Terence W O'Neill

Publications (53)284.47 Total impact

• Article: Active Vitamin D (1,25-Dihydroxyvitamin D) and Bone Health in Middle-Aged and Elderly Men: The European Male Aging Study (EMAS).

  Dirk Vanderschueren, Stephen R Pye, Terence W O'Neill, David M Lee, Ivo Jans, Jaak Billen, Evelien Gielen, Michaël Laurent, Frank Claessens, Judith E Adams, [......], Gianni Forti, Aleksander Giwercman, Thang S Han, Ilpo T Huhtaniemi, Krzysztof Kula, Michael E J Lean, Neil Pendleton, Margus Punab, Frederick C W Wu, Steven Boonen
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  ABSTRACT: Context:There is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)(2)D] on bone health including turnover.Objective:The objective of the study was to determine the influence of 1,25(OH)(2)D 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)(2)D, 25(OH)D, and PTH were measured. 1,25(OH)(2)D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β-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 β-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)(2)D 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)(2)D was associated negatively with QUS and DXA parameters and associated positively with β-cTX. 1,25(OH)(2)D 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)(2)D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest β-cTX levels.Conclusions:Serum 1,25(OH)(2)D 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)(2)D and low 25(OH)D is associated with the poorest bone health.
  The Journal of clinical endocrinology and metabolism 02/2013; · 6.50 Impact Factor
• Article: The association of frailty with serum 25-hydroxyvitamin D and parathyroid hormone levels in older European men.

  Abdelouahid Tajar, David M Lee, Stephen R Pye, Matthew D L O'Connell, Rathi Ravindrarajah, Evelien Gielen, Steven Boonen, Dirk Vanderschueren, Neil Pendleton, Joseph D Finn, [......], Felipe F Casanueva, Gianni Forti, Aleksander Giwercman, Thang S Han, Ilpo T Huhtaniemi, Krzysztof Kula, Michael E J Lean, Margus Punab, Frederick C W Wu, Terence W O'Neill
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  ABSTRACT: BACKGROUND: the link between the vitamin D endocrine axis and frailty remains undefined, with few studies examining the joint effect of vitamin D and parathyroid hormone (PTH) levels. Our objective was to determine the association of frailty with serum 25-hydroxyvitamin D (25(OH)D) and PTH.Setting: cross-sectional analysis within the European Male Ageing Study (EMAS).Participants: a total of 1,504 community-dwelling men aged 60-79 years. METHODS: frailty was classified using a frailty phenotype (FP) and frailty index (FI). The association of frailty with 25(OH)D and PTH was examined using multinomial logistic regression; individual FP criteria with 25(OH)D and PTH using binary logistic regression. Results were expressed as relative odds ratios (ROR) and 95% confidence intervals (CIs) for multinomial; odds ratios (OR) and 95% CIs for binary models. RESULTS: using the FP, 5.0% of subjects were classified as frail and 36.6% as prefrail. Lower levels of 25(OH)D were associated with being prefrail (per 1 SD decrease: ROR = 1.45; 95% CI: 1.26-1.67) and frail (ROR = 1.89; 95% CI: 1.30-2.76), after adjusting for age, centre and health and lifestyle confounders (robust group = base category). Higher levels of PTH were associated with being frail after adjustment for confounders (per 1 SD increase: ROR = 1.24; 95% CI: 1.01-1.52). Comparable results were found using the FI. Among the five FP criteria only sarcopenia was not associated with 25(OH)D levels, while only weakness was associated with PTH. CONCLUSION: lower 25(OH)D and higher PTH levels were positively associated with frailty in older men. Prospective data would enable the temporal nature of this relationship to be explored further.
  Age and Ageing 10/2012; · 3.09 Impact Factor
• Article: Frailty and Sexual Health in Older European Men.

  David M Lee, Abdelouahid Tajar, Rathi Ravindrarajah, Stephen R Pye, Daryl B O'Connor, Giovanni Corona, Matthew O'Connell, Evelien Gielen, Steven Boonen, Dirk Vanderschueren, [......], Felipe F Casanueva, Gianni Forti, Aleksander Giwercman, Thang S Han, Ilpo T Huhtaniemi, Krzysztof Kula, Michael E J Lean, Margus Punab, Frederick C W Wu, Terence W O'Neill
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  ABSTRACT: 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.
  The Journals of Gerontology Series A Biological Sciences and Medical Sciences 10/2012; · 4.60 Impact Factor
• Article: Epidemiological evidence against a role for C-reactive protein causing leptin resistance.

  Martin Kenneth Rutter, Naveed Sattar, Abdeloahid Tajar, Terence W O'Neill, David M Lee, Gyorgy Bartfai, Steven Boonen, Felipe F Casanueva, Joseph D Finn, Gianni Forti, [......], Michael Lean, Neil Pendleton, Margus Punab, Alan J Silman, Dirk Vanderschueren, Gordon D Lowe, Stephen O'Rahilly, Richard Morris, Fredrick C W Wu, S Goya Wannamethee
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  ABSTRACT: OBJECTIVE: It has been suggested that elevated levels of C-reactive protein (CRP) might interfere with leptin signalling and contribute to leptin resistance. Our aim was to assess whether plasma levels of CRP influence leptin resistance in humans; and our hypothesis was that CRP levels would modify the cross-sectional relationships between leptin and measures of adiposity. DESIGN AND METHODS: We assessed 4 measures of adiposity: body mass index, waist circumference, fat mass, and % body fat in 2113 British Regional Heart Study (BRHS) men (mean (SD) age 69 (5) years), with replication in 760 (age 69 (6) years) European Male Aging Study (EMAS) subjects. RESULTS: In BRHS subjects leptin correlated with CRP (Spearman's r=0.22, p<0.0001). Leptin and CRP correlated with all 4 measures of adiposity (r-value range: 0.22 to 0.57, all p<0.0001). Age-adjusted mean levels for adiposity measures increased in relation to leptin levels; but CRP level did not consistently influence the β coefficients of the regression lines in a CRP-stratified analysis. In BRHS subjects, the BMI vs. leptin relationship demonstrated a weak statistical interaction with CRP (p=0.04). We observed no similar interaction in EMAS subjects, and no significant interactions with other measures of adiposity in BRHS or EMAS cohorts. CONCLUSION: We have shown that plasma CRP has little influence on the relationship between measures of adiposity and serum leptin levels in these middle-aged and elderly male European cohorts. This study provides epidemiological evidence against CRP having a significant role in causing leptin resistance.
  European Journal of Endocrinology 10/2012; · 3.42 Impact Factor
• Article: Influence of inflammatory polyarthritis on quantitative heel ultrasound measurements.

  Stephen R Pye, Tarnya Marshall, Karl Gaffney, Robert Luben, Kay-Tee Khaw, Alan J Silman, Deborah Pm Symmons, Terence W O'Neill
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  ABSTRACT: There are few data concerning the impact of inflammatory polyarthritis (IP) on quantitative heel ultrasound (QUS) measurements. The aims of this analysis were i) to determine the influence of IP on QUS measurements at the heel and, ii) among those with IP to determine the influence of disease related factors on these measurements. Men and women aged 16 years and over with recent onset IP were recruited to the Norfolk Arthritis Register (NOAR). Individuals with an onset of joint symptoms between 1989 and 1999 were included in this analysis. At the baseline visit subjects underwent a standardised interview and clinical examination with blood taken for rheumatoid factor. A population-based prospective study of chronic disease (EPIC-Norfolk) independently recruited men and women aged 40 to 79 years from the same geographic area between 1993 and 1997. At a follow up assessment between 1998 and 2000 subjects in EPIC-Norfolk were invited to have quantitative ultrasound measurements of the heel (CUBA-Clinical) performed. We compared speed of sound (SOS) and broadband ultrasound attenuation (BUA), in those subjects recruited to NOAR who had ultrasound measurements performed (as part of EPIC-Norfolk) subsequent to the onset of joint symptoms with a group of age and sex matched non-IP controls who had participated in EPIC-Norfolk. Fixed effect linear regression was used to explore the influence of IP on the heel ultrasound parameters (SOS and BUA) so the association could be quantified as the mean difference in BUA and SOS between cases and controls. In those with IP, linear regression was used to examine the association between these parameters and disease related factors. 139 men and women with IP and 278 controls (mean age 63.2 years) were studied. Among those with IP, mean BUA was 76.3 dB/MHz and SOS 1621.8 m/s. SOS was lower among those with IP than the controls (difference = -10.0; 95% confidence interval (CI) -17.4, -2.6) though BUA was similar (difference = -1.2; 95% CI -4.5, +2.1). The difference in SOS persisted after adjusting for body mass index and steroid use. Among those with IP, disease activity as determined by the number of swollen joints at baseline, was associated with a lower SOS. In addition SOS was lower in the subgroup that satisfied the 1987 ACR criteria. By contrast, disease duration, steroid use and HAQ score were not associated with either BUA or SOS. In this general population derived cohort of individuals with inflammatory polyarthritis there is evidence from ultrasound of a potentially adverse effect on the skeleton. The effect appears more marked in those with active disease.
  BMC Musculoskeletal Disorders 07/2012; 13:133. · 1.58 Impact Factor
• Article: Comparison of serum testosterone and estradiol measurements in 3174 European men using platform immunoassay and mass spectrometry; relevance for the diagnostics in aging men.

  Ilpo T Huhtaniemi, Abdelouahid Tajar, David M Lee, Terence W O'Neill, Joseph D Finn, György Bartfai, Steven Boonen, Felipe F Casanueva, Aleksander Giwercman, Thang S Han, Krzysztof Kula, Fernand Labrie, Michael E J Lean, Neil Pendleton, Margus Punab, Alan J Silman, Dirk Vanderschueren, Gianni Forti, Frederick C W Wu
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  ABSTRACT: The limitations of serum testosterone and estradiol (E(2)) measurements using non-extraction platform immunoassays (IAs) are widely recognized. Switching to more specific mass spectrometry (MS)-based methods has been advocated, but directly comparative data on the two methods are scarce. We compared serum testosterone and E(2) measurements in a large sample of middle-aged/elderly men using a common platform IA and a gas chromatography (GC)-MS method, in order to assess their limitations and advantages, and to diagnose male hypogonadism. Of subjects from the European Male Aging Study (n=3174; age 40-79 years), peripheral serum testosterone and E(2) were analyzed using established commercial platform IAs (Roche Diagnostics E170) and in-house GC-MS methods. Over a broad concentration range, serum testosterone concentration measured by IA and MS showed high correlation (R=0.93, P<0.001), which was less robust in the hypogonadal range (<11 nmol/l; R=0.72, P<0.001). The IA/MS correlation was weaker in E(2) measurements (R=0.32, P<0.001, at E(2) <40.8 pmol/l, and R=0.74, P<0.001, at E(2) >40.8 pmol/l). Using MS as the comparator method, IA ascertained low testosterone compatible with hypogonadism (<11 nmol/l), with 75% sensitivity and 96.3% specificity. The same parameters with IA for the detection of low E(2) (<40.7 pmol/l) were 13.3 and 99.3%, and for high E(2) (>120 pmol/l) 88.4 and 88.6%. A validated platform IA is sufficient to detect subnormal testosterone concentrations in the diagnosis of male hypogonadism. The IA used for E(2) measurements showed poor correlation with MS and may only be suitable for the detection of high E(2) in men.
  European Journal of Endocrinology 03/2012; 166(6):983-91. · 3.42 Impact Factor
• Article: Characteristics of androgen deficiency in late-onset hypogonadism: results from the European Male Aging Study (EMAS).

  Abdelouahid Tajar, Ilpo T Huhtaniemi, Terence W O'Neill, Joseph D Finn, Stephen R Pye, David M Lee, György Bartfai, Steven Boonen, Felipe F F Casanueva, Gianni Forti, Aleksander Giwercman, Thang S Han, Krzysztof Kula, Fernand Labrie, Michael E J Lean, Neil Pendleton, Margus Punab, Dirk Vanderschueren, Frederick C W Wu
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  ABSTRACT: Late-onset hypogonadism (LOH) has been defined as a syndrome in middle-aged and elderly men reporting symptoms in the presence of low testosterone (T). The objective of the study was to seek objective biochemical and end-organ evidence of androgen deficiency in men classified as having LOH according to our previously published criteria. The design of the study included cross-sectional data from the European Male Aging Study on 2966 community-dwelling men aged 40-79 years in eight European countries. Waist circumference, body mass index, muscle mass, estimated heel bone mineral density (eBMD), hemoglobin, insulin sensitivity, physical activity, metabolic syndrome, insulin resistance index, and cardiovascular disease were measured. Sixty-three men (2.1%) were classified as having LOH: 36 moderate and 27 severe. They were older and more obese than eugonadal men and had, in proportion to the graded T deficiency, lower muscle mass, eBMD, and hemoglobin, with poorer general health. Both moderate and severe LOH was associated with lower hemoglobin, mid-upper arm circumference, eBMD, physical function (measured by the Short Form-36 questionnaire), slower gait speed and poorer general health. Only men with severe LOH showed significant associations with larger waist circumference (β=1.93 cm; 0.04-3.81), insulin resistance (β=2.81; 1.39-4.23), and the metabolic syndrome (odds ratio 9.94; 2.73-36.22) after adjustments for confounders. Men with low testosterone only (irrespective of symptoms) showed lesser magnitudes of association with the same end points. LOH is associated with multiple end-organ deficits compatible with androgen deficiency. These data support the existence of a syndrome of LOH in only a minority of aging men, especially those with T below 8 nmol/liter.
  The Journal of clinical endocrinology and metabolism 03/2012; 97(5):1508-16. · 6.50 Impact Factor
• Article: Cohort Profile: The European Male Ageing Study.

  David M Lee, Stephen R Pye, Abdelouahid Tajar, Terence W O'Neill, Joseph D Finn, Steven Boonen, Gyorgy Bartfai, Felipe F Casanueva, Gianni Forti, Aleksander Giwercman, Thang S Han, Ilpo T Huhtaniemi, Krzysztof Kula, Michael Ej Lean, Neil Pendleton, Margus Punab, Alan J Silman, Dirk Vanderschueren, Frederick Cw Wu
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  ABSTRACT: The European Male Ageing Study (EMAS) was designed to examine the hypothesis that inter-individual and regional variability in symptomatic dysfunctions, alterations in body composition and health outcomes in ageing men can be explained by different rates of decline in anabolic hormones, the most important of which being testosterone. Between 2003 and 2005, 3369 community-dwelling men, aged between 40 and 79 years, were recruited from population-based registers in eight European centres to participate in the baseline survey, with follow-up investigations performed a median of 4.3 years later. Largely, identical questionnaire instruments and clinical investigations were used in both phases to capture contemporaneous data on general health (including cardiovascular diseases and chronic conditions), physical and cognitive functioning, mental health, sexual function, quality of life, bone health, chronic pain, disease biomarkers, hormones (sex hormones and metabolic hormones) and genetic polymorphisms. EMAS actively encourages new collaborations, data sharing for validation studies and participation in genetic study consortia. Potential collaborators should contact the principal investigator (F.C.W.W.) in the first instance.
  International Journal of Epidemiology 02/2012; · 6.41 Impact Factor
• Article: Association of hypogonadism with vitamin D status: the European Male Ageing Study.

  David M Lee, Abdelouahid Tajar, Stephen R Pye, Steven Boonen, Dirk Vanderschueren, Roger Bouillon, Terence W O'Neill, Gyorgy Bartfai, Felipe F Casanueva, Joseph D Finn, Gianni Forti, Aleksander Giwercman, Thang S Han, Ilpo T Huhtaniemi, Krzysztof Kula, Michael E J Lean, Neil Pendleton, Margus Punab, Frederick C W Wu
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  ABSTRACT: 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. 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. 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). Secondary and compensated hypogonadism were associated with vitamin D deficiency and the clinical significance of this relationship warrants further investigation.
  European Journal of Endocrinology 11/2011; 166(1):77-85. · 3.42 Impact Factor
• Source

  Available from: Margus Punab

  Article: Influence of polymorphisms in the RANKL/RANK/OPG signaling pathway on volumetric bone mineral density and bone geometry at the forearm in men.

  Delnaz Roshandel, Kate L Holliday, Stephen R Pye, Kate A Ward, Steven Boonen, Dirk Vanderschueren, Herman Borghs, Ilpo T Huhtaniemi, Judith E Adams, Gyorgy Bartfai, [......], Aleksander Giwercman, Thang S Han, Krzysztof Kula, Michael E Lean, Neil Pendleton, Margus Punab, Alan J Silman, Frederick C Wu, Wendy Thomson, Terence W ONeill
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  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) ≥ 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 (β [95% CI] = 9.35 [2.12-16.58], P = 0.011), cortical vBMD (β [95% CI] = 5.62 [2.10-9.14], P = 0.002), cortical thickness (β [95% CI] = 0.08 [0.03-0.13], P = 0.002), and medullary area (β [95% CI] = -2.90 [-4.94 to -0.86], P = 0.005) and rs2073618 associated with cortical vBMD (β [95% CI] = -4.30 [-7.78 to -0.82], P = 0.015) and cortical thickness (β [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 (β [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 (β [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.
  Calcified Tissue International 10/2011; 89(6):446-55. · 2.38 Impact Factor
• Article: Lower vitamin D levels are associated with depression among community-dwelling European men.

  David M Lee, Abdelouahid Tajar, Terence W O'Neill, Daryl B O'Connor, Gyorgy Bartfai, Steven Boonen, Roger Bouillon, Felipe F Casanueva, Joseph D Finn, Gianni Forti, Aleksander Giwercman, Thang S Han, Ilpo T Huhtaniemi, Krzysztof Kula, Michael Ej Lean, Margus Punab, Alan J Silman, Dirk Vanderschueren, Frederick Cw Wu, Neil Pendleton
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  ABSTRACT: Low serum 25-hydroxyvitamin D (25(OH)D) and elevated parathyroid hormone (PTH) levels have been linked with depressive symptoms among adults in various clinical settings. Data in generally healthy, community-dwelling individuals remain inconclusive. We investigated whether depression was associated with 25(OH)D and/or PTH in a sample of middle-aged and older men (n = 3369; mean age 60 ± 11) participating in the European Male Ageing Study, and whether any associations were explained by lifestyle and health factors. The Beck Depression Inventory-II (BDI-II) was used to screen for depression, and serum 25(OH)D and PTH levels measured by radioimmunoassay. Univariate analysis revealed that 25(OH)D levels were lower (p < 0.001) and PTH higher (p = 0.004) in people with depression. In age- and centre-adjusted linear regressions a higher BDI-II score was significantly associated with lower levels of 25(OH)D (p = 0.004). After adjustment for lifestyle and health factors this relationship was attenuated but remained significant (p = 0.01). Using multivariable logistic regression the odds for depression increased approximately 70% across decreasing 25(OH)D quartiles (p (trend) = 0.04). There was no independent association between PTH and depression in any of the multivariable regressions. Our results reveal an inverse association between 25(OH)D levels and depression, largely independent of several lifestyle and health factors. Further studies are required to determine whether higher levels of vitamin D have an antidepressant effect in older adults.
  Journal of Psychopharmacology 10/2011; 25(10):1320-8. · 3.04 Impact Factor
• Article: Influence of bone remodelling rate on quantitative ultrasound parameters at the calcaneus and DXA BMDa of the hip and spine in middle-aged and elderly European men: the European Male Ageing Study (EMAS).

  Steven Boonen, Stephen R Pye, Terence W O'Neill, Pawel Szulc, Evelien Gielen, Herman Borghs, Sabine Verschueren, Frank Claessens, Judith E Adams, Kate A Ward, [......], Ilpo T Huhtaniemi, Krzysztof Kula, Fernand Labrie, Michael E J Lean, Neil Pendleton, Margus Punab, Alan J Silman, Abdelouahid Tajar, Frederick C W Wu, Dirk Vanderschueren
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  ABSTRACT: To assess the influence of sex hormones on markers of bone turnover and to explore the association between these markers and bone health in middle-aged and elderly European men. A cross-sectional population-based survey. Men aged 40-79 years were recruited from population registers in eight European centres. Subjects completed a postal questionnaire which included questions concerning lifestyle and were invited to undergo quantitative ultrasound (QUS) of the calcaneus and to provide a fasting blood sample from which the bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β C-terminal cross-linked telopeptide (β-cTX)), total testosterone, total oestradiol (E(2)), sex hormone-binding globulin (SHBG) and insulin-like growth factor 1 (IGF1) were measured. Dual-energy X-ray absorptiometry (DXA) of the hip and lumbar spine was performed in two centres. A total of 3120, mean age 59.9 years (s.d.=11.0) were included. After adjustment for centre, age, height, weight, lifestyle factors, season and other hormones, total and free E(2) were negatively associated with β-cTX but not P1NP while SHBG, IGF1 and parathyroid hormone (PTH) were positively associated with both β-cTX and P1NP. Total or free testosterone was not independently associated with either bone marker. After the same adjustments, higher levels of both bone markers were significantly associated with lower QUS parameters and lower DXA-assessed bone density at the total hip and lumbar spine. E(2), SHBG, IGF1 and PTH contribute significantly to the regulation/rate of bone turnover in middle-aged and older European men. Higher rates of bone remodelling are negatively associated with male bone health.
  European Journal of Endocrinology 09/2011; 165(6):977-86. · 3.42 Impact Factor
• Article: The relationships between sex hormones and sexual function in middle-aged and older European men.

  Daryl B O'Connor, David M Lee, Giovanni Corona, Gianni Forti, Abdelouahid Tajar, Terence W O'Neill, Neil Pendleton, Gyorgy Bartfai, Steven Boonen, Felipe F Casanueva, [......], Aleksander Giwercman, Thang S Han, Ilpo T Huhtaniemi, Krzysztof Kula, Fernand Labrie, Michael E J Lean, Margus Punab, Alan J Silman, Dirk Vanderschueren, Frederick C W Wu
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  ABSTRACT: 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. 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. 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. We conducted a community-based population survey in eight European centers. Self-reported sexual function (overall sexual function, sexual function-related distress, erectile dysfunction, masturbation) was measured. 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. 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.
  The Journal of clinical endocrinology and metabolism 08/2011; 96(10):E1577-87. · 6.50 Impact Factor
• Article: Bone health in adult men and women with a history of juvenile idiopathic arthritis.

  Judith Thornton, Stephen R Pye, Terence W O'Neill, David Rawlings, Roger M Francis, Deborah P M Symmons, Darren M Ashcroft, Helen E Foster
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  ABSTRACT: Our aim was to determine areal bone mineral density (BMD(a)) and disease-related factors linked with BMD(a) in adults with a history of juvenile idiopathic arthritis (JIA). Men and women with a history of JIA attending a young adult rheumatology clinic in Newcastle, UK, underwent dual energy x-ray absorptiometry (DEXA) of the lumbar spine and total hip. Information was obtained about disease duration and subtype, previous treatment including corticosteroid and methotrexate therapy, and large-joint replacement. Subjects completed the modified Health Assessment Questionnaire (HAQ). Blood was taken for assessment of C-reactive protein, erythrocyte sedimentation rate, and rheumatoid factor (RF). Seventy-one women and 16 men, mean age 28.7 and 31.4 years, and mean disease duration 20.6 and 24.0 years, respectively, were studied. Mean BMD(a) was 0.982 (Z-score = -0.328; 95% CI -0.657, 0.001) and 1.028 g/cm(2) (Z-score = -0.251; 95% CI -1.266, 0.764) in women and men, respectively, at the spine and 0.817 (Z-score = -0.542; 95% CI -0.975, -0.109) and 0.857 g/cm(2) (Z-score = -0.176; 95% CI -2.323, 1.971) at the hip. After adjusting for age and sex, increasing HAQ score was associated with both lower spine BMD(a) and hip BMD(a). Compared with patients with oligoarticular disease, those with enthesitis-related arthritis had higher BMD(a) at the spine, while those with extended oligoarticular and polyarticular RF-negative disease had lower hip BMD(a). Oral corticosteroids and the presence of a large-joint replacement were associated with lower BMD(a) at both the spine and hip. There was a trend toward low BMD(a) in women with a history of JIA. These patients may be at risk of the complications of osteoporosis including fragility fractures and should be considered for targeted preventive measures.
  The Journal of Rheumatology 06/2011; 38(8):1689-93. · 3.69 Impact Factor
• Article: Influence of insulin-like growth factor binding protein (IGFBP)-1 and IGFBP-3 on bone health: results from the European Male Ageing Study.

  Stephen R Pye, Bader Almusalam, Steven Boonen, Dirk Vanderschueren, Herman Borghs, Evelien Gielen, Judith E Adams, Kate A Ward, Gyorgy Bartfai, Felipe F Casanueva, [......], Thang S Han, Ilpo T Huhtaniemi, Krzysztof Kula, Fernand Labrie, Michael E J Lean, Neil Pendleton, Margus Punab, Alan J Silman, Frederick C W Wu, Terence W O'Neill
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  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.
  Calcified Tissue International 06/2011; 88(6):503-10. · 2.38 Impact Factor
• Article: Frailty in relation to variations in hormone levels of the hypothalamic-pituitary-testicular axis in older men: results from the European male aging study.

  Abdelouahid Tajar, Matthew D L O'Connell, Arnold B Mitnitski, Terence W O'Neill, Samuel D Searle, Ilpo T Huhtaniemi, Joseph D Finn, György Bartfai, Steven Boonen, Felipe F Casanueva, [......], Thang S Han, Krzysztof Kula, Fernand Labrie, Michael E J Lean, Neil Pendleton, Margus Punab, Alan J Silman, Dirk Vanderschueren, Kenneth Rockwood, Frederick C W Wu
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  ABSTRACT: To explore the associations between frailty and reproductive axis hormones (as an important regulatory system) in middle aged and older men. Cross-sectional. The European Male Aging Study. Three thousand two hundred nineteen community-dwelling European men aged 40 to 79. Interviewer-assisted questionnaires to assess physical activity, health status, and mood were administered. Testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH), dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin (SHBG) were measured in a fasting morning blood sample. Frailty was assessed as an index (FI) according to the number (out of 43 possible) of health deficits (symptoms, signs, and functional impairments). Relationships between FI and hormone levels (as outcomes) were explored using regression models. Mean FI was 0.12 ± 0.11 (range 0-0.67) was highest in the oldest group. After adjustment for confounders, higher levels of FI were significantly associated with lower levels of total T, free T, and DHEAS and higher levels of gonadotropins and SHBG; a 1-standard deviation cross-sectional increase in FI was associated with a regression coefficient of -0.30 nmol/L (95% confidence interval (CI)=-0.53 to -0.07) decrease in total T and 0.66 U/L (95% CI=0.48-0.83) increase in LH. The associations between high FI, high gonadotropins, and well-maintained circulating T suggest that these changes are markers of aging-related disruptions of multiple physiological regulation, of which alterations in pituitary-testicular function represent a sensitive marker rather than an underlying pathogenic mechanism for frailty.
  Journal of the American Geriatrics Society 05/2011; 59(5):814-21. · 3.74 Impact Factor
• Article: Impaired quality of life and sexual function in overweight and obese men: the European Male Ageing Study.

  Thang S Han, Abdelouahid Tajar, Terence W O'Neill, Min Jiang, György Bartfai, Steven Boonen, Felipe Casanueva, Joseph D Finn, Gianni Forti, Aleksander Giwercman, Ilpo T Huhtaniemi, Krzysztof Kula, Neil Pendleton, Margus Punab, Alan J Silman, Dirk Vanderschueren, Michael E J Lean, Frederick C W Wu
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  ABSTRACT: Few published data link overweight and obesity with measures of quality of life (QoL) including sexual health in men. To assess the association of overweight/obesity with impairment of physical and psychological QoL and sexual functions in men. Cross-sectional, multicentre survey of 3369 community-dwelling men aged 40-79 (mean±s.d., 60±11) years randomly selected from eight European centres. Adiposity was assessed by body mass index (BMI) and waist circumference (WC), QoL and functional impairments by physical and psychological function domains of the Short Form-36 questionnaire, Beck's Depression Inventory and the European Male Ageing Study sexual function questionnaire. Complete data on sexual activities and erectile function were available in 2734 (92%) and 3193 (95%) of the participants respectively. From the population studied, 814 men were obese (BMI ≥30 kg/m(2)) and 1171 had WC ≥102 cm, 25% of all men were unable to do vigorous activity and 2-13% reported depressive symptoms. Symptoms of sexual dysfunction ranged between 22% (low sexual desire) and 40% (infrequent morning erections) of the participants. Among obese men with both BMI ≥30 kg/m(2) and WC ≥102 cm, at least one symptom of impaired physical, psychological and sexual function was reported by 41, 43 and 73% of the participants respectively. Compared with the reference group of non-obese men (BMI <30 kg/m(2) and WC <102 cm), men with BMI ≥30 kg/m(2) and WC ≥102 cm more frequently reported at least one symptom of impaired physical function (odds ratio (OR)=2.67; confidence interval (CI): 2.07-3.45, P<0.001), impaired psychological function (OR=1.48; CI: 1.14-1.90, P<0.01) and impaired sexual function (OR=1.45; CI: 1.14-1.85, P<0.01). These functional impairments were also more prevalent in men who had WC ≥102 cm even with BMI <30 kg/m(2), but those with BMI ≥30 kg/m(2) and WC <102 cm generally did not suffer from increased impaired physical or sexual health. Men with high BMI and WC were at even greater likelihood of having a composite of two or more or three or more symptoms compared with those with normal BMI and WC. Men with high WC, including those who are 'non-obese' with BMI <30 kg/m(2), have poor QoL with symptoms of impaired physical, psychological and sexual functions. Health promotion to improve QoL should focus on prevention of obesity and central fat accumulation.
  European Journal of Endocrinology 04/2011; 164(6):1003-11. · 3.42 Impact Factor
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  Available from: Margus Punab

  Article: Elevated levels of gonadotrophins but not sex steroids are associated with musculoskeletal pain in middle-aged and older European men.

  Abdelouahid Tajar, John McBeth, David M Lee, Gary J Macfarlane, Ilpo T Huhtaniemi, Joseph D Finn, Gyorgy Bartfai, Steven Boonen, Felipe F Casanueva, Gianni Forti, [......], Thang S Han, Krzysztof Kula, Fernand Labrie, Michael E J Lean, Neil Pendleton, Margus Punab, Alan J Silman, Dirk Vanderschueren, Terence W O'Neill, Frederick C W Wu
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  ABSTRACT: The aim of this study was to determine the association of hormone levels with the occurrence of musculoskeletal pain. Men ages 40 to 79 years were recruited from population registers in 8 European centres. Subjects were asked to complete a postal questionnaire, which enquired about lifestyle and the occurrence of musculoskeletal pain over the past month. Total testosterone (T), oestradiol (E2), luteinising hormone (LH), and follicle-stimulating hormone (FSH) were assayed from a fasting blood sample. The association between pain status and hormone levels was assessed using multinomial logistic regression with results expressed as relative risk ratios (RRR) and 95% confidence intervals (CI). A total of 3206 men had complete data on pain status. Of these, 8.7% reported chronic widespread pain (CWP), whereas 50% had some pain although not CWP and were classified as having some pain. T and E2 were not associated with musculoskeletal pain, whereas significant differences in LH and FSH levels were found between pain groups. After adjustment for age and other possible confounders, the association between pain status and both LH and FSH persisted. Compared with those in the lowest tertile of LH, those in the highest tertile were more likely to report some pain (vs no pain, RRR=1.28; 95% CI 1.09 to 1.50) and also CWP (vs no pain, RRR=1.51; 95% CI 1.10 to 2.07). Similar results were found for FSH. Gonadotrophins, but not sex steroid hormone levels, are associated with musculoskeletal pain in men.
  Pain 03/2011; 152(7):1495-501. · 5.78 Impact Factor
• Article: The effect of musculoskeletal pain on sexual function in middle-aged and elderly european men: results from the european male ageing study.

  Abdelouahid Tajar, Terence W O'Neill, David M Lee, Daryl B O'Connor, Giovanni Corona, Joseph D Finn, Gyorgy Bartfai, Steven Boonen, Felipe F Casanueva, Gianni Forti, [......], Ilpo T Huhtaniemi, Krzysztof Kula, Michael E J Lean, Neil Pendleton, Margus Punab, Nitin Purandare, Alan J Silman, Dirk Vanderschueren, Frederick C W Wu, John McBeth
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  ABSTRACT: To determine whether musculoskeletal pain was associated with impaired sexual function in a population sample of middle-aged and older men. The European Male Ageing Study (EMAS), a multicenter population-based study of men aged 40-79 years, was used to investigate this hypothesis. A questionnaire asked about the presence and duration of musculoskeletal pain, allowing subjects to be classified into 1 of 3 groups: those reporting chronic widespread pain (CWP), those reporting pain but not CWP ("some pain"), and those with no pain. Subjects completed a sexual function questionnaire from which 3 domains were considered: overall sexual functioning (OSF), sexual functioning-related distress (SFD), and change in sexual functioning compared to 1 year ago (CSF). A total of 3206 men [mean age 60 (SD 11) yrs] had complete data on pain status. Of these, 8.7% had CWP and 50.34% had "some pain." Pain was associated with lower OSF, and higher SFD and CSF scores. After adjustment for putative confounding factors, the associations became non-significant with OSF and CSF but persisted for SFD. Associations between pain status and some items within the sexual functioning domains, including frequency of sexual intercourse, frequency of morning erections, sexual desire, and orgasm were also significant, although these associations varied by pain status. Musculoskeletal pain is associated with several aspects of sexual functioning. These relationships differ depending on the extent of the pain (chronic or not) and are also largely confounded by other health-related factors, primarily depression.
  The Journal of Rheumatology 02/2011; 38(2):370-7. · 3.69 Impact Factor
• Article: Association of HTR2A polymorphisms with chronic widespread pain and the extent of musculoskeletal pain: results from two population-based cohorts.

  Barbara I Nicholl, Kate L Holliday, Gary J Macfarlane, Wendy Thomson, Kelly A Davies, Terence W O'Neill, Gyorgy Bartfai, Steven Boonen, Felipe F Casanueva, Joseph D Finn, Gianni Forti, Aleksander Giwercman, Ilpo T Huhtaniemi, Krzysztof Kula, Margus Punab, Alan J Silman, Dirk Vanderschueren, Frederick C W Wu, John McBeth
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  ABSTRACT: The aim of the current study was to investigate whether genetic variation in genes across the serotoninergic system is associated with chronic widespread pain (CWP) and the number of pain sites reported. A discovery cohort, with pain data at 3 time points, was used to investigate genetic associations with 2 phenotypes: 1) CWP (at ≥ 2 time points; n = 164) compared with pain-free controls (at 3 time points; n = 172), and 2) the maximum number of pain sites reported at any 1 of the 3 time points (range of sites 0-29; n = 989). A cohort of 2,285 men for whom a DNA sample and pain data were available (including 203 CWP cases and 929 controls) was used for validation. Pairwise tagging (r(2) > 0.8) single-nucleotide polymorphisms (SNPs) were genotyped. Logistic and zero-inflated negative binomial regression analyses were used to test for SNP associations with CWP and the number of pain sites, respectively. SNPs in HTR2A were associated with both pain phenotypes in the discovery cohort, and a number of these SNP associations were replicated in the validation cohort, some of which were attenuated after adjustment for depression. There was an increased likelihood of having CWP in subjects with 1 or 2 copies of the T allele of rs12584920 (odds ratio [OR] 1.64, 95% confidence interval [95% CI] 1.01-2.60 [P = 0.03] in the discovery cohort, and OR 1.46, 95% CI 1.07-2.00 [P = 0.018] in the validation cohort). A similar association was observed between rs17289394 and the maximum number of pain sites reported in both cohorts. Results from a meta-analysis of the data from the 2 cohorts further strengthened these findings. The findings of this study support the role of HTR2A in the genetic predisposition to musculoskeletal pain.
  Arthritis & Rheumatism 01/2011; 63(3):810-8. · 7.87 Impact Factor