| 1. |
- Ahern, Tomás, et al.
(författare)
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Natural history, risk factors and clinical features of primary hypogonadism in ageing men : Longitudinal Data from the European Male Ageing Study
- 2016
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664. ; 85:6, s. 891-901
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Tidskriftsartikel (refereegranskat)abstract
- Objective: In ageing men, the incidence and clinical significance of testosterone (T) decline accompanied by elevated luteinizing hormone (LH) are unclear. We describe the natural history, risk factors and clinical features associated with the development of biochemical primary hypogonadism (PHG, T < 10·5 nmol/l and LH>9·4U/l) in ageing men. Design, Patients and Measurements: A prospective observational cohort survey of 3,369 community-dwelling men aged 40-79 years, followed up for 4·3 years. Men were classified as incident (i) PHG (eugonadal [EUG, T ≥ 10·5 nmol/l] at baseline, PHG at follow-up), persistent (p) PHG (PHG at baseline and follow-up), pEUG (EUG at baseline and follow-up) and reversed (r) PHG (PHG at baseline, EUG at follow-up). Predictors and changes in clinical features associated with the development of PHG were analysed by regression models. Results: Of 1,991 men comprising the analytical sample, 97·5% had pEUG, 1·1% iPHG, 1·1% pPHG and 0·3% rPHG. The incidence of PHG was 0·2%/year. Higher age (>70 years) [OR 12·48 (1·27-122·13), P = 0·030] and chronic illnesses [OR 4·24 (1·08-16·56); P = 0·038] predicted iPHG. Upon transition from EUG to PHG, erectile function, physical vigour and haemoglobin worsened significantly. Men with pPHG had decreased morning erections, sexual thoughts and haemoglobin with increased insulin resistance. Conclusions: Primary testicular failure in men is uncommon and predicted by old age and chronic illness. Some clinical features attributable to androgen deficiency, but not others, accompanied the T decline in men who developed biochemical PHG. Whether androgen replacement can improve sexual and/or physical function in elderly men with PHG merits further study.
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| 2. |
- Antonio, Leen, et al.
(författare)
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Low Free Testosterone is Associated with Hypogonadal Signs and Symptoms in Men with Normal Total Testosterone.
- 2016
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 101:7, s. 2647-2657
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Tidskriftsartikel (refereegranskat)abstract
- During ageing, total testosterone (TT) declines and SHBG increases, resulting in a greater decrease in calculated free testosterone (cFT). Currently, guidelines suggest using TT to diagnose androgen deficiency and to reserve cFT only for men with borderline TT.
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| 3. |
- Bentmar Holgersson, Magdalena, et al.
(författare)
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Androgen receptor polymorphism dependent variation in prostate specific antigen concentrations of European men.
- 2014
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 23:10, s. 2048-2056
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Tidskriftsartikel (refereegranskat)abstract
- Background Androgens acting via the androgen receptor (AR) stimulate production of prostate specific antigen (PSA), which is a clinical marker of prostate cancer (PCa). Since genetic variants in the AR may have a significant impact on the risk of being diagnosed with PCa, the aim was to investigate if AR-variants were associated with the risk of having PSA above clinically used cut-off thresholds of 3 or 4 ng/mL in men without PCa. Methods Men without PCa history (n=1744) were selected from the European Male Ageing Study (EMAS) cohort of 40-80 year old men from 8 different European centers. Using linear and logistic regression models, with age and center as covariates, we investigated whether AR-variants (CAG repeat-length and/or SNP genotype) were associated with having serum PSA concentrations above 3 or 4 ng/mL, which often are set as cut-off concentrations for further investigation of PCa. Results Carriers of the SNP rs1204038 A-allele (16% of the men) were more likely to have PSA>3 and 4 ng/mL (OR; 95%CI 1.65; 1.13-2.40 and 1.87; 1.18-2.96, respectively) than G-allele carriers. They also had shorter CAG-repeats (median 20 vs. 23, p<0.0005), but CAG repeat length per se did not affect the PSA concentrations. Conclusion The A-allele of the SNP rs1204038 gives a 65% higher risk of having PSA above 3 ng/mL than the G-allele in men without PCa, and thereby an increased risk of being referred for further examination on suspicion of PCa. Impact Serum PSA as a clinical marker could be improved by adjustment for AR-genotype.
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| 4. |
- Eendebak, Robert J A H, et al.
(författare)
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The androgen receptor gene CAG repeat in relation to 4-year changes in androgen-sensitive endpoints in community-dwelling older European men
- 2016
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Ingår i: European Journal of Endocrinology. - 0804-4643. ; 175:6, s. 583-593
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Tidskriftsartikel (refereegranskat)abstract
- Context: The androgen receptor (AR) gene exon 1 CAG repeat length has been proposed to be a determinant of between-individual variations in androgen action in target tissues, which might regulate phenotypic differences of human ageing. However, findings on its phenotypic effects are inconclusive. Objective: To assess whether the AR CAG repeat length is associated with longitudinal changes in endpoints that are influenced by testosterone (T) levels in middle-Aged and elderly European men. Design: Multinational European observational prospective cohort study. Participants: A total of 1887 men (mean ± s.d. age: 63 ± 11 years; median follow up: 4.3 years) from centres of eight European countries comprised the analysis sample after exclusion of those with diagnosed diseases of the hypothalamic-pituitary-testicular (HPT) axis. Main outcome measures: Longitudinal associations between the AR CAG repeat and changes in androgen-sensitive endpoints (ASEs) and medical conditions were assessed using regression analysis adjusting for age and centre. The AR CAG repeat length was treated as both a continuous and a categorical (6-20; 21-23; 24-39 repeats) predictor. Additional analysis investigated whether results were independent of baseline T or oestradiol (E2) levels. Results: The AR CAG repeat, when used as a continuous or a categorical predictor, was not associated with longitudinal changes in ASEs or medical conditions after adjustments. These results were independent of T and E2 levels.
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| 5. |
- Han, Thang S., et al.
(författare)
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Changes in prevalence of obesity and high waist circumference over four years across European regions : the European male ageing study (EMAS)
- 2017
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Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 55:2, s. 456-469
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Tidskriftsartikel (refereegranskat)abstract
- Diversity in lifestyles and socioeconomic status among European populations, and recent socio-political and economic changes in transitional countries, may affect changes in adiposity. We aimed to determine whether change in the prevalence of obesity varies between the socio-politically transitional North-East European (Łódź, Poland; Szeged, Hungary; Tartu, Estonia), and the non-transitional Mediterranean (Santiago de Compostela, Spain; Florence, Italy) and North-West European (Leuven, Belgium; Malmö, Sweden; Manchester, UK) cities. This prospective observational cohort survey was performed between 2003 and 2005 at baseline and followed up between 2008 and 2010 of 3369 community-dwelling men aged 40–79 years. Main outcome measures in the present paper included waist circumference, body mass index and mid-upper arm muscle area. Baseline prevalence of waist circumference ≥ 102 cm and body mass index ≥ 30 kg/m2, respectively, were 39.0, 29.5 % in North-East European cities, 32.4, 21.9 % in Mediterranean cities, and 30.0, 20.1 % in North-West European cities. After median 4.3 years, men living in cities from transitional countries had mean gains in waist circumference (1.1 cm) and body mass index (0.2 kg/m2), which were greater than men in cities from non-transitional countries (P = 0.005). North-East European cities had greater gains in waist circumference (1.5 cm) than in Mediterranean cities (P < 0.001). Over 4.3 years, the prevalence of waist circumference ≥ 102 cm had increased by 13.1 % in North-East European cities, 5.8 % in the Mediterranean cities, 10.0 % in North-West European cities. Odds ratios (95 % confidence intervals), adjusted for lifestyle factors, for developing waist circumference ≥ 102 cm, compared with men from Mediterranean cities, were 2.3 (1.5–3.5) in North-East European cities and 1.6 (1.1–2.4) in North-West European cities, and 1.6 (1.2–2.1) in men living in cities from transitional, compared with cities from non-transitional countries. These regional differences in increased prevalence of waist circumference ≥ 102 cm were more pronounced in men aged 60–79 years than in those aged 40–59 years. Overall there was an increase in the prevalence of obesity (body mass index ≥ 30 kg/m2) over 4.3 years (between 5.3 and 6.1 %) with no significant regional differences at any age. Mid-upper arm muscle area declined during follow-up with the greatest decline among men from North-East European cities. In conclusion, increasing waist circumference is dissociated from change in body mass index and most rapid among men living in cities from transitional North-East European countries, presumably driven by economic and socio–political changes. Information on women would also be of value and it would be of interest to relate the changes in adiposity to dietary and other behavioural habits.
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| 6. |
- Huhtaniemi, Ilpo T, et al.
(författare)
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Effect of Polymorphisms in Selected Genes Involved in Pituitary-Testicular Function on Reproductive Hormones and Phenotype in Aging Men.
- 2010
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95, s. 1898-1908
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Tidskriftsartikel (refereegranskat)abstract
- Context: Polymorphisms in genes involved in regulation, biosynthesis, metabolism, and actions of testicular sex hormones may influence hormone balance and phenotype of aging men. Objective: We investigated the relationships between polymorphisms in genes related to pituitary-testicular endocrine function and health status. Design and Setting: Using cross-sectional baseline data, we conducted a multinational prospective cohort observational study consisting of a population survey of community-dwelling men. Participants: A total of 2748 men, aged 40-79 (mean +/- SD, 60.2 + 11.2) yr, were randomly recruited from eight European centers. Forty-three polymorphisms were genotyped in the following genes: androgen receptor (AR), estrogen receptor-alpha and -beta (ESR1 and ESR2), steroid 5alpha-reductase type II (SRD5A2), 17alpha-hydroxylase/17,20-lyase (CYP17A1), aromatase (CYP19A1), sex hormone-binding globulin (SHBG), LH beta-subunit (LHB), and LH receptor (LHCGR). Main Outcome Measures: We measured the associations between gene polymorphisms and endocrine, metabolic, and phenotypic parameters related to aging and sex hormone action. Results: Several polymorphisms in SHBG, ESR2, AR, CYP19A1, and LHB were significantly associated with circulating levels of SHBG, LH, total, free, and bioavailable testosterone and estradiol, the LH x testosterone product, and indices of insulin sensitivity. Apart from several previously reported associations between genes affecting estrogen levels and heel ultrasound parameters, no associations existed between polymorphisms and nonhormonal variables (anthropometry, blood lipids, blood pressure, hemoglobin, prostate symptoms, prostate-specific antigen, sexual dysfunction, cognition). Conclusion: In aging men, polymorphisms in genes related to the pituitary-testicular endocrine function significantly influence circulating LH, testosterone, and estradiol levels, but the downstream effects may be too small to influence secondary phenotypic parameters.
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| 7. |
- Huhtaniemi, Ilpo T, et al.
(författare)
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Increased Estrogen Rather Than Decreased Androgen Action Is Associated with Longer Androgen Receptor CAG Repeats.
- 2009
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 94, s. 277-284
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Tidskriftsartikel (refereegranskat)abstract
- Context: The individual variability in the waning androgenic-anabolic functions of aging men may be influenced by the CAG repeat polymorphism in exon 1 of the androgen receptor (AR), affecting androgen sensitivity. However, findings on its phenotypic effects are inconclusive. Objective: To investigate the relationships between health status, various reproductive hormones and the AR CAG repeat length. Design: A multi-national prospective cohort observational study - cross-sectional baseline data. Setting: Population survey of community-dwelling men. Participants: Men (40-79-yr-old; n=3,369) randomly recruited from centers in eight European countries; CAG repeat analysis was performed in 2,878 men. Main outcome measures: The correlations of the CAG repeat length with selected endocrine, metabolic and phenotypic parameters related to aging and sex hormone action. Results: Only minor differences were found in CAG repeat lengths between the eight European countries. They showed significant positive association with total, free and bioavailable levels of testosterone (T) and estradiol (E2). FSH but not LH correlated inversely with CAG repeat length. Significant associations were found with bone ultrasound parameters at the calcaneus. Negative correlation was found with triglycerides, but not with other blood lipids, or with anthropometry, blood pressure, hemoglobin, insulin sensitivity, or sexual and prostatic functions. Conclusions: The AR CAG repeat length correlates significantly with serum T and E2 of aging men. Weaker transcriptional activity of the AR with longer CAG-encoded polyglutamine repeats appears to be totally or near-totally compensated for by higher T levels. The residual phenotypic correlations may reflect differences in estrogen levels/actions following aromatization of the higher T levels.
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| 8. |
- Pye, Stephen R, et al.
(författare)
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Low heel ultrasound parameters predict mortality in men: results from the European Male Ageing Study (EMAS).
- 2015
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Ingår i: Age and Ageing. - : Oxford University Press (OUP). - 1468-2834 .- 0002-0729. ; 44:5, s. 801-807
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Tidskriftsartikel (refereegranskat)abstract
- low bone mineral density measured by dual-energy x-ray absorptiometry is associated with increased mortality. The relationship between other skeletal phenotypes and mortality is unclear. The aim of this study was to determine the relationship between quantitative heel ultrasound parameters and mortality in a cohort of European men.
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| 9. |
- Tajar, Abdelouahid, et al.
(författare)
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Characteristics of Androgen Deficiency in Late-Onset Hypogonadism: Results from the European Male Aging Study (EMAS).
- 2012
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 97:5, s. 1508-1516
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Tidskriftsartikel (refereegranskat)abstract
- Context: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). Objective: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. Design, Setting, and Participants: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. Main Outcome Measure(s):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. Results: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= 1.93cm; 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. Conclusions: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.
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| 10. |
- Tajar, Abdelouahid, et al.
(författare)
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Characteristics of Secondary, Primary, and Compensated Hypogonadism in Aging Men: Evidence from the European Male Ageing Study.
- 2010
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95, s. 1810-1818
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Tidskriftsartikel (refereegranskat)abstract
- Context: The diagnosis of late-onset hypogonadism (LOH) in older men with age-related declines in testosterone (T) is currently not well characterized. Objective: Our objective was to investigate whether different forms of hypogonadism can be distinguished among aging men. Design: The study was a cross-sectional survey on 3369 community-dwelling men aged 40-79 yr in eight European centers. Methods: Four groups of subjects were defined: eugonadal (normal T and normal LH), secondary (low T and low/normal LH), primary (low T and elevated LH), and compensated (normal T and elevated LH) hypogonadism. Relationships between the defined gonadal status with potential risk factors and clinical symptoms were investigated by multilevel regression models. Results: Among the men, 11.8, 2.0, and 9.5% were classified into the secondary, primary, and compensated hypogonadism categories, respectively. Older men were more likely to have primary [relative risk ratio (RRR) = 3.04; P < 0.001] and compensated (RRR = 2.41; P < 0.001) hypogonadism. Body mass index of 30 kg/m(2) or higher was associated with secondary hypogonadism (RRR = 8.74; P < 0.001). Comorbidity was associated with both secondary and primary hypogonadism. Sexual symptoms were more prevalent in secondary and primary hypogonadism, whereas physical symptoms were more likely in compensated hypogonadism. Conclusions: Symptomatic elderly men considered to have LOH can be differentiated on the basis of endocrine and clinical features and predisposing risk factors. Secondary hypogonadism is associated with obesity and primary hypogonadism predominately with age. Compensated hypogonadism can be considered a distinct clinical state associated with aging. Classification of LOH into different categories by combining LH with T may improve the diagnosis and management of LOH.
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