Estriol Ratio Research Articles

Dynamics of steroid estrogen daily concentrations in hospital effluent and connected waste water treatment plant

Hospital effluent and connected waste water treatment plant (WWTP) influent and effluent were sampled daily to determine the levels and inter-day variations of three naturally occurring steroid estrogens: estrone, 17β-estradiol, estriol, and synthetic 17α-ethinylestradiol. After solid phase extraction, interferences were removed with a silica gel clean-up step and the samples analysed using gas chromatography with mass selective detection (GC-MSD). The determined inter-day concentrations in hospital effluent were between 8.6 to 31.3 ng L(-1) for estrone, <LOD (limit of detection) to 4.2 ng L(-1) for 17β-estradiol and 6.4 to 385.5 ng L(-1) for estriol. In the WWTP influent concentrations were 18.9 to 49.7 ng L(-1) for estrone, 2.4 to 12.7 ng L(-1), for 17β-estradiol and <LOQ (limit of quantitation) to 63.9 ng L(-1) for estriol. Reduced levels were found in the WWTP effluent: <7.1 ng L(-1) for estrone, <LOQ for 17β-estradiol and <5.2 ng L(-1) for estriol. 17α-ethinylestradiol was detected in only one influent sample. Calculated estradiol equivalents (EEQ) were 33.4, 22.4, 1.7 ng (EEQ) L(-1) in the hospital effluent, WWTP influent and WWTP effluent, respectively. Interestingly, the estrone: 17β-estradiol:estriol ratio in the hospital effluent (1:0.1:9.4) is comparable to that found in the urine of pregnant women (1:0.3:20) indicating the most likely source of steroid estrogens. In WWTP influent the ratio was similar to that found in the non-pregnant population. Our result recognise estriol as being one of the most important steroid estrogens, accounting for up to 92% of the total EEQ present in hospital samples and 37% and 46% in WWTP influent and effluent samples, respectively. The study reveals how concentrations of steroid estrogens vary on a daily basis and concludes that careful sampling strategies must be adopted when making a risk assessment. In addition, the low potency steroid estrogens that contribute towards overall estrogenicity of the sample, e.g. estriol, should be incorporated into environmental monitoring programs.

Salivary hormones and parturition in healthy, primigravid women

Hormonal predictors of labor initiation are of considerable interest but are not clearly elucidated. Current hypotheses suggest a surge in the ratio of estriol to progesterone from b1 to N1 marks the impending onset of labor [1–3]. Little research exists examining relationships between other steroid hormones and parturition in healthy, uncomplicated, late-term pregnancies [4]. The purpose of this study was to assess prospectively associations between salivary progesterone, DHEAS, testosterone, estrone, estradiol, and estriol concentrations and parturition. Twenty-four healthy, medication free, primigravid women were recruited from area childbirth education classes and gave their informed consent to participate. This study was approved by the UNLV institutional review board. Pre-prandial, un-stimulated saliva samples were collected from participants at 9:00 am at 37 weeks +/−2 days of pregnancy. Specimen were mailed via two-day courier to AllVia Diagnostic Lab in Phoenix, AZ for analysis, enzyme immunosorbent assays. Pearson's bivariate correlations were calculated to determine relationships between salivary hormones and length of gestation. Normality was tested using Shapiro–Wilks, pb .05. The mean age of the participants was 29.63, SD 4.16. The average length of gestation was 277 days +/−6.68 days. Participants were tested at 259 days +/−2 days. The mean number of days from test time to delivery was 18 days. All participants began labor naturally without assistance. After labor initiated 11 women required medical intervention either via medication (n=9) or cesarean section (n=2) to deliver. Thirteen women delivered without assistance. All delivered healthy infants. The intraand inter-assay coefficients of variation did not exceed 10% except for inter-day estrone (16.25%). Descriptive hormone data are presented in Table 1. Progesterone was correlated with longer pregnancies (r=.414, pb .05) while estradiol was associated with shorter pregnancies (r= −.519, pb .01). No significant correlations between estriol values or the mean ratio of estriol to progesterone (.57) and delivery was found. No other hormone was correlated with parturition. Researchers have identified a pre-delivery surge of estriol either alone [3] or relative to progesterone [1,2] associated with labor initiation, suggesting that fetal input contributes to the onset of labor and that an estriol surgemarks impending delivery. Our study does not support these findings. Here, progesterone and estradiol, but not estriol either alone or relative to progesterone were associated with parturition in healthy, late-

A high-sensitivity alternative to “routine” genetic amniocentesis: Multiple urinary analytes, nuchal thickness, and age

Objective: Our purpose was to evaluate the Down syndrome screening efficiency of a new algorithm consisting of multiple urinary biochemical and ultrasound markers for use in high-risk groups such as women of advanced maternal age. Study Design: The urinary β-core fragment of human chorionic gonadotropin (β-core fragment) and total urinary estriol, along with fetal nuchal thickness, were measured prospectively in pregnant women who were undergoing genetic amniocentesis at midtrimester (15 to 24 weeks). The most common indication for amniocentesis was advanced maternal age (90.2%). An analyte ratio (β-core fragment/total estriol ratio) was developed. The values were expressed as multiples of the normal median. An increase in the observed nuchal thickness (delta nuchal thickness) above that expected on the basis of the biparietal diameter was calculated. On the basis of the mean and standard deviations of the urinary analyte ratio in normal fetuses and also Down syndrome, we calculated individual Down syndrome likelihood ratios for each of the two parameters, using gaussian analysis. The product of the likelihood ratios, based on delta nuchal thickness and urinary β-core fragment–total estriol values times the maternal age–related risk, gave the overall Down syndrome risk. The screening efficiency of our algorithm at various risk thresholds was determined. Results: There were 13 (2.8%) cases of Down syndrome in a total study population of 457. At a risk threshold of >1 in 70, the sensitivity was 92.3% for a false-positive rate of 4.5%. Corresponding values at a risk threshold of >1 in 78 were a sensitivity of 100% with a false-positive rate of 5.2%. Conclusion: By combining urinary analyte, nuchal thickness, and maternal age data, we achieved a high Down syndrome detection rate with a low false-positive rate. This algorithm would be attractive as an alternative to “routine” amniocentesis based solely on advanced maternal age. The potential benefits of this protocol could include a significant reduction in the rate of amniocentesis, along with substantial savings in medical expenditures. (Am J Obstet Gynecol 1999;180:169-73.)

Diet and hormone profiles in teenage girls in four countries at different risk for breast cancer

In an attempt to assess the effects of diet on estrogen and prolactin levels, dietary histories, anthropometric measurements, and age at menarche were obtained, and Day 11 plasma and urine hormone levels measured in teenage girls in the United States (U.S.), Chile, Japan, and Papua New Guinea (PNG). Highly significant differences in diet were found, with the consumption of meat, dairy products, and fat being highest in the U.S., followed by Chile, Japan, and PNG. No significant differences in plasma levels of prolactin, estradiol, or estrone were found, suggesting that the dietary intake of meat and fat does not have a major role in determining the levels of these hormones. Subjects in PNG excreted significantly more estriol and had a significantly higher urinary estriol ratio [estriol/(estrone + estradiol)] than those in the other three countries; the Japanese and U.S. estriol ratio results were very close, with the results from Chile being intermediate (and statistically significantly different from both PNG and the U.S.-Japan results). No correlation of this pattern with any dietary component could be identified.

Elevated Urine Estrogen and Pregnanediol Levels in Daughters of Breast Cancer Patients&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;

Urine levels of three major estrogens and of pregnanediol were measured for 76 nulliparous daughters of breast cancer patients and for 115 control women of similar age and parity. Concentrations of estrone and estradiol tended to be higher in the daughters of breast cancer patients than in the controls; total estrogens were elevated in both phases than in the controls; total estrogens were elevated in both phases of the menstrual cycle and significantly so in the luteal phase. There was little difference between the daughters and the controls in estriol ratios--the ratios of the concentration of estriol to the sum of the concentrations of estrone and estradiol. Pregnanediol levels were higher in the daughters than in the controls.

Urine estrogen profiles in European countries with high or low breast cancer rates

Urine estrogens of women in two age groups, 15–18 and 30–39, were measured in four northern European countries where breast cancer rates are high, two southern European countries where they are low, and in Finland, a northern country where incidence rates are comparable to those of the southern countries and mortality rates are intermediate. The estriol ratio (the ratio of the concentration of estriol to the sum of those of estrone and estradiol) was lower in the high-risk countries than in the low-risk areas in both age-groups and in both the follicular and luteal phases of the menstrual cycle. In two of the four comparisons the difference was statistically significant. This provides modest support to the hypothesis that a population's breast cancer risk is inversely related to the estriol ratios of its young women. However, the data from Finland are not consistent with this hypothesis, the Finnish women having lower mean estriol ratios than the women in the high-risk areas. The pregnanediol levels of the young Finnish women were also unusually low, suggesting a high frequency of anovulatory menstrual cycles.

Estrogen Profiles of Primiparous and Nulliparous Women in Athens, Greece23

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.

Socioeconomic Status, Urine Estrogens, and Breast Cancer Risk&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;

Urine estrogens were measured in 46 women students, ages 15-18, at a middle-class high school in Athens and in 40 women of the same age residing at one of three orphanages in the same city. The lower socioeconomic status (SES) of the latter group was documented by their lower mean height (by 5.2 cm) and weight (by 5.3 kg) relative to the high school students. Both in follicular and luteal phases of the menstrual cycle, the women with lower SES had 50% higher estriol ratios (ratio of the concentration of estriol to the sum of the concentrations of estrone and estradiol). In luteal specimens the concentration of all three major estrogens was higher in the group with low SES than in the women in the other group, but the concentration of estriol was most increased. There was also an indication of less frequent anovular cycles among the women with low SES. These findings are consistent with hypotheses linking either the estriol ratio or the frequency of anovular cycles to breast cancer risk.

The role of hormones in the etiology of human breast cancer

It has long been suspected that endocrine factors play a promoting or contributory role in the genesis of human breast cancer. Attempts to define and quantify such factors, however, have proven elusive. 1) Estrogens: Women at increased risk for breast cancer were shown to excrete less estriol (E3) vs estrone and estradiol. Conversely, women at low risk for breast cancer had higher urinary “estriol ratios.” These data led to the hypothesis that E3 is a “protective” estrogen. Recent studies of estriol production rates, its origin and circulating levels, however, have shown no differences in these crucial parameters in women with high E3 ratios vs low E3 ratios or in women with previous breast cancer. These data imply that high vs low urinary E3 ratios simply reflect different pathways of estrogen metabolism, and not differences in estrogen production. In women with established breast cancer, earlier studies of urinary estrogens as well as recent measurements of estrogen blood production rates have shown no significant abnormalities. Further, the contribution of androstenedione, estrone's principle prehormone, is normal in women with breast cancer. 2) Androgens: Earlier studies by Bulbrook in women with breast cancer correlated decreased urinary 17-KS with poor responses to endocrine ablative procedures. These workers also found low urinary etiocholanolane in women destined to develop breast cancer. Thus, decreased androgen excretion seems to be associated with poor response to endocrine therapy and increased risk for breast cancer. Similarly, dehydroepiandrosterone and its metabolites were found to be decreased in women with breast cancer. Androstenedione production, however, was found to be normal in women with post-menopausal breast cancer. The significance of androgen alterations in women with breast cancer (or at high risk) is still unclear. 3) Progesterone: No abnormalities in progesterone production have been reported in women with breast cancer. The Sherman-Korenman hypothesis that women with inadequate corpus luteum formation are at increased risk for breast cancer still requires confirmation. 4) Prolactin: Most reports to date indicate no abnormalities of prolactin in women with breast cancer. Henderson's data showing high plasma prolactin and estradiol in daughters of women with breast cancer (high risk) need confirmation. 5) Thyroid: In spite of several intriguing associations of thyroid function with steroid and peptide hormone metabolism, no consistent evidence has emerged implicating abnormal thyroid function in women with breast cancer. From the above, it is apparent that in spite of tantalizing bits of data linking breast cancer development with possible alteration of endocrine function, no clear-cut or comprehensible patterns are yet evident.

Gas — Liquid chromatographic analysis of urinary estrogens as a breast cancer detection procedure

Most earlier studies of estrogenic steroids in urine with a clinical bias have been based upon colorimetric evaluation after purification of the urinary steroid fraction. Frequently, in systematic studies, samples have not been standardized with respect to time of collection or to inherent diurnal variation. In the present investigation, in order to provide an inherently higher level of sensitivity and resolution, gas-liquid chromatography of silylated estrogens derived from urine has been adopted as the analytic method. Analysis was made upon 24-hr samples taken under standardized conditions. In post-menopausal women, the ratio of estriol to estrone + estradiol (17β-estradiol) did not differ in subjects with mammary tumors when compared with normal subjects. In premenopausal women, however, breast cancer patients had a markedly lower ratio of estriol to estrone + estradiol than did normal subjects. The data reported substantiate the potential utility of the procedure as a cancer detection test applicable to high-risk groups of premenopausal women.

Estetrol in molar pregnancies quantitated by a rapid gas chromatographic method in conjunction with estrone, estradiol-17β, estriol, and pregnanediol

A gas-liquid chromatographic method allowing the simultaneous quantitation of urinary estetrol, estriol, estradiol, estrone, and pregnanediol in urine throughout the duration of pregnancy is presented. The method consists of an enzymatic hydrolysis, ether extraction, chromatography on Sephadex LH-20 and AGI-X2, and final quantitation of the steroids as heptafluorobutyric anhydride derivative in a gas chromatograph. Ten samples may be assayed for estetrol in one working day. The method was applied to 23 urine specimens of 13 different patients with molar pregnancies prior to evacuation and to 21 urine specimens from women with nonmolar pregnancies as controls. In 77 per cent of the molar pregnancies, no estetrol was detected, and, in the remaining 23 per cent, it was present in a much lower concentration than expected for nonmolar pregnancies. The ratio of estriol to that of estradiol plus estrone was generally lower in the molar than in the nonmolar pregnancies. No discernible pattern for pregnanediol in molar pregnancies was established. It is concluded that: (1) estetrol in some cases of molar pregnancy is synthesized to a small degree by either placental or maternal tissue and the fetal liver is not solely responsible for 15α-hydroxylation of estetrol precursors, and (2) determinations of estetrol are useful in the diagnosis of molar pregnancy.

性ホルモンの皮膚内代謝

Estradiol-3H and estrone-14C were incubated with minced normal corium, endometrium, myometrium and corium of sclerodermia. Following the incubation, radioactive Estradiol estrone, 16-epi-estriol and estriol were recovered. The conversion ratio of each tissue which was calculated as the rate of converted estrogen to estrogen that was incubated as substrate, was constant and different each other. The conversion ratio of normal corium was the highest and the corium of sclerodermia had the lowest ratio. In the corium of sclerodermia, the estriol ratios which were calculated as the rates of recovered estriol to estradiol and estrone recovered, were much lower than those of other normal tissues significantly. These findings extend that 1) human corium, endometrium and myometrium might convert estrogens to estriol and 2) the conversion of estrogens to others especially to estriol seems to be inhibited considerably in the corium of sclerodermia.

Contribution of Estriol to Total Urinary Estrogens during Pregnancy

Abstract Estriol accounts for an average of 74% of the principal Kober-positive steroids in the urine of 13 women during uncomplicated pregnancies. This proportion is independent of the stage of pregnancy, from 20 weeks until term. The average ratio of estriol to ring-D α-ketols (mainly 16α-hydroxyestrone and 16-ketoestradiol-17β) is about 5:1 over the same period. In 17 pregnant women with diabetes, urinary estriol averaged 63% of the "total steroids" during a similar period, and the average ratio of estriol to ring-D α-ketols was 3:1. The quantitative importance of these ketolic steroids may introduce a problem in deciding whether to measure estriol or "total estrogens" when evaluating fetal viability in complicated pregnancies.

Solubility Studies of Estriol in Organic Solvents Using Gas-Liquid Chromatography

This solubility study of estriol (E3) by gas-liquid chromatography (GLC) is part of our program for studying the basic chemistry of the steroid hormones, especially that of the estrogens. GLC is used to quantitate E3 as the free steroid and also to evaluate how protonic and aprotic solvents affect the dissolved molecule. This data is of particular significance in all phases of estrogen analysis and in evaluating modern theories of solution. Solubility was approached from supersaturation equilibrium at 0°, 15°, 25°, 30°, and 40°C ±0.01°, in 13 organic solvents, depending upon individual freezing and boiling points. Triplicate determinations, each of a different ratio of estriol and pregnantriol (the internal standard) were measured for each solvent at each temperature. This article contains more of what is known about the solubility of E3 (through our work) than has previously been found in the literature.

Metabolic Fate of 3H-Testosterone Administered into the Fetoplacental Compartments

A tracer amount of 3 H-testosterone was administered into the umbilical vein at full term cesarean section and was allowed to circulate in the feto-placental compartments for 10 min before the baby was delivered. Cord blood and maternal and neonatal urine were analysed for radioactive metabolites. Besides unchanged testosterone, androstenedione, estrone, estradiol-17β and estriol were found in these samples. In urine, radioactive 17-KS was also detected. It was noteworthy that estrogens were detected in the circulating cord blood after such a short time. Among three classical estrogens, the ratio of estriol was the highest of all the samples analysed. This fact suggests that testosterone, if produced at all in the fetal testis, would undergo metabolic changes in the placenta and consequently it is not related to the concentration in the cord blood.

A study of the metabolism of single therapeutic dose (2.0 mg.) of estrone in the preovulatory and postovulatory phases of the menstrual cycle in healthy women.

ZONDEK'S demonstration in 1934 (1) of the tremendous capacity of the rat to inactivate the natural estrogens has focused attention on the intermediary metabolism of these hormones. Treatment and recovery experiments in man (2–5) have revealed that, regardless of sex, only from 0 to 20 per cent of the administered hormone can be recovered from the urine in recognizable forms and that α-estradiol⇄estrone→estriol conversion appears to characterize one phase of this catabolic process. Although interest recently has centered on the role of the liver in estrogen metabolism, other organs in the intact animal have not been excluded. In fact, in clinical endocrinology the view is often expressed (6–12) that progesterone, acting through the endometrium of the uterus, converts estrone to estriol and thereby exerts a sparing action on the destruction of the estrogens. Thus an elevated recovery of exogenous urinary estrogens and a high ratio of estriol to estrone should characterize the progestational phase of the men...