| 1. |
- Rastrelli, Giulia, et al.
(författare)
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Symptomatic androgen deficiency develops only when both total and free testosterone decline in obese men who may have incident biochemical secondary hypogonadism : Prospective results from the EMAS
- 2018
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664. ; 89:4, s. 459-469
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Limited evidence supports the use of free testosterone (FT) for diagnosing hypogonadism when sex hormone–binding globulin (SHBG) is altered. Low total testosterone (TT) is commonly encountered in obesity where SHBG is typically decreased. We aimed to assess the contribution of FT in improving the diagnosis of symptomatic secondary hypogonadism (SH), identified initially by low total testosterone (TT), and then further differentiated by normal FT (LNSH) or low FT (LLSH). Design: Prospective observational study with a median follow-up of 4.3 years. Patients: Three thousand three hundred sixty-nine community-dwelling men aged 40-79 years from eight European centres. Measurements: Subjects were categorized according to baseline and follow-up biochemical status into persistent eugonadal (referent group; n = 1880), incident LNSH (eugonadism to LNSH; n = 101) and incident LLSH (eugonadism to LLSH; n = 38). Predictors and clinical features associated with the transition from eugonadism to LNSH or LLSH were assessed. Results: The cumulative incidence of LNSH and LLSH over 4.3 years was 4.9% and 1.9%, respectively. Baseline obesity predicted both LNSH and LLSH, but the former occurred more frequently in younger men. LLSH, but not LNSH, was associated with new/worsened sexual symptoms, including low desire [OR = 2.67 (1.27-5.60)], erectile dysfunction [OR = 4.53 (2.05-10.01)] and infrequent morning erections [OR = 3.40 (1.48-7.84)]. Conclusions: These longitudinal data demonstrate the importance of FT in the diagnosis of hypogonadism in obese men with low TT and SHBG. The concurrent fall in TT and FT identifies the minority (27.3%) of men with hypogonadal symptoms, which were not present in the majority developing low TT with normal FT.
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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- Dupont, Jolan, et al.
(författare)
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Inflammatory markers are associated with quality of life, physical activity, and gait speed but not sarcopenia in aged men (40–79 years)
- 2021
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Ingår i: Journal of Cachexia, Sarcopenia and Muscle. - : Wiley. - 2190-5991 .- 2190-6009. ; 12:6, s. 1818-1831
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Tidskriftsartikel (refereegranskat)abstract
- Background: Age-related chronic low-grade inflammation (inflammaging) is one of the proposed mechanisms behind sarcopenia. However, findings regarding inflammatory markers in sarcopenic older adults are conflicting. This study aimed to determine the association between inflammatory markers, prevalent as well as incident sarcopenia, sarcopenia-defining parameters, quality of life (QoL), and physical activity in middle-aged and older men. Methods: Men aged 40–79 years (mean 59.66 ± 11.00y) were recruited from population registers in eight European centres for participation in the European Male Aging study (EMAS). Subjects were assessed at baseline (2003–2005) and again after a median follow-up of 4.29 years. In 2577 participants, associations between baseline inflammatory markers [high-sensitive C-reactive protein (hs-CRP), white blood cell count (WBC), albumin] and baseline physical activity (PASE) and QoL (SF-36) were analysed. In the Leuven and Manchester cohort (n = 447), data were available on muscle mass (whole-body dual X-ray absorptiometry) and strength. In this subgroup, cross-sectional associations between baseline inflammatory markers and sarcopenia-defining parameters (handgrip strength, chair stand test, appendicular lean mass, and gait speed) and prevalent sarcopenia were examined. In a further subgroup (n = 277), associations with knee extensor strength were explored. Longitudinally, predictive value of baseline inflammation on functional decline, physical activity, QoL, and incident sarcopenia was examined. Subgroup analyses were performed in subgroups with chronic inflammation and stratified by age. Linear and logistic regressions were used, adjusted for age, body mass index, centre, and smoking. Results: At baseline, hs-CRP and WBC were negatively associated with PASE score (hs-CRP: β = −7.920, P < 0.001; and WBC: β = −4.552, P < 0.001) and the physical component score of SF-36 (hs-CRP: β = −1.025, P < 0.001; and WBC: β = −0.364, P < 0.001). Baseline WBC levels were negatively associated with gait speed (β = −0.013; P = 0.025), quadriceps isometric 90° (β = −5.983; P = 0.035) and isokinetic 60°/s peak torque/body weight (β = −5.532; P = 0.027). The prevalence of sarcopenia at baseline was 18.1% (n = 81). Of those without sarcopenia at baseline, 64 (18.6%) satisfied criteria for sarcopenia at follow-up. There were no significant associations between baseline inflammatory markers and either prevalent or incident sarcopenia, or change in level of sarcopenia-defining parameters between baseline and follow-up. Conclusions: In middle-aged and older men, hs-CRP and WBC were negatively associated with QoL and PASE scores, while WBC was negatively associated with gait speed and knee strength. Associations with hs-CRP remained significant in all ages, whereas WBC levels were only associated with PASE, gait speed and knee strength in older adults (60–79 years). Baseline inflammatory markers (hs-CRP, WBC and albumin) did not predict functional decline, decline in physical activity, decreased QoL or incident sarcopenia.
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| 6. |
- 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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| 7. |
- 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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| 8. |
- 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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| 9. |
- 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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| 10. |
- 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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