| 1. |
- Antonio, Leen, et al.
(författare)
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Associations Between Sex Steroids and the Development of Metabolic Syndrome: A Longitudinal Study in European Men
- 2015
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 100:4, s. 1396-1404
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Tidskriftsartikel (refereegranskat)abstract
- Context: Low testosterone (T) has been associated with incident metabolic syndrome (MetS), but it remains unclear if this association is independent of sex hormone binding globulin (SHBG). Estradiol (E2) may also be associated with MetS, but few studies have investigated this. Objective: To study the association between baseline sex steroids and the development of incident MetS and to investigate the influence of SHBG, body mass index (BMI) and insulin resistance on this risk. Methods: Three thousand three hundred sixty nine community-dwelling men aged 40-79 years were recruited for participation in EMAS. MetS was defined by the updated NCEP ATP III criteria. Testosterone and E2 levels were measured by liquid and gas chromatography/mass spectrometry, respectively. Logistic regression was used to assess the association between sex steroids and incident MetS. Results: One thousand six hundred fifty one men without MetS at baseline were identified. During follow-up, 289 men developed incident MetS, while 1362 men did not develop MetS. Men with lower baseline total T levels were at higher risk for developing MetS [odds ratio (OR) = 1.72, P < .001), even after adjustment for SHBG (OR = 1.43, P < .001), BMI (OR = 1.44, P < .001) or homeostasis model assessment of insulin resistance (HOMA-IR) (OR = 1.64, P < .001). E2 was not associated with development of MetS (OR = 1.04; P = .56). However, a lower E2/T ratio was associated with a lower risk of incident MetS (OR = 0.38; P < .001), even after adjustment for SHBG (OR = 0.48; P < .001), BMI (OR = 0.60; P = .001) or HOMA-IR (OR = 0.41; P < .001). Conclusions: Inmen, lower Tlevels, but not E2, are linked with an increased risk of developing MetS, independent of SHBG, BMI or insulin resistance. A lower E2/T ratio may be protective against developing MetS.
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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. |
- 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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| 4. |
- 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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| 5. |
- O'Connor, Daryl B, et al.
(författare)
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The Relationships between Sex Hormones and Sexual Function in Middle-Aged and Older European Men.
- 2011
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 96, s. 1577-1587
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Tidskriftsartikel (refereegranskat)abstract
- Context: 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. Objectives: 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. Design: 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. Setting: We conducted a community-based population survey in eight European centers. Main Outcome Measures: Self-reported sexual function (overall sexual function, sexual function-related distress, erectile dysfunction, masturbation) was measured. Results: 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. Conclusions: 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.
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| 6. |
- Rastrelli, Giulia, et al.
(författare)
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Development of and Recovery from Secondary Hypogonadism in Aging Men: Prospective Results from the EMAS
- 2015
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 100:8, s. 3172-3182
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Tidskriftsartikel (refereegranskat)abstract
- Context: Secondary hypogonadism is common in aging men; its natural history and predisposing factors are unclear. Objectives: The objectives were 1) to identify factors that predispose eugonadal men (T >= 10.5 nmol/L) to develop biochemical secondary hypogonadism (T < 10.5 nmol/L; LH <= 9.4 U/L) and secondary hypogonadal men to recover to eugonadism; and 2) to characterize clinical features associated with these transitions. Design: The study was designed as a prospective observational general population cohort survey. Setting: The setting was clinical research centers. Participants: The participants were 3369 community-dwelling men aged 40-79 years in eight European centers. Intervention: Interventions included observational follow-up of 4.3 years. Main Outcome Measure: Subjects were categorized according to change/no change in biochemical gonadal status during follow-up as follows: persistent eugonadal (n = 1909), incident secondary hypogonadal (n = 140), persistent secondary hypogonadal (n = 123), and recovered from secondary hypogonadism to eugonadism (n = 96). Baseline predictors and changes in clinical features associated with incident secondary hypogonadism and recovery from secondary hypogonadism were analyzed by regression models. Results: The incidence of secondary hypogonadism was 155.9/10 000/year, whereas 42.9% of men with secondary hypogonadism recovered to eugonadism. Incident secondary hypogonadism was predicted by obesity(body mass index >= 30 kg/m(2); odds ratio [OR] = 2.86 [95% confidenceinterval, 1.67; 4.90]; P < .0001), weight gain (OR = 1.79 [1.15; 2.80]; P = .011), and increased waist circumference (OR = 1.73 [1.07; 2.81], P = .026; and OR = 2.64 [1.66; 4.21], P < .0001, for waist circumference 94-102 and >= 102 cm, respectively). Incident secondary hypogonadal men experienced new/worsening sexual symptoms (low libido, erectile dysfunction, and infrequent spontaneous erections). Recovery from secondary hypogonadism was predicted by nonobesity(OR = 2.28 [1.21; 4.31]; P = .011), weight loss (OR = 2.24 [1.04; 4.85]; P = .042), normal waist circumference (OR = 1.93 [1.01; 3.70]; P = .048), younger age (<60 y; OR = 2.32 [1.12; 4.82]; P = .024), and higher education (OR = 2.11 [1.05; 4.26]; P = .037), but symptoms did not show significant concurrent improvement. Conclusion: Obesity-related metabolic and lifestyle factors predispose older men to the development of secondary hypogonadism, which is frequently reversible with weight loss.
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| 7. |
- Swiecicka, Agnieszka, et al.
(författare)
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Nonandrogenic anabolic hormones predict risk of frailty : European male ageing study prospective data
- 2017
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 102:8, s. 2798-2806
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Tidskriftsartikel (refereegranskat)abstract
- Context: Low levels of nonandrogenic anabolic hormones have been linked with frailty, but evidence is conflicting and prospective data are largely lacking. Objective: To determine associations between nonandrogenic anabolic hormones and prospective changes in frailty status. Design/Setting: A 4.3-year prospective observational study of community-dwelling men participating in the European Male Ageing Study. Participants: Men (n = 3369) aged 40 to 79 years from eight European centers. Main Outcome Measures: Frailty status was determined using frailty phenotype (FP; n = 2114) and frailty index (FI; n = 2444). Analysis: Regression models assessed relationships between baseline levels of insulinlike growth factor 1 (IGF-1), its binding protein 3 (IGFBP-3), dehydroepiandrosterone sulfate (DHEA-S), 25-hydroxyvitamin D (25OHD), and parathyroid hormone (PTH), with changes in frailty status (worsening or improving frailty). Results: The risk of worsening FP and FI decreased with 1 standard deviation higher IGF-1, IGFBP-3, and 25OHD in models adjusted for age, body mass index, center, and baseline frailty [IGF-1: odds ratio (OR) for worsening FP, 0.82 (0.73, 0.93), percentage change in FI, -3.7% (-6.0, -1.5); IGFBP-3: 0.84 (0.75, 0.95), -4.2% (-6.4, -2.0); 25OHD: 0.84 (0.75, 0.95); -4.4%, (-6.7, -2.0)]. Relationships between IGF-1 and FI were attenuated after adjusting for IGFBP-3. Higher DHEA-S was associated with a lower risk of worsening FP only in men >70 years old [OR, 0.57 (0.35, 0.92)]. PTH was unrelated to change in frailty status. Conclusions: These longitudinal data confirm the associations between nonandrogenic anabolic hormones and the changes in frailty status. Interventional studies are needed to establish causality and determine therapeutic implications.
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| 8. |
- Swiecicka, Agnieszka, et al.
(författare)
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Reproductive hormone levels predict changes in frailty status in community-dwelling older men : European male ageing study prospective data
- 2018
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 103:2, s. 701-709
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Tidskriftsartikel (refereegranskat)abstract
- Context: Clinical sequelae of androgen deficiency share common features with frailty. Evidence supporting the role of androgens in the development of frailty is limited and conflicting. Objective: To determine associations between male reproductive hormones and prospective changes in frailty status. Design/Setting: A 4.3-year prospective cohort study of community-dwelling men participating in the European Male Ageing Study. Participants: A total of 3369 men aged 40 to 79 from eight European centers. Intervention: None. Main Outcome Measure: Frailty status was determined using frailty index (FI; n = 2278) and frailty phenotype (FP; n = 1980). Results: After adjusting for baseline frailty, age, center, and smoking, the risk ofworsening FI decreased with higher testosterone (T), free T, and dihydrotestosterone (DHT) [percentage change (95% confidence interval) in FI associated with 1 standard deviation higher hormone level: -3.0 (-5.9, -1.0) for total T; -3.9 (-6.8, -2.0) for free T; and -3.9 (-6.8, -2.0) forDHT]. After further adjustment for bodymass index, only free T remained a significant predictor of FI change. In fully adjusted models, higher luteinizing hormone and follicle-stimulating hormone were positively related to worsening FI only in men ,60 years, and higher estradiol predicted lower likelihood of improving FP [odds ratio: 0.68 (0.52, 0.88)]. Conclusions: These prospective data support the hypothesis that higher androgen levels may protect elderly men from worsening frailty. However, the causal nature of these relationships requires further investigation.Whereas raised gonadotropins inmen,60 yearsmight be an earlymarker of frailty, the role of estradiol in frailty needs further clarification.
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| 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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