RESUMO
BACKGROUND: Because of the vast range of physiological relevant estradiol concentrations the requirements to be met by an estradiol assay are high. In the present study the performance of various commercially available estradiol assays was evaluated with regard to imprecision and long-term stability. METHODS: Precision and long-term stability of 7 commercially available estradiol immunoassays were assessed in a multi-centre quality control study based on the repeated measurement of liquid BIOREF estradiol control sera by 18 laboratories during a 14-month study period. RESULTS: The mean estradiol concentrations determined in 594 runs performed for each control level were 71 pg/ml, 349 pg/ml and 676 pg/ml. A high variation was found for the method specific mean values calculated from all results measured with the same method, which ranged between 32 - 90 pg/ml, 187 - 392 pg/ml and 373 - 790 pg/ml, resulting in a similar high inter-laboratory variation with coefficients of variation (CVs) of 25.0%, 16.7% and 17.5%. In contrast, the intra-laboratory variation of estradiol values as well as the variation of values measured with the same method were found to be considerably lower with coefficients of variation < 10% for most laboratories and methods; only the low control level was measured with CV values > 10% by the majority of laboratories and methods. For none of the laboratories a tendency was observed in the results from beginning to end of the 14 month study period indicating a high uniformity in assay production and a good long-term stability of the control material used. CONCLUSIONS: The present data demonstrate that also with the currently available estradiol immunoassays the comparability of results measured with different methods is limited. With most assays very low estradiol concentrations, as observed in postmenopausal women, can be determined only with a precision which is not adequate for clinical assessment.
Assuntos
Estradiol/sangue , Imunoensaio/normas , Estabilidade de Medicamentos , Feminino , Fase Folicular/fisiologia , Humanos , Laboratórios/normas , Masculino , Pós-Menopausa , Controle de Qualidade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Caracteres SexuaisRESUMO
This communication deals with a longitudinal evaluation of C-reactive protein (CRP) analysis during a one-year period using a single lot of liquid control sera (3 levels) (BIOREF-CRP levels 1, 2 and 3) in different laboratories. A total of 652 sets of data were returned from 20 participating laboratories using 13 different reagent-measuring device combinations. The use of the control materials was defined in a standard operating procedure. Data was returned to the organizers on a monthly basis and questions could be asked or problems presented during the evaluation period. Although the performance of different reagents varied, the control materials were shown to be stable over the whole of the evaluation period when stored at 4-7 degrees C in a refrigerator/cold room. Typical problems were encountered, examples of which are presented here in graphical and tabular form.
Assuntos
Proteína C-Reativa/análise , Humanos , Indicadores e Reagentes , Estudos Longitudinais , Nefelometria e Turbidimetria/métodos , Reprodutibilidade dos TestesRESUMO
The effects of RU 486 together with estradiol and progesterone on estrogen receptor alpha and progesterone receptor (isoforms A and B) expression were studied in human endometrial long term cultures at the mRNA and protein level. We asked whether ligand induced receptor regulation, found in mammals in vivo, is also found in human cultured endometrial cells with special regard to the progesterone isoforms A and B. Endometrial cultures were maintained for 27 days. Media were supplemented with progesterone and/or estradiol alone or in combination with RU 486. Receptor expression (estrogen receptor alpha and progesterone receptor isoform A and B) was examined at the mRNA level by RT-PCR and at the protein level by western blot analysis. All receptor types examined were expressed in our culture model. Estradiol led to a general increase of receptor expression whereas treatment with estradiol in combination with progesterone down regulated receptor expression. The receptor down regulation was not found when RU 486 was additionally supplemented into the medium. Activation or inhibition of expression due to these treatments was similar for both PR isoforms. Our results (1) show that in our culture system estradiol induced up regulation of estrogen receptor and progesterone receptor A and B and suggest that the estrogen induced up regulation is prevented by progesterone (2) a clear cut antigestagenic effect of RU 486 and (3) suggest that both progesterone isoforms are analogously regulated in our culture model. We conclude that human endometrial cell cultures are suitable for the study of the dynamics of steroid receptor expression.
Assuntos
Endométrio/metabolismo , Regulação da Expressão Gênica , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , Western Blotting , Células Cultivadas , Interações Medicamentosas , Endométrio/química , Estradiol/farmacologia , Receptor alfa de Estrogênio , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Antagonistas de Hormônios/farmacologia , Humanos , Mifepristona/farmacologia , Pré-Menopausa , Progesterona/antagonistas & inibidores , Progesterona/farmacologia , RNA Mensageiro/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análiseRESUMO
A strict and adequate quality assurance program is the only real guarantee of the reliability of laboratory test results. Such proficiency testing was carried out for the CA 125 test system in five university laboratories over a period of three years (1984-1987) using five different reference materials (BIOREF, FRG). A concentration-dependent performance profile could thus be established evaluating a total of 301 assays. Intra-assay precision of the test ranged between 4.8 and 11.5%, and interassay precision between 13.6 and 19.1%. Laboratory specific average values of the individual reference materials ranged between 26 and 32 U/ml for reference 1, 51 and 59 U/ml for reference 2, 109 and 121 U/ml and 193 to 240 U/ml for references 3 and 4, respectively. Mean values for reference 5 ranged between 401 and 458 U/ml. There was no significant difference between mean values for the laboratories. Considerable batch-dependent variations of values became evident during the study but these were not indicated by the kit control supplied by the manufacturer. During the whole investigation period no systematic drift in values could be observed using trend analysis, indicating excellent stability of the reference material if stored frozen (-20 degrees C).
Assuntos
Antígenos Glicosídicos Associados a Tumores/normas , Biomarcadores Tumorais/normas , Radioimunoensaio/normas , Kit de Reagentes para Diagnóstico/normas , Antígenos Glicosídicos Associados a Tumores/análise , Biomarcadores Tumorais/análise , Estabilidade de Medicamentos , Humanos , Cooperação Internacional , Valor Preditivo dos Testes , Controle de Qualidade , Padrões de ReferênciaRESUMO
BACKGROUND: Studies indicate that gastrectomy might alter calcium and bone metabolism, resulting in bone disorders. No data are currently available on the prevalence of bone disorders after gastrectomy. METHODS: Sixty gastrectomy patients were investigated for serum parameters of calcium and bone metabolism 5 to 20 years postoperatively and compared to an age- and sex-matched healthy control population. Forty patients agreed to a radiological investigation of the spine by anterior-posterior and lateral radiographs of the thoracic and lumbar spine and by computed tomography (CT) osteodensitometry. RESULTS: Serum calcium and 25-(OH)-vitamin D were decreased in gastrectomized patients, while parathyroid hormone and 1,25-(OH)2-vitamin D were increased. Serum parameters of calcium metabolism were altered in as many as 68% of patients. We found 31 vertebral fractures in 13 patients, 30 grade 2 vertebral deformities in 18 patients, and osteopenia in 15 patients, corresponding to a prevalence of 33%, 45%, and 37% in gastrectomized patients, respectively. The overall rate of gastrectomy patients having vertebral fractures and/or osteopenia was 55%. The risk of having a vertebral deformity was increased by more than sixfold after gastrectomy. Our study is the first report evaluating vertebral deformities in gastrectomized patients, and the largest series of gastrectomized patients investigated by CT osteodensitometry. CONCLUSION: We found a high prevalence of bone disorders in gastrectomized patients, possibly resulting from disorders in calcium metabolism. Postgastrectomy bone disease might derive from a calcium deficit, which increases calcium release from bone and impairs calcification of newly build bone matrix.
Assuntos
Doenças Ósseas Metabólicas/epidemiologia , Distúrbios do Metabolismo do Cálcio/epidemiologia , Fraturas Espontâneas/epidemiologia , Síndromes Pós-Gastrectomia/epidemiologia , Fraturas da Coluna Vertebral/epidemiologia , Absorciometria de Fóton , Adenocarcinoma/cirurgia , Densidade Óssea , Doenças Ósseas Metabólicas/diagnóstico por imagem , Doenças Ósseas Metabólicas/etiologia , Osso e Ossos/metabolismo , Cálcio/metabolismo , Distúrbios do Metabolismo do Cálcio/diagnóstico , Distúrbios do Metabolismo do Cálcio/etiologia , Estudos de Casos e Controles , Feminino , Fraturas Espontâneas/diagnóstico por imagem , Fraturas Espontâneas/etiologia , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Prevalência , Fraturas da Coluna Vertebral/etiologia , Neoplasias Gástricas/cirurgia , Úlcera Gástrica/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Because of the beneficial effects of estrogen, premenopausal women are normally protected against coronary heart disease (CHD) and are at lower risk for myocardial infarction; consequently, CHD occurs very rarely in menstrually active women. Given this background, the aim of the present study was to test the hypothesis that decreased concentrations of estrogen are associated with CHD in premenopausal women. METHODS: Fourteen premenopausal women with CHD were investigated and compared with a healthy control group comparable for age and cardiovascular risk factors. Relevant characteristics of patients and controls were assessed: age, blood pressure, body mass index, total cholesterol and high-density lipoprotein cholesterol, triglycerides, former pregnancies, ovariectomy and related surgical interventions, smoking history and former use of oral contraceptives. To ensure the premenopausal status of the participants, the regularity of the menstrual cycle and the follicle-stimulating hormone concentrations were also assessed. Plasma estradiol and progesterone and urine estrone concentrations (24 h urine collection) were measured at day 6 after estimated ovulation to assess the relative increase in plasma estradiol and progesterone during the second half of the menstrual cycle. RESULTS: Compared with the control group, premenopausal women with CHD had significantly lower concentrations of plasma estradiol (408.9 +/- 141 pmol/l and 287.8 +/- 109 pmol/l respectively; P = 0.0228) and total estrogen (2061 +/- 693 pg/mumol creatinine and 1607 +/- 448 pg/mumol creatinine respectively; P = 0.025) in the urine. However, the progesterone concentrations were not significantly different between the groups. These findings might be explained by a partial ovarian dysfunction, as the patient group had a significantly higher number of tubal sterilizations (eight compared with one). CONCLUSION: Our data provide support for the hypothesis that decreased concentrations of estradiol might be an additional pathogenetic factor for the development of CHD in menstrually active premenopausal women.
Assuntos
Doença das Coronárias/sangue , Estradiol/sangue , Pré-Menopausa/sangue , Adulto , Doença das Coronárias/epidemiologia , Doença das Coronárias/etiologia , Estradiol/biossíntese , Estrogênios/urina , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Valores de Referência , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
Serotonin, known for its beneficial action on mood and well-being, is also involved in cardiovascular functions. Thus the current work was undertaken to study the effect of hormone replacement therapy on serotonin turnover in postmenopausal women. Eighteen women received estradiol transdermally and 17 women estradiol valerate orally for 4 weeks. The serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA) was determined in the urine before, and after 2 and 4 weeks' estradiol treatment. With both administration routes estradiol produced a significant increase in urinary 5-HIAA excretion, greatest with transdermal estradiol after 28 days of treatment. The enhancement of serotonin turnover may contribute not only to an improvement of mood and well-being but also to a cardioprotective effect of estradiol observed after hormone substitution in postmenopausal women.
Assuntos
Estradiol/uso terapêutico , Terapia de Reposição de Estrogênios , Ácido Hidroxi-Indolacético/urina , Pós-Menopausa , Serotonina/metabolismo , Administração Cutânea , Administração Oral , Afeto/efeitos dos fármacos , Creatinina/urina , Estradiol/administração & dosagem , Estradiol/análogos & derivados , Estradiol/urina , Estrogênios Conjugados (USP)/administração & dosagem , Estrogênios Conjugados (USP)/uso terapêutico , Estrogênios Conjugados (USP)/urina , Estrona/urina , Feminino , Saúde , Coração/efeitos dos fármacos , Humanos , Hipertensão/urina , Pessoa de Meia-Idade , Estudos Prospectivos , Serotonina/urinaRESUMO
The E-Screen assay serves as an in vitro tool for the detection of estrogenic activity of chemicals and extracts of environmental samples. Based on the induction of proliferation in human estrogen receptor-positive MCF-7 breast cancer cells we could substantially simplify the assay. As one important step of validation we applied the modified assay for testing nine known xenoestrogens. We could confirm the results of other groups assuring the reproducibility of the E-Screen assay. The results provide evidence that the E-Screen assay is suitable for determination of estradiol equivalency factors (EEFs) for environmental estrogens to rank their estrogenic potency relative to the natural estrogen 17 beta-estradiol. Further, we used the optimized proliferation test to screen nine halogenated phenolic compounds for their possible estrogenic potency. Three widely applied chemicals expressed a weak receptor-mediated estrogenic activity: the flame retardant Tetrabromo-Bisphenol-A, the disinfectant 4-chloro-3-methylphenol, and the herbicide educt 4-chloro-2-methylphenol. Their estrogenic potencies were five to six orders of magnitude lower than that of 17 beta-estradiol.
Assuntos
Estrogênios/farmacologia , Fenóis/toxicidade , Receptores de Estrogênio/efeitos dos fármacos , Bioensaio/métodos , Neoplasias da Mama , Feminino , Halogênios , Humanos , Reprodutibilidade dos Testes , Testes de Toxicidade/métodos , Células Tumorais CultivadasRESUMO
The influence of estradiol treatment on the urinary excretion of relaxin, a hormone in earlier years only found during pregnancy and presently associated with functions in the cardiovascular system, was investigated in postmenopausal women. Thirteen postmenopausal women were treated with transdermal estradiol and 12 women with oral estradiol for 4 weeks. A new radioimmunoassay for human-relaxin (rec-hRLX-2) was used. With transdermal, but not with oral administration, a significant increase of urinary relaxin excretion was registered. Further experiments are necessary to elucidate the source of urinary relaxin and its role in the hormone replacement therapy of postmenopausal women.
Assuntos
Estradiol/farmacologia , Terapia de Reposição de Estrogênios , Pós-Menopausa/urina , Relaxina/urina , Administração Cutânea , Administração Oral , Adulto , Idoso , Estatura/fisiologia , Peso Corporal/fisiologia , Fenômenos Fisiológicos Cardiovasculares , Sistema Cardiovascular/efeitos dos fármacos , Estradiol/administração & dosagem , Estradiol/sangue , Estrogênios/urina , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa/efeitos dos fármacos , Pós-Menopausa/fisiologia , Fatores de Tempo , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologiaRESUMO
CA125 is currently the most widely used tumor marker for ovarian epithelial cancer. The aim of this article is to provide guidelines for the routine clinical use of CA125 in patients with ovarian cancer. Due to lack of sensitivity for stage I disease and lack of specificity, CA125 is of little value in the detection of early ovarian cancer. At present, therefore, CA125, either alone or in combination with other modalities, cannot be recommended for screening for ovarian cancer in asymptomatic women outside the context of a randomized controlled trial. Preoperative levels in postmenopausal women, however, may aid the differentiation of benign and malignant pelvic masses. Serial levels during chemotherapy for ovarian cancer are useful for assessing response to treatment. Although serial monitoring following initial chemotherapy can lead to the early detection of recurrent disease, the clinical value of this lead-time is unclear. CA125 is the ovarian cancer marker against which new markers for this malignancy should be judged.
Assuntos
Biomarcadores Tumorais/sangue , Antígeno Ca-125/sangue , Neoplasias Ovarianas/sangue , Diagnóstico Diferencial , Europa (Continente) , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Prognóstico , Sociedades CientíficasRESUMO
23 women of reproductive age were treated with Buserelin nose-spray for endometriosis, which had been diagnosed by laparoscopic and bioptic methods. The treatment period was 6 months. Various hormones in serum were determined after 2, 4, 8, 12, 16, 20 and 24 weeks during treatment. LH, E2, prolactin, progesterone, and testosterone concentrations were significantly decreased under Buserelin therapy, whereas there was only a slight decrease in FSH, free testosterone and androstendion. No changes were observed in the concentrations of DHEAS and SHEBG. Buserelin had no androgenic effect. There was a significant decrease of endometriosis as judged by the implantation score.
Assuntos
Androgênios/sangue , Busserrelina/administração & dosagem , Endometriose/tratamento farmacológico , Hormônios Esteroides Gonadais/sangue , Neoplasias Pélvicas/tratamento farmacológico , Administração Intranasal , Adolescente , Adulto , Busserrelina/efeitos adversos , Endometriose/sangue , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Neoplasias Pélvicas/sangue , Progesterona/sangue , Prolactina/sangue , Globulina de Ligação a Hormônio Sexual/metabolismoRESUMO
Buserelin has been applied intranasal in 31 women of the reproductive age for endometriosis that had been diagnosed by laparoscopic and bioptic means. The treatment period was 6 month and hormonal changes were evaluated after 2, 4, 8, 12, 17, 20, and 24 weeks. After 2 weeks we observed a decrease of FSH to the lower normogonadotropic range, and of progesteron to less than 0.5 ng/ml. After 4 weeks LH decreased to the lower normogonadotropic range and E2 was below 55 pg/ml. Prolactin concentrations varied between 6 and 8 ng/ml.
Assuntos
Busserrelina/uso terapêutico , Endometriose/tratamento farmacológico , Neoplasias dos Genitais Femininos/tratamento farmacológico , Hormônios Esteroides Gonadais/sangue , Adulto , Endometriose/sangue , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Seguimentos , Neoplasias dos Genitais Femininos/sangue , Humanos , Hormônio Luteinizante/sangue , Pessoa de Meia-Idade , Progesterona/sangue , Prolactina/sangueRESUMO
Twenty-eight hyperandrogenemic women suffering from infertility owing to chronic anovulation were treated with hMG. Only 7 patients exhibited the typical polycystic ovarian appearance of multiple subcortical cysts, however, a wide range (6-15 cm3) of ovarian volume was observed. The LH/FSH ratio was consistently lower than 2.5 and circulating androgens of both ovarian and adrenal origin were elevated. The 4 days dexamethasone suppression test showed more than 80% suppression of dehydroepiandrosterone-sulphate and a variable (40-60%) reduction of testosterone and androstenedione levels. Two different patterns of follicular development were observed in response to hMG. Sixteen patients exhibited polycystic ovarian reaction, whereas 12 women had a follicular growth pattern similar to that seen in hMG-stimulated normo-ovulatory subjects. Patients with polycystic ovarian reaction showed a significantly increased androstenedione response to hMG when compared with the other group. Moreover, the non-stimulated ovarian volume was found to be markedly greater than in subjects without polycystic reaction. Thus, ovarian stimulation of patients with mixed hyperandrogenemia may elucidate the presence of borderline polycystic ovaries; furthermore the increased accumulation of androstenedione may suggest an inherent ovarian failure.
Assuntos
Androgênios/sangue , Anovulação/etiologia , Infertilidade Feminina/etiologia , Menotropinas , Ovário/fisiopatologia , Síndrome do Ovário Policístico/diagnóstico , Adulto , Androstenodiona/sangue , Anovulação/fisiopatologia , Desidroepiandrosterona/análogos & derivados , Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona , Dexametasona , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Infertilidade Feminina/fisiopatologia , Hormônio Luteinizante/sangue , Ovário/patologia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/patologia , Síndrome do Ovário Policístico/fisiopatologia , Testosterona/sangueRESUMO
In 46 patients with the diagnosis of "premature menopause" menstrual history, clinical findings and hormonal quantitations were analysed. This clinical entity was evaluated with regard to a rapid verification of the diagnosis. The age of the investigated women with secondary failure to menstruate varied between 13 to 39 years (mean value 29 years). Menstrual history varied considerably. 20 women complained about menopausal symptoms. 5 women had adnexal operations before. Vaginal hormonal cytology, gestagen test and quantitation of the circulating oestradiol concentrations were of little value for establishing the diagnosis, since many of these women revealed premenopausal oestradiol levels. Quantitation of FSH is decisive for establishing the diagnosis. In women under the age of 40 with FSH values above 1000 ng LER 907/ml or above 40 mIU/ml premature ovarian failure can be assumed; however, in individual cases the "gonadotropin resistant ovary syndrome" must be differentiated.
Assuntos
Menopausa Precoce , Menopausa , Adolescente , Adulto , Amenorreia/diagnóstico , Clomifeno , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Cariotipagem , Menopausa/sangue , Menopausa Precoce/sangue , Menopausa Precoce/fisiologiaRESUMO
Progesterone and 5 alpha-pregnane-3,20-dione (5 alpha-DHP) were determined by radioimmunoassay in 242 amniotic fluid samples from 16-19 weeks of gestation. 165 samples fulfilled the criteria of the normal collective. There is a positive correlation (r = 0.359, p less than 0.001) between progesterone and 5 alpha-DHP. The mean concentration (+/- SD) of progesterone for normal pregnancies was 68.04 +/- 35.56 ng/ml, the mean for 5 alpha-DHP was 6.6 +/- 4.76 ng/ml. A slight decrease of the hormone concentrations with increase of the week of gestation was observed. 7 cases, who later developed EPH-gestosis showed a significant higher progesterone concentration (p less than 0.05). 16 women with premature labor had a significant higher 5 alpha-DHP concentration (p less than 0.05). Significantly elevated progesterone and 5 alpha-DHP values were found in 36 cases of bleedings in early pregnancy. Pregnant women older than 35 years proved to have a significant higher 5 alpha-DHP concentration (p less than 0.05). Also women, who delivered a child weighing less than 2,500 g (n = 8), showed a significant higher progesterone concentration (p less than 0.01). There was no difference in amniotic fluid progesterone and 5 alpha-DHP concentration depending on the sex of the child. The hormone concentrations of 3 cases with Morbus Langdon-Down were slightly below the mean concentration for progesterone and 5 alpha-DHP. Progesterone and 5 alpha-DHP concentrations were found to be normal in one case each of open Ductus Botalli, esophagial atresia, conjunctival bleeding with eyelid edema, teleangiectasia, Morbus Gaucher, sicklefoot, omphalocele, clubfoot, and stillbirth respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Líquido Amniótico/metabolismo , Progesterona/metabolismo , 5-alfa-Di-Hidroprogesterona , Feminino , Idade Gestacional , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Idade Materna , Trabalho de Parto Prematuro/metabolismo , Pré-Eclâmpsia/metabolismo , Gravidez , Gravidez de Alto Risco , Pregnanodionas/metabolismo , Diagnóstico Pré-NatalRESUMO
Relaxin and human chorionic gonadotropin (HCG) were determined in the blood serum of women during normal and pathological pregnancy in the 1st trimester. In normal pregnancy, the hormones showed similar behavior in their secretion pattern up to the 7th week with continuously increasing concentrations. Thereafter different patterns in their secretion developed. In pathological pregnancy, both relaxin and HCG concentrations were significantly lower than in undisturbed pregnancy, following an almost parallel course without peaks.
Assuntos
Gonadotropina Coriônica/sangue , Complicações na Gravidez/sangue , Gravidez/sangue , Relaxina/sangue , Feminino , Humanos , Primeiro Trimestre da GravidezRESUMO
Anovulatory patients with clomiphene-resistant polycystic ovarian syndrome were treated by two different stimulation protocols. Follicular maturation was induced in 14 women with hMG; 12 of them received pure FSH in a later series after previous pituitary desensitization with the LHRH agonist D-Trp-6-LHRH (Decapeptyl). Both basal and stimulated serum androstenedione, testosterone, and free testosterone were elevated in the hMG-treated group compared with controls. However, only androstenedione exhibited a significant increase between early and late follicular levels. Marked suppression of these androgens has been observed after two weeks of LHRH agonist pretreatment, but nearly the same concentrations were obtained with pure FSH on the day of hCG administration. Again, only the increase of androstenedione levels proved to be significant. Polycystic follicular maturation, hyperstimulation, and peak estradiol levels were comparable with the two protocols. Nevertheless, more pregnancies were achieved using the LHRH agonist+FSH combination (4 vs. 1). It is suggested that 2 weeks' suppression of ovarian androgens with LHRH agonist is not sufficient to neutralize the unfavourable intraovarian mechanisms interfering with normal folliculogenesis. More data are required to confirm the superiority of LHRH agonist pretreatment in the management of polycystic ovarian syndrome.
Assuntos
Androgênios/sangue , Hormônio Foliculoestimulante/uso terapêutico , Hormônio Liberador de Gonadotropina/análogos & derivados , Menotropinas/uso terapêutico , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/tratamento farmacológico , Androstenodiona/sangue , Anovulação/etiologia , Desidroepiandrosterona/sangue , Estradiol/sangue , Feminino , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Hormônio Luteinizante/sangue , Luteolíticos/sangue , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Síndrome do Ovário Policístico/complicações , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue , Pamoato de TriptorrelinaRESUMO
The clinical validity of tumor markers in breast cancer is reevaluated. Though ideal tumor markers are presently not available for breast cancer patients, optimizing markers can be achieved, applying markers in special situations and in selected fields of oncology. Tumor markers like carcinoembryonic antigen (CEA) and tissue polypeptide antigen are only of limited value in the primary diagnosis of breast cancer due to their low sensitivity and their poor specificity. Single postsurgical CEA values in selected groups of mammary carcinomas, however, can be used to predict patients with high risk of recurrence and they imply considerable prognostic information. Serial CEA determination in the follow-up of patients with operated breast cancer are highly sensitive in early detection of recurrences and are also useful in controlling therapy in individual cases. The biological basis of tumor marker measurements reflecting tumor growth is pointed out and newly developed methodologies for the potential establishment of more specific tumor markers for serodiagnosis and for immunolocalization of tumors are discussed.
Assuntos
Neoplasias da Mama/análise , Adulto , Idoso , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Antígeno Carcinoembrionário/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Peptídeos/análise , Prognóstico , Antígeno Polipeptídico TecidualRESUMO
Granulosa cells from 85 patients undergoing in-vitro fertilization were cultured to investigate the impact of different stimulation protocols on in-vitro steroid secretion. A luteinizing hormone-releasing hormone analogue (LHRHa) was used either in the long protocol (pituitary desensitization) or in the short, 'flare-up' regime. The steroidogenesis of granulosa cell cultures was investigated under basal conditions as well as after stimulation with luteinizing hormone (LH). The results were compared to the secretory capacity of cells obtained after treatment with gonadotrophins only. No correlation was found between the preovulatory oestradiol peak and subsequent in-vitro progesterone production. Granulosa-luteal cells from long protocol cycles exhibited lower progesterone production on day 2 after follicular aspiration. On days 3 and 4 there was no difference between the three stimulation protocols regarding either basal or stimulated progesterone secretion. Cells from poor responders produced significantly (P less than 0.05) less basal progesterone during culture but they responded sufficiently to an LH stimulus. Granulosa cells from polycystic ovaries showed the lowest basal progesterone secretion (P less than 0.01 versus control); however, a normal stimulated level was achieved by adding LH to the culture medium. It is concluded that long protocol LHRHa pretreatment affects the very early progesterone formation of granulosa-luteal cells. Based on these in-vitro results, both poor responders and patients with polycystic ovaries should be supported vigorously in the luteal phase.
Assuntos
Hormônio Liberador de Gonadotropina/fisiologia , Células da Granulosa/efeitos dos fármacos , Células Lúteas/efeitos dos fármacos , Ovário/efeitos dos fármacos , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/metabolismo , Progesterona/biossíntese , Adulto , Células Cultivadas , Feminino , Células da Granulosa/metabolismo , Humanos , Células Lúteas/metabolismo , RadioimunoensaioRESUMO
The time course of free oestradiol and oestrone as well as of total (free and conjugated) oestrone was determined in plasma of women after oral ingestion of 3.75 mg conjugated equine oestrogens, or 9.74 micromol of oestrone sulfate, oestrone, and oestradiol, respectively. All these oestrogen preparations led to transiently increased plasma oestrogen levels which fell to normal values after 48 h. The main difference observed between administration of free oestrone or oestradiol and of conjugated oestrogens (oestrone sulfate or equine oestrogens) was a much more protracted influx of oestrogens from the intestine into the plasma compartment, with a tendency to more sustained plasma levels, if conjugated oestrogens were administered. There was a consistent discontinuity in plasma oestrogen levels 10--12 h after oral ingestion of all the preparations examined indicating enterohepatic circulation. Comparison of "areas under the curve" obtained with the present preparations to similar previous studies on ethinyl oestradiol indicated that the bioavailability of the non-ethinyl oestrogens is by more than one order of magnitude less than that of ethinyl oestradiol after oral administration. The ratio of oestrone/oestradiol was the highest with free oestrone and similar among the other three preparations indicating an increased metabolism of sulfoconjugated oestrone to oestradiol after oral application when compared with free oestrone.
PIP: The time course of free estradiol and estrone as well as of total (free and conjugated) estrone was determined in plasma of women after oral ingestion of 3.75 mg conjugated equine estrogens, or 9.74 mcmol of estrone sulfate, estrone, and estradiol, respectively. All these estrogen preparations led to transiently increased plasma estrogen levels which fell to normal values after 48 hours. The main difference observed between administration of free estrone or estradiol and of conjugated estrogens (estrone sulfate or equine estrogens) was a much more protracted influx of estrogens from the intestines into the plasma compartment, with a tendency to more sustained plasma levels, if conjugated estrogens were administered. There was consistent discontinuity in plasma estrogen levels 10-12 hours after oral ingestion of all preparations examined, indicating enterohepatic circulation. Comparison of areas under the curve obtained with the present preparations similar to previous studies on ethinyl estradiol indicated that the bioavailability of the nonethinyl estrogens is by more than 1 order of magnitude less than that of ethinyl estradiol after oral administration. The ratio of estrone/estradiol was the highest with free estrone and similar among the other 3 preparations. This indicates an increased metabolism of sulfoconjugated estrone to estradiol after oral application when compared to free estrone. (author's modified)