Urinary Estrogen Excretion Research Articles

La determinación de estrógenos urinarios durante el embarazo por cromatografía de gas y capa fina

Hemos estudiado la excreción urinaria de estrógenos en 15 gestantes normales a término por el método de Cromatografía de gas y capa fino de Wotiz y Chottoraj, con los siguientes resultados: Estrona: 1.90 + 0,73 mgm./24 h.s Estradiol: 0.56 ± 0.20 mgm./24 hs. Estriol: 27.2 + 9.2 mgm./24 horas. (Promedio ± Desviación standard). Se describe el método empleado y se discute la aplicación clínica de las determinaciones de estrógenos durante el embarazo. En un caso de Mola hidatiforme, se encontró gonadotropinas coriónicas elevadas con baja excreción urinaria de estrógenos, estando el estriol muy disminuído.

Unraveling Genes, Hormones, and Breast Cancer

Unraveling Genes, Hormones, and Breast Cancer

Urinary estrogens and estrogen metabolites and subsequent risk of breast cancer among premenopausal women.

Endogenous estrogens and estrogen metabolism are hypothesized to be associated with premenopausal breast cancer risk but evidence is limited. We examined 15 urinary estrogens/estrogen metabolites and breast cancer risk among premenopausal women in a case-control study nested within the Nurses' Health Study II (NHSII). From 1996 to 1999, urine was collected from 18,521 women during the mid-luteal menstrual phase. Breast cancer cases (N = 247) diagnosed between collection and June 2005 were matched to two controls each (N = 485). Urinary estrogen metabolites were measured by liquid chromatography-tandem mass spectrometry and adjusted for creatinine level. Relative risks (RR) and 95% confidence intervals (CI) were estimated by multivariate conditional logistic regression. Higher urinary estrone and estradiol levels were strongly significantly associated with lower risk (top vs. bottom quartile RR: estrone = 0.52; 95% CI, 0.30-0.88; estradiol = 0.51; 95% CI, 0.30-0.86). Generally inverse, although nonsignificant, patterns also were observed with 2- and 4-hydroxylation pathway estrogen metabolites. Inverse associations generally were not observed with 16-pathway estrogen metabolites and a significant positive association was observed with 17-epiestriol (top vs. bottom quartile RR = 1.74; 95% CI, 1.08-2.81; P(trend) = 0.01). In addition, there was a significant increased risk with higher 16-pathway/parent estrogen metabolite ratio (comparable RR = 1.61; 95% CI, 0.99-2.62; P(trend) = 0.04). Other pathway ratios were not significantly associated with risk except parent estrogen metabolites/non-parent estrogen metabolites (comparable RR = 0.58; 95% CI, 0.35-0.96; P(trend) = 0.03). These data suggest that most mid-luteal urinary estrogen metabolite concentrations are not positively associated with breast cancer risk among premenopausal women. The inverse associations with parent estrogen metabolites and the parent estrogen metabolite/non-parent estrogen metabolite ratio suggest that women with higher urinary excretion of parent estrogens are at lower risk.

Prepubertal urinary estrogen excretion and its relationship with pubertal timing

Whether prepubertal estrogen production impacts on the timing of puberty is not clear. We aimed to investigate prepubertal 24-h estrogen excretion levels and their association with early and late pubertal markers. Daily urinary excretion rates of estrogens of 132 healthy children, who provided 24-h urine samples 1 and 2 yr before the start of the pubertal growth spurt [age at takeoff (ATO)], were quantified by stable isotope dilution/GC-MS. E-sum3 (estrone + estradiol + estriol) was used as a marker for potentially bioactive estrogen metabolites and E-sum5 (E-sum3 + 16-epiestriol + 16-ketoestradiol) for total estrogen production. Pubertal outcomes were ATO, age at peak height velocity (APHV), duration of pubertal growth acceleration (APHV-ATO), age at Tanner stage 2 for pubic hair (PH2), genital (G2, boys) and breast (B2, girls) development, and age at menarche. Prepubertal urinary estrogen excretions (E-sum3 and E-sum5) were not associated with ATO, APHV, and age at PH2 but with duration of pubertal growth acceleration (P < 0.01) in both sexes. Girls with higher E-sum3 reached B2 0.9 yr (P = 0.04) and menarche 0.3 yr earlier (P = 0.04) than girls with lower E-sum3. E-sum3 was not associated with age at G2 in boys (P = 0.6). For most pubertal variables, the associations with E-sum3 were stronger than with E-sum5. In conclusion, prepubertal estrogens may not be critical for the onset of the pubertal growth spurt but are correlated with its duration in both boys and girls. Prepubertal estrogen levels may already predict the timing of girls' menstruation and breast development but do not appear to affect sexual maturation in boys.

Total Urinary Oestrogen Excretion of Normal Pregnant Malaysian Women in The Last Trimester of Pregnancy*

Total Urinary Oestrogen Excretion of Normal Pregnant Malaysian Women in The Last Trimester of Pregnancy*

Effect of gestyl on the urinary excretion of oestrogen in ewes during the non-breeding season.

Summary Merino ewes were injected with serum gonadotrophin (Gestyl) During June and July. The maximum values for the total urinary excretion of oestrone, 17 alpha oestradiol and oestriol occurred 9 and 36 hours after the injection in June and July, respectively. Activity in the vagina and cervix and the presence of arborization resulting from the injection were more marked during June than during July. Zusammenfassung Der Einfluß von Gestyl auf die Oestrogen-Ausscheidung im Harn bei Schafen während der sexuellen Ruheperiode (Non-Breeding Season) Während der Monate Juni und Juli wurde Merino-Schafen das Serum Gonadotropin Gestyl injiziert. Die maximalen Ausscheidungen von Oestron, 17-alpha-oestradiol und Oestriol traten 9 und 36 Stunden nach der Injektion auf. Im Juni war die Aktivität der Vagina und der Zervix und die Arborisation des Zervixschleimes ausgeprägter als im Juli. Résumé L'influence du «Gestyl» sur la sécrétion de oestrogènes dans l'urine chez le mouton pendant la période de repos sexuel On a injecté à des moutons de la race mérino du «Gestyl» (gonadotropine sérique) pendant les mois de juin et juillet. Les sécrétions maximales d'oestrone, de 17-α-oestradiol et d'oestriol sont intervenues 9 et 36 heures après l'injection. On a observé une plus grande activité du vagin et du cervix ainsi qu'une mucosité arborisante plus accrue du cervix en juin qu'en juillet. Resumen Efecto de Gestyl sobre la excreción urinaria de estrógeno en ovejas durante la temporada no gravidica Durante los meses Junio y Julio se inyectó a ovejas merinas la gonadotropina sérica Gestyl. Las excreciones máximas de oestrona, 17 alfa oestradiol y oestriol acaecían 9 y 36 horas después de la inyección. En Junio era bastante más marcada la actividad en la vagina y cuello uterino y la arborización del moco cervical que en Julio.

Investigations on urinary oestrogen excretion from ewes with special reference to the clinical condition of the genital tract. 3. Non-breeding season.

Summary Urinary oestrogen excretion was determined quantitatively by thin layer chromatography and the Kober-Ittrich-Reaction in 31 Merino ewes grazed on Hungarian farms during the anoestrous period (April—July). The total amount of oestrogen excreted decreased markedly from April and May to June and July. The vagina and cervix of the animals examined were static and the cervical smears exhibited only granulation. A marked drop in the urinary output of oestrogen was observed one day before abortion and just after it in a single ewe which was examined every other day. On the 10th and 16th days of the puerperium a relative increase in the output of oestrogen was seen. Zusammenfassung Untersuchungen über die Oestrogen-Ausscheidung im Harn bei Schafen mit besonderer Berücksichtigung verschiedener klinischer Zustände des Genitaltraktes. III. Anoestrie-Phase Mit Hilfe der Dünnschicht-Chromatographie und der Kober-Ittrich-Reaktion wurde bei 31 Merino-Schafen, welche auf ungarischen Farmen während des Anöstrus (April bis Juli) gehalten wurden, die Oestrogen-Ausscheidung im Harn bestimmt. Die Oestrogen-Ausscheidung sank vom April bis zum Juli deutlich ab. Der Vaginal- und Zervikalbefund änderte sich praktisch nicht und die Zervikalausstriche zeigten nur eine Granulation. Ein Tag vor und unmittelbar nach dem Abort sank die Oestrogen-Ausscheidung im Harn bei einem Schaf stark ab. Am 10. und 16. Tag des Puerperiums wurde eine Erhöhung der Oestrogen-Ausscheidung beobachtet. Résumé Recherches sur la sécrétion d'oestrogènes dans l'urine chez des moutons en tenant compte particulièrement des différents étants cliniques de l'appareil génital III. Période d'anoestrus On a déterminé au moyen de la chromatographie sur couche mince et par la réaction de Kober-Ittrich la sécrétion d'oestrogènes dans l'urine chez 31 moutons de la race mérino pendant la période d'anoestrus (avril à juillet) dans des exploitations hongroises. La sécrétion d'oestrogènes a nettement diminué d'avril à juillet. L'examen du vagin et du cervix n'a pratiquement pas montré de changements et les frottis du cervix n'ont présenté qu'une granulation. Il y a eu chez un mouton une forte diminution de la sécrétion d'oestrogènes dans l'urine un jour avant et immédiatement après avortement. On a observé une élévation de la sécrétion d'oestrogènes au dixième et au seizième jour de la puerpéralité. Resumen La excreción estrógena en la orina de ovejas con la consideración especial del hallazgo clínico en el tracto genital III. Temporada no gravídica Se determinó cuantitativamente la excreción urinaria de estrógenos por medio de la cromatografía en capa delgada y la reacción de Kober-Ittrich en 31 ovejas merinas que pastaron en granjas húngaras durante el periodo anoestrico (Abril—Julio). La cantidad total de estrógeno excretada disminuía de modo evidente desde Abril hasta Julio. Prácticamente no se modificaron los hallazgos vaginales ni los cervicales y sólo los frotes cervicales evidenciaban una granulación. Un día antes e inmediatamente después del aborto disminuyó de forma notable la excreción estrógena con la orina en una sola oveja. El 10° y 16° días del puerperio se observó un aumento relativo en la excreción de estrógeno.

Abstract 2784: Urinary estrogen metabolites in the luteal phase and subsequent risk of breast cancer among premenopausal women

Abstract Higher levels of endogenous estrogen are associated with increased breast cancer risk in postmenopausal women. Data for premenopausal women are sparse, in part due to the complexity of measuring hormones that vary throughout the menstrual cycle. We previously reported increased breast cancer risks with higher plasma free and total estradiol in the follicular phase, but no statistically significant associations with plasma luteal phase estrogens. Individual patterns of estrogen metabolism may relate to breast cancer risk, though the hypothesized relationships have not been thoroughly explored, particularly among premenopausal women. Estrogen metabolism occurs via three main pathways, with hydroxylation of estrone and estradiol occurring at the C-2, C-4, and C-16 positions. We prospectively evaluated associations between 15 mid-luteal urinary estrogens and estrogen metabolites (EM) and breast cancer risk among premenopausal women in a case-control study nested within the Nurses' Health Study II. From 1996 to 1999, urine samples were collected from 18,521 premenopausal women during the mid-luteal phase of their menstrual cycle. 251 cases of breast cancer were diagnosed among these women after urine collection and before June 1, 2005. These cases were matched to 500 controls. Urinary EM were measured using a liquid chromatography-tandem mass spectrometry method with high sensitivity, specificity, and precision. We used logistic regression models, controlling for breast cancer risk factors, to calculate relative risks (RRs) and 95% confidence intervals (CIs). Using both absolute (pmol/mg creatinine) and relative (% of total EM) levels, we assessed the associations with breast cancer risk of individual EM, as well as EM grouped according to chemical or metabolic characteristics. Overall, in preliminary analyses, we did not observe significant positive associations between any of the 15 EM and breast cancer risk, except with 17-epiestriol, a low concentration metabolite in the 16-hydroxylation pathway (absolute level top vs. bottom quartile RR=1.5, 95% CI (0.9-2.3), p-trend=0.05; relative level top vs. bottom quartile RR=1.7, 95% CI (1.1-2.8), p-trend=0.03). We observed inverse associations with absolute and relative measures of estrone and estradiol (e.g., absolute estrone top vs. bottom quartile RR=0.5, 95% CI (0.3-0.9), p-trend=0.005; absolute estradiol top vs. bottom quartile RR=0.6, 95% CI (0.3-0.9), p-trend=0.01). Ratios of grouped metabolites (e.g., 2-hydroxylation:16-hydroxylation pathways) were not significantly associated with risk. These data suggest that most mid-luteal urinary EM are not positively associated with breast cancer risk among premenopausal women. Our findings of inverse associations with urinary estrone and estradiol suggest that women with higher urinary excretion of parent estrogens may be at lower breast cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2784.

Excretion of estrogens, catecholestrogens and phytoestrogens in carriers of BRCA1 gene mutations: effects of metformin

BRCA1 gene mutation is associated with a combination of excessive aromatase activity/expression, predominantly estrogen receptor-negative phenotypes of tumors, and only scarce information about estrogen contents in body fluids. In the present work, isotope dilution capillary gas chromatography/mass spectrometry was used to study urinary excretion of estrogens, their catechol metabolites, and phytoestrogens in 22 women (11 with BCRA1 gene mutations and 11 without these mutations) in average 5.1+/-0.4 years before surgery for breast cancer. BCRA1 mutation carriers (including 3 premenopausal females) compared with respective controls showed significantly higher urinary estradiol and estrone excretion and a trend to an increased 2-OH-E2 excretion. In the subgroup of untreated postmenopausal women, BCRA1 mutation carriers showed a trend to increased estradiol and estrone excretion and to a higher value of the mean levels of all estrogen metabolites tested. The treatment after the baseline laboratory investigation of 6 women from postmenopausal group with the antidiabetic biguanide metformin for 3 months was associated with decreases in the excretion rates of 4-hydroxyestradiol, 2-methoxyestradiol, and 16-epiestriol and did not influence phytoestrogen excretion. The decrease in 2-methoxyestrogen excretion was more consistent in women without BCRA1 mutations than in BCRA1 mutation carriers. The data suggest the possibility that aromatase complex activation in BCRA1 mutation carriers is combined with increases in both, estrogen metabolism into catecholestrogens and their inactivation by methoxylation, and that metformin may affect both of these pathways.

Abnormal urinary estrogen excretion after Methopyrapone (SU - 4885) in males with defective spermatogenesis1

AndrologiaVolume 2, Issue 1 p. 37-40 Abnormal urinary estrogen excretion after Methopyrapone (SU - 4885) in males with defective spermatogenesis1 D. G. Ikkos, Corresponding Author D. G. Ikkos Department of Endocrinology, Evangelismos Hospital, Athens 140 (Greece) Evangelismo Hospital, Athen, Greece „Alexandra” Maternity Hospital, Athen, GreeceSearch for more papers by this authorAnastasia Dellia-Sfikaki, Corresponding Author Anastasia Dellia-Sfikaki Department of Endocrinology, Evangelismos Hospital, Athens 140 (Greece) Evangelismo Hospital, Athen, Greece „Alexandra” Maternity Hospital, Athen, GreeceSearch for more papers by this authorJ. Danezis, Corresponding Author J. Danezis Fertility and Sterility Center, “Alexandra” Maternity Hospital, Athens 140 (Greece) Evangelismo Hospital, Athen, Greece „Alexandra” Maternity Hospital, Athen, GreeceSearch for more papers by this author D. G. Ikkos, Corresponding Author D. G. Ikkos Department of Endocrinology, Evangelismos Hospital, Athens 140 (Greece) Evangelismo Hospital, Athen, Greece „Alexandra” Maternity Hospital, Athen, GreeceSearch for more papers by this authorAnastasia Dellia-Sfikaki, Corresponding Author Anastasia Dellia-Sfikaki Department of Endocrinology, Evangelismos Hospital, Athens 140 (Greece) Evangelismo Hospital, Athen, Greece „Alexandra” Maternity Hospital, Athen, GreeceSearch for more papers by this authorJ. Danezis, Corresponding Author J. Danezis Fertility and Sterility Center, “Alexandra” Maternity Hospital, Athens 140 (Greece) Evangelismo Hospital, Athen, Greece „Alexandra” Maternity Hospital, Athen, GreeceSearch for more papers by this author First published: January‐March 1970 https://doi.org/10.1111/j.1439-0272.1970.tb00431.x 1 Supported in part by a grant of the Royal Hellenic Research Foundation to one of us (A. D.-S.) AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume2, Issue1January‐March 1970Pages 37-40 RelatedInformation

Sex hormones and bile acids in intrahepatic cholestasis of pregnancy

Sex hormones and bile acids in intrahepatic cholestasis of pregnancy

A Case of Estrogen-secreting Adrenocortical Carcinoma with Subclinical Cushing's Syndrome

A 25-year-old man was found to have a large right adrenal mass detected by abdominal echography and computed tomography, and presented with a mild gynecomastia. Endocrine study showed increased serum concentrations and urinary excretion of estrogens and dehydroepiandorosterone sulfate (DHEA-S). The patient had no Cushingoid features but autonomous cortisol secretion, compatible with the diagnosis of subclinical Cushing's syndrome. Surgical removal of the adrenal tumor led to normalization of serum and urinary excretion of estrogens and DHEA-S. Histopathological examination revealed a high-grade adrenocortical carcinoma (ACC). The disorganized expression of all the steroidogenic enzymes in individual tumor cells was demonstrated by immunohistochemical analysis, and the abundant expression of both aromatase mRNA and insulin-like growth factor (IGF)-II mRNA was shown by RT-PCR. These data suggest the excessive secretion of estrogen as well as the ineffective steroidogenesis by the adrenal tumor. This is a very rare case of estrogen-secreting ACC associated with subclinical Cushing's syndrome.

Consecutive Urinary Gonadotropin and Ovarian Hormone Excretory Patterns during LH-RH Analog Treatment in Female Patients with Central Precocious Puberty

To study the initial stimulative and subsequent suppressive effects of Luteinizing hormone releasing hormone analog (LHRH-a) therapy on the hypothalamic-pituitary-ovarian axis, serial urinary excretion of gonadotropin and ovarian steroids were investigated in 23 female patients with central precocious puberty. Among them, seven were treated with intranasal administration of buserelin (G1), seven with daily subcutaneous injection of buserelin (G2) and nine with subcutaneous injection of super-long-acting LHRH-a every 28 days (G3). After the initial therapy in G1, the levels of urinary gonadotropin excretion increased greatly with a high level persisting for a longer period. Responding to these increases, the levels of urinary total estrogen excretion increased to an excessively high maximum level. After the initial injection in G3, the levels of urinary gonadotropin and total estrogen excretion were augmented at the same time for a shorter period with a lesser excretion of urinary total estrogen. Ovarian cysts developed after urinary total estrogen attained a maximum and tended to grow depending on the duration and degree of high urinary total estrogen excretion.The size of ovarian cysts was greater in G1 than in G3. During therapy in all groups, the mean urinary gonadotropins were significantly suppressed compared with pretreatment. The mean urinary total estrogen excretory level during treatment in G1 was not significantly suppressed compared with before treatment, but on the other hand, with significant suppression in G3. During therapy, urinary FSH excretion increased within 24 hours of every injection of super-long-acting LHRH-a with a slight rise in LH only in all patients in G3 studied. Studies in many more patients are required because the number of subjects was limited in this study.

Epidemiology of prostate cancer.

Malignant transformation of the prostate and progression of carcinoma appear to be the consequence of a complex series of initiation and promotional events under genetic and environmental influences. Increased incidence of the condition may be the result of improved detection, greater awareness of the condition, and possibly an increased life expectancy accompanied by a decrease in competing causes of death rather than a true increase in the prevalence of the disease. The marked racial and geographic differences are probably multifactorial, with genetic, environmental, and possibly social influences affecting progression of the disease. Among several risk factors, evidence for the familial inheritance of some prostate cancers is compelling. Dietary influences, hormonal milieu, and the role of environmental carcinogens are currently under intense investigation. As further risk factors are identified, it will become increasingly important to identify individuals at increased risk for the disease. These men should undergo regular evaluation with state-of-the-art methods.

Endogenous estrogen and postmenopausal breast cancer: a quantitative review.

This paper systematically reviews the results from epidemiologic studies investigating the hypothesis that breast cancer risk in postmenopausal women increases with increasing concentrations of estradiol in blood and with increasing urinary estrogen excretion rates. Data from 29 epidemiologic studies of endogenous hormones and postmenopausal breast cancer were used. The ratio of the average estrogen concentration in the women with breast cancer to that in the women without breast cancer (and its 95 percent confidence interval [CI]) was calculated for each study, and the results were summarized by calculating weighted averages of the log ratios. In six prospective studies of serum estradiol concentration, 329 women who subsequently developed breast cancer had, overall, a 15 percent (CI = 6-24 percent, P = 0.0003) higher mean concentration of estradiol in their blood than the 1,105 women who remained free of cancer. The results of these prospective studies did not differ significantly from each other (chi2 for heterogeneity = 8.7; degrees of freedom = 5; P > 0.1). Similar differences in mean estrogen levels were seen in the case-control studies which reported either estradiol concentrations in the blood or urinary estrogen excretion. However, the case-control studies showed significant heterogeneity among their results. The data from the prospective studies strongly suggest that breast cancer risk in postmenopausal women is associated with relatively high concentrations of endogenous estradiol.

Cigarette smoking and urinary oestrogen excretion in premenopausal and post-menopausal women.

Cigarette smoking is associated with a reduction in the risk for endometrial cancer in post-menopausal women and it has been suggested that this is because smoking has an anti-oestrogenic effect. To investigate this, concentrations of oestrone, oestradiol and oestriol were measured in 24 h urine samples from 167 premenopausal women (53 smokers, 114 non-smokers) and 200 post-menopausal women (54 smokers, 146 non-smokers). Among premenopausal women there were no significant differences in oestrogen excretion between smokers and non-smokers. Among post-menopausal women, geometric mean excretion rates for oestrone and oestradiol did not differ significantly between groups, but oestriol excretion was 19% lower (95% confidence interval -34% to -1%) in smokers than in non-smokers. This may partly explain the reduced risk for endometrial cancer among post-menopausal smokers.

Wheat bran and psyllium diets: effects on N-methylnitrosourea-induced mammary tumorigenesis in F344 rats.

Experimental and epidemiologic evidence suggests that increased dietary fiber is associated with decreased breast cancer risk. Little is known about the role played by different types of fiber and, particularly, mixtures of soluble and insoluble fibers similar to those consumed by human populations in reducing breast cancer risk. High intake of fiber may suppress bacterial hydrolysis of biliary estrogen conjugates to free (absorbable) estrogens in the colon and thus may decrease the availability of circulating estrogens necessary for the development and growth of breast cancers. The purpose of this study was to evaluate the effect of wheat bran (an insoluble fiber) and psyllium (a soluble fiber) alone and in combination on overall estrogen status, on fecal bacterial beta-D-glucuronidase (a key diet-responsive estrogen-deconjugating enzyme) activity, and on the induction of mammary tumors in rats treated with N-methylnitrosourea (MNU). One hundred fifty virgin female F344 rats were fed the NIH-07 diet from 28 days of age until 50 days of age; they were then given a single dose (40 mg/kg of body weight) of MNU by tail vein injection. Three days later, they were randomly assigned to one of five experimental dietary groups (30 animals per group). Soft, white wheat bran (45% dietary fiber content) and psyllium (80% dietary fiber content) were added to a modified (high-fat) American Institute of Nutrition (AIN)-76A diet at the following percents, respectively: 12% + 0% (group 1), 8% + 2% (group 2), 6% + 3% (group 3), 4% + 4% (group 4), and 0% + 6% (group 5). Blood, urine, and feces were collected and analyzed by radioimmunoassay techniques for estrogens. Cecal contents were analyzed for bacterial beta-D-glucuronidase activity. After 19 weeks on the experimental diets, the rats were killed, and mammary tumors were counted and classified by histologic type. Cumulative tumor incidence was evaluated by the Kaplan-Meier life-table method and the logrank test. Tumor number was evaluated by the chi-squared test of association, and tumor multiplicity was evaluated by the Mantel-Haenszel chi-squared test. All statistical tests were two-tailed. As the level of psyllium relative to that of wheat bran increased, the total tumor number and multiplicity of mammary adenocarcinomas in rats decreased as a statistically significant linear trend across groups 1-5 (P < .05). Compared with the group given wheat bran alone, the group given the 1:1 (wheat bran:psyllium) combination had maximum protection against mammary tumorigenesis, while the groups given the 4:1 or 2:1 (wheat bran:psyllium) combination or psyllium alone had intermediate protection. No statistically significant differences in circulating estrogens or urinary estrogen excretion patterns were observed among the five experimental groups. Fecal estrogen excretion, however, decreased with increasing levels of psyllium (P < .01), and cecal beta-D-glucuronidase activity exhibited a decreasing trend with respect to the increasing psyllium content of the diet across groups 1-5 (P < .01). The addition of a 4%:4% mixture of an insoluble (wheat bran) fiber and a soluble (psyllium) fiber to a high-fat diet provided the maximum tumor-inhibiting effects in this mammary tumor model. Although increasing levels of dietary psyllium were associated with decreased cecal bacterial beta-D-glucuronidase activity, these changes were not reflected in decreased circulating levels of tumor-promoting estrogens. Therefore, the mechanism(s) by which mixtures of soluble and insoluble dietary fibers protect against mammary tumorigenesis remains to be clarified.

A prospective study of urinary oestrogen excretion and breast cancer risk

To test the hypothesis that high levels of endogenous oestrogens increase the risk for developing breast cancer, concentrations of oestrone, oestradiol and oestriol were measured in 24 h urine samples from 1000 women participants in a prospective study of breast cancer on the island of Guernsey. Sixty-nine subjects were diagnosed with breast cancer subsequent to urine collection. Among women who were premenopausal at the time of urine collection, cases excreted less oestrogen than controls; the odds ratios (95% CI) for breast cancer in the middle and upper thirds of the distribution of oestrogen excretion, in comparison with the lower third (reference group, assigned odds ratio = 1.0), were 0.5(0.2-1.2) and 0.4(0.2-1.1) respectively for oestrone, 0.8(0.4-1.8 and 0.4(0.2-1.1) for oestradiol, 0.7(0.3-1.6) and 0.7(0.3-1.6) for oestriol and 0.9(0.4-2.0) and 0.5(0.2-1.3) for total oestrogens. Among women who were post-menopausal at the time of urine collection, the trend was in the opposite direction, with an increase in risk associated with increased oestrogen excretion; the odds ratios were 0.9(0.3-2.2) and 1.1(0.5-2.8) for oestrone, 0.8(0.3-2.3) and 1.9(0.8-4.6) for oestradiol, 1.5(0.6-3.9) and 1.8(0.7-4.6) for oestriol and 0.9(0.4-2.6) and 1.9(0.7-4.7) for total oestrogens. The trends of increasing risk with increasing oestrogen excretion among post-menopausal women were statistically significant for oestradiol (P = 0.022) and for total oestrogens (P = 0.016). We conclude that high levels of endogenous oestrogens in post-menopausal women are associated with increased breast cancer risk, but that the relationship of oestrogens in premenopausal women with risk is unclear.

Dose-response effects of dietary fiber on NMU-induced mammary tumorigenesis, estrogen levels and estrogen excretion in female rats

The dose-related effects of the fiber-rich isolate, soft white wheat bran (SWWB), and the pure fiber, cellulose, on N-nitrosomethylurea (NMU)-induced mammary tumorigenesis was assessed in F344 female rats. SWWB (45% total dietary fiber, TDF) was added to the AIN-76A high-fat diet at 9, 12, 15 and 18%; cellulose (98% TDF) was added to the same diet at 4.5, 6, 7.5 and 9%, to give equivalent amounts of TDF. The experimental diets were fed 3 days post-NMU and continued for a period of 25 weeks, at which time the experiment was terminated and tumors enumerated. It was found that significant inhibition of mammary carcinoma occurred only at 9% SWWB, non-significant inhibition occurred at 12% SWWB, and no inhibition was seen at higher doses. Cellulose-fed animals exhibited consistently higher tumor yields regardless of dose. The difference in tumor yields between the 9% SWWB group and the remaining seven groups was attributable to an increased incidence in tumors characterized histologically as intraductal proliferation and ductal carcinoma in situ in the latter. Analysis of blood, urine and fecal estrogens was conducted to test whether dietary fiber exerted its tumor-inhibiting effect by altering the enterohepatic recycling of estrogens. Although SWWB, in general, lowered urinary estrogen excretion, increased fecal estrogen excretion and lowered blood estrogens, there was no consistent correlation between the amount of SWWB consumed, estrogen status and tumor yields. These results suggest that (i) wheat bran fiber at 9%, or minor constituents associated with it, contain anti-promoting properties that cellulose lacks; (ii) SWWB appears to exert its effects by suppressing the clonal expansion phase of mammary carcinogenesis; (iii) there is an upper limit (12-15% w/w) to the protective effects of SWWB; and (iv) the effects of SWWB on mammary tumorigenesis may not be attributed to alterations in the enterohepatic recycling of estrogens.

Endocrinology: The impact of cigarette smoking on the plasma concentrations of gonadotrophins, ovarian steroids and androgens and upon the metabolism of oestrogens in the human female

This study compares the plasma gonadotrophin, oestradiol, and androgen and salivary progesterone concentrations in a single menstrual cycle between 25 normal pre-menopausal women who smoke cigarettes and 21 who are non-smokers. The effect of smoking on luteinizing hormone (LH) pulsatility and the urinary excretion of oestrogens is also described. Cigarette smoking did not consistently suppress LH pulsatility. There was no significant difference in the length of either the follicular or luteal phases. There were no significant differences in the mean plasma oestradiol concentrations in the follicular phase in smokers compared to non-smokers. There were no significant differences in the mean salivary progesterone concentration in the luteal phase in smokers compared to non-smokers. There was no significant difference in plasma concentrations of testosterone, androstenedione and dehydroepiandrosterone sulphate. There was also no significant difference between the urinary concentrations of oestradiol, oestrone or oestriol. We have been unable to demonstrate a detrimental effect of cigarette smoking on any of the important endocrine characteristics of the menstrual cycle, and we conclude that these data suggest that the anti-oestrogenic effect of smoking does not work through alterations in pituitary or follicular endocrine function or in alterations in the metabolism of oestrogens.