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1.
Eur J Endocrinol ; 184(1): 107-122, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33112262

RESUMO

Objective: Hypogonadism is common in HIV-infected men. The relationship between health status, sex steroids and body composition is poorly known in HIV. The aim was to investigate the association between health status (comorbidities/frailty), body composition, and gonadal function in young-to-middle-aged HIV-infected men. Design: Prospective, cross-sectional, observational study. Methods: HIV-infected men aged <50 years and ongoing Highly Active Antiretroviral Therapy were enrolled. Serum total testosterone (TT), estradiol (E2), estrone (E1) were measured by liquid chromatography-tandem mass spectrometry, LH and FSH by immunoassay. Free testosterone (cFT) was calculated by Vermeulen equation. Body composition was assessed by dual-energy X-ray absorptiometry and abdominal CT scan. Multimorbidity (MM) and frailty were defined as ≥3 comorbidities and by a 37-item index, respectively. Results: A total of 316 HIV-infected men aged 45.3 ± 5.3 years were enrolled. Body fat parameters were inversely related to cFT and TT, and directly related to E1 and E2/testosterone (TS) ratio. Patients with MM had lower cFT (P < 0.0001) and TT (P = 0.036), and higher E1 (P < 0.0001) and E2/TS ratio (P = 0.002). Frailty was inversely related to cFT (R2 = 0.057, P < 0.0001) and TT (R2 = 0.013, P = 0.043), and directly related to E1 (R2 = 0.171, P < 0.0001), E2 (R2 = 0.041, P = 0.004) and E2/TS ratio (R2 = 0.104, P < 0.0001). Conclusions: Lower TT and cFT, higher E1, E2/TS ratio and visceral fat were independently associated to poor health status and frailty, being possible hallmarks of unhealthy conditions in adult HIV-infected men. Overall, MM, frailty and body fat mass are strictly associated to each other and to sex steroids, concurring together to functional male hypogonadism in HIV.


Assuntos
Tecido Adiposo , Estrona/sangue , Infecções por HIV/fisiopatologia , Hipogonadismo/fisiopatologia , Testosterona/sangue , Absorciometria de Fóton , Adulto , Terapia Antirretroviral de Alta Atividade , Composição Corporal , Estudos Transversais , Fragilidade/fisiopatologia , Fragilidade/virologia , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Nível de Saúde , Indicadores Básicos de Saúde , Humanos , Hipogonadismo/virologia , Masculino , Pessoa de Meia-Idade , Multimorbidade , Estudos Prospectivos
2.
Artigo em Inglês | MEDLINE | ID: mdl-32012981

RESUMO

BACKGROUND: Breast cancer rates in Asia are much lower than in Europe and North America. Within Asia, rates are lower in Mongolia than in neighboring countries. Variation in pregnancy exposure to endogenous hormone concentrations may explain the differences, but data are lacking. METHODS: We measured maternal serum progesterone, prolactin, estradiol and estrone concentrations in the second half of pregnancy in a cross-sectional study of urban (n = 143-194 depending on the analyte) and rural (n = 150-193) Mongolian women, and U.S. women from Boston (n = 66-204). Medical records provided information on maternal and perinatal factors. Geometric mean hormones were estimated from standard linear models with the log-hormone as the dependent variable and country as the independent variable adjusted for maternal and gestational age at blood draw. RESULTS: Mean concentrations of prolactin (5722 vs. 4648 uIU/mL; p < 0.0001) and estradiol (17.7 vs. 13.6 ng/mL; p < 0.0001) were greater in Mongolian than U.S. women, while progesterone (147 vs. 201 ng/mL; p < 0.0001) was lower. Mean hormone concentrations were similar in rural and urban Mongolian women. Results were generally similar, with additional adjustment for gravidity, parity, height, body mass index at blood draw, education and alcohol use during pregnancy, and when stratified by offspring sex or parity. CONCLUSIONS: Mongolian women had greater concentrations of prolactin and estrogen and lower concentrations of progesterone than U.S. women, while hormone concentrations were similar in rural and urban Mongolian pregnancies. IMPACT: These data do not support the hypothesis that estrogen concentrations in pregnant women are lower in Mongolian compared with Caucasian women.


Assuntos
Neoplasias da Mama/epidemiologia , Estradiol/sangue , Estrona/sangue , Gravidez/sangue , Progesterona/sangue , Prolactina/sangue , Adulto , Boston/epidemiologia , Estudos Transversais , Feminino , Humanos , Mongólia/epidemiologia , Adulto Jovem
3.
Am J Obstet Gynecol ; 222(4): 365.e1-365.e18, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31610152

RESUMO

BACKGROUND: Obesity disproportionately affects more women than men. The loss of ovarian function during the menopause transition coincides with weight gain, increases in abdominal adiposity, and impaired metabolic health. Racial differences in obesity prevalence that results from the menopause transition are not well understood. OBJECTIVE: The purpose of the study was to assess longitudinal changes in body composition and cardiometabolic risk among black and white women during the menopausal transition. STUDY DESIGN: In a secondary analysis of a prospective, observational cohort study (the Healthy Transitions study), 161 women ≥43 years old with a body mass index of 20-40 kg/m2 and who had not yet transitioned through menopause were enrolled at Pennington Biomedical Research Center. Women were seen annually for body composition by dual-energy X-ray absorptiometry, for abdominal adipose tissue distribution by computed tomography, for sex steroid hormones, and for cardiometabolic risk factors that include fasting glucose, insulin, and lipids. Surrogate measures of insulin sensitivity were also calculated. RESULTS: Ninety-four women (25 black, 69 white) transitioned through menopause and were included within the analyses. At menopause onset, black women weighed more (77.8±3.0 vs 70.8±1.8 kg) and had a higher systolic (125±16 vs 118±14 mm Hg) and diastolic (80±8 vs 74±7 mm Hg) blood pressure compared with white women (all P≤.05). No other differences in body composition, sex steroid hormones, or cardiometabolic risk factors were observed at menopause onset. Before menopause, white women gained significant weight (3 kg), total body adiposity (6% percent body fat, 9% fat mass, 12% trunk fat mass) and abdominal adipose tissue (19% subcutaneous fat, 15% visceral fat, 19% total adipose tissue), which coincided with significant decreases in estradiol, sex hormone-binding globulin, and estrone sulfate and increases in follicle-stimulating hormone, total cholesterol, and low-density lipoprotein cholesterol. Conversely, black women had more abdominal adipose tissue before menopause, which was maintained across the menopause transition. Black women also had significant decreases in estrone sulfate and total testosterone and increases in follicle-stimulating hormone before menopause. In the postmenopausal years, abdominal subcutaneous adipose tissue, total adipose tissue, follicle-stimulating hormone, total cholesterol, and low-density and high-density lipoprotein cholesterol increased only in white women. CONCLUSION: White women gained more abdominal adiposity during the menopause transition compared with black women, which, in part, may be due to differences in the pattern of sex steroid hormone changes between women of different racial backgrounds. The gains in abdominal adiposity in white women were observed in tandem with increased cardiometabolic risk factors. Future studies should consider comprehensive lifestyle approaches to target these increased gains in abdominal adiposity (ie, nutrition and physical activity coaching), while taking into account the potential interactions of race, body adiposity, sex steroid hormones, and their influence on cardiometabolic risk.


Assuntos
Adiposidade , Afro-Americanos , Grupo com Ancestrais do Continente Europeu , Hormônios Esteroides Gonadais/sangue , Pós-Menopausa/etnologia , Pré-Menopausa/etnologia , Glicemia/metabolismo , Pressão Sanguínea , Peso Corporal , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estradiol/sangue , Estrona/análogos & derivados , Estrona/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Insulina/sangue , Resistência à Insulina , Gordura Intra-Abdominal , Pessoa de Meia-Idade , Pós-Menopausa/fisiologia , Pré-Menopausa/fisiologia , Estudos Prospectivos , Globulina de Ligação a Hormônio Sexual/metabolismo , Gordura Subcutânea Abdominal
4.
Gynecol Endocrinol ; 36(2): 143-147, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31242783

RESUMO

The aim of this study was to investigate the relationship between serum estrone (E1) level and other cardinal features in women with polycystic ovary syndrome (PCOS). 133 Korean women aged 18-35 years who were newly diagnosed with PCOS at a university hospital were included in the present study. Blood samples were collected from all participants during the early follicular phase to determine the serum E1 level and other biochemical hormonal parameters. The total antral follicle count (TFC) and the total ovarian volume (TOV) were assessed using transvaginal or transrectal ultrasound. A significant correlation was found between serum E1 and luteinizing hormone (LH) levels in women with PCOS. In addition, statistically significant correlations were observed between serum E1 level and other hormonal parameters, including testosterone, free testosterone, dehydroepiandrosterone sulfate, and 17α-hydroxyprogesterone. With respect to the ultrasound features, serum E1 levels were significantly correlated with TFC and TOV. All results did not change after adjusting for body mass index (BMI). In conclusion, serum E1 level is significantly correlated with serum LH and androgen levels, and it may be a useful marker for representing the status of the ovarian volume in women with PCOS.


Assuntos
Estrona/sangue , Ovário/diagnóstico por imagem , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/diagnóstico por imagem , 17-alfa-Hidroxiprogesterona/sangue , Adolescente , Adulto , Sulfato de Desidroepiandrosterona/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Tamanho do Órgão/fisiologia , Folículo Ovariano/diagnóstico por imagem , Testosterona/sangue , Ultrassonografia , Adulto Jovem
5.
J Steroid Biochem Mol Biol ; 197: 105538, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31734493

RESUMO

Measuring some sex and precursor steroids is still challenging even by liquid chromatography - tandem mass spectrometry (LC-MS/MS), and few normal values are available. We developed a LC-MS/MS method for estradiol, estrone, dihydrotestosterone and 17-hydroxypregnenolone measurement, compared it with direct immunoassays, and generated sex, age, menopausal and menstrual status specific reference intervals. Liquid-liquid extraction was optimized on 300 µL serum spiked with isotopic internal standards. A 2D-LC system allowed on-line purification and separation in 11 min run. Electrospray ionization was enhanced by ammonium fluoride. MS-detection was obtained by multiple reaction monitoring. Direct ECLIA for estradiol (n = 80) and RIA for estrone (n = 41) were compared with LC-MS/MS. Reference values were estimated in healthy, lean women in reproductive age (n = 118), menopausal women (n = 33) and men (n = 159). The assay showed satisfying imprecision, trueness, recovery and selectivity. Adequate functional sensitivity was achieved for measuring estrone (18.1 pmol/L) and 17-hydroxypregnenolone (117 pmol/L) in all subjects, and estradiol (35.9 pmol/L) and dihydrotestosterone (134 pmol/L) in women in reproductive age and men, but not in menopausal women. Compared with LC-MS/MS, immunoassays showed good agreement for estradiol but severe disagreement for estrone. Estrogens exhibited sex, menopausal and menstrual variations. Dihydrotestosterone and 17-hydroxypregnenolone depended on sex and menopause, the latter also declining with age in men. Strictly defined reference intervals in the adult female and male population were generated for challenging steroids such as estrogens, dihydrotestosterone and 17-hydroxypregnenolone by a novel LC-MS/MS method. Our achievement can be used to deepen the comprehension of several endocrine diseases.


Assuntos
17-alfa-Hidroxipregnenolona/sangue , Cromatografia Líquida/métodos , Di-Hidrotestosterona/sangue , Estradiol/sangue , Estrona/sangue , Espectrometria de Massas em Tandem/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Adulto Jovem
6.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31720688

RESUMO

CONTEXT: The lack of sensitive and robust analytical methods has hindered the reliable quantification of estrogen metabolites in subjects with low concentrations. OBJECTIVE: To establish sex-specific reference ranges for estrone (E1) and estradiol (E2) throughout life and to evaluate sex-differences using the state-of-the-art liquid chromatography tandem mass spectrometry (LC-MS/MS) method for quantification of E1, E2, and estriol (E3). DESIGN: LC-MS/MS method development and construction of estrogen reference ranges. SETTINGS: Population-based cross-sectional cohorts from the greater Copenhagen and Aarhus areas. PARTICIPANTS: Healthy participants aged 3 months to 61 years (n = 1838). RESULTS: An isotope diluted LC-MS/MS method was developed and validated for measurements of serum E1, E2, and E3. Limits of detections (LODs) were 3 pmol/L (E1), 4 pmol/L (E2), and 12 pmol/L (E3), respectively. This sensitive method made it possible to differentiate between male and female concentration levels of E1 and E2 in children. In girls, E2 levels ranged from

Assuntos
Cromatografia Líquida/estatística & dados numéricos , Estradiol/sangue , Estrona/sangue , Fatores Sexuais , Espectrometria de Massas em Tandem/estatística & dados numéricos , Adolescente , Adulto , Criança , Pré-Escolar , Cromatografia Líquida/métodos , Feminino , Voluntários Saudáveis , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Valores de Referência , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem/métodos , Adulto Jovem
7.
J Steroid Biochem Mol Biol ; 197: 105528, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31712118

RESUMO

Long-term studies investigating hormone-dependent cancers and reproductive health often require prolonged frozen storage of serum which assumes that the steroid molecules and measurements are stable over that time. Previous studies of reproducibility of circulating steroids have relied upon flawed historical rather than contemporaneous controls. We measured serum testosterone (T), dihydrotestosterone (DHT), estradiol (E2) and estrone (E1) in 150 randomly selected serum samples by liquid chromatography-mass spectrometry (LC-MS) from men 70 years or older (mean age 77 years) in the CHAMP study. The original measurements in 2009 were repeated 10 years later using the identical serum aliquot (having undergone 2-4 freeze-thaw cycles in the interim) in 2019 together with another never-thawed aliquot of the same serum sample. The results of all three sets of measurements were evaluated by Passing-Bablok regression and Bland-Altman difference analysis. Serum androgens (T, DHT) and estrogens (E2, E1) measured by LC-MS display excellent reproducibility when stored for 10 years at -80 C without thawing. Serum T and DHT displayed high level of reproducibility across all three sets of measurements. Multiple freeze-thaw cycles over those storage conditions do not significantly affect serum T, DHT and E1 concentrations but produce a modest increase (21%) in serum E2 measurements.


Assuntos
Androgênios/sangue , Di-Hidrotestosterona/sangue , Estradiol/sangue , Estrona/sangue , Secções Congeladas/estatística & dados numéricos , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue , Idoso , Humanos , Estudos Longitudinais , Masculino
8.
Gynecol Oncol ; 156(2): 400-406, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31813586

RESUMO

OBJECTIVE: Blood-based biomarkers are attractive due to ease of sampling and standardized measurement technology, reducing obstacles to clinical implementation. The objective of this study was to evaluate a clinically available method of steroid hormone measurement for its prognostic potential in endometrial cancer. METHODS: We quantified seven steroid hormones by liquid chromatography-tandem mass spectrometry in 100 endometrial cancer patients from a prospective cohort. Abdominal fat distribution was assessed from abdominal computed tomography (CT) scans. Steroid hormone levels were compared to clinical characteristics, fat distribution and gene expression in primary tumor samples. RESULTS: Low levels of 17OH-progesterone, 11-deoxycortisol and androstenedione were associated with aggressive tumor characteristics and poor disease specific survival (p = .003, p = .001 and p = .02 respectively). Adjusting for preoperative risk based on histological type and grade, low 17OH-progesterone and 11-deoxycortisol independently predicted poor outcome with hazard ratios of 2.69 (p = .033, 95%CI: 1.09-6.68) and 3.40 (p = .020, 1.21-9.51), respectively. Tumors from patients with low steroid level displayed increased expression of genes related to mitosis and cell cycle progression, whereas high steroid level was associated with upregulated estrogen signaling and genes associated with inflammation. Estrone and estradiol correlated to abdominal fat volume in all compartments (total, visceral, subcutaneous, p < .001 for all), but not to the visceral fat proportion. Patients with higher levels of circulating estrogens had increased expression of estrogen signaling related genes. CONCLUSION: Low levels of certain endogenous steroids are associated with aggressive tumor traits and poor survival and may provide preoperative information independent of histological biomarkers already in use.


Assuntos
17-alfa-Hidroxiprogesterona/sangue , Androstenodiona/sangue , Cortodoxona/sangue , Neoplasias do Endométrio/sangue , Estrogênios/sangue , Biomarcadores Tumorais/sangue , Carcinoma Endometrioide/sangue , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/mortalidade , Cromatografia Líquida , Estudos de Coortes , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/mortalidade , Estradiol/sangue , Estrona/sangue , Feminino , Expressão Gênica , Humanos , Noruega/epidemiologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Transdução de Sinais , Espectrometria de Massas em Tandem
9.
Adipocyte ; 8(1): 379-385, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31755351

RESUMO

We previously reported that postmenopausal obese women exhibit increased levels of circulating adipocyte fatty acid binding protein (A-FABP), which is associated with breast cancer (BC) development. In postmenopause, increased oestrogen levels are reported to be associated with increased BC risk. Herein, we assessed if oestrogens, including oestrone (E1), oestradiol (E2) and oestriol (E3), are associated with A-FABP in the obesity-related BC development. We collected 249 serum samples from women with or without BC and measured serum levels of E1, E2, E3 and A-FABP. Considering all subjects, E1 and E2 but not E3 levels were significantly higher in pre- than in postmenopause individuals. E3 and E1 levels were higher in non-obese than in obese women. When samples were separated by BC status, E2 levels were significantly higher, while E1 and E3 levels were significantly lower in postmenopausal obese than non-obese women without BC. These differences based on body mass index (BMI) were not observed among women with BC. E3 levels were higher in obese women with BC than those without. A-FABP levels were significantly higher in postmenopausal obese women regardless of BC status. In addition, A-FABP was not associated with E1, E2 or E3. Altogether, our data suggest that A-FABP is independently regulated by obesity and menopausal status compared to oestrogens, thus playing a unique role in the development of BC.


Assuntos
Neoplasias da Mama/metabolismo , Estrogênios/sangue , Proteínas de Ligação a Ácido Graxo/metabolismo , Obesidade/metabolismo , Pós-Menopausa/metabolismo , Pré-Menopausa/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Método Duplo-Cego , Estradiol/sangue , Estriol/sangue , Estrona/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa/sangue , Pré-Menopausa/sangue , Regulação para Cima , Adulto Jovem
10.
Artigo em Alemão | MEDLINE | ID: mdl-31634940

RESUMO

OBJECTIVE: To assess testicular endocrine function in the male donkey (Equus asinus) during the course of the year. MATERIAL AND METHODS: In 5 miniature and 4 standard donkey stallions, peripheral blood concentrations of testosterone (T), estrone (E1) and estrone sulfate (E1S) were determined using radioimmunoassay. RESULTS: There was a highly significant influence of the season (p < 0.0001) on the course of all 3 steroids. Values were low in November until January and high in April, May and June. As delineated by the measurement of E1 the breed also had an effect on the expression of seasonality. Mean T concentration (X̅g × SF ±â€…1) was 1.58 × 1.20 ±â€…1 ng/ml, values ranged between 0.39 and 5.95 ng/ml, which is approximately double the plasma T concentrations observed in horse stallions. As in horse stallions, E1 levels were only slightly above the detection limit of the assay (0.10-0.17 ng/ml). Mean E1S concentration amounted to 0.91 ±â€…0.23 ng/ml, values ranged between 0.34-1.36 ng/ml and taking peak levels into account measured approximately 300-fold lower than in the horse stallion. CONCLUSIONS: The data obtained confirm that the donkey belongs to the group of long day breeders. Irrespective of the close phylogenetical relationship the course of E1S concentrations reveals distinct differences between horse and donkey. CLINICAL RELEVANCE: Even between closely related species established reference values for sex steroids cannot be transferred without verification.


Assuntos
Equidae/sangue , Estrona/análogos & derivados , Estrona/sangue , Testosterona/sangue , Animais , Equidae/fisiologia , Masculino , Radioimunoensaio/veterinária , Estações do Ano
11.
Anim Sci J ; 90(11): 1426-1431, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31486265

RESUMO

In this study, we measured plasma concentrations of progesterone, pregnenolone, estradiol, estrone, estrone sulfate, and cortisol and analyzed the correlations between these hormones during gestation in 13 Suffolk ewes, the main breed in Japan. Progesterone increased during gestation and decreased a few days before parturition; however, this pattern was different in samples with high progesterone concentrations (P4 spike samples). This P4 spike was associated with a high pregnenolone concentration. Apart from the P4 spike, the progesterone change was similar to that in other sheep breeds. Pregnenolone increased during gestation and decreased after parturition. A significant correlation between progesterone and pregnenolone was observed a few days before parturition. Estrone sulfate and estradiol concentrations increased during gestation, but estrone did not. They increased shortly before parturition, and then decreased immediately after parturition. At parturition, the correlation between estrone and estrone sulfate was significantly stronger. Moreover, a strong correlation between estrone sulfate and estradiol was observed after parturition. Cortisol did not change during gestation and increased shortly before parturition. The results showed steroid hormone dynamics in normal pregnant Suffolk ewes, which were mostly in line with those of other sheep breeds. It should be noted that high progesterone concentrations altered the typical patterns.


Assuntos
Estradiol/sangue , Parto/sangue , Gravidez/sangue , Pregnenolona/sangue , Progesterona/sangue , Animais , Estrona/análogos & derivados , Estrona/sangue , Feminino , Hidrocortisona/sangue , Ovinos
12.
Cancer Epidemiol Biomarkers Prev ; 28(10): 1725-1734, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31383718

RESUMO

BACKGROUND: The optimal lifestyle for breast cancer prevention over the long term is unclear. We aimed to determine whether or not the amount of exercise prescribed in a year-long exercise intervention influences breast cancer biomarker levels 1 year later. METHODS: We conducted a 24-month follow-up study (2012-2014) to the Breast Cancer and Exercise Trial in Alberta (BETA), a 12-month, two-armed (1:1), two-center randomized controlled trial of exercise in 400 cancer-free, postmenopausal women. The exercise prescription was moderate-vigorous aerobic exercise, 5 days/week (3 days/week supervised) for 30 minutes/session (MODERATE) or 60 minutes/session (HIGH). Participants were asked not to change their usual diet. We used linear mixed models to compare biomarker concentrations (C-reactive protein, insulin, glucose, HOMA-IR, estrone, sex hormone binding globulin, total estradiol, and free estradiol) over time (0, 12, and 24 months) by group (MODERATE, HIGH), using group-time interactions. RESULTS: After 12 months of no intervention, 24-month fasting blood samples were available for 84.0% and 82.5% of MODERATE and HIGH groups, respectively (n = 333/400). We found no evidence that 0 to 24- or 12 to 24-month biomarker changes differed significantly between randomized groups (HIGH:MODERATE ratio of mean biomarker change ranged from 0.97 to 1.06, P values >0.05 for all). We found more favorable biomarker profiles among participants who experienced greater than the median fat loss during the trial. CONCLUSIONS: Prescribing aerobic exercise for 300 versus 150 minutes/week for 12 months to inactive, postmenopausal women had no effects on longer-term biomarkers. IMPACT: Exercise may lead to larger improvements in breast cancer biomarkers after intervention among women who also experience fat loss with exercise.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Exercício Físico/fisiologia , Idoso , Proteína C-Reativa/metabolismo , Dieta , Estradiol/sangue , Estrona/sangue , Feminino , Seguimentos , Humanos , Estilo de Vida , Pessoa de Meia-Idade , Pós-Menopausa/sangue , Risco , Comportamento Sedentário , Globulina de Ligação a Hormônio Sexual/metabolismo , Fatores de Tempo
13.
Clin Biochem ; 73: 105-108, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31442440

RESUMO

OBJECTIVE: We aimed to establish correlations for the levels of follicle-stimulating hormone (FSH), estrone (E1) and estradiol (E2) between urine and serum in premenopausal and postmenopausal women using immunoassays. METHODS: In this study of 92 women (61 postmenopausal, 31 premenopausal), both urine and blood specimens were collected on the same day and stored at 4 °C for analysis by chemiluminescent immunoassay, radioimmunoassay and/or electrochemiluminescent immunoassay. RESULTS: There were correlations in the levels of FSH, E1 and E2 between urine and serum in both postmenopausal (r = 0.96 for FSH, r = 0.91 for E1, r = 0.80 for E2) and premenopausal (r = 0.98 for FSH, r = 0.92 for E1, r = 0.90 for E2) women. It is indicated that the correlations were stronger in the premenopausal group compared with the postmenopausal group, especially for FSH. CONCLUSION: The levels of FSH, E1 and E2 in urine correlated with those in the serum in premenopausal and postmenopausal women. Urine samples could be used instead of serum samples to measure hormone levels, which would reduce the difficulty of conducting large survey studies.


Assuntos
Estradiol , Estrona , Hormônio Foliculoestimulante , Pós-Menopausa , Pré-Menopausa , Adulto , Idoso , Estradiol/sangue , Estradiol/urina , Estrona/sangue , Estrona/urina , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Foliculoestimulante/urina , Humanos , Pessoa de Meia-Idade , Pós-Menopausa/sangue , Pós-Menopausa/urina , Pré-Menopausa/sangue , Pré-Menopausa/urina
14.
J Clin Endocrinol Metab ; 104(12): 6291-6300, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31408149

RESUMO

CONTEXT: There is a lack of understanding of what is normal in terms of sex steroid levels in older women. OBJECTIVE: To determine whether sex steroid levels vary with age in and establish reference ranges for women >70 years of age. DESIGN AND SETTING: Cross-sectional, community-based study. PARTICIPANTS: Included 6392 women ≥70 years of age. MAIN OUTCOME MEASURES: Sex steroids measured by liquid chromatography-tandem mass spectrometry. A reference group, to establish sex steroid age-specific reference ranges, excluded women using systemic or topical sex steroid, antiandrogen or glucocorticoid therapy, or an antiglycemic agent. RESULTS: The reference group of 5326 women had a mean age of 75.1 (±4.2) years, range of 70 to 94.7 years. Median values (range) were 181.2 pmol/L (3.7 to 5768.9) for estrone (E1), 0.38 nmol/L (0.035 to 8.56) for testosterone (T), 2.60 nmol/L (0.07 to 46.85) for dehydroepiandrosterone (DHEA), and 41.6 nmol/L (2.4 to 176.6) for SHBG. Estradiol and DHT were below method sensitivity in 66.1% and 72.7% of the samples, respectively. Compared with women aged 70 to 74 years, women aged ≥85 years had higher median levels of E1 (11.7%, P = 0.01), T (11.3%, P = 0.02), and SHBG (22.7%, P < 0.001) and lower DHEA (30% less, P < 0.001). Women with overweight and obesity had higher E1 (P < 0.001) and T (P < 0.03) and lower SHBG (P < 0.001) than did women with normal body mass index. Smokers had 17.2% higher median T levels (P = 0.005). CONCLUSION: From the age of 70 years, T and E1 increase with age, despite a steady decline in DHEA. Whether E1 and T are biomarkers for longevity or contribute to healthy aging merits investigation.


Assuntos
Envelhecimento , Biomarcadores/sangue , Desidroepiandrosterona/sangue , Estrona/sangue , Obesidade/sangue , Sobrepeso/sangue , Testosterona/sangue , Idoso , Idoso de 80 Anos ou mais , Pesquisa Participativa Baseada na Comunidade , Estudos Transversais , Feminino , Seguimentos , Humanos , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Prognóstico
15.
J Clin Endocrinol Metab ; 104(12): 6079-6089, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31408174

RESUMO

CONTEXT: The age of pubertal onset is influenced by many variables in young girls. Previous studies have not examined sex hormones longitudinally around the time of breast development and their relationship to pubertal onset. OBJECTIVE: We sought to use an unbiased statistical approach to identify phenotypes of sex hormones in young girls and examine their relationship with pubertal milestones. DESIGN AND SETTING: Longitudinal observational study. PARTICIPANTS AND MAIN OUTCOME MEASURES: In 269 girls, serum concentrations of steroid sex hormones [estradiol (E2), estrone, testosterone, and dehydroepiandrosterone sulfate] were measured by HPLC-mass spectrometry at time points before, at, and after thelarche. Girls were classified into four hormone phenotypes using objective principal components and cluster analyses of longitudinal hormone data. The association between the identified phenotypes and age of pubertal milestones was estimated using Cox proportional hazards modeling. RESULTS: Mean ages at thelarche, pubarche, and menarche were 9.02, 9.85, and 12.30 years, respectively. Girls with low levels of all four hormones, phenotype 3b, were youngest at thelarche (8.67 years); those in phenotype 2, with the highest E2 levels and E2 surge 6 months after thelarche, were youngest at menarche (11.87 years) with shortest pubertal tempo. When controlling for race, maternal age of menarche, caregiver education, and body mass, different phenotypes were associated with the age of pubertal events. CONCLUSIONS: Hormone phenotypic clustering can identify clinically relevant subgroups with differing ages of thelarche, pubarche, and menarche. These findings may enhance the understanding of timing of pubertal milestones and risk of adult disease.


Assuntos
Hormônios Esteroides Gonadais/sangue , Puberdade/sangue , Adolescente , Criança , Sulfato de Desidroepiandrosterona/sangue , Estradiol/sangue , Estrona/sangue , Feminino , Humanos , Estudos Longitudinais , Menarca/sangue , Fenótipo , Puberdade/fisiologia , Testosterona/sangue
16.
Anim Reprod Sci ; 205: 115-125, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31040054

RESUMO

This study was designed to investigate plasma profile of pregnancy-associated glycoprotein (PAG), progesterone (P4) and estrone sulfate (E1S) during early- and mid-pregnancy. The goal was to explore the relationships with values for reproductive variables, to detect the most reliable predictor variable, and to identify the most desirable time point for blood collection for determining fetal number in goats. After ultrasonographic examination at d35-40 post-mating, blood sampling of 15 pregnant goats (total 18) was continued until d114. The PAG profile was characterized by gradual increase during early pregnancy from d26 to d51 and thereafter concentrations were relatively constant until d114 of gestation. The effect of fetal number on plasma PAG, P4 and E1S was first evident on d28, d51 and d26, respectively. During mid-pregnancy, does with twins had a greater (P < 0.05) PAG (S-N = 2.54 ± 0.12 compared with 1.59 ± 0.11), P4 (18.91 ± 0.67 compared with 14.51 ± 0.47 ng/mL) and E1S (16.34 ± 0.76 compared with 11.32 ± 0.44 ng/dL) as compared with does with a singleton fetus. Plasma PAG but not P4 and E1S was positively correlated with fetal number and birth weight of kids during early pregnancy. Multivariate linear regression and discriminant function analyzes allowed for identification of plasma PAG as the most reliable predictor for fetal number and birth weight of kids. Furthermore, d58 was the most suitable single time point for prediction of fetal number using PAG as a biomarker. In conclusion, plasma profile of PAG, P4 and E1S was affected by fetal count. Plasma PAG was identified as the most reliable predictor variable of fetal number and birth weight of kids as compared to plasma P4 and E1S.


Assuntos
Estrona/análogos & derivados , Cabras/sangue , Tamanho da Ninhada de Vivíparos/fisiologia , Proteínas da Gravidez/sangue , Prenhez , Progesterona/sangue , Animais , Estrona/sangue , Feminino , Cabras/fisiologia , Masculino , Análise Multivariada , Gravidez , Prenhez/sangue , Fatores de Tempo
17.
J Pharm Biomed Anal ; 171: 164-170, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31003006

RESUMO

A Liquid Chromatography coupled to tandem mass spectrometry (LC-MS/MS) based method have been developed for the determination of the main estrogen compounds -estrone (E1) and 17ß-estradiol (E2)- in human serum. Two isotope dilution mass spectrometry (IDMS) quantification procedures have been used: a classical calibration curve-based method were compared to a recently developed isotope pattern deconvolution (IPD) method. IPD is based on isotopic abundance measurements and multiple linear regression. Validation was performed in terms of intra-assay repeatability (n = 5), inter-assay reproducibility (n = 9) and accuracy using spiked steroid-free serum at 5 concentration levels and 3 certified reference materials. Both methodologies meet EMEA requirements yielding recoveries between 79-106% and coefficient of variations of 1.7-8.3% along all experiments. Limits of quantification as low as 5 ng/L were achieved. 40 real samples were analysed for comparison purposes showing a great correlation between calibration and IPD concentration values. Real samples were also quantified by routine immunoassay analysis, which showed a significant proportional bias of 2.55 for E1 and good correlation for E2. While methods were considered suitable for routine or countercheck analysis within the context of hospital's needs, IPD has demonstrated to be faster and cost saving.


Assuntos
Cromatografia Líquida/métodos , Estradiol/sangue , Estrona/sangue , Espectrometria de Massas em Tandem/métodos , Calibragem , Humanos , Técnicas de Diluição do Indicador , Marcação por Isótopo , Limite de Detecção , Padrões de Referência , Reprodutibilidade dos Testes , Microextração em Fase Sólida
18.
Equine Vet J ; 51(6): 802-808, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30891816

RESUMO

BACKGROUND: Few studies have provided a longitudinal analysis of systemic concentrations of conjugated oestrogens (and androgens) throughout pregnancy in mares, and those only using immunoassay. The use of liquid chromatography tandem mass spectrometry (LC-MS/MS) will provide more accurate concentrations of circulating conjugated steroids. OBJECTIVES: To characterise circulating concentrations of individual conjugated steroids throughout equine gestation by using LC-MS/MS. STUDY DESIGN: Longitudinal study and comparison of pregnant mares treated with vehicle or letrozole in late gestation. METHODS: Sulphated oestrogens and androgens were measured in mares throughout gestation and mares in late gestation (8-11 months) treated with vehicle or letrozole to inhibit oestrogen synthesis in late gestation. An analytical method was developed using LC-MS/MS to evaluate sulphated estrone, estradiol, testosterone and dehydroepiandrosterone (DHEAS) during equine gestation. RESULTS: Estrone sulphate concentrations peaked by week 26 at almost 60 µg/mL, 50-fold higher than have been reported in studies using immunoassays. An increase in DHEAS was detected from 7 to 9 weeks of gestation, but concentrations remained consistently low (if detected) for the remainder of gestation and testosterone sulphate was undetectable at any stage. Estradiol sulphate concentrations were highly correlated with estrone sulphate but were a fraction of their level. Concentrations of both oestrogen sulphates decreased from their peak to parturition. Letrozole inhibited estrone and estradiol sulphate concentrations at 9.25 and 10.5 months of gestation but, no increase in DHEAS was observed. MAIN LIMITATIONS: Limited number of mares sampled and available for analysis, lack of analysis of 5α-reduced and B-ring unsaturated steroids due to lack of available standards. CONCLUSIONS: Dependent on methods of extraction and chromatography, and the specificity of primary antisera, immunoassays may underestimate oestrogen conjugate concentrations in blood from pregnant mares and may detect androgen conjugates (neither testosterone sulphate nor DHEAS were detected here by LC-MS/MS) that probably peak coincident with oestrogen conjugates between 6 and 7 months of equine gestation.


Assuntos
Desidroepiandrosterona/sangue , Estradiol/metabolismo , Estrona/análogos & derivados , Cavalos/sangue , Espectrometria de Massas/veterinária , Prenhez/sangue , Animais , Desidroepiandrosterona/metabolismo , Estradiol/sangue , Estrona/sangue , Estrona/metabolismo , Feminino , Espectrometria de Massas/métodos , Gravidez
19.
Climacteric ; 22(2): 169-174, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30612472

RESUMO

OBJECTIVE: This study aimed to determine the effect of oophorectomy on baseline serum levels of androgens and estrogens in premenopausal and postmenopausal women. METHODS: Fourteen premenopausal and 10 postmenopausal women underwent total hysterectomy and bilateral oophorectomy for benign disease of the uterus. Serum levels of dehydroepiandrosterone sulfate (DHEAS), androstenedione (A), testosterone (T), dihydrotestosterone (DHT), 5α-androstane-3α,17ß-diol-17ß-glucuronide (3α-diol G), estrone (E1), estradiol (E2), and sex hormone-binding globulin (SHBG) were measured by highly specific immunoassays prior to surgery and 2 weeks afterward. Free T and free E2 were calculated. Differences were determined between preoperative (preop) and postoperative (postop) samples, and between premenopausal and postmenopausal women. RESULTS: In premenopausal women, postop levels of total and free T, DHT, and total and free E2 decreased significantly from preop. Postop levels of DHEAS, A, 3α-diol G, and SHBG were decreased, but not significantly different from preop. In postmenopausal women, postop levels of total and free T and total and free E2 decreased significantly from preop, but there was little change in the other compounds. Significant differences in the mean change from baseline between premenopausal and postmenopausal women were observed only for E1 and total and free E2. CONCLUSION: The significant decrease in serum T in postmenopausal women following oophorectomy adds to the evidence that the postmenopausal ovary continues to produce T.


Assuntos
Androgênios/sangue , Estrogênios/sangue , Ovariectomia/efeitos adversos , Pós-Menopausa/sangue , Pré-Menopausa/sangue , Idoso , Sulfato de Desidroepiandrosterona/sangue , Di-Hidrotestosterona/sangue , Estradiol/sangue , Estrona/sangue , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue , Doenças Uterinas/cirurgia
20.
Menopause ; 26(7): 720-727, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30694918

RESUMO

OBJECTIVE: In the REPLENISH trial, women receiving TX-001HR-an oral, softgel capsule, combining 17ß-estradiol (E2) and progesterone (E2 mg/P4 mg 1/100, 0.5/100), had significantly improved vasomotor symptoms, while having their endometrium protected from hyperplasia. The objective here was to describe P4 levels sufficient to counteract the potential endometrial effects of 1 or 0.5 mg oral E2 with TX-001HR. METHODS: In REPLENISH (phase 3; NCT01942668), serum P4, E2, and estrone (E1) levels were characterized in postmenopausal women treated with TX-001HR (E2 mg/P4 mg: 1/100, 0.5/100, [0.5/50, 0.25/50 and placebo not reported here]) at baseline, week 12, and month 12 for P4, and at baseline, weeks 4 and 12, and months 6, 9, and 12 for E2 and E1. In a phase 1 study, pharmacokinetic parameters were assessed after 7 daily doses of oral E2 mg/P4 mg (1/100 and 0.5/100). RESULTS: In REPLENISH (n = 1,835), mean P4 levels were 0.39 to 0.55 ng/mL with 100-mg P4 doses; E2 levels were 42.3 to 45.6 pg/mL and 23.0 to 27.4 pg/mL for the 1-mg and 0.5-mg E2 doses, respectively; E1 levels were 214 to 242 pg/mL and 114 to 129 pg/mL for the 1-mg and 0.5-mg E2 doses. In the phase 1 study (n = 40; day 7), mean Cavg for P4 was 0.66 ng/mL with 100-mg P4 doses; E2 was 38.1 pg/mL and 29.2 pg/mL for 1 mg and 0.5 mg E2, respectively; and E1 was 211 and 106 pg/mL for 1 mg and 0.5 mg E2. All three analytes reached steady state within 7 days; accumulation ratios were 1.36 to 1.94. CONCLUSIONS: P4 levels observed with TX-001HR were similar in the phase 1 and 3 studies, and were associated with no endometrial hyperplasia with either E2 daily dose over 1 year in the REPLENISH phase 3 study, which showed significant improvements in menopausal vasomotor symptoms.


Assuntos
Hiperplasia Endometrial/epidemiologia , Estradiol/farmacocinética , Pós-Menopausa/efeitos dos fármacos , Progesterona/farmacocinética , Adulto , Idoso , Disponibilidade Biológica , Hiperplasia Endometrial/induzido quimicamente , Estradiol/administração & dosagem , Estradiol/efeitos adversos , Estrona/sangue , Feminino , Fogachos/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Placebos , Pós-Menopausa/fisiologia , Progesterona/administração & dosagem
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