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1.
J Clin Endocrinol Metab ; 103(3): 991-1004, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29325096

RESUMO

Context: Serum estradiol (E2) and estrone (E1) levels exhibit substantial heritability. Objective: To investigate the genetic regulation of serum E2 and E1 in men. Design, Setting, and Participants: Genome-wide association study in 11,097 men of European origin from nine epidemiological cohorts. Main Outcome Measures: Genetic determinants of serum E2 and E1 levels. Results: Variants in/near CYP19A1 demonstrated the strongest evidence for association with E2, resolving to three independent signals. Two additional independent signals were found on the X chromosome; FAMily with sequence similarity 9, member B (FAM9B), rs5934505 (P = 3.4 × 10-8) and Xq27.3, rs5951794 (P = 3.1 × 10-10). E1 signals were found in CYP19A1 (rs2899472, P = 5.5 × 10-23), in Tripartite motif containing 4 (TRIM4; rs17277546, P = 5.8 × 10-14), and CYP11B1/B2 (rs10093796, P = 1.2 × 10-8). E2 signals in CYP19A1 and FAM9B were associated with bone mineral density (BMD). Mendelian randomization analysis suggested a causal effect of serum E2 on BMD in men. A 1 pg/mL genetically increased E2 was associated with a 0.048 standard deviation increase in lumbar spine BMD (P = 2.8 × 10-12). In men and women combined, CYP19A1 alleles associated with higher E2 levels were associated with lower degrees of insulin resistance. Conclusions: Our findings confirm that CYP19A1 is an important genetic regulator of E2 and E1 levels and strengthen the causal importance of E2 for bone health in men. We also report two independent loci on the X-chromosome for E2, and one locus each in TRIM4 and CYP11B1/B2, for E1.


Assuntos
Aromatase/genética , Densidade Óssea/genética , Estradiol/sangue , Densidade Óssea/fisiologia , Cromossomos Humanos X , Estudos de Coortes , Estradiol/genética , Estradiol/fisiologia , Estrona/sangue , Estrona/genética , Feminino , Regulação da Expressão Gênica/fisiologia , Estudo de Associação Genômica Ampla , Genótipo , Hormônios Esteroides Gonadais/sangue , Humanos , Resistência à Insulina/genética , Resistência à Insulina/fisiologia , Vértebras Lombares/fisiologia , Masculino , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Testosterona/sangue
2.
Clin Endocrinol (Oxf) ; 88(3): 479-490, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29178359

RESUMO

OBJECTIVE: Elevated luteinizing hormone (LH) with normal testosterone (T) suggests compensated dysregulation of the gonadal axis. We describe the natural history, risk factors and clinical parameters associated with the development of high LH (HLH, LH >9.4 U/L) in ageing men with normal T (T ≥ 10.5 nmol/L). DESIGN, PATIENTS AND MEASUREMENTS: We conducted a 4.3-year prospective observational study of 3369 community-dwelling European men aged 40-79 years. Participants were classified as follows: incident (i) HLH (n = 101, 5.2%); persistent (p) HLH (n = 128, 6.6%); reverted (r) HLH (n = 46, 2.4%); or persistent normal LH (pNLH, n = 1667, 85.8%). Potential predictors and changes in clinical features associated with iHLH and rHLH were analysed using regression models. RESULTS: Age >70 years (OR = 4.12 [2.07-8.20]), diabetes (OR = 2.86 [1.42-5.77]), chronic pain (OR = 2.53 [1.34-4.77]), predegree education (OR = 1.79 [1.01-3.20]) and low physical activity (PASE ≤ 78, OR = 2.37 [1.24-4.50]) predicted development of HLH. Younger age (40-49 years, OR = 8.14 [1.35-49.13]) and nonsmoking (OR = 5.39 [1.48-19.65]) predicted recovery from HLH. Men with iHLH developed erectile dysfunction, poor health, cardiovascular disease (CVD) and cancer more frequently than pNLH men. In pHLH men, comorbidities, including CVD, developed more frequently, and cognitive and physical function deteriorated more, than in pNLH men. Men with HLH developed primary hypogonadism more frequently (OR = 15.97 [5.85-43.60]) than NLH men. Men with rHLH experienced a small rise in BMI. CONCLUSIONS: Elevation of LH with normal T is predicted by multiple factors, reverts frequently and is not associated with unequivocal evidence of androgen deficiency. High LH is a biomarker for deteriorating health in aged men who tend to develop primary hypogonadism.


Assuntos
Hormônio Luteinizante/metabolismo , Testosterona/sangue , Adulto , Fatores Etários , Idoso , Envelhecimento , Disfunção Erétil/etiologia , Europa (Continente) , Humanos , Hipogonadismo/etiologia , Hormônio Luteinizante/sangue , Masculino , Pessoa de Meia-Idade , História Natural , Prognóstico , Estudos Prospectivos , Fatores de Risco
3.
J Cachexia Sarcopenia Muscle ; 8(4): 598-606, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28474432

RESUMO

BACKGROUND: Ageing is associated with sarcopenia, osteoporosis, and increased fall risk, all of which contribute to increased fracture risk. Mechanically, bone strength adapts in response to forces created by muscle contractions. Adaptations can be through changes in bone size, geometry, and bending strength. Muscle mass is often used as a surrogate for muscle force; however, force can be increased without changes in muscle mass. Increased fall risk with ageing has been associated with a decline in muscle power-which is a measure of mobility. The aims of this study were as follows: (i) to investigate the relationship between muscle parameters in the upper and lower limbs with age in UK men and the influence of ethnicity on these relationships; (ii) to examine the relationships between jump force/grip strength/cross-sectional muscle area (CSMA) with bone outcomes at the radius and tibia. METHODS: White European, Black Afro-Caribbean, and South Asian men aged 40-79 years were recruited from Manchester, UK. Cortical bone mineral content, cross-sectional area, cortical area, cross-sectional moment of inertia, and CSMA were measured at the diaphysis of the radius and tibia using peripheral quantitative computed tomography. Lower limb jump force and power were measured from a single two-legged jump performed on a ground-reaction force platform. Grip strength was measured using a dynamometer. Associations between muscle and bone outcomes was determined using linear regression with adjustments for age, height, weight, and ethnicity. RESULTS: Three hundred and one men were recruited. Jump force was negatively associated with age; for every 10 year increase in age, there was a 4% reduction in jump force (P < 0.0001). There was a significant age-ethnicity interaction for jump power (P = 0.039); after adjustments, this was attenuated (P = 0.088). For every 10 year increase in age, grip strength decreased by 11%. Jump force was positively associated with tibial bone outcomes: a 1 standard deviation greater jump force was associated with significantly higher cortical bone mineral content 3.1%, cross-sectional area 4.2%, cortical area 3.4%, and cross-sectional moment of inertia 6.8% (all P < 0.001). Cross-sectional muscle area of the lower leg was not associated with tibial bone outcomes. Both grip strength and CSMA of the arm were positively associated, to a similar extent, with radius diaphyseal bone outcomes. CONCLUSIONS: Jump force and power are negatively associated with age in UK men. In the lower limb, the measurement of jump force is more strongly related to bone outcomes than CSMA. It is important to consider jump force and power when understanding the aetiology of bone loss and mobility in ageing men.


Assuntos
Osso e Ossos/anatomia & histologia , Força da Mão/fisiologia , Força Muscular/fisiologia , Músculos/anatomia & histologia , Adulto , Idoso , Anatomia Transversal , Densidade Óssea/fisiologia , Etnicidade , Exercício Físico/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Tíbia/anatomia & histologia , Reino Unido/epidemiologia
4.
BMC Musculoskelet Disord ; 17: 32, 2016 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-26774507

RESUMO

BACKGROUND: The association between low levels of vitamin D and the occurrence of chronic widespread pain (CWP) remains unclear. The aim of our analysis was to determine the relationship between low vitamin D levels and the risk of developing CWP in a population sample of middle age and elderly men. METHODS: Three thousand three hundred sixty nine men aged 40-79 were recruited from 8 European centres for a longitudinal study of male ageing, the European Male Ageing Study. At baseline participants underwent assessment of lifestyle, health factors, physical characteristics and gave a fasting blood sample. The occurrence of pain was assessed at baseline and follow up (a mean of 4.3 years later) by shading painful sites on a body manikin. The presence of CWP was determined using the ACR criteria for fibromyalgia. Serum 25-hydroxyvitamin D (25-(OH) D) was assessed by radioimmunoassay. Logistic regression was used to determine the relationship between baseline vitamin D levels and the new occurrence of CWP. RESULTS: Two thousand three hundred thirteen men, mean age 58.8 years (SD = 10.6), had complete pain and vitamin data available and contributed to this analysis. 151 (6.5%) developed new CWP at follow up and 577 (24.9%) were pain free at both time points, the comparator group. After adjustment for age and centre, physical performance and number of comorbidities, compared to those in upper quintile of 25-(OH) D ( ≥36.3 ng/mL), those in the lowest quintile (<15.6 ng/mL) were more likely to develop CWP (Odds Ratio [OR] = 1.93; 95% CI = 1.0-3.6). Further adjustment for BMI (OR = 1.67; 95% CI = 0.93-3.02) or depression (OR = 1.77; 95% CI = 0.98-3.21), however rendered the association non-significant. CONCLUSIONS: Low vitamin D is linked with the new occurrence of CWP, although this may be explained by underlying adverse health factors, particularly obesity and depression.


Assuntos
Envelhecimento/sangue , Dor Crônica/sangue , Dor Crônica/epidemiologia , Medição da Dor/tendências , Vitamina D/sangue , Adulto , Idoso , Envelhecimento/patologia , Biomarcadores/sangue , Dor Crônica/diagnóstico , Europa (Continente)/epidemiologia , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Medição da Dor/métodos , Fatores de Risco
5.
Age Ageing ; 45(2): 268-74, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26679698

RESUMO

BACKGROUND: we hypothesised that chronic widespread pain (CWP), by acting as a potential stressor, may predispose to the development of, or worsening, frailty. SETTING: longitudinal analysis within the European Male Ageing Study (EMAS). PARTICIPANTS: a total of 2,736 community-dwelling men aged 40-79. METHODS: subjects completed a pain questionnaire and shaded a manikin, with the presence of CWP defined using the American College of Rheumatology criteria. Physical activity, smoking, alcohol consumption and depression were measured. Repeat assessments took place a median of 4.3 years later. A frailty index (FI) was used, with frail defined as an FI >0.35. The association between CWP at baseline and the new occurrence of frailty was examined using logistic regression; the association between CWP at baseline and change in FI was examined using negative binomial regression. RESULTS: at baseline, 218 (8.3%) men reported CWP. Of the 2,631 men who were defined as non-frail at baseline, 112 (4.3%) were frail at follow-up; their mean FI was 0.12 (SD 0.1) at baseline and 0.15 (SD 0.1) at follow-up, with a mean change of 0.03 (SD 0.08) P ≤ 0.001. Among men who were non-frail at baseline, those with CWP were significantly more likely to develop frailty. After adjustment for age and centre, compared with those with no pain, those with CWP at baseline had a 70% higher FI at follow-up; these associations remained significant after further adjustment for smoking, body mass index, depression, physical activity and FI at baseline. CONCLUSION: the presence of CWP is associated with an increased risk of frailty in older European men.


Assuntos
Envelhecimento , Dor Crônica/epidemiologia , Idoso Fragilizado , Adulto , Fatores Etários , Idoso , Dor Crônica/diagnóstico , Comorbidade , Progressão da Doença , Europa (Continente)/epidemiologia , Avaliação Geriátrica , Humanos , Incidência , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Razão de Chances , Medição da Dor , Prognóstico , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , Inquéritos e Questionários , Fatores de Tempo
6.
J Cachexia Sarcopenia Muscle ; 6(3): 242-52, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26401471

RESUMO

BACKGROUND: In men, the long-term consequences of low serum levels of sex steroids, vitamin D metabolites, and insulin-like growth factor 1 (IGF-1) on the evolution of muscle mass, muscle strength, or physical performance are unclear. Moreover, there are no data about the relationship between these hormones and incident sarcopenia defined as low muscle mass and function. The aim of this study was to determine whether the baseline levels of sex hormones, vitamin D metabolites, and IGF-1 predict changes in muscle mass, muscle strength, physical performance, and incident sarcopenia. METHODS: In 518 men aged 40-79 years, recruited for participation in the European Male Ageing Study, total, free, and bioavailable testosterone (T), oestradiol (E), sex hormone-binding globulin, IGF-1, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)2D), and parathyroid hormone were assessed at baseline. Appendicular lean mass (aLM), gait speed, and grip strength were measured at baseline and after a mean follow-up of 4.3 years. Sarcopenia was defined by the definition of Baumgartner (relative aLM ≤7.26 kg/m(2)), the International Working Group on Sarcopenia (IWGS), and the European Working Group on Sarcopenia in Older People (EWGSOP). RESULTS: aLM significantly decreased from age 50 years, while gait speed and grip strength significantly decreased from age 70 years. The incidence of sarcopenia by the definitions of Baumgartner, IWGS, and EWGSOP was 8.1%, 3.0%, and 1.6%, respectively. After adjustment for age, centre, body mass index, smoking, and number of comorbidities at baseline, baseline levels of T and vitamin D metabolites were not associated with change in aLM, gait speed, and/or grip strength, while a high baseline level of total E2 was associated with a greater decrease in aLM. In men aged ≥70 years, low IGF-1 was associated with a greater decrease in gait speed. Baseline endocrine variables were not independently associated with an increased risk of incident sarcopenia by any definition. CONCLUSIONS: Low levels of T and 25OHD do not predict loss of muscle mass, gait speed, or grip strength in middle-aged and elderly community-dwelling European men. Low IGF-1 predicts change in gait speed in men aged ≥70 years.

7.
Age Ageing ; 44(5): 801-7, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26162912

RESUMO

BACKGROUND: 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. METHODS: men aged 40-79 years were recruited for participation in a prospective study of male ageing: the European Male Ageing Study (EMAS). At baseline, subjects attended for quantitative ultrasound (QUS) of the heel (Hologic-SAHARA) and completed questionnaires on lifestyle factors and co-morbidities. Height and weight were measured. After a median of 4.3 years, subjects were invited to attend a follow-up assessment, and reasons for non-participation, including death, were recorded. The relationship between QUS parameters (broadband ultrasound attenuation [BUA] and speed of sound [SOS]) and mortality was assessed using Cox proportional hazards model. RESULTS: from a total of 3,244 men (mean age 59.8, standard deviation [SD] 10.8 years), 185 (5.7%) died during the follow-up period. After adjusting for age, centre, body mass index, physical activity, current smoking, number of co-morbidities and general health, each SD decrease in BUA was associated with a 20% higher risk of mortality (hazard ratio [HR] per SD = 1.2; 95% confidence interval [CI] = 1.0-1.4). Compared with those in higher quintiles (2nd-5th), those in the lowest quintile of BUA and SOS had a greater mortality risk (BUA: HR = 1.6; 95% CI = 1.1-2.3 and SOS: HR = 1.6; 95% CI = 1.2-2.2). CONCLUSION: lower heel ultrasound parameters are associated with increased mortality in European men.


Assuntos
Envelhecimento , Nível de Saúde , Calcanhar/diagnóstico por imagem , Adulto , Fatores Etários , Idoso , Índice de Massa Corporal , Causas de Morte , Comorbidade , Europa (Continente) , Avaliação Geriátrica , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo , Ultrassonografia
8.
Age Ageing ; 43(4): 528-35, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24375224

RESUMO

BACKGROUND: vitamin D deficiency has been associated with an increased risk of mortality, but whether this relationship is causal or linked to co-existent comorbidity and adverse life factors remains uncertain. Our objective was to determine whether endogenous 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D) and parathyroid hormone (PTH) levels predicted all-cause, cardiovascular and cancer mortality independently of health and lifestyle factors. SETTING: : prospective cohort analysis within the European Male Ageing Study. PARTICIPANTS: : 2,816 community-dwelling men aged 40-79 years at baseline. METHODS: : Cox regression was used to examine the association of all-cause mortality with 25(OH)D, 1,25(OH)2D and PTH; cardiovascular and cancer mortality were modelled using competing-risks regression. Results were expressed as hazard ratios (HR) and 95% confidence intervals (CIs) for Cox models; sub-hazard ratios (SHR) and 95% CIs for competing-risks models. RESULTS: : a total of 187 men died during a median of 4.3 years of follow-up. Serum levels of 25(OH)D (per 1 SD decrease: HR = 1.45; 95% CI = 1.16, 1.81) and 1,25(OH)2D (per 1 SD decrease: HR = 1.20; 95% CI = 1.00, 1.44) were associated with an increased risk of all-cause mortality after adjusting for age, centre, smoking, self-reported morbidities, physical activity and functional performance. Only levels of 25(OH)D <25 nmol/l predicted cancer mortality (SHR = 3.33; 95% CI = 1.38, 8.04). CONCLUSION: : lower 25(OH)D and 1,25(OH)2D levels independently predicted all-cause mortality in middle-aged and older European men. Associations with cancer mortality were only observed among men with very low levels of 25(OH)D. These associations were only partially explained by the range of adverse health and lifestyle factors measured here.


Assuntos
Envelhecimento/sangue , Doenças Cardiovasculares/mortalidade , Neoplasias/mortalidade , Hormônio Paratireóideo/sangue , Vitamina D/análogos & derivados , Adulto , Idoso , Biomarcadores/sangue , Estudos de Coortes , Europa (Continente) , Seguimentos , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Regressão , Fatores de Risco , Inquéritos e Questionários , Taxa de Sobrevida , Vitamina D/sangue
9.
Arch Gerontol Geriatr ; 57(3): 360-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23871598

RESUMO

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.


Assuntos
Idoso Fragilizado/estatística & dados numéricos , Mortalidade , Atividades Cotidianas , Adulto , Fatores Etários , Idoso , Europa (Continente)/epidemiologia , Nível de Saúde , Humanos , Estimativa de Kaplan-Meier , Masculino , Estado Civil/estatística & dados numéricos , Pessoa de Meia-Idade , Modelos Estatísticos , Modelos de Riscos Proporcionais , Fatores de Risco , Fumar/mortalidade , Inquéritos e Questionários , Análise de Sobrevida
10.
J Clin Endocrinol Metab ; 98(6): E1097-102, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23633197

RESUMO

CONTEXT: Immunoassay-based techniques, routinely used to measure serum estradiol (E2), are known to have reduced specificity, especially at lower concentrations, when compared with the gold standard technique of mass spectrometry (MS). Different measurement techniques may be responsible for the conflicting results of associations between serum E2 and clinical phenotypes in men. OBJECTIVE: Our objective was to compare immunoassay and MS measurements of E2 levels in men and evaluate associations with clinical phenotypes. DESIGN AND SETTING: Middle-aged and older male subjects participating in the population-based Osteoporotic Fractures in Men (MrOS) Sweden study (n = 2599), MrOS US (n = 688), and the European Male Aging Study (n = 2908) were included. MAIN OUTCOME MEASURES: Immunoassay and MS measurements of serum E2 were compared and related to bone mineral density (BMD; measured by dual energy x-ray absorptiometry) and ankle-brachial index. RESULTS: Within each cohort, serum E2 levels obtained by immunoassay and MS correlated moderately (Spearman rank correlation coefficient rS 0.53-0.76). Serum C-reactive protein (CRP) levels associated significantly (albeit to a low extent, rS = 0.29) with immunoassay E2 but not with MS E2 levels. Similar associations of immunoassay E2 and MS E2 were seen with lumbar spine and total hip BMD, independent of serum CRP. However, immunoassay E2, but not MS E2, associated inversely with ankle-brachial index, and this correlation was lost after adjustment for CRP. CONCLUSIONS: Our findings suggest interference in the immunoassay E2 analyses, possibly by CRP or a CRP-associated factor. Although associations with BMD remain unaffected, this might imply for a reevaluation of previous association studies between immunoassay E2 levels and inflammation-related outcomes.


Assuntos
Estradiol/sangue , Imunoensaio , Espectrometria de Massas , Idoso , Densidade Óssea , Proteína C-Reativa/análise , Humanos , Masculino , Pessoa de Meia-Idade
11.
J Clin Endocrinol Metab ; 98(3): 995-1005, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23386642

RESUMO

CONTEXT: There is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)2D] on bone health including turnover. OBJECTIVE: The objective of the study was to determine the influence of 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] on bone health in middle-aged and older European men. DESIGN, SETTING, AND PARTICIPANTS: Men aged 40-79 years were recruited from population registers in 8 European centers. Subjects completed questionnaires that included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, assessment of height and weight, and a fasting blood sample from which 1,25(OH)2D, 25(OH)D, and PTH were measured. 1,25(OH)2D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (ß-cTX) were also measured. Dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine was performed in 2 centers. MAIN OUTCOME MEASURE(S): QUS of the heel, bone markers P1NP and ß-cTX, and DXA of the hip and lumbar spine were measured. RESULTS: A total of 2783 men, mean age 60.0 years (SD 11.0) were included in the analysis. After adjustment for age and center, 1,25(OH)2D was positively associated with 25(OH)D but not with PTH. 25(OH)D was negatively associated with PTH. After adjustment for age, center, height, weight, lifestyle factors, and season, 1,25(OH)2D was associated negatively with QUS and DXA parameters and associated positively with ß-cTX. 1,25(OH)2D was not correlated with P1NP. 25(OH)D was positively associated with the QUS and DXA parameters but not related to either bone turnover marker. Subjects with both high 1,25(OH)2D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest ß-cTX levels. CONCLUSIONS: Serum 1,25(OH)2D is associated with higher bone turnover and poorer bone health despite being positively related to 25(OH)D. A combination of high 1,25(OH)2D and low 25(OH)D is associated with the poorest bone health.


Assuntos
Envelhecimento/metabolismo , Doenças Ósseas Metabólicas/metabolismo , Remodelação Óssea/fisiologia , Calcitriol/sangue , Deficiência de Vitamina D/metabolismo , Vitamina D/análogos & derivados , Absorciometria de Fóton , Adulto , Idoso , Biomarcadores/metabolismo , Densidade Óssea/fisiologia , Doenças Ósseas Metabólicas/diagnóstico por imagem , Calcâneo/diagnóstico por imagem , Calcâneo/metabolismo , Colágeno Tipo I/metabolismo , Articulação do Quadril/diagnóstico por imagem , Humanos , Estilo de Vida , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/metabolismo , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Peptídeos/metabolismo , Inquéritos e Questionários , Ultrassonografia , Vitamina D/sangue , População Branca
12.
J Gerontol A Biol Sci Med Sci ; 68(7): 837-44, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23105045

RESUMO

BACKGROUND: There has been little research on how late-life frailty interrelates with sexual health. Our objective was to examine the association of frailty with sexual functioning and satisfaction among older men. METHODS: The study population consisted of 1,504 men aged 60 to 79 years, participating in the European Male Aging Study. Self-report questionnaires measured overall sexual functioning, sexual function-related distress, and erectile dysfunction. Frailty status was defined using a phenotype (FP) or index (FI). Associations between frailty and sexual function were explored using regression models. RESULTS: Based on the frailty phenotype, 5% of men were classified as frail, and the mean frailty index was 0.18 (SD = 0.12). Frailty was associated with decreasing overall sexual functioning and increasing sexual function-related distress in multiple linear regressions adjusted for age, smoking, alcohol consumption, living arrangements, comorbidities, and depression. Frailty was also associated with an increased odds of erectile dysfunction after adjustment for the same confounders: odds ratio = 1.99 (95% confidence interval = 1.14, 3.48) and 4.08 (95% confidence interval = 2.63, 6.36) for frailty phenotype and frailty index, respectively. CONCLUSIONS: Frailty was associated with impaired overall sexual functioning, sexual function-related distress, and erectile dysfunction. Individuals assessed for frailty-related deficits may also benefit from an appraisal of sexual health as an important aspect of well-being and quality of life.


Assuntos
Disfunção Erétil/epidemiologia , Idoso Fragilizado , Qualidade de Vida , Saúde Reprodutiva , Idoso , Avaliação Geriátrica/métodos , Humanos , Masculino , Satisfação Pessoal , Fatores de Risco , Autorrelato , Inquéritos e Questionários , Reino Unido/epidemiologia , População Branca/estatística & dados numéricos
13.
Eur J Endocrinol ; 166(1): 77-85, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22048968

RESUMO

OBJECTIVE: Interrelationships between hormones of the hypothalamic-pituitary-testicular (HPT) axis, hypogonadism, vitamin D and seasonality remain poorly defined. We investigated whether HPT axis hormones and hypogonadism are associated with serum levels of 25-hydroxyvitamin D (25(OH)D) in men. DESIGN AND METHODS: Cross-sectional survey of 3369 community-dwelling men aged 40-79 years in eight European centres. Testosterone (T), oestradiol (E(2)) and dihydrotestosterone were measured by gas chromatography-mass spectrometry; LH, FSH, sex hormone binding globulin (SHBG), 25(OH)D and parathyroid hormone by immunoassay. Free T was calculated from total T, SHBG and albumin. Gonadal status was categorised as eugonadal (normal T/LH), secondary (low T, low/normal LH), primary (low T, elevated LH) and compensated (normal T, elevated LH) hypogonadism. Associations of HPT axis hormones with 25(OH)D were examined using linear regression and hypogonadism with vitamin D using multinomial logistic regression. RESULTS: In univariate analyses, free T levels were lower (P=0.02) and E(2) and LH levels were higher (P<0.05) in men with vitamin D deficiency (25(OH)D <50 nmol/l). 25(OH)D was positively associated with total and free T and negatively with E(2) and LH in age- and centre-adjusted linear regressions. After adjusting for health and lifestyle factors, no significant associations were observed between 25(OH)D and individual hormones of the HPT axis. However, vitamin D deficiency was significantly associated with compensated (relative risk ratio (RRR)=1.52, P=0.03) and secondary hypogonadism (RRR=1.16, P=0.05). Seasonal variation was only observed for 25(OH)D (P<0.001). CONCLUSIONS: Secondary and compensated hypogonadism were associated with vitamin D deficiency and the clinical significance of this relationship warrants further investigation.


Assuntos
Hipogonadismo/metabolismo , Deficiência de Vitamina D/metabolismo , Adulto , Idoso , Estudos Transversais , Di-Hidrotestosterona/metabolismo , Estradiol/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Imunoensaio , Modelos Logísticos , Hormônio Luteinizante/metabolismo , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo , Globulina de Ligação a Hormônio Sexual/metabolismo , Testosterona/metabolismo , Vitamina D/análogos & derivados , Vitamina D/metabolismo
14.
PLoS Genet ; 7(10): e1002313, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21998597

RESUMO

Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871) and two de novo replication cohorts (n = 4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p = 1.2×10(-41) and rs6258, p = 2.3×10(-22)). Subjects with ≥ 3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6×10(-16)). The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation.


Assuntos
Proteínas Nucleares/genética , Globulina de Ligação a Hormônio Sexual/genética , Testosterona/sangue , Adulto , Idoso de 80 Anos ou mais , Alelos , Índice de Massa Corporal , Cromossomos Humanos X/genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
15.
Calcif Tissue Int ; 89(6): 446-55, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21964949

RESUMO

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) ≥ 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 (ß [95% CI] = 9.35 [2.12-16.58], P = 0.011), cortical vBMD (ß [95% CI] = 5.62 [2.10-9.14], P = 0.002), cortical thickness (ß [95% CI] = 0.08 [0.03-0.13], P = 0.002), and medullary area (ß [95% CI] = -2.90 [-4.94 to -0.86], P = 0.005) and rs2073618 associated with cortical vBMD (ß [95% CI] = -4.30 [-7.78 to -0.82], P = 0.015) and cortical thickness (ß [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 (ß [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 (ß [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.


Assuntos
Densidade Óssea/genética , Osso e Ossos/diagnóstico por imagem , Osteoprotegerina/genética , Ligante RANK/genética , Receptor Ativador de Fator Nuclear kappa-B/genética , Adulto , Idoso , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Rádio (Anatomia)/diagnóstico por imagem , Transdução de Sinais/genética , Tomografia Computadorizada por Raios X/métodos
16.
PLoS One ; 6(7): e22037, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21760950

RESUMO

PURPOSE: Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor α gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMD(a)) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of European men. METHODS: Eight single nucleotide polymorphisms (SNP) in the 6q25 locus were genotyped in men aged 40-79 years from 7 European countries, participating in the European Male Ageing Study (EMAS). The associations between SNPs and measured bone parameters were tested under an additive genetic model adjusting for centre using linear regression. RESULTS: 2468 men, mean (SD) aged 59.9 (11.1) years had QUS measurements performed and bone turnover marker levels measured. A subset of 628 men had DXA and pQCT measurements. Multiple independent SNPs showed significant associations with BMD using all three measurement techniques. Most notably, rs1999805 was associated with a 0.10 SD (95%CI 0.05, 0.16; p = 0.0001) lower estimated BMD at the calcaneus, a 0.14 SD (95%CI 0.05, 0.24; p = 0.004) lower total hip BMD(a), a 0.12 SD (95%CI 0.02, 0.23; p = 0.026) lower lumbar spine BMD(a) and a 0.18 SD (95%CI 0.06, 0.29; p = 0.003) lower trabecular BMD at the distal radius for each copy of the minor allele. There was no association with serum levels of bone turnover markers and a single SNP which was associated with cortical density was also associated with cortical BMC and thickness. CONCLUSIONS: Our data replicate previous associations found between SNPs in the 6q25 locus and BMD(a) at the hip and extend these data to include associations with calcaneal ultrasound parameters and radial volumetric BMD.


Assuntos
Densidade Óssea/genética , Calcâneo/diagnóstico por imagem , Receptor alfa de Estrogênio/genética , Estudos de Associação Genética , Loci Gênicos/genética , Rádio (Anatomia)/fisiologia , População Branca/genética , Absorciometria de Fóton , Idoso , Alelos , Estradiol/metabolismo , Genótipo , Saúde , Quadril/fisiologia , Humanos , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Rádio (Anatomia)/diagnóstico por imagem , Ultrassonografia
17.
Calcif Tissue Int ; 88(6): 503-10, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21503646

RESUMO

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.


Assuntos
Envelhecimento/fisiologia , Osso e Ossos/fisiologia , Saúde , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/fisiologia , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Envelhecimento/etnologia , Densidade Óssea , Estudos de Coortes , Europa (Continente) , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , População Branca
18.
BMC Musculoskelet Disord ; 11: 106, 2010 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-20509941

RESUMO

BACKGROUND: The aim of this analysis was to determine the relative influence of disease and non-disease factors on areal bone mineral density (BMDa) in a primary care based cohort of women with inflammatory polyarthritis. METHODS: Women aged 16 years and over with recent onset inflammatory polyarthritis were recruited to the Norfolk Arthritis Register (NOAR) between 1990 and 1993. Subjects were examined at both baseline and follow up for the presence of tender, swollen and deformed joints. At the 10th anniversary visit, a sub-sample of women were invited to complete a bone health questionnaire and attend for BMDa (Hologic, QDR 4000). Linear regression was used to examine the association between BMDa with both (i) arthritis-related factors assessed at baseline and the 10th anniversary visit and (ii) standard risk factors for osteoporosis. Adjustments were made for age. RESULTS: 108 women, mean age 58.0 years were studied. Older age, decreasing weight and BMI at follow up were all associated with lower BMDa at both the spine and femoral neck. None of the lifestyle factors were linked. Indices of joint damage including 10th anniversary deformed joint count and erosive joint count were the arthritis-related variables linked with a reduction in BMDa at the femoral neck. By contrast, disease activity as determined by the number of tender and or swollen joints assessed both at baseline and follow up was not linked with BMDa at either site. CONCLUSION: Cumulative disease damage was the strongest predictor of reduced femoral bone density. Other disease and lifestyle factors have only a modest influence.


Assuntos
Artrite/diagnóstico por imagem , Artrite/fisiopatologia , Densidade Óssea/fisiologia , Osteoporose/diagnóstico por imagem , Osteoporose/fisiopatologia , Adulto , Fatores Etários , Idoso , Artrite/complicações , Índice de Massa Corporal , Peso Corporal/fisiologia , Causalidade , Doença Crônica , Estudos de Coortes , Progressão da Doença , Feminino , Terapia de Reposição Hormonal , Humanos , Articulações/patologia , Articulações/fisiopatologia , Pessoa de Meia-Idade , Osteoporose/etiologia , Aptidão Física , Valor Preditivo dos Testes , Atenção Primária à Saúde/estatística & dados numéricos , Radiografia , Índice de Gravidade de Doença , Fumar/efeitos adversos , Inquéritos e Questionários
19.
Ann Rheum Dis ; 69(8): 1448-52, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20498201

RESUMO

INTRODUCTION: A study was undertaken to test the hypothesis that musculoskeletal pain is associated with low vitamin D levels but the relationship is explained by physical inactivity and/or other putative confounding factors. METHODS: Men aged 40-79 years completed a postal questionnaire including a pain assessment and attended a clinical assessment (lifestyle questionnaire, physical performance tests, 25-hydroxyvitamin D3 (25-(OH)D) levels from fasting blood sample). Subjects were classified according to 25-(OH)D levels as 'normal' (> or = 15 ng/ml) or 'low' (< 15 ng/ml). The relationship between pain status and 25-(OH)D levels was assessed using logistic regression. Results are expressed as ORs and 95% CIs. RESULTS: 3075 men of mean (SD) age 60 (11) years were included in the analysis. 1262 (41.0%) subjects were pain-free, 1550 (50.4%) reported 'other pain' that did not satisfy criteria for chronic widespread pain (CWP) and 263 (8.6%) reported CWP. Compared with patients who were pain-free, those with 'other pain' and CWP had lower 25-(OH)D levels (n=239 (18.9%), n=361 (23.3) and n=67 (24.1%), respectively, p<0.05). After adjusting for age, having 'other pain' was associated with a 30% increase in the odds of having low 25-(OH)D while CWP was associated with a 50% increase. These relationships persisted after adjusting for physical activity levels. Adjusting for additional lifestyle factors (body mass index, smoking and alcohol use) and depression attenuated these relationships, although pain remained moderately associated with increased odds of 20% of having low vitamin D levels. CONCLUSIONS: These findings have implications at a population level for the long-term health of individuals with musculoskeletal pain.


Assuntos
Doenças Musculoesqueléticas/etiologia , Dor/etiologia , Deficiência de Vitamina D/complicações , Adulto , Idoso , Envelhecimento/sangue , Calcifediol/sangue , Fatores de Confusão Epidemiológicos , Europa (Continente)/epidemiologia , Fibromialgia/sangue , Fibromialgia/epidemiologia , Fibromialgia/etiologia , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Atividade Motora , Doenças Musculoesqueléticas/sangue , Doenças Musculoesqueléticas/epidemiologia , Dor/sangue , Dor/epidemiologia , Medição da Dor/métodos , Prevalência , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia
20.
Eur J Endocrinol ; 162(6): 1155-64, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20231367

RESUMO

OBJECTIVE: Data remain divergent regarding the activational effects of endogenous hormones on adult cognitive function. We examined the association between cognition, hormones and androgen receptor (AR) CAG repeat length in a large cohort of men. DESIGN: Community-based, cross-sectional study of 3369 men aged 40-79 years. METHODS: Cognition tests were the Rey-Osterrieth Complex Figure, Camden Topographical Recognition Memory and Digit-Symbol Substitution. A fluid cognition (FC) z-score was computed from the individual tests. Testosterone, oestradiol (OE(2)) and 5alpha-dihydrotestosterone were measured by gas chromatography-mass spectrometry; DHEAS, LH, FSH and sex hormone-binding globulin (SHBG) by electrochemiluminescence. Free testosterone and OE(2) were calculated from total hormone, SHBG and albumin. CAG repeat lengths were assayed by PCR genotyping. RESULTS: Total testosterone and free testosterone were associated with higher FC z-scores, LH and FSH with lower FC z-scores in age-adjusted linear regressions. After adjusting for health, lifestyle and centre, a modest association was only observed between DHEAS and a lower FC z-score (beta=-0.011, P=0.02), although this was driven by subjects with DHEAS levels >10 micromol/l. Locally weighted plots revealed no threshold effects between hormones and FC. There was no association between CAG repeat length and FC z-score after adjustment for age and centre (beta=-0.007, P=0.06), nor any interaction effect between CAG repeat length and hormones. CONCLUSION: Our results suggest that endogenous hormones are not associated with a vision-based measure of FC among healthy, community-dwelling men. Further studies are warranted to determine whether 'high' DHEAS levels are associated with poorer performance on a broader range of neuropsychological tests.


Assuntos
Envelhecimento/fisiologia , Cognição/fisiologia , Di-Hidrotestosterona/sangue , Estradiol/sangue , Receptores Androgênicos/genética , Testosterona/sangue , Repetições de Trinucleotídeos/genética , Adulto , Fatores Etários , Idoso , Europa (Continente) , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Valores de Referência , Análise de Regressão , Inquéritos e Questionários
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