chemical measurements.

The objective of this study was to assess the removal efficiencies of secondary wastewater treatment processes for compounds causing endocrine disrupting activity. The study used bioassays and chemical measurements, such as gas chromatography with mass spectrometry and enzyme immunosorbent assays. A total of seven full-scale water reclamation facilities using different unit operations and two pilot-scale membrane bioreactors were examined. Findings of this study imply that estrogenic disrupting activity in primary effluent is mainly caused by two steroidal hormones (17beta-estradiol and estriol) and, to a lesser extent, by synthetic chemicals, such as bisphenol A, 4-nonylphenol, and 4-tert-octylphenol. During secondary treatment, steroidal hormones were removed to a higher degree than nonylphenol and bisphenol A. The total estrogenic activity was removed by an average of 96%. The remaining concentrations of targeted steroids in secondary effluents, except for estriol, still had the potential to elicit a positive response in the human breast cell cancer assay. For the majority of facilities, the remaining activity was likely attributed to residual concentrations of two steroidal hormones (17beta-estradiol and estriol).

Biological Assay↗
PubMed1993

A model for the effect of estrogen antagonists on cooperative estradiol binding.

Partial agonists such as estriol and estrone have been reported to diminish or even eliminate the upward convexity of the Scatchard plot of the binding of labeled estradiol to estrogen receptor. This has been interpreted as agonist interference with the receptor dimerization induced by estradiol. In order to investigate how a partial agonist or antagonist might interfere with dimerization we have developed a theoretical mass-action law model, where soluble receptors can dimerize and bind to two different ligands. Special attention was devoted to manifestations of positive cooperativity to determine whether they could be modified by competition with a second ligand. This was done using a computer program that evaluated a large set of combinations of affinity constants in an effort to explore all possible situations. The model could reproduce the effect of a second ligand on the cooperative binding of estradiol to the estrogen receptor but only if the second ligand was anticooperative, which is not the case of estriol, estrone and tamoxifen. Furthermore, even when the Scatchard plot was linear, the model still required dimerization of the receptor in most of the cases, showing that the addition of an antagonist may eliminate the upward curvature of the Scatchard without truly eliminating dimerization or cooperativity. We conclude that the effect of a second ligand on the binding of labeled estradiol to estrogen receptor is not necessarily due to interference with dimerization and/or cooperativity. The inability of this model to fully explain the published data for estriol, estrone, clomiphene, and tamoxifen suggests that a more complex mechanism is involved.

Animals↗
PubMed2003

Estrogen and androgen concentrations are not lower in the umbilical cord serum of pre-eclamptic pregnancies.

Reductions in breast cancer risk observed in daughters of pre-eclamptic pregnancies are hypothesized to be mediated by lower in utero estrogen concentrations. Whereas maternal urinary estriol excretion is generally lower in pre-eclamptic women, results for maternal blood concentrations are equivocal, and little is known about estrogen concentrations in the cord of pre-eclamptic pregnancies. Unconjugated estrogen and androgen concentrations were measured in mixed umbilical cord sera from 86 pre-eclamptic and 86 uncomplicated, singleton pregnancies, matched on length of gestation, maternal age, parity, and type of delivery. Pre-eclamptic and uncomplicated pregnancies were similar in maternal age, prepregnancy weight, maternal height, type of delivery, use and type of anesthesia, and sex of offspring. Estriol, estradiol, estrone, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androstenedione, and testosterone concentrations measured in cord sera were not significantly different in pre-eclamptics compared with uncomplicated pregnancies. Estriol was 9% lower (P = 0.43), and all of the other hormones were actually higher in pre-eclamptics with testosterone and estradiol approaching statistical significance (P = 0.06 and P = 0.12, respectively). These data do not support the hypothesis that the lower breast cancer risk in daughters of pre-eclamptic pregnancies is explained by lower in utero estrogen exposure.

Adolescent↗
PubMed2004

Analysis and occurrence of estrogen in wastewater in Japan.

This paper describes an analytical procedure for free estrogens and their conjugates in domestic wastewater. The procedure demonstrated in this study is innovative in terms of levels of detection and quantification of the following substances: estrone (E1); 17beta-estradiol (E2); 17alpha-ethynylestradiol (EE2); estriol (E3); estrone-3-sulfate (E1-S); beta-estradiol 3-sulfate (E2-S); estriol 3-sulfate (E3-S); estrone beta-D-glucuronide (E1-G); beta-estradiol 17-(beta-D)-glucuronide (E2-G); estriol 3-(beta-D)-glucuronide (E3-G); beta-estradiol 3-sulfate 17-glucuronide (E2-SandG); and estradiol 3,17-disulfate (E2-diS). The detection limits of this method ranged from 0.1 to 1.4 ng/l. The recovery efficiencies of the estrogens in the analysis from influent and effluent of the secondary settling tank in a wastewater treatment plant (WWTP) were higher than 94% for the free estrogens, but were less than 50% for the conjugated estrogens. The field study using this method was conducted at twenty WWTPs in Japan. The median concentrations of the estrogens ranged from ND to as high as >100 ng/l. In the influent and secondary effluent samples, the concentrations of E1, E2 and E3 were the same levels as those previously reported. We found that the conjugated estrogens exist at higher concentrations in the influent and the secondary effluent than in the other studies, and that the concentrations of the conjugated estrogens were higher than those of the free estrogens.

Environmental Pollutants↗
PubMed1991

[Hormonal changes in aging from the viewpoint of the gynecologist].

The major relevant age-related changes that take place in women are caused by estrogen deficiency of rapid onset. This deficiency results in such changes as vaginal and vulval atrophy, atrophic urethrocystitis, breast flabbiness, thinning of the skin and its appendages, and also the severe metabolic changes like osteoporosis and cardiovascular disorders. All of these changes, in concert or alone, are capable of impairing a woman's sex life. Numerous genital complaints can be eliminated by local treatment with estriol cream, estriol vaginal suppositories, or systemic estriol. For the successful treatment of pronounced menopausal symptoms and the prevention of osteoporosis and cardiovascular disorders, estrogens at medium, so-called replacement, doses, given in combination with progestagen, are applied sequentially.

Aged↗
PubMedDate not supplied

Influence of a purified diet and route of administration on the metabolism and disposition of estradiol in B6C3F1 mice.

The metabolism and disposition of [6,7-3H]estradiol ([3H]E2) given by gavage (po) or intravenously (iv) were examined in female B6C3F1 mice fed either the purified AIN-76A (AIN) or cereal-based NIH-07 (NIH) diet for a period of 8 weeks prior to treatment with E2. Initially, 40.6 Ci of [3H]E2 was given iv to each mouse. Subsequently, 45.6 Ci of [3H]E2 was given po to the same mice. Samples of blood, urine, and feces were obtained during a 48-hr period after each dosing. Total radioactivity was determined for each sample. Urine and plasma samples were analyzed by HPLC, and the radiolabeled metabolites were tentatively identified and quantified. Statistical comparisons were made of the effects of diet, route of administration, and interactions among groups. Analysis revealed: 1) greater fecal than urinary excretion of radioactivity regardless of route of administration or diet fed, 2) more radioactivity excreted in the urine of AIN-fed than in NIH-fed mice, significantly different only after iv administration (p less than 0.02), and 3) a greater feces:urine ratio of excreted radioactivity following iv than po administration and from NIH-than AIN-fed mice. Metabolite profiles showed: 1) no differences in urine due to route of administration, 2) estriol conjugates dominated urinary metabolites, 3) accumulation of radioactive material in plasma that apparently was tritiated water, with more rapid accumulation of tritiated water after po than iv administration, 4) relatively more plasma estradiol-17-glucuronide, estriol-3-sulfate, and estriol in po- than in iv-treated mice, 5) estradiol-3, 17-sulfate in plasma of iv- but not po-treated mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1984

Combined pregnancy after gonadotropin therapy.

Three cases of combined pregnancy are described after gonadotropin therapy; two cases after human pituitary gonadotropin and one after human menopausal gonadotropin administration. In each case the intrauterine gestation was a multiple pregnancy. After salpingectomy, two of the women have proceeded to the delivery of healthy infants; the third woman aborted. In each case the gonadotropin stimulation regimen was ceased at the appropriate stage when the estriol excretion was between 60 and 125 micrograms/day, but the subsequent rate of rise of estriol was 2.3- to 3.2-fold during the coasting phase before the human chorionic gonadotropin trigger when the estriol excretion rate was 140 to 350 micrograms/day.

Abortion, Spontaneous↗
PubMed1980

Estrogen profiles of primiparous and nulliparous women in Athens, Greece.

Urine estrogens of 144 primiparous women and 122 nulliparous women of similar age were measured. The primiparae were at least 6 months post pregnancy. The ratio of the estriol concentration to the sum of the concentrations of estrone and estradiol (the estriol ratio) was higher among primiparous women under 25 years of age than among nulliparous women of the same age. The difference was greater in specimens collected in the luteal phase of the menstrual cycle than in those collected in the follicular phase and was statistically significant (P less than 0.05, one-tailed t-test) only in the luteal phase. The high estriol ratios of the primiparous women did not decline with increasing interval after pregnancy, at least up to 24 months. Among the younger women, significantly lower levels of pregnanediol, suggestive of a higher frequency of anovular menstrual cycles, were also seen in the nulliparous women. The findings were consistent with the hypothesis that the protective effect against breast cancer of a full-term pregnancy at an early age operates either through a change in the pattern of estrogen metabolism induced by the pregnancy or through a change in the frequency of ovular cycles.

Adolescent↗
PubMed1982

A comparison of qualitative and quantitative evaluation of cardiotocogram in the monitoring of high-risk pregnancy.

85 high risk pregnant women were evaluated by RIA of total estriol, unconjugated estriol and HPL by ultrasonic measurement of foetal BPD and by NST and Fischer's score. In all, 277 evaluations were made. The Authors found a good correlation between results of the cardiotocographic tests and levels of HPL and measurements of foetal BPD. A low correlation was noticed between the levels of total and unconjugated estriol and the characteristics of cardiotocography. The evaluation of the cardiotocographic tests, according to Lee and Coll., resulted better than according to Fischer's score. The contemporary qualitative and quantitative evaluation of the cardiotocograms seems to reduce significantly the false-positive results and to half the false-negative results of the other tests for foeto-placental function. Result were analysed.

Estradiol↗