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PubMed2001

Short term oral estriol treatment restores normal premenopausal vaginal flora to elderly women.

OBJECTIVE: Estriol is an estrogen with considerably weaker stimulatory effects on endometrial proliferation than estradiol. A study was conducted to determine the effects of oral estriol on vaginal flora and endometrial thickness. METHODS: Fifty-nine postmenopausal women (50-75 years of age), complaining of pruritus or vaginal discharge, participated in the study. Vaginal flora and endometrial thickness were evaluated before treatment and after receiving oral estriol (2 mg/day) for 14 days. RESULTS: Prior to treatment, lactobacilli were found in vaginal cultures from only six of the 59 study participants, whereas after treatment, the vaginal flora of 27 women showed a presence of lactobacilli (P<0.0001). Endometrial thickness exceeded 5 mm in only five cases. No side effects were reported. CONCLUSION: Estriol, which has little effect on the endometrium, has the potential to be highly useful for the treatment of atrophic vaginitis.

Administration, Oral↗

PubMed1992

Determination of trace amounts of estriol and estradiol by adsorptive cathodic stripping voltammetry.

Estriol and estradiol are electroinactive in the potential range from -200 to -1000 mV versus a silver-silver chloride electrode at a mercury electrode. The conversion of these estrogens into electroactive nitro derivatives of estrogens, which are used for voltammetric determination, was studied. Such nitro derivatives give a well defined cathodic stripping wave at -600 mV in pH 10.5 borate buffer. Estriol and estradiol are determined in the ranges 1 x 10(-9)-1.5 x 10(-6) and 5 x 10(-9)-2 x 10(-6) mol dm-3, respectively, by differential-pulse adsorptive stripping voltammetry at a hanging mercury drop electrode. Some steroids, such as estrone, interfere because the three estrogens have almost the same molecular structure and have similar nitro derivatives, but progesterone does not interfere and is reduced at significantly more negative potentials than the nitrated estrogens. It can be determined simultaneously with estriol or estradiol. A method was developed for the assay of estriol in pharmaceutical preparations.

Adsorption↗

PubMed1987

Results of a 5 years prospective study of estriol succinate treatment in patients with climacteric complaints.

In a prospective study 911 patients were treated over a period of 5 years (M = 2.2) or a total of 2007 treatment years with estriol succinate oral (Synapause, 2-12 mg per day). The treatment was very effective in the removal of all typical climacteric complaints and of the atrophic genital changes caused by estrogen deficiency. Subjective side effects were seldom seen and without practical importance for the treatment. Objective, grave side effects were only few: one superficial phlebo-thrombosis, 2 cases of thrombophlebitis, one carcinoma in situ of the portio vaginalis uteri and 2 mammary cancers were seen. The carcinoma had probably no causal relationship to the treatment. Embolies, myocardial infarctions, cerebrovascular and liver-gall bladder complications did not occur during treatment. The rate of uterine bleedings was low. The incidence of all complications was not increased by estriol succinate; but was even lower than expected. Endometrial and ovarian cancers were not seen. Estriol succinate is accordingly a very effective and well tolerated preparation against climacteric complaints, exerting no significant side effects. It is remarkable that it does not proliferate the endometrium when given in one dose a day. Estriol succinate can therefore be characterized as the estrogen to be favoured for the treatment of postclimacteric women, who do not want to have uterine bleedings any longer.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

PubMed2001

Plasma progesterone, dehydroepiandrosterone sulfate and estriol levels during labor induction with a sustained-release prostaglandin E2 vaginal insert.

OBJECTIVE: To measure plasma progesterone, dehydroepiandrosterone sulfate (DHEAS) and estriol levels in women induced for labor with a sustained-release vaginal polymer prostaglandin E2 insert, and to analyze the relationships between the changes in hormone levels and Bishop score. METHODS: Twelve primipara and 12 multipara were treated with a sustained-release polymer vaginal prostaglandin E2 insert (0.3 mg/h) for up to 24 h. The Bishop score was assessed at the start and end of therapy, and serum samples were collected at 4-h intervals. Plasma levels of progesterone, DHEAS and estriol were measured by specific radioimmunoassays. RESULTS: Exposure averaged 13.5 +/- 7.2 h. Progesterone levels decreased in the majority of patients (79.2%) after the start of therapy. Higher baseline DHEAS and estriol levels were observed among women who achieved an improvement in Bishop score of at least 4 during prostaglandin E2 treatment. CONCLUSIONS: Higher DHEAS and estriol levels prior to labor induction with prostaglandin E2 may be indicators of a favorable labor outcome. Additional studies are needed to substantiate the decrease in progesterone levels observed in this study and the importance of this phenomenon for the mechanism of labor induction with prostaglandin E2.

Administration, Intravaginal↗

PubMed2003

The correlations between estradiol, estrone, estriol, progesterone, and sex hormone-binding globulin and anterior cruciate ligament stiffness in healthy, active females.

BACKGROUND: Injury to the anterior cruciate ligament (ACL) often requires surgery and extensive rehabilitation. Women who participate in collegiate sports and military drills are more likely to injure their ACL than are men participating in similar activities. The influence of the normal fluctuation of sex hormones on the physical properties of the ACL is one potential cause for this disparity. The purpose of this study was to report the correlation between estradiol, estrone, estriol, progesterone, and sex hormone binding globulin (SHBG) and ACL stiffness during three phases of the menstrual cycle in normally cycling, healthy females. METHODS: We tested ACL stiffness and collected blood from 20 female subjects who were not using oral contraception during three phases of their menstrual cycle. Ligament stiffness was tested with the KT-2000 trade mark knee arthrometer (MEDmetric, San Diego, CA). Concentrations of estradiol and SHBG were assessed via radioimmunoassay (RIA). Progesterone, estriol, and estrone concentrations were determined via enzyme-linked immunoassay. RESULTS: Spearman rank correlation analysis indicated a significant correlation between estradiol concentration and ACL stiffness (-0.70, p < 0.001) and estrone concentration and ACL stiffness near ovulation (0.46, p = 0.040). With the effects of the other variables controlled, there was a significant partial correlation between estradiol (-0.80, p < 0.001), estriol (0.70, p = 0.003), and progesterone (0.66, p = 0.005) and ACL stiffness near ovulation. CONCLUSIONS: Our results indicate that there is a significant correlation between estradiol, estriol, and progesterone and ACL stiffness suggesting that fluctuating levels of sex hormones may influence the stiffness of the ACL near ovulation. Future studies that examine the relationship between sex hormones and the physical properties of the ACL should be focused near the ovulation phase of the menstrual cycle.

Adult↗

PubMed1989

Application of inclusion chromatography to the determination of in vitro metabolites of estriol.

The application of inclusion chromatography with beta-cyclodextrin as a mobile phase additive in high-performance liquid chromatography to the determination of in vitro metabolites of estriol is reported. Compared to conventional methods, the inclusion chromatography gives much more satisfactory separation of isomeric estriol derivatives in a short time. Species difference (rat and guinea pig liver homogenates) is observed in the glucuronidation of estriol. The hydroxylation of estriol with rat liver homogenate occurs preferentially at the 2-position. Methylation of this product with catechol-O-methyl transferase in rat liver gives almost equal amounts of 2- and 3-methyl ethers. In contrast, 4-hydroxyestriol gives 4-methyl ether as a main product.

Animals↗

PubMed1978

Short-term variations in urinary estriol and renal function. Possible effects of extraneous conditions.

Variation in urinary excretion of estriol was found to be related to physical activity and climate conditions. Estriol content of sweat was studied but was found not to be of an order to explain the variation observed. Estriol clearance rate was significantly reduced even by moderate physical activity. Creatinine clearance was not affected to the same extent. Different explanations to the findings are discussed. The need for strictly standardized conditions during urine sampling for estriol assays in risk pregnancies is stressed.

Activity Cycles↗

PubMed1967

The effects of estradiol and estriol on plasma levels of cortisol and thyroid hormone-binding globulins and on aldosterone and cortisol secretion rates in man.

The effects of estriol and estradiol on the plasma levels of cortisol- and thyroxine-binding globulin activity, and on the secretion rates of aldosterone and cortisol were studied in man. The metabolite estriol had no consistent or significant influence on plasma levels of the hormone-binding globulin activities; the hormone estradiol increased these binding capacities significantly, as expected. Cortisol secretion rate rose slightly after estriol but was unchanged after estradiol. Both compounds induced substantial increases in the aldosterone secretion rate of most treated subjects. The mechanism of this apparently paradoxical effect of estrogens is not clear; it is suggested that the "salt-retaining" action of estrogens is mediated in part by the rapid enhancement of aldosterone output which follows their administration in man. Balance experiments in four subjects suggest that both estradiol and estriol may induce a transient early natriuresis in man; but other mechanisms for estrogen stimulation of aldosterone secretion may be operative as well.

Aldosterone↗

PubMed1969

Studies on phenolic steroids in human subjects. IX. Role of the intestine in the conjugation of estriol.

In order to compare the enteric circulation of estriol-16alpha-glucosiduronate (see preceding paper) with that of estriol (E(3)), labeled estriol was administered to six women by several routes: both injection and infusion (300 min) into the cubital vein, injection into the portal vein system, ingestion and instillation into the jejunum and ileum. Urine, collected from 0-2, 2-4, 4-8, 8-12, and 12-24 hr, was analyzed by countercurrent distribution for its content of radioactive 3- and 16-glucosiduronate (E(3)-3Gl,E(3)-16Gl) and sulfoglucosiduronate (E(3)-3S,16Gl) of estriol. After peripheral injection of E(3), E(3)-16Gl was excreted rapidly and E(3)-3S,16Gl at a slower and more constant rate. E(3)-3Gl was barely detectable after infusion. After injection of E(3) into the portal vein, the excretion of E(3)-3S,16Gl was greater and quicker than after peripheral injection. Even in a subject with a complete bile fistula, the urinary excretion of E(3)-3S,16Gl was essentially unchanged. Ingestion also produced the same result. Only after instillation into the ileum was a large and rapid excretion of E(3)-3Gl obtained, whereas the excretion of E(3)-3S,16Gl, and E(3)-16Gl were depressed. These results together with those of the preceding paper suggest that E(3) does not readily appear in the small intestine except via a hepatoenteric circulation that produces very little E(3)-3Gl. When present in the distal segment of the small intestine, however, absorption, conjugation, and elimination proceed readily.

Biliary Fistula↗

PubMed1984

Changes in placental lactogen, beta 1-chorionic gonadotropin, and unconjugated and total estriol levels in the late course of normal human pregnancy.

The levels of human placental lactogen (hPL), beta-human chorionic gonadotropin (beta-hCG), unconjugated estriol (UE3) and total estriol (TE3) were measured radioimmunologically in women along their course of pregnancy. The serum hPL and beta-hCG levels were relatively constant in uncomplicated pregnancy, while UE3 and TE3 significantly rose towards 41 weeks of gestation. There were positive correlations between hPL and beta-hCG (n = 49, r = 0.737, p less than 0.001), and between UE3 and TE3 (n = 49, r = 0.904, p less than 0.0001). The ratios of placental hormones to estriol showed moderate declines towards 41 weeks of gestation. These data suggest that the fetal adrenal function increased toward the term, while the placental peptide hormones decrease or remain unchanged. Determination of serum unconjugated estriol was found to be convenient and useful for monitoring the fetoplacental function.

Chorionic Gonadotropin↗

PubMedDate not supplied

Urinary estriols: are they of value in normoglycemic diabetic pregnancy?

The purpose of the study was to assess the value of 24-h urinary estriols in the management of diabetic pregnancies. Twenty-seven pregnant diabetic patients (White's class B through R) received insulin dosages twice daily as a combination of NPH and regular insulin. Laboratory and home monitored blood glucose was maintained within the range of 70-150 mg/dl. From 32 wk onward daily 24-h urinary estriols, weekly fetal heart rate monitoring, and, when indicated, amniotic fluid lecithin/sphingomyelin ratio were used to evaluate fetal well-being. Fetal heart rate and amniotic fluid testing were of value while urinary estriols failed to be useful in management or timing of delivery. We conclude that when third-trimester normoglycemia is maintained in pregnant diabetic patients, one obviates the need for the costly and odious task of daily urine estriol measurements.

Cesarean Section↗

PubMed1986

Sub-hourly variations in salivary estriol concentrations in the last trimester of pregnancy.

Sub-hourly variations in salivary estriol were measured in women in the last trimester of pregnancy. The mean and variation of salivary estriol concentrations in specimens collected at 5-min intervals for 30 min were greater on awakening in the morning (when subjects were recumbent and fasting) than in the afternoon. The differences in variation between morning and afternoon serial specimens were eliminated by the omission of the first two specimens collected in the morning. Significant differences between the mean concentrations obtained for morning and afternoon specimens were minimized by use of a recumbent posture for the afternoon specimen collection. The mean estriol concentration of four saliva samples collected at 5-min intervals for 15 min did not differ significantly from the concentration of saliva collected continuously over the subsequent 15 min. For routine estriol monitoring, therefore, samples should be collected over a 15-min period. This ought to be carried out at the same time of day, in the same posture on each occasion, but preferably not in the early morning.

Circadian Rhythm↗

PubMed1999

Estriol add-back therapy in the long-acting gonadotropin-releasing hormone agonist treatment of uterine leiomyomata.

The hypoestrogenic state induced by gonadotropin-releasing hormone agonists (GnRHa) has been shown to be effective in the treatment of uterine leiomyomas but to induce bone loss. Estriol has been described to be a weak and short-acting estrogen without an increased risk of endometrial proliferation and hyperplasia. The purpose of this study was to evaluate whether treatment of uterine leiomyomata with GnRHa plus oral estriol add-back therapy could prevent bone loss, without deteriorating the therapeutic effect of GnRHa. Twelve premenopausal women with symptomatic uterine leiomyomas were randomized to receive either leuprolide acetate depot alone at a dose of 3.75 mg s.c. every month for 6 months (non add-back group; n = 6), or GnRHa for 6 months plus oral estriol 4 mg/day for 4 months commencing with the third GnRHa injection (add-back group; n = 6). In the add-back group, leiomyoma volume, as measured by transvaginal ultrasound, decreased to 59.1% of baseline at 2 months of GnRHa therapy with no significant change in size during the remaining treatment period. In contrast, it decreased to 31.3% of pretreatment size at the end of treatment in the non add-back group. The levels of bone metabolic markers such as CrossLaps, deoxypyridinoline, osteocalcin and bone-specific alkaline phosphatase, increased significantly throughout the treatment in the non add-back group, whereas they were suppressed by the add-back therapy. The bone mineral density of lumbar spine (L2-L4) as measured by dual-energy X-ray absorptiometry decreased significantly by 7.5% at the end of treatment in the non add-back group, but did not change significantly in the add-back group. In conclusion, GnRHa plus estriol add-back therapy might be considered for long-term treatment of uterine leiomyomata.

Absorptiometry, Photon↗

PubMed2001

Estrogen replacement therapy in postmenopausal women: a study of the efficacy of estriol and changes in plasma gonadotropin levels.

The purpose of this study was to clarify the efficacy of estriol for estrogen replacement therapy in postmenopausal women with undefined symptoms and to evaluate endocrinological changes during therapy in relation to clinical outcome. Administration of 2 mg estriol in 168 postmenopausal patients was markedly effective in 22.6% of cases, effective in 45.2%, fairly effective in 14.3%, and ineffective in 17.9% of cases. The plasma concentration of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) after administration of estriol decreased significantly (p < 0.001), by 52.2% and 32.9%, respectively for markedly effective cases, and by 39.1% and 48.0% for effective cases. In contrast, the plasma estradiol concentration remained unchanged. On the other hand, decreases in FSH and LH concentration were 13.9% and 5.9% for the fairly effective and 8.2% and 1.9% for ineffective cases, demonstrating a significantly lower decrease in plasma FSH and LH levels than in the markedly effective and effective cases (p < 0.001). For cases showing side-effects, the plasma FSH and LH levels decreased by 52.0% and 64.3%, respectively, whereas the plasma estradiol level remained unchanged. In conclusion, the efficacy of estriol was significantly correlated to the degree of decrease in plasma FSH and LH levels in patients with undefined symptoms. In addition, efficacy appeared to be correlated to the incidence of side-effects. The degree of reduction of FSH (39.1-52.2%) and LH (48.0-64.3%) from the baseline may possibly be used as a guide to the therapeutic hormone levels during HRT. The present results suggest that plasma gonadotropin levels could be a useful indicator in the management of patients undergoing estrogen replacement therapy.

Biomarkers↗

PubMed2001

Effects of 17-beta estradiol and estriol on NMDA-induced toxicity and apoptosis in primary cultures of rat cortical neurons.

Estrogens possess neuroprotective and antiapoptotic properties, however, the issue of involvement of estrogen receptors (ER)-dependent genomic pathway in these effects still remains controversial. Moreover, the majority of data on antiapoptotic effects of estrogens concern non-neuronal cells. In the present study we compared effects of the potent ER agonist, estradiol-17beta (E2), and its metabolite with a weak affinity for ER, estriol, on the neurotoxicity induced by high (1 and 5 mM) NMDA concentrations and on the apoptosis induced by low (0.1 mM) concentration of NMDA in rat primary cortical neurons. The obtained data showed that 24-hour exposure of cortical neurons to NMDA (0.1-5 mM) resulted in a dose-dependent increase in LDH level. Twenty four-hour pretreatment with estriol (100 nM and 500 nM) reduced the NMDA (1 and 5 mM)-induced toxicity by 16-26%, while estradiol-17beta (500 nM) reduced NMDA (5 mM)- induced toxicity by 14%. Twenty four hour exposure of cortical neurons to NMDA (0.1 mM) resulted in decrease of the level of antiapoptotic protein - Bcl-2 by 60% and increased the number of apoptotic cells by 50% compared to the control. Twenty four hour pretreatment with estradiol-17beta or estriol (100 and 1000 nM) prevented the NMDA-induced apoptotic changes. The specific estrogen receptor antagonist ICI 182,780 (100 nM) had no effect alone and did not antagonize the effects of estrogens on NMDA-induced toxicity as well as on changes in Bcl-2 level. The higher efficacy of estriol, together with the fact that the specific ER receptor antagonist, ICI 182,780, did not inhibit the above-described effects support the hypothesis about a nongenomic mechanism of the anti-NMDA action of estrogens.

Adrenocorticotropic Hormone↗

PubMed1975

[Experimental investigation of the effects of estriol on menopausal symptoms (author's transl)].

The mechanical writing scales are micromotor method of investigation of psychomotor discoordination capable of producing objective records of menopausal symptoms. With this method, the therapeutic effect of estriol on the menopausal symptoms can be recorded. Changes in the micromotor symptoms such as reduction in the time of writing, a decrease in the unphysiologically high writing pressure and a decrease of in inhibition and relaxation symptoms show clearly that estriol enhances a co-ordination of the motor processes of writing. The positive effects of estriol on the psychomotor co-ordination are demonstrated in the improvement of the menopausal symptoms and the improvement of the vaginal cytology. Uterine bleeding is absent since estriol has a low endometriopic action.

Climacteric↗

PubMed1976

Nonchromatographic radioimmunoassay of unconjugated estriol in plasma, with polyethylene glycol as precipitant.

We describe a rapid, reliable radioimmunoassay for unconjugated estriol in plasma. Polyethylene glycol (Carbowax 6000) is used to separate antibody-bound and free steroid. The assay is sensitive (25 pg for standards), precise, and accurate. At high and low concentrations of estriol, intra-assay coefficients of variation were 7.1% and 7.6%, respectively, and inter-assay coefficients of variation were 7.2% and 10.0 %, respectively. Free [3H] estriol is not precipitated by polyethylene glycol. This radioimmunoassay of estriol, with a highly specific antiserum and with polyethylene glycol as the antibody precipitant, is a reliable one-day assay that is practical both for the clinical laboratory and the obstetrician.

Analysis of Variance↗

PubMed1976

[The monitoring of high risk pregnancies by determination of the estriol-16-glucoronide excretion. I. Methods and normal values (author's transl)].

A thin layer chromatographic method for the specific determination of estriol-16-glucoronide as azo dye is described. With this simple method the estriol excretion during pregnancy can be determined with omission of several steps in the determination such as the hydrolysis or evaporation of solvents. A single determination including the thin layer chromatography takes approximately 40 minutes. Based on 210 single determinations from the urine of pregnant women the normal range of excretion between the 28-42 week of pregnancy is determined. The mean excretion rises from 10.8 mg/24 hours at 28 weeks gestation to 25.8 mg/24 hours at 41 weeks gestation. The excretion of estriol-16-glucoronide is a measure of the estriol synthesis in the fetal-placental unit.

Chromatography, Thin Layer↗