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BACKGROUND: Tamoxifen and the citrus flavonoid tangeretin exhibit similar inhibitory effects on the growth and invasive properties of human mammary cancer cells in vitro; furthermore, the two agents have displayed additive effects in vitro. In this study, we examined whether tangeretin would enhance tamoxifen's therapeutic benefit in vivo. METHODS: Female nude mice (n = 80) were inoculated subcutaneously with human MCF-7/6 mammary adenocarcinoma cells. Groups of 20 mice were treated orally by adding the following substances to their drinking water: tamoxifen (3 x 10(-5) M), tangeretin (1 x 10(-4) M), tamoxifen plus tangeretin (3 x 10(-5) M plus 1 x 10(-4) M), or solvent. RESULTS AND CONCLUSIONS: Oral treatment of mice with tamoxifen resulted in a statistically significant inhibition of tumor growth compared with solvent treatment (two-sided P = .001). Treatment with tangeretin did not inhibit tumor growth, and addition of this compound to drinking water with tamoxifen completely neutralized tamoxifen's inhibitory effect. The median survival time of tumor-bearing mice treated with tamoxifen plus tangeretin was reduced in comparison with that of mice treated with tamoxifen alone (14 versus 56 weeks; two-sided P = .002). Tangeretin (1 x 10(-6) M or higher) inhibited the cytolytic effect of murine natural killer cells on MCF-7/6 cells in vitro, which may explain why tamoxifen-induced inhibition of tumor growth in mice is abolished when tangeretin is present in drinking water. IMPLICATIONS: We describe an in vivo model to study potential interference of dietary compounds, such as flavonoids, with tamoxifen, which could lead to reduced efficacy of adjuvant therapy. In our study, the tumor growth-inhibiting effect of oral tamoxifen was reversed upon addition of tangeretin to the diet. Our data argue against excessive consumption of tangeretin-added products and supplements by patients with mammary cancer during tamoxifen treatment.

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A method is presented, based on high performance liquid chromatography (HPLC) with u.v. absorbance detection, to simultaneously analyse all major unconjugated steroids in ovarian follicular fluids. The total analysis time is only 30 min. The use of a 3 mm i.d. column allows us to obtain detection limits for 3-oxo-4-ene steroids of 2 ng/ml. Calibration curves are linear in the 10-20,000 ng range per injection. Excellent agreement is obtained with the results using a previously published gaschromatography method.

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OBJECTIVE: Is there any correlation between follicular fluid (FF) steroid levels and the occurrence of cytogenetic abnormalities in unfertilized human oocytes? DESIGN: Cytogenetic analysis was carried out on 397 oocytes, and the steroid content of 104 corresponding FF was analyzed using high-pressure liquid chromatography. Ovarian stimulation was performed by clomiphene citrate and human menopausal gonadotropin (hMG) or by hMG combined with a gonadotropin-releasing hormone agonist (GnRH-a) pretreatment. RESULTS: Oocyte maturity was correlated with an increasing FF progestin content and a significant decrease of androstenedione (A) levels. Chromosomal analysis revealed 84 of all oocytes to be abnormal (polyploid or aneuploid and/or prematurely condensed chromosomes present). In this group, A levels and A to estradiol ratios were significantly higher. Although progestin levels were higher in GnRH-a/hMG cycles, the incidence of oocyte normality was not different between the two stimulation schemes. More abnormal oocytes were found in patients with good sperm morphology. CONCLUSIONS: Oocyte abnormality correlates with higher A levels in the corresponding FF. Oocyte fertilization is also determined by intrinsic oocytic factors other than maturity.

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Steroid levels in follicular fluid (FF) obtained from stimulated ovaries in patients undergoing in vitro fertilization (IVF) were measured by capillary gas chromatography. The correlation between these levels and the maturity of the oocyte, judged from the morphology of the oocyte corona cumulus complex (OCCC) and the fertilizability of the oocytes was analysed. Oocyte maturity was associated with higher FF levels of progesterone, 17-hydroxyprogesterone, 16 alpha-hydroxyprogesterone and 20 alpha-dihydroprogesterone. Follicular fluids containing oocytes that became fertilized had significantly higher levels of 20 alpha-dihydroprogesterone and progesterone and lower levels of androstenedione. Of all the steroids determined, 20 alpha-dihydroprogesterone provides the most significant group differences. Enhanced 20 alpha-dihydrogenation in the presence of decreased 16 alpha- and 17-hydroxylation appears to be an important characteristic of the ultimate ripening stages and early luteinization, at least in stimulated cycles.

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A method is presented based on capillary GLC using both a thermionic and a flame ionization detector to simultaneously analyse all major unconjugated steroids in ovarian follicular fluids (FF). Although specificity can not always be guaranteed for the smaller concentrations of androstenedione and cortisol, accuracy and reproducibility are excellent for the major progestagens and estrogens (progesterone, 17- and 16 alpha-hydroxyprogesterone, pregnenolone, 20 alpha-dihydroprogesterone, estradiol and estrone). Above all the analysis is performed with relatively cheap instrumentation and products. Apart from the "profiles" of unconjugated steroids, a semi-quantitative analysis of steroid conjugates is possible if a preliminary group separation with disposable anion exchanger columns is included.

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Adsorption and desorption modes have been elaborated which allow the separation of complex steroid mixtures of biological fluids into an unconjugated, a glucuronic acid conjugated and a sulphuric acid and mixed conjugated fraction. Capillary gas chromatographic analysis of the fractions obtained provides "total steroid profiles" of urine, blood, ovarian follicle fluid and amniotic fluid.

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This prospective study represents an attempt to find a link between subclinical intra-amniotic infection and preterm singleton labor in 27 asymptomatic patients with intact membranes. Liquor amnii was obtained by transabdominal amniocentesis and cultured for anaerobic and aerobic bacteria and mycoplasmas. None of these cultures was positive. The value of gas-liquid chromatographic determination of volatile and non-volatile acids in liquor amnii could not be determined because amniotic infections did not occur in the population under study.

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By applying capillary gas chromatography (GC) and gas chromatography mass spectrometry (GC-MS), a simultaneous quantitation of all important steroid sulfates present in a number of breast cyst fluids, has been obtained. The fact that prevailing androgen sulfate structures in the cyst fluids are different from those in blood suggests at least intracystic metabolism of blood-born precursors. Particularly greater amounts of 5 alpha-reduced steroids are found in breast cysts. 5 alpha-Androstane-3 alpha,17 beta-diol is a major androgen sulfate of breast cyst fluids, its concentration being some 2000-fold that of blood. After prolonged topical application of progesterone on the breast, an accumulation of the sulfates of several pregnanediol isomers could be observed.

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The relationship between the presence or absence of an ovulation stigma and (1) the fertility status, (2) the incidence of endometriosis, (3) the concentration of progesterone and estradiol in the peritoneal fluid, and (4) the blood levels of luteinizing hormone, follicle-stimulating hormone, progesterone, and estradiol in 21 fertile and 45 infertile patients who underwent a laparoscopy in the early (n = 48) or late luteal phase (n = 18) was investigated. An ovulation stigma was observed in about half of the patients, irrespective of their fertility status (past and subsequent), the presence of endometriosis, or the time of the luteal phase. Progesterone and estradiol concentrations in the peritoneal fluid were highest in the early luteal phase, but they were not correlated with the presence or absence of an ovulation stigma. No significant differences were observed in peripheral hormone levels between women with and those without an ovulation stigma nor between women with high or low concentrations of progesterone in the peritoneal fluid. From the data, it is concluded that hormone assays are of no aid in the diagnosis of the luteinized unruptured follicle syndrome and that the absence of an ovulation stigma on laparoscopic examination cannot be equated with the luteinized unruptured follicle syndrome.

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Steroid profiling by capillary gas chromatography has been applied to the analysis of free and conjugated steroids in serum, ovarian follicles, lutein cyst and peritoneal fluids. Sep-Pak C18 octadecylsilica was used for extraction, whereas the separation of free and different conjugates was accomplished by successive hydrolysis and liquid extraction steps.

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Seven anorexia nervosa (A.N.) patients had reduced urinary excretion values of tetrahydrocortisone (THE), androsterone (A) and 5alpha-tetrahydrocortisol (5alpha-THF). THE to tetrahydrocortisol (THF), A to aetiocholanolone (Ae) and 5alpha-THF to THF ratios were all significantly reduced. Six A.N. patients had oral metyrapone tests with quantitatively normal but delayed urinary 3alpha,17alpha,21-trihydroxy-5beta-pregnan-20-one (THS) response. The steroid determinations were done by capillary gaschromatography, which proves to be of value in the study of the above mentioned metabolic abnormalities.

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Neutral steroids in urine were determined quantitatively with gaschromatography on capillary columns in a case of benign hydatidiform mole associated with bilateral theca-lutein cysts. A remarkable finding was the very high levels of 17-hydroxypregnanolone and pregnanetriol, which continued to rise until the 15th day after molar evacuation.

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