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41.
  • 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 Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 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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42.
  • Pye, Stephen R., et al. (författare)
  • Influence of Lifestyle Factors on Quantitative Heel Ultrasound Measurements in Middle-Aged and Elderly Men
  • 2010
  • Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 86:3, s. 211-219
  • Tidskriftsartikel (refereegranskat)abstract
    • We examined the distribution of quantitative heel ultrasound (QUS) parameters in population samples of European men and looked at the influence of lifestyle factors on the occurrence of these parameters. Men aged between 40 and 79 years were recruited from eight European centers and invited to attend for an interviewer-assisted questionnaire, assessment of physical performance, and quantitative ultrasound (QUS) of the calcaneus (Hologic; Sahara). The relationships between QUS parameters and lifestyle variables were assessed using linear regression with adjustments for age, center, and weight. Three thousand two hundred fifty-eight men, mean age 60.0 years, were included in the analysis. A higher PASE score (upper vs. lower tertile) was associated with a higher BUA (beta coefficient = 2.44 dB/Mhz), SOS (beta = 6.83 m/s), and QUI (beta = 3.87). Compared to those who were inactive, those who walked or cycled more than an hour per day had a higher BUA (beta = 3.71 dB/Mhz), SOS (beta = 6.97 m/s), and QUI (beta = 4.50). A longer time to walk 50 ft was linked with a lower BUA (beta = -0.62 dB/Mhz), SOS (beta = -1.06 m/s), and QUI (beta = -0.69). Smoking was associated with a reduction in BUA, SOS, and QUI. There was a U-shaped association with frequency of alcohol consumption. Modification of lifestyle, including increasing physical activity and stopping smoking, may help optimize bone strength and reduce the risk of fracture in middle-aged and elderly European men.
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43.
  • Pye, Stephen R, et al. (författare)
  • Low heel ultrasound parameters predict mortality in men: results from the European Male Ageing Study (EMAS).
  • 2015
  • Ingår i: Age and Ageing. - : Oxford University Press (OUP). - 1468-2834 .- 0002-0729. ; 44:5, s. 801-807
  • Tidskriftsartikel (refereegranskat)abstract
    • low bone mineral density measured by dual-energy x-ray absorptiometry is associated with increased mortality. The relationship between other skeletal phenotypes and mortality is unclear. The aim of this study was to determine the relationship between quantitative heel ultrasound parameters and mortality in a cohort of European men.
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44.
  • Rastrelli, Giulia, et al. (författare)
  • Development of and Recovery from Secondary Hypogonadism in Aging Men: Prospective Results from the EMAS
  • 2015
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 100:8, s. 3172-3182
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Secondary hypogonadism is common in aging men; its natural history and predisposing factors are unclear. Objectives: The objectives were 1) to identify factors that predispose eugonadal men (T >= 10.5 nmol/L) to develop biochemical secondary hypogonadism (T < 10.5 nmol/L; LH <= 9.4 U/L) and secondary hypogonadal men to recover to eugonadism; and 2) to characterize clinical features associated with these transitions. Design: The study was designed as a prospective observational general population cohort survey. Setting: The setting was clinical research centers. Participants: The participants were 3369 community-dwelling men aged 40-79 years in eight European centers. Intervention: Interventions included observational follow-up of 4.3 years. Main Outcome Measure: Subjects were categorized according to change/no change in biochemical gonadal status during follow-up as follows: persistent eugonadal (n = 1909), incident secondary hypogonadal (n = 140), persistent secondary hypogonadal (n = 123), and recovered from secondary hypogonadism to eugonadism (n = 96). Baseline predictors and changes in clinical features associated with incident secondary hypogonadism and recovery from secondary hypogonadism were analyzed by regression models. Results: The incidence of secondary hypogonadism was 155.9/10 000/year, whereas 42.9% of men with secondary hypogonadism recovered to eugonadism. Incident secondary hypogonadism was predicted by obesity(body mass index >= 30 kg/m(2); odds ratio [OR] = 2.86 [95% confidenceinterval, 1.67; 4.90]; P < .0001), weight gain (OR = 1.79 [1.15; 2.80]; P = .011), and increased waist circumference (OR = 1.73 [1.07; 2.81], P = .026; and OR = 2.64 [1.66; 4.21], P < .0001, for waist circumference 94-102 and >= 102 cm, respectively). Incident secondary hypogonadal men experienced new/worsening sexual symptoms (low libido, erectile dysfunction, and infrequent spontaneous erections). Recovery from secondary hypogonadism was predicted by nonobesity(OR = 2.28 [1.21; 4.31]; P = .011), weight loss (OR = 2.24 [1.04; 4.85]; P = .042), normal waist circumference (OR = 1.93 [1.01; 3.70]; P = .048), younger age (<60 y; OR = 2.32 [1.12; 4.82]; P = .024), and higher education (OR = 2.11 [1.05; 4.26]; P = .037), but symptoms did not show significant concurrent improvement. Conclusion: Obesity-related metabolic and lifestyle factors predispose older men to the development of secondary hypogonadism, which is frequently reversible with weight loss.
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45.
  • Rastrelli, Giulia, et al. (författare)
  • Symptomatic androgen deficiency develops only when both total and free testosterone decline in obese men who may have incident biochemical secondary hypogonadism : Prospective results from the EMAS
  • 2018
  • Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664. ; 89:4, s. 459-469
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Limited evidence supports the use of free testosterone (FT) for diagnosing hypogonadism when sex hormone–binding globulin (SHBG) is altered. Low total testosterone (TT) is commonly encountered in obesity where SHBG is typically decreased. We aimed to assess the contribution of FT in improving the diagnosis of symptomatic secondary hypogonadism (SH), identified initially by low total testosterone (TT), and then further differentiated by normal FT (LNSH) or low FT (LLSH). Design: Prospective observational study with a median follow-up of 4.3 years. Patients: Three thousand three hundred sixty-nine community-dwelling men aged 40-79 years from eight European centres. Measurements: Subjects were categorized according to baseline and follow-up biochemical status into persistent eugonadal (referent group; n = 1880), incident LNSH (eugonadism to LNSH; n = 101) and incident LLSH (eugonadism to LLSH; n = 38). Predictors and clinical features associated with the transition from eugonadism to LNSH or LLSH were assessed. Results: The cumulative incidence of LNSH and LLSH over 4.3 years was 4.9% and 1.9%, respectively. Baseline obesity predicted both LNSH and LLSH, but the former occurred more frequently in younger men. LLSH, but not LNSH, was associated with new/worsened sexual symptoms, including low desire [OR = 2.67 (1.27-5.60)], erectile dysfunction [OR = 4.53 (2.05-10.01)] and infrequent morning erections [OR = 3.40 (1.48-7.84)]. Conclusions: These longitudinal data demonstrate the importance of FT in the diagnosis of hypogonadism in obese men with low TT and SHBG. The concurrent fall in TT and FT identifies the minority (27.3%) of men with hypogonadal symptoms, which were not present in the majority developing low TT with normal FT.
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46.
  • Ravindrarajah, Rathi, et al. (författare)
  • The ability of three different models of frailty to predict all-cause mortality: Results from the European Male Aging Study (EMAS)
  • 2013
  • Ingår i: Archives of Gerontology and Geriatrics. - : Elsevier BV. - 1872-6976 .- 0167-4943. ; 57:3, s. 360-368
  • Tidskriftsartikel (refereegranskat)abstract
    • Few studies have directly compared the ability of the most commonly used models of frailty to predict mortality among community-dwelling individuals. Here, we used a frailty index (FI), frailty phenotype (FP), and FRAIL scale (FS) to predict mortality in the EMAS. Participants were aged 40-79 years (n = 2929) at baseline and 6.6% (n = 193) died over a median 4.3 years of follow-up. The FI was generated from 39 deficits, including self-reported health, morbidities, functional performance and psychological assessments. The FP and FS consisted of five phenotypic criteria and both categorized individuals as robust when they had 0 criteria, prefrail as 1-2 criteria and frail as 3+ criteria. The mean FI increased linearly with age (r(2) = 0.21) and in Cox regression models adjusted for age, center, smoking and partner status the hazard ratio (HR) for death for each unit increase of the FI was 1.49. Men who were prefrail or frail by either the FP or FS definitions, had a significantly increased risk of death compared to their robust counterparts. Compared to robust men, those who were FP frail at baseline had a HR for death of 3.84, while those who were FS frail had a HR of 3.87. All three frailty models significantly predicted future mortality among community-dwelling, middle-aged and older European men after adjusting for potential confounders. Our data suggest that the choice of frailty model may not be of paramount importance when predicting future risk of death, enabling flexibility in the approach used. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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47.
  • Roshandel, Delnaz, et al. (författare)
  • Influence of Polymorphisms in the RANKL/RANK/OPG Signaling Pathway on Volumetric Bone Mineral Density and Bone Geometry at the Forearm in Men
  • 2011
  • Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 89:6, s. 446-455
  • Tidskriftsartikel (refereegranskat)abstract
    • We sought to determine the influence of single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG on volumetric bone mineral density (vBMD) and bone geometry at the radius in men. Pairwise tag SNPs (r (2) a parts per thousand yen 0.8) for RANKL (n = 8), RANK (n = 44), and OPG (n = 22) and five SNPs near RANKL and OPG strongly associated with areal BMD in genomewide association studies were previously genotyped in men aged 40-79 years in the European Male Ageing Study (EMAS). Here, these SNPs were analyzed in a subsample of men (n = 589) who had peripheral quantitative computed tomography (pQCT) performed at the distal (4%) and mid-shaft (50%) radius. Estimated parameters were total and trabecular vBMD (mg/mm(3)) and cross-sectional area (mm(2)) at the 4% site and cortical vBMD (mg/mm(3)); total, cortical, and medullary area (mm(2)); cortical thickness (mm); and stress strain index (SSI) (mm(3)) at the 50% site. We identified 12 OPG SNPs associated with vBMD and/or geometric parameters, including rs10505348 associated with total vBMD (beta [95% CI] = 9.35 [2.12-16.58], P = 0.011), cortical vBMD (beta [95% CI] = 5.62 [2.10-9.14], P = 0.002), cortical thickness (beta [95% CI] = 0.08 [0.03-0.13], P = 0.002), and medullary area (beta [95% CI] = -2.90 [-4.94 to -0.86], P = 0.005) and rs2073618 associated with cortical vBMD (beta [95% CI] = -4.30 [-7.78 to -0.82], P = 0.015) and cortical thickness (beta [95% CI] = -0.08 [-0.13 to -0.03], P = 0.001). Three RANK SNPs were associated with vBMD, including rs12956925 associated with trabecular vBMD (beta [95% CI] = -7.58 [-14.01 to -1.15], P = 0.021). There were five RANK SNPs associated with geometric parameters, including rs8083511 associated with distal radius cross-sectional area (beta [95% CI] = 8.90 [0.92-16.88], P = 0.029). No significant association was observed between RANKL SNPs and pQCT parameters. Our findings suggest that genetic variation in OPG and RANK influences radius vBMD and geometry in men.
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48.
  • Roshandel, Delnaz, et al. (författare)
  • Polymorphisms in Genes Involved in the NF-kappa B Signalling Pathway Are Associated with Bone Mineral Density, Geometry and Turnover in Men
  • 2011
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: In this study, we aimed to investigate the association between single nucleotide polymorphisms (SNPs) within two genes involved in the NF-kappa B cascade (GPR177 and MAP3K14) and bone mineral density (BMD) assessed at different skeletal sites, radial geometric parameters and bone turnover. Methods: Ten GPR177 SNPs previously associated with BMD with genome-wide significance and twelve tag SNPs (r(2) >= 0.8) within MAP3K14 (+/-10 kb) were genotyped in 2359 men aged 40-79 years recruited from 8 centres for participation in the European Male Aging Study (EMAS). Measurement of bone turnover markers (PINP and CTX-I) in the serum and quantitative ultrasound (QUS) at the calcaneus were performed in all centres. Dual energy X-ray absorptiometry (DXA), at the lumbar spine and hip, and peripheral quantitative computed tomography (pQCT), at the distal and midshaft radius, were performed in a subsample (2 centres). Linear regression was used to test for association between the SNPs and bone measures under an additive genetic model adjusting for study centre. Results: We validated the associations between SNPs in GPR177 and BMDa previously reported and also observed evidence of pleiotrophic effects on density and geometry. Rs2772300 in GPR177 was associated with increased total hip and LS BMDa, increased total and cortical vBMD at the radius and increased cortical area, thickness and stress strain index. We also found evidence of association with BMDa, vBMD, geometric parameters and CTX-I for SNPs in MAP3K14. None of the GPR177 and MAP3K14 SNPs were associated with calcaneal estimated BMD measured by QUS. Conclusion: Our findings suggest that SNPs in GPR177 and MAP3K14 involved in the NF-kappa B signalling pathway influence bone mineral density, geometry and turnover in a population-based cohort of middle aged and elderly men. This adds to the understanding of the role of genetic variation in this pathway in determining bone health.
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49.
  • Swiecicka, Agnieszka, et al. (författare)
  • Reproductive hormone levels predict changes in frailty status in community-dwelling older men : European male ageing study prospective data
  • 2018
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 103:2, s. 701-709
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Clinical sequelae of androgen deficiency share common features with frailty. Evidence supporting the role of androgens in the development of frailty is limited and conflicting. Objective: To determine associations between male reproductive hormones and prospective changes in frailty status. Design/Setting: A 4.3-year prospective cohort study of community-dwelling men participating in the European Male Ageing Study. Participants: A total of 3369 men aged 40 to 79 from eight European centers. Intervention: None. Main Outcome Measure: Frailty status was determined using frailty index (FI; n = 2278) and frailty phenotype (FP; n = 1980). Results: After adjusting for baseline frailty, age, center, and smoking, the risk ofworsening FI decreased with higher testosterone (T), free T, and dihydrotestosterone (DHT) [percentage change (95% confidence interval) in FI associated with 1 standard deviation higher hormone level: -3.0 (-5.9, -1.0) for total T; -3.9 (-6.8, -2.0) for free T; and -3.9 (-6.8, -2.0) forDHT]. After further adjustment for bodymass index, only free T remained a significant predictor of FI change. In fully adjusted models, higher luteinizing hormone and follicle-stimulating hormone were positively related to worsening FI only in men ,60 years, and higher estradiol predicted lower likelihood of improving FP [odds ratio: 0.68 (0.52, 0.88)]. Conclusions: These prospective data support the hypothesis that higher androgen levels may protect elderly men from worsening frailty. However, the causal nature of these relationships requires further investigation.Whereas raised gonadotropins inmen,60 yearsmight be an earlymarker of frailty, the role of estradiol in frailty needs further clarification.
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50.
  • Tajar, Abdelouahid, et al. (författare)
  • Characteristics of Secondary, Primary, and Compensated Hypogonadism in Aging Men: Evidence from the European Male Ageing Study.
  • 2010
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95, s. 1810-1818
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: The diagnosis of late-onset hypogonadism (LOH) in older men with age-related declines in testosterone (T) is currently not well characterized. Objective: Our objective was to investigate whether different forms of hypogonadism can be distinguished among aging men. Design: The study was a cross-sectional survey on 3369 community-dwelling men aged 40-79 yr in eight European centers. Methods: Four groups of subjects were defined: eugonadal (normal T and normal LH), secondary (low T and low/normal LH), primary (low T and elevated LH), and compensated (normal T and elevated LH) hypogonadism. Relationships between the defined gonadal status with potential risk factors and clinical symptoms were investigated by multilevel regression models. Results: Among the men, 11.8, 2.0, and 9.5% were classified into the secondary, primary, and compensated hypogonadism categories, respectively. Older men were more likely to have primary [relative risk ratio (RRR) = 3.04; P < 0.001] and compensated (RRR = 2.41; P < 0.001) hypogonadism. Body mass index of 30 kg/m(2) or higher was associated with secondary hypogonadism (RRR = 8.74; P < 0.001). Comorbidity was associated with both secondary and primary hypogonadism. Sexual symptoms were more prevalent in secondary and primary hypogonadism, whereas physical symptoms were more likely in compensated hypogonadism. Conclusions: Symptomatic elderly men considered to have LOH can be differentiated on the basis of endocrine and clinical features and predisposing risk factors. Secondary hypogonadism is associated with obesity and primary hypogonadism predominately with age. Compensated hypogonadism can be considered a distinct clinical state associated with aging. Classification of LOH into different categories by combining LH with T may improve the diagnosis and management of LOH.
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