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Sökning: WFRF:(Labrie Fernand)

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21.
  • O'Connor, Daryl B, et al. (författare)
  • The Relationships between Sex Hormones and Sexual Function in Middle-Aged and Older European Men.
  • 2011
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : Oxford University Press. - 1945-7197. ; 96, s. 1577-1587
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Limited data are available exploring the associations between sex hormones, multiple domains of sexual functioning, and sexual function-related distress in nonpatient samples in Europe. Objectives: The aim of the study was to investigate the relationships between serum testosterone (T), estradiol (E2), and dihydrotestosterone (DHT) and sexual function in a multicenter population-based study of aging in men. Design: Using stratified random sampling, 2838 men aged 40-79 yr completed the European Male Ageing Study-Sexual Function Questionnaire and provided a blood sample for hormone measurements. T, E2, and DHT were measured using gas chromatography-mass spectrometry. Setting: We conducted a community-based population survey in eight European centers. Main Outcome Measures: Self-reported sexual function (overall sexual function, sexual function-related distress, erectile dysfunction, masturbation) was measured. Results: Total and free T, but not E2 or DHT, was associated with overall sexual function in middle-aged and older men. E2 was the only hormone associated with sexual function-related distress such that higher levels were related to greater distress. Free T levels were associated with masturbation frequency and erectile dysfunction in the fully adjusted models, such that higher T was associated with less dysfunction and greater frequency. Moreover, there was a T threshold for the relationship between total T, sexual function, and erectile dysfunction. At T concentrations of 8 nmol/liter or less, T was associated with worse sexual functioning, whereas at T levels over 8 nmol/liter, the relationship came to a plateau. Conclusions: These findings suggest that different hormonal mechanisms may regulate sexual functioning (T) vs. the psychological aspects (E2) of male sexual behavior. Moreover, there was a T threshold for overall sexual function such that at levels greater than 8 nmol/liter the relationship between T and sexual function did not become stronger.
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22.
  • Ohlsson, Claes, 1965, et al. (författare)
  • High Serum Testosterone is Associated with Reduced Risk of Cardiovascular Events in Elderly Men
  • 2011
  • Ingår i: Journal of the American College of Cardiology. - 0735-1097 .- 1558-3597. ; 58:16, s. 1674-1681
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives We tested the hypothesis that serum total testosterone and sex hormone-binding globulin (SHBG) levels predict cardiovascular (CV) events in community-dwelling elderly men. Background Low serum testosterone is associated with increased adiposity, an adverse metabolic risk profile, and atherosclerosis. However, few prospective studies have demonstrated a protective link between endogenous testosterone and CV events. Polymorphisms in the SHBG gene are associated with risk of type 2 diabetes, but few studies have addressed SHBG as a predictor of CV events. Methods We used gas chromatography/mass spectrometry to analyze baseline levels of testosterone in the prospective population-based MrOS (Osteoporotic Fractures in Men) Sweden study (2,416 men, age 69 to 81 years). SHBG was measured by immunoradiometric assay. CV clinical outcomes were obtained from central Swedish registers. Results During a median 5-year follow-up, 485 CV events occurred. Both total testosterone and SHBG levels were inversely associated with the risk of CV events (trend over quartiles: p = 0.009 and p = 0.012, respectively). Men in the highest quartile of testosterone (>= 550 ng/dl) had a lower risk of CV events compared with men in the 3 lower quartiles (hazard ratio: 0.70, 95% confidence interval: 0.56 to 0.88). This association remained after adjustment for traditional CV risk factors and was not materially changed in analyses excluding men with known CV disease at baseline (hazard ratio: 0.71, 95% confidence interval: 0.53 to 0.95). In models that included both testosterone and SHBG, testosterone but not SHBG predicted CV risk. Conclusions High serum testosterone predicted a reduced 5-year risk of CV events in elderly men. (J Am Coll Cardiol 2011;58:1674-81) (C) 2011 by the American College of Cardiology Foundation
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23.
  • Ohlsson, Claes, et al. (författare)
  • High Serum Testosterone Is Associated With Reduced Risk of Cardiovascular Events in Elderly Men The MrOS (Osteoporotic Fractures in Men) Study in Sweden
  • 2011
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier USA. - 0735-1097. ; 58:16, s. 1674-1681
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives We tested the hypothesis that serum total testosterone and sex hormone-binding globulin (SHBG) levels predict cardiovascular (CV) events in community-dwelling elderly men. Background Low serum testosterone is associated with increased adiposity, an adverse metabolic risk profile, and atherosclerosis. However, few prospective studies have demonstrated a protective link between endogenous testosterone and CV events. Polymorphisms in the SHBG gene are associated with risk of type 2 diabetes, but few studies have addressed SHBG as a predictor of CV events. Methods We used gas chromatography/mass spectrometry to analyze baseline levels of testosterone in the prospective population-based MrOS (Osteoporotic Fractures in Men) Sweden study (2,416 men, age 69 to 81 years). SHBG was measured by immunoradiometric assay. CV clinical outcomes were obtained from central Swedish registers. Results During a median 5-year follow-up, 485 CV events occurred. Both total testosterone and SHBG levels were inversely associated with the risk of CV events (trend over quartiles: p = 0.009 and p = 0.012, respectively). Men in the highest quartile of testosterone (>= 550 ng/dl) had a lower risk of CV events compared with men in the 3 lower quartiles (hazard ratio: 0.70, 95% confidence interval: 0.56 to 0.88). This association remained after adjustment for traditional CV risk factors and was not materially changed in analyses excluding men with known CV disease at baseline (hazard ratio: 0.71, 95% confidence interval: 0.53 to 0.95). In models that included both testosterone and SHBG, testosterone but not SHBG predicted CV risk. Conclusions High serum testosterone predicted a reduced 5-year risk of CV events in elderly men. (J Am Coll Cardiol 2011;58:1674-81) (C) 2011 by the American College of Cardiology Foundation
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24.
  • Ohlsson, Claes, 1965, et al. (författare)
  • Low serum levels of dehydroepiandrosterone sulfate predict all-cause and cardiovascular mortality in elderly Swedish men.
  • 2010
  • Ingår i: The journal of clinical endocrinology and metabolism. - : Oxford University Press. - 1945-7197 .- 0021-972X. ; 95:9, s. 4406-14
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: The age-related decline in dehydroepiandrosterone (DHEA) levels is thought to be of importance for general and vascular aging. However, data on the association between DHEA and mortality are conflicting. Objectives: We tested the hypothesis that low serum DHEA and DHEA sulfate (DHEA-S) levels predict all-cause and cardiovascular disease (CVD) death in elderly men. Design, Setting, and Participants: We used gas/liquid chromatography-mass spectrometry to analyze baseline levels of DHEA and DHEA-S in the prospective population-based MrOS Sweden study (2644 men, aged 69-81 yr). Mortality data were obtained from central registers and analyzed using Cox proportional hazards regressions. Main Outcome Measures: All-cause and CVD mortality by serum DHEA(-S) levels. Results: During a mean 4.5-yr follow-up, 328 deaths occurred. Low levels of DHEA-S (quartile 1 vs. quartiles 2-4), predicted death from all causes [hazard ratio (HR) 1.54, 95% confidence interval (CI) 1.21-1.96; adjusted for traditional cardiovascular risk factors], from CVD (n = 123 deaths; HR 1.61, 95% CI 1.10-2.37) and ischemic heart disease (n = 73; HR 1.67, 95% CI 1.02-2.74) but not cancer. Analyses with DHEA gave similar results. The association between low DHEA-S and CVD death remained after adjustment for C-reactive protein and circulating estradiol and testosterone levels. When stratified by the median age of 75.4 yr, the mortality prediction by low DHEA-S was more pronounced among younger (age adjusted HR for CVD death 2.64, 95% CI 1.37-5.09) than older men (HR 1.30, 95% CI 0.83-2.04). Conclusions: Low serum levels of DHEA(-S) predict death from all causes, CVD, and ischemic heart disease in older men.
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25.
  • Orwoll, Eric S, et al. (författare)
  • Evidence for geographical and racial variation in serum sex steroid levels in older men.
  • 2010
  • Ingår i: The journal of clinical endocrinology and metabolism. - : Oxford University Press. - 1945-7197 .- 0021-972X. ; 95:10, s. E151-60
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Despite considerable racial and geographical differences in human phenotypes and in the incidence of diseases that may be associated with sex steroid action, there are few data concerning variation in sex steroid levels among populations. We designed an international study to determine the degree to which geography and race influence sex steroid levels in older men. Methods: Using mass spectrometry, concentrations of serum androgens, estrogens, and sex steroid precursors/metabolites were measured in 5003 older men from five countries. SHBG levels were assessed using radioimmunoassay. Results: There was substantial geographical variation in the levels of sex steroids, precursors, and metabolites, as well as SHBG. For instance, Asian men in Hong Kong and Japan, but not in the United States, had levels of total testosterone approximately 20% higher than in other groups. Even greater variation was present in levels of estradiol, SHBG, and dihydrotestosterone. Group differences in body mass index did not explain most geographical differences. In addition, body mass index-independent racial differences were present; Black men had higher levels of estrogens (estradiol, estrone), and Asian men had lower levels of glucuronidated androgen metabolites. Conclusions: On a global scale, there are important geographical and racial differences in the concentrations of serum sex steroids and SHBG in older men.
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26.
  • Pye, Stephen R., et al. (författare)
  • Influence of Insulin-Like Growth Factor Binding Protein (IGFBP)-1 and IGFBP-3 on Bone Health: Results from the European Male Ageing Study
  • 2011
  • Ingår i: Calcified Tissue International. - : Springer. - 1432-0827. ; 88:6, s. 503-510
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to determine the influence of insulin-like growth factor binding protein (IGFBP)-1, IGFBP-3, and IGF-I on calcaneal ultrasound parameters in middle-aged and elderly European men. Men aged 40-79 years were recruited from population registers for participation in the European Male Ageing Study (EMAS). Subjects were invited by letter to complete a postal questionnaire and to attend for an interviewer-assisted questionnaire, quantitative ultrasound (QUS) of the calcaneus, and a fasting blood sample from which serum levels of IGFBP-1, IGFBP-3, IGF-I, estradiol (E-2), and SHBG were assayed. The questionnaires included the Physical Activity Scale for the Elderly (PASE) and questions about smoking and alcohol consumption. Estimated bone mineral density (eBMD) was derived as a function of the QUS parameters speed of sound and broadband ultrasound attenuation. Height and weight were measured in all subjects. 3057 men, mean age 59.7 years (standard deviation 11.0) were included in the analysis. After adjusting for age, center, and BMI, higher levels of IGFBP-1 were associated with lower eBMD. Higher levels of both IGFBP-3 and IGF-I were associated with higher eBMD. After further adjustment for PASE score, current smoking, alcohol consumption, free E-2, and SHBG, IGFBP-3 and IGF-I, though not IGFBP-1, remained significantly associated with eBMD. IGFBP-1 was associated with bone health, though the effect could be explained by other factors. IGFBP-3 and IGF-I were independent determinants of bone health in middle-aged and elderly European men.
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27.
  • Shattuck Eidens, Donna, et al. (författare)
  • A Collaborative Survey of 80 Mutations in the BRCA1 Breast and Ovarian Cancer Susceptibility Gene : Implications for Presymptomatic Testing and Screening
  • Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association. - 0098-7484. ; 273:7, s. 535-541
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES:To report the initial experience of an international group of investigators in identifying mutations in the BRCA1 breast and ovarian cancer susceptibility gene, to assess the spectrum of such mutations in samples from patients with different family histories of cancer, and to determine the frequency of recurrent mutations.DESIGN:Nine laboratories in North America and the United Kingdom tested for BRCA1 mutations in DNA samples obtained from a total of 372 unrelated patients with breast or ovarian cancer largely chosen from high-risk families. Three of these laboratories also analyzed a total of 714 additional samples from breast or ovarian cancer cases, including 557 unselected for family history, for two specific mutations that had been found to recur in familial samples.PARTICIPANTS:A total of 1086 women with either breast or ovarian cancer.MAIN OUTCOME MEASURE:The detection of sequence variation in patients' DNA samples that is not found in sets of control samples.RESULTS:BRCA1 mutations have now been identified in a total of 80 patient samples. Thirty-eight distinct mutations were found among 63 mutations identified through a complete screen of the BRCA1 gene. Three specific mutations appeared relatively common, occurring eight, seven, and five times, respectively. When specific tests for the two most common mutations were performed in larger sets of samples, they were found in 17 additional patients. Mutations predicted to result in a truncated protein accounted for 86% of the mutations detected by complete screening.CONCLUSIONS:The high frequency of protein-terminating mutations and the observation of many recurrent mutations found in a diverse set of samples could lead to a relatively simple diagnostic test for BRCA1 mutations. More data must be accumulated to address specifically the sensitivity and specificity of such a diagnostic testing procedure and to better estimate the age-specific risk for breast and ovarian cancer associated with such mutations.
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28.
  • Stener-Victorin, Elisabet, 1964, et al. (författare)
  • Are there any sensitive and specific sex steroid markers for polycystic ovary syndrome?
  • 2010
  • Ingår i: The Journal of clinical endocrinology and metabolism. - 1945-7197. ; 95:2, s. 810-819
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Despite the high prevalence of hyperandrogenemia, the principal biochemical abnormality in women with polycystic ovary syndrome (PCOS), a definitive endocrine marker for PCOS has so far not been identified. Objective: To identify a tentative diagnostic marker for PCOS, we compared serum levels of sex steroids, their precursors, and main metabolites in women with PCOS and controls. Design and Methods: In this cross-sectional study of 74 women with PCOS and 31 controls, we used gas and liquid chromatography/mass spectrometry to analyze serum sex steroid precursors, estrogens, androgens, and glucuronidated androgen metabolites; performed immunoassays of SHBG, LH, and FSH; and calculated the LH/FSH ratio. Results: Androgens and estrogens, sex steroid precursors, and glucuronidated androgen metabolites were higher in women with PCOS than in controls. In multivariate logistic regression analyses, estrone and free testosterone were independently associated with PCOS. The odds ratios per sd increase were 24.2 for estrone [95% confidence interval (CI), 4.0-144.7] and 12.8 for free testosterone (95% CI, 3.1-53.4). In receiver operating characteristic analyses, the area under curve was 0.93 for estrone (95% CI, 0.88-0.98) and 0.91 for free testosterone (95% CI, 0.86-0.97), indicating high sensitivity and specificity. Conclusion: Women with PCOS have elevated levels of sex steroid precursors, estrogens, androgens, and glucuronidated androgen metabolites as measured with a specific and sensitive mass spectrometry-based technique. The combination of elevated estrone (>50 pg/ml) and free testosterone (>3.3 pg/ml) appeared to discriminate with high sensitivity and specificity between women with and without PCOS.
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29.
  • Swanson, Charlotte, 1975, et al. (författare)
  • The UDP Glucuronosyltransferase 2B15 D85Y and 2B17 Deletion Polymorphisms Predict the Glucuronidation Pattern of Androgens and Fat Mass in Men.
  • 2007
  • Ingår i: Journal of clinical endocrinology and metabolism. - 0021-972X. ; 92:12, s. 4878-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Previous in vitro studies have demonstrated that the UDP glucuronosyltransferase (UGT) 2B15 and UGT2B17 glucuronidate androgens and their metabolites. Objective: To determine in vivo if the UGT2B15 D(85)Y and the UGT2B17 deletion polymorphisms predict androgen glucuronidation and body composition. Participants: Two population-based cohorts including young adult (n=1068, age=18.9 years) and elderly (n=1001, age=75.3 years) men. Main Outcome Measures: Serum and urine levels of testosterone (T) and dihydrotestosterone (DHT) measured by GC-MS and serum levels of the major glucuronidated androgen metabolites androstane-3alpha,17beta-diol(androstanediol)-3glucuronide, androstanediol-17glucuronide and androsterone-glucuronide measured by LC-MS/MS. Body composition measured by DXA. Results: Both the UGT2B15 D(85)Y and the UGT2B17 deletion polymorphisms were associated with serum levels of androstanediol-17glucuronide (p<0.001) but not with levels of androstanediol-3glucuronide or androsterone-glucuronide in both cohorts. Glucuronidation of T and DHT was associated with the UGT2B17 deletion but not with the UGT2B15 D(85)Y polymorphism, suggested by strong associations between the deletion polymorphism and urine levels of these two hormones. Both polymorphisms were associated with several different measures of fat mass (p<0.01). The UGT2B17 deletion polymorphism was associated with insulin sensitivity (p<0.05) as indicated by the HOMA index. Conclusions: The UGT2B15 D(85)Y and the UGT2B17 deletion polymorphisms are both predictors of the glucuronidation pattern of androgens/androgen metabolites. Our findings indicate that UGT2B17 is involved in 17 glucuronidation of mainly T but also of DHT and androstanediol and that UGT2B15 is involved in the 17 glucuronidation of androstanediol. Furthermore, these two polymorphisms are predictors of fat mass in men.
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30.
  • Swanson, Charlotte, et al. (författare)
  • The uridine diphosphate glucuronosyltransferase 2B15 (DY)-Y-85 and 2B17 deletion Polymorphisms predict the glucuronidation pattern of androgens and fat mass in men
  • 2007
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 1945-7197. ; 92:12, s. 4878-4882
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Previous in vitro studies have demonstrated that the UDP glucuronosyltransferase (UGT) 2B15 and UGT2B17 glucuronidate androgens and their metabolites. Objective: Our objective was to determine in vivo whether the UGT2B15 (DY)-Y-85 and the UGT2B17 deletion polymorphisms predict androgen glucuronidation and body composition. Participants: Two population-based cohorts including young adult (n = 1068; age = 18.9 yr) and elderly ( n = 1001; age = 75.3 yr) men were included in the study. Main Outcome Measures: Serum and urine levels of testosterone ( T) and dihydrotestosterone (DHT) were measured by gas chromatography-mass spectrometry, and serum levels of the major glucuronidated androgen metabolites androstane-3 alpha, 17 beta- diol(androstanediol)-3-glucuronide, androstanediol-17-glucuronide, and androsterone-glucuronide were measured by liquid chromatography-tandem mass spectrometry. Body composition was measured by dual-energy x-ray absorptiometry. Results: Both the UGT2B15 D85Y and the UGT2B17 deletion polymorphisms were associated with serum levels of androstanediol-ediol-17-glucuronide (P < 0.001) but not with levels of androstanediol-3-glucuronide or androsterone-glucuronide in both cohorts. Glucuronidation of T and DHT was associated with the UGT2B17 deletion but not with the UGT2B15 (DY)-Y-85 polymorphism, suggested by strong associations between the deletion polymorphism and urine levels of these two hormones. Both polymorphisms were associated with several different measures of fat mass ( P < 0.01). The UGT2B17 deletion polymorphism was associated with insulin sensitivity ( P < 0.05) as indicated by the homeostasis model assessment index. Conclusions: The UGT2B15 D85Y and the UGT2B17 deletion polymorphisms are both predictors of the glucuronidation pattern of androgens/androgen metabolites. Our findings indicate that UGT2B17 is involved in 17- glucuronidation of mainly T but also of DHT and androstanediol and that UGT2B15 is involved in the 17- glucuronidation of androstanediol. Furthermore, these two polymorphisms are predictors of fat mass in men.
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  • Föregående 12[3]4Nästa
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