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PubMed1999

The inhibition of low density lipoprotein oxidation by 17-alpha estradiol.

The inhibition of LDL-oxidation by 17-alpha estradiol was assessed in vitro by the determination of the duration of the lag-phase in copper ion-induced oxidation and compared to that of 17-beta estradiol, estriol, and probucol. Addition of 0.2, 0.4, and 1 micromol/l of the test substances prolonged the lag-phase of LDL-oxidation 1.3-(+/-0.09 SD), 1.7-(+/-0.14 SD), and 2.7-(+/-0.25 SD) fold for 17-alpha estradiol; 1.4-(+/-0.14 SD), 1.8-(+/-0.1 SD), and 2.6-(+/-0.16 SD) fold for 17-beta estradiol; 1.1-(+/-0.07 SD), 1.4-(+/-0.11 SD), and 1.6-(+/-0.11 SD) fold for estriol as well as 1.4-(+/-0.14 SD), 1.6-(+/-0.1 SD), and 3.0-(+/-0.21) fold for probucol, thus proving that 17-alpha estradiol is as effective as 17-beta estradiol or similar to probucol and more effective than estriol (n = 6 in all cases). These data demonstrate that 17-alpha estradiol is able to delay LDL-oxidation, hence providing a basis for clinical examination of the protective effects of 17-alpha estradiol against atherosclerosis in patients where hormonal effects of 17-beta estradiol are undesirable.

Antioxidants↗
PubMed1984

The effect of phenobarbital on serum hormone levels and their diurnal variations in pregnancy.

The effect of phenobarbital (PB) on serum hormones in late pregnancy was investigated. 18 pregnant women were studied before and after 2 weeks of PB treatment (100 mg per os, daily at 8 p.m.) by measuring serum estradiol, estriol, progesterone, testosterone, prolactin and cortisol concentrations. 7 pregnant women without PB therapy served as controls. Estradiol levels in the morning decreased, whereas those of estriol increased both in the morning and evening during PB treatment. The estriol/estradiol ratio increased in women on PB. PB affected the diurnal variation of hormones; the decrease in estradiol concentration between 8 a.m. and 8 p.m. was eliminated and the decrease in estriol concentration became more clear. PB did not significantly affect the serum levels of the other hormones investigated. As an enzyme-inducer PB may affect the fate of sex hormones.

Adolescent↗
PubMed1996

Prenatal diagnosis of congenital adrenal hypoplasia.

Congenital adrenal hypoplasia is a rare disorder and one of the possible causes of low maternal plasma and/or urine estriol during pregnancy. We studied 2 cases pre- and postnatally. Dehydroepiandrosteronesulfate (DHAS) and estriol (E3) studied longitudinally in maternal plasma were at or below the lower limit of the normal range. Prior to substitution treatment, an ACTH test revealed low plasma levels of aldosterone, cortisol and all their precursors, with no rise after ACTH. ACTH plasma levels were elevated. It is possible to detect congenital adrenal hypoplasia prenatally in families at risk by repeated measurements of DHAS and estriol in maternal plasma during pregnancy.

Adrenal Insufficiency↗
PubMed1984

Effects of an antiestrogen on subfractions of HDL cholesterol during estrogen replacement therapy.

The antiestrogenic effects of tamoxifen and estriol were compared in 39 postmenopausal women during estrogen replacement therapy. Subfractions of HDL cholesterol and its apolipoproteins and the serum levels of two estrogen sensitive liver proteins were followed during three cycles of unopposed estrogen therapy with 10 micrograms ethinyl estradiol daily. During the last 10 days of the following three cycles the women received sequential addition of either 10 mg tamoxifen twice daily or 2 mg estriol twice daily. Tamoxifen clearly reduced the estrogen-induced increase of apolipoprotein AI, HDL2 cholesterol and total HDL cholesterol. In comparison the pregnancy zone protein and sex hormone-binding globulin were more sensitive to the estrogenic as well as to the antiestrogenic effect than the lipoproteins. Tamoxifen also counteracted the therapeutic effect on climacteric symptoms and it seems unlikely that this compound may be clinically useful as an alternative to progestogens during estrogen replacement therapy. The sequential addition of estriol had no apparent effects as compared to unopposed estrogen treatment.

Adult↗
PubMed1977

Vasodilating effect of estrogen on the human umbilical artery.

The effects of estradiol, estrone and estriol on the tonus of the isolated vascular segments of human umbilical artery were studied by a perfusion technique. Estradiol (10 microgram/ml), estrone (10 microgram/ml) or estriol (2 and 10 microgram/ml) produce relaxation of the vascular bed which was reflected in a significant reduction in basal pressure of segments perfused at constant rate. A dose-dependent relationship was demonstrated for estriol. The time dependence and extent of relation were similar for all three natural estrogens.

Dose-Response Relationship, Drug↗
PubMed1974

Effect of maternal intrahepatic cholestasis on fetal steroid metabolism.

Estriol, estriol sulfate, progesterone, and 17 neutral steroid sulfates, including estriol precursors and progesterone metabolites, were determined in 27 cord plasma samples collected after pregnancies complicated by intrahepatic cholestasis of the mother. The levels of these steroids were compared with those in the cord plasma of 42 healthy controls. In the cord plasma, the steroid profile after pregnancies complicated by maternal intrahepatic cholestasis differed greatly from that seen after uncomplicated pregnancy. Two main differences were found. In the disulfate fraction, the concentrations of two pregnanediol isomers, 5alpha-pregnane-3alpha,20alpha-diol and 5beta-pregnane-3alpha,20alpha-diol, were high after cholestasis. Other investigators have shown that, as a result of cholestasis, these pregnanediol sulfates circulate in greatly elevated amounts in the maternal plasma. Our results indicate that in cholestasis these steroids cross the placenta into the fetal compartment, where they circulate in elevated amounts as disulfates. Secondly, the concentrations of several steroid sulfates known to be synthesized by the fetus were significantly lower in the cholestasis group than in the healthy controls. This was especially true of 16alpha-hydroxydehydroepiandrosterone sulfate and 16alpha-hydroxypregnenolone sulfate. These results suggest that, in pregnancies complicated by maternal intrahepatic cholestasis, impairment of fetal steroid synthesis, and especially of 16alpha-hydroxylation, occurs in the fetal compartment.Thus, the changes in maternal steroid metabolism caused by cholestasis are reflected in the steroid profile of the fetoplacental circulation. Furthermore, maternal intrahepatic cholestasis may result in the production of some substance which crosses the placenta and affects fetal steroid metabolism.

17-alpha-Hydroxypregnenolone↗
PubMed1975

Metabolism of estradiol in greyhounds and German shepherd dogs. An investigation with special reference to hip dysplasia.

Metabolism of estradiol was investigated in 5 dogs, 3 female Greyhounds with radiographically perfect hip joints and 2 female German Shepherd dogs with hip dysplasia (one pregnant and the other non-pregnant). One of the Greyhounds was studied both when pregnant and non-pregnant. The non-pregnant dogs were injected with C14-labelled estradiol-17beta i.v. and 5 mg estradiol-17beta benzoate i.m. The pregnant dogs were given only radiolabelled estradiol-17beta. Twenty-four-hour-specimens of urine were collected from the dogs for 6--8 days. Determination of urinary estrone, estradiol-17beta, and estriol was made. It was found that most of the injected estradiol was excreted unmetabolized in all dogs. A significant amount of the injected estradiol was converted to estrone and a small amount to estriol. There was no significant difference in the excretion patterns of estrone, estradiol, and estriol between the Greyhounds with perfect hip joints and the German Shepherds with hip dysplasia, regardless whether the dogs were pregnant or not. The conclusion was drawn that the capacity of dogs with hip dysplasia to metabolize estradiol and to eliminate estradiol and metabolites is not impaired.

Animals↗
PubMedDate not supplied

Low serum estradiol and high serum progesterone concentrations characterize hypertensive pregnancies at high altitude.

OBJECTIVE: Intrauterine growth retardation and preeclampsia are more common at high than at low altitude. Because altered hormonal profiles have been linked with these disorders, we asked whether placental steroid hormone concentrations were altered during pregnancy at high altitude. METHODS: We measured progesterone, unconjugated estradiol, and estriol (by radioimmunoassay) at weeks 20, 30, and 36 of pregnancy in 18 women at low altitude (1600 m) and 40 women at high altitude (3100 m). RESULTS: Women at 3100 m compared with 1600 m had lower serum estradiol concentrations at week 36 of pregnancy, and lower estriol and higher progesterone concentrations throughout pregnancy. As a result, the progesterone/estradiol ratio was greater in the high- versus the low-altitude women. Estradiol fell between weeks 30 and 36 in women who developed transient hypertension or preeclampsia. The fall in estradiol was accompanied by a marked increase in progesterone concentrations among the preeclamptic women. At 3100 m, estradiol correlated negatively (r = -0.37, P < .05) and progesterone positively (r = 0.46, P < .05) with mean arterial pressure at week 36 of pregnancy. CONCLUSIONS: We speculate that reduced placental oxygen pressure (PO2) at high altitude may decrease placental aromatase activity and thereby lower estradiol and estriol concentrations. The factor(s) responsible for the rise in progesterone is unknown. Possibly, high progesterone relative to estradiol concentrations contributes to the development of preeclampsia at high altitude.

Adult↗
PubMed1977

Direction of estradiol metabolism as a control of its hormonal action--uterotrophic activity of estradiol metabolites.

The uterotrophic activities of the catechol metabolites of estradiol 2-hydroxyestrone, 2-methoxyestrone and 2-hydroxyestradiol were measured under conditions of continuous administration of sc implanted paraffin pellets. The activity of these estrogens was compared to that of estradiol-17beta and its other principal metabolites estrone, estriol and 15alpha-hydroxyestriol (estetrol). The major catechol estrogens, 2-hydroxyestrone and 2-methoxyestrone, and the pregnancy metabolite, 15alpha-hydroxyestriol, exhibited no uterotrophic activity. The minor catecholestrogen, 2-hydroxyestradiol, showed some activity whose character was different from that exhibited by implants of estradiol, estrone and estriol all of which were equipotent uterotrophic agents. Implants of 2-hydroxyestrone in the presence of estradiol or estriol pellets did not diminish the response to the latter indicating that the 2-hydroxyestrone is not antiestrogenic under these conditions. It is concluded that the direction of estradiol metabolism can have a profound influence on the expression of peripheral hormonal activity with hydroxylation at C-2 terminating and hydroxylation at C-16 extending it.

Animals↗
PubMed1978

Evidence for a discontinuous requirement for estrogen in stimulation of deoxyribonucleic acid synthesis in the immature rat uterus.

Estriol is rapidly lost from uterine target cell nuclei. Therefore, it has been used to study the relative time of exposure to estrogen that is necessary to elicit the late growth responses of increased DNA polymerase activity or increased rate of DNA synthesis observed after 17beta-estradiol treatment. Estriol administered during a second critical phase from 9-15 h after the initial injection elicits maximal DNA synthesis. Our results suggest that there is a discontinuous requirement for estrogen in the sequence of events which result in the uterine growth response to estrogenic hormones. If estriol is present during critical phases of this sequence of events, it is equipotent to estradiol in eliciting the full uterotropic response.

Animals↗
PubMed1976

Ultrasound and biochemical findings in intrauterine growth retardation.

An attempt was made to make an early diagnosis of intrauterine growth retardation due to chronic placental insufficiency using ultrasound cephalometry and biochemical tests of placental function. We examined 83 hospitalised patients in whom there was a risk or suspicion of chronic placental insufficiency. For each patient an average of 4 determinations were made of head diameter, 10 of estriol and 3 of pregnandiol urinary excretion, 6 serum HPL and 7 of heat stable alkaline phosphatase (HSAP). Fetal growth retardation was assumed if the last 2 determined head diameters were below the normal curve with the same tendency and with term being well predicted. Biochemical parameters were considered to indicate pathological changes if they were 95% below normal values, with 2 below this range or 3 continuously falling below the normal level. Infants were assessed after birth both neurologically and somatically according to DUBOWITZ. Small for date infants were those whose birth weight was below the 10th percentile (LUBCHENKO). This was found to be the case in 15 out of 83 newborns five of whom were younger than 37 weeks. These 15 could be diagnosed before birth with various degrees of certainty. For estriol and HPL this was 67% or 53% and these two parameters were found to be the most valuable. Cephalometry was found to be less valuable with 20%, pregnandiol levels with 9% and placental HSAP with 33%. Hence it is recommended to perform serial determinations of estriol and HPL in the third trimester of pregnancy in all patients with histories indicative of fetal growth retardation and in those in whom the uterus appears small for date.

Alkaline Phosphatase↗
PubMed1983

Evaluation of placental function in women on antiepileptic drugs.

Placental function in the presence of antiepileptic drugs was assessed in 144 unselected late pregnancies of women with epilepsy. The most common drugs of the mothers were phenytoin (104 pregnancies), carbamazepine (42) and phenobarbitone (26). 144 control parturients matched for maternal age, parity, fetal sex and social class were also studied. No significant associations between the types or the serum concentrations of the mother's antiepileptic drugs and her serum HPL, 24-hour total urinary estriol excretion, placental weight or her child's birth weight were observed. However, since the serum levels of antiepileptic drugs were usually within or below the therapeutic ranges the study does not exclude the possibility that very high drug concentrations might have some effects. The incidences of common pregnancy complications did not differ between epileptics and controls. Serum HPL and urinary estriol values in epileptic women agreed well with the references for normal. It is concluded that the long-term use of antiepileptic drugs during pregnancy has no clinically important effects on placental function or on its biochemical tests in spite of the enzyme induction properties of these drugs. Values of serum HPL and 24-hour total urinary estriol excretion can thus be interpreted in the usual manner in women who are on antiepileptic medication.

Adult↗
PubMed1979

Measurement of estrogens in cow's milk, human milk, and dairy products.

Free natural estrogens in raw and commercial whole milk were quantitated by radioimmunoassay. The ranges of concentration of estrone, estradiol 17-beta, and estriol were 34 to 55, 4 to 14, and 9 to 31 pg/ml. Proportions of active estrogens (estrone and estradiol) in the fat phases of milk by radioactive tracer on separated milk were 80% and 65%. These findings were supported by radioimmunoassay of skim milk and butter. Equilibrium dialysis of skim milk with hydrogen 3 labeled estrogens showed that 84 to 85% of estrone and estradiol and 61 to 66% of estriol were protein bound. Whey proteins demonstrated a greater binding capacity than casein. This result was confirmed by radioimmunoassay of dry curd cottage cheese and whey. The concentrations in curd were 35, 11, and 6 pg/g. In whey they were 4, 2, and 3 pg/ml. The quantity of active estrogens in dairy products is too low to demonstrate biological activity. Butter was highest with concentrations of 539, 82, and 87 pg/g. Human colostrum demonstrated a maximum concentration of 4 to 5 ng/ml for estrone and estriol and about .5 ng/ml for estradiol. By the 5th day postpartum, they decreased to become similar to cow's milk.

Animals↗
PubMed1999

Reproducibility and validity of radioimmunoassays for urinary hormones and metabolites in pre- and postmenopausal women.

The reproducibility of RIAs of circulating sex hormones has been evaluated as part of recent epidemiological investigations, but none seem to have addressed the reproducibility or validity of RIAs for urinary hormones or their metabolites. As part of a case-control study of breast cancer in Asian-American women, 12-h overnight urine samples were obtained, and a methodological study was conducted to identify laboratories capable of assaying urinary hormones. For the reproducibility component of this study, two laboratories with extensive experience in hormone assays measured urinary estrone, estradiol, estriol, pregnanediol glucuronide, and estrone glucuronide using samples from 15 women (5 midfollicular, 5 midluteal, and 5 postmenopausal). Variance estimates from these measurements were used to calculate the laboratory variability (coefficient of variation) and to assess the magnitude of the biological variability among the women in relation to the total variability (intraclass correlation coefficient). For the validity component, urinary estrone, estradiol, and estriol levels were measured in the same samples by gas chromatography-mass spectroscopy in the laboratory of Dr. Herman Adlercreutz (University of Helsinki, Helsinki, Finland). We found that the degree of assay reproducibility differed between the laboratories, but that laboratory variability was usually low compared with the range of hormone values among women, particularly for the estrogens. Values for estrone and estradiol were well correlated among all of the laboratories. For estriol, the RIAs tended to overestimate levels compared with gas chromatography-mass spectroscopy. In one laboratory, assays for pregnanediol glucuronide and estrone glucuronide were consistently reproduced; in the other, the reproducibility of the RIA for pregnanediol glucuronide was problematic, and estrone glucuronide was not measured. Despite some limitations, urinary hormones and their metabolites can be reliably measured by current RIAs in large investigations attempting to link hormone level to disease risk and may be particularly advantageous for studies of postmenopausal women, where serum concentrations of estrone and estradiol are low and assay measurements are not as dependable.

Adult↗
PubMed2000

[Relationship between endothelial function and female hormone level in very old females: evaluation from ischemic reactive hyperemic response in forearm vessels].

Recently, the mechanism of longevity in females was proposed to be associated with female hormones. This study examined the effect of aging and sex on vascular endothelial function, and the relationship between female hormone level and endothelial function by ischemic reactive hyperemic response in the forearm using plethysmography. The study population consisted of 246 healthy subjects aged from 20 to 76 years (119 males, 127 females) and 20 healthy females aged 85 years and older (85 to 103 years; mean age 94 years) without distinct cardiovascular disease, hypertension, diabetes mellitus, renal disease, liver dysfunction or anemia. Levels of the female hormones, estradiol and estriol, were measured in females aged more than 85 years. The duration of reactive hyperemia decreased with aging, but the difference between males and females was not significant at any age. In females, the duration was markedly decreased from 110 +/- 36 sec in the fifties to 81 +/- 29 sec in the sixties or older (p < 0.05). Excess flow also showed similar changes to the duration of reactive hyperemia. The duration of reactive hyperemia and excess flow in females aged 85 years and older were similar to those in the fifties, but was significantly longer than those in females 60 years or older. The concentrations of estradiol (44.9 +/- 27.1 pg/ml) and estriol (22.1 +/- 13.4 pg/ml) in females aged 85 years were higher than in the sixties. There was a positive correlation between the duration of reactive hyperemia and the concentration of estradiol (r = 0.56, p < 0.01) or estriol (r = 0.57, p < 0.01). In summary, vascular endothelial function was impaired gradually with aging, but preservation of the function in healthy, very old females was closely associated with levels of female hormone.

Adult↗
PubMed2001

Hormone replacement therapy plus pelvic floor muscle exercise for postmenopausal stress incontinence. A randomized, controlled trial.

OBJECTIVE: To investigate the effects of the combination of pelvic floor muscle exercise (PFME) and estriol on postmenopausal stress incontinence (SI). STUDY DESIGN: Sixty-six patients with postmenopausal SI were randomized to a group treated with a combination of estriol (1 mg/d) and PFME (group A, n = 32) and a group treated with PFME alone (group B, n = 34). Efficacy was evaluated every three months based on stress scores obtained from a urinary incontinence (UI) questionnaire. RESULTS: A significant decrease in stress score was observed in mild and moderate UI patients in both groups three months after the commencement of therapy (A and B, P < .0001). The therapeutic effect in group A was more prominent for up to 18 months in mild UI and for up to 12 months in moderate UI (A vs. B, P < .05). Kaplan-Meier analysis showed that the cumulative morbidity rate in mild SI patients was significantly lower in group A (0%) than in group B (12%, P < .005). CONCLUSION: Combination therapy with estriol plus PFME was effective and is capable of serving as first-line treatment for mild SI.

Combined Modality Therapy↗
PubMed1976

Initiation of labor by intraamniotic cortisol instillation in prolonged human pregnancy.

The fetal adrenal cortex has recently been implicated in the etiology of postmaturity on the basis of low cortisol levels found in the plasma of postmature neonates. These findings suggested that labor could be initiated in prolonged pregnancy by iatrogenic elevation of fetal plasma cortisol. In the current investigation designed to test this hypothesis, 500 mg of hydrocortisone sodium succinate, dissolved in the accompanying diluent of bacteriostatic water to form 4 ml of solution, was injected intraamniotically in 10 patients with unfavorable cervices who were 12 or more days past their expected date of confinement. Nine similar patients serving as controls received 4 ml of bacteriostatic water intraamniotically. All patients were followed with daily determinations of urinary estriol. Eight of the 10 patients who received cortisol went into labor within 120 hours of instillation, as compared with 2 of the 9 patients in the control group. Comparison of the two groups revealed a significant difference (p less than 0.01). The mean instillation-labor time for the cortisol group was 86 hours compared with 228 hours in the control group. This difference was also significant (p less than 0.001). Urinary estriol excretion declined sequentially following cortisol but not after infusion of water. These findings are consistent with the hypotheses that a) spontaneous labor in the human may be preceded by a sudden rise in fetal plasma cortisol, as in the sheep; b) the fetal pituitary-hypothalamic axis is responsive to cortisol, hence the falling estriol excretion; and c) ACTH may be the tropic hormone for the provisional zone of the fetal adrenal cortex.

Adolescent↗
PubMed1977

Hydrolysis of steroid glucuronides with beta-glucuronidase preparations from bovine liver, Helix pomatia, and E. coli.

We determined the enzymic activity of beta-glucuronidase preparations from bovine liver, Helix pomatia, and Escherischia coli with steroid glucuronides and nonsteroid glucuronides as substrates. We also studied the effect of Na2SO4 on the enzymic hydrolysis of several substrates with the three preparations of beta-glucuronidase. Na2SO4 increases the rate of hydrolysis of all substrates with beta-glucuronidase from bovine liver. Hydrolysis of a steroid glucoronide with beta-glucuronidase from Helix pomatia and E. coli is inhibited by Na2SO4. None of the three enzyme preparations gives complete hydrolysis of urinary steroid conjugates, because urine contains inhibitors, which can be removed by absorption chromatography of the urine on a column of neutral polystyrene resin Amberlite XAD-2. But when Amberlite XAD-2 is not used, hydrolysis of urinary glucuronides of androsterone, etiocholanolone, pregnanediol, estriol, and 17-hydroxycorticosteroids proves that, given an incubation time of 24 h, the beta-glucuronidase preparation from bovine liver, in the presence of Na2SO4, is suited for determining all of the above steroids except esriol; the preparation from Helix pomatia is good for determining estriol and 17-hydroxycorticosteroids; the preparation from E. coli is good for determining androsterone, 17-hydroxycorticosteroids, and especially estriol, the glucuronide, of which is maximally hydrolyzed in 2 h.

17-Hydroxycorticosteroids↗