Similar reference intervals for total testosterone in healthy young and elderly men: results from the Odense Androgen Study.

CONTEXT: Ageing in men is associated with changes in levels of sex hormones. OBJECTIVE: To evaluate differences in sex hormones in young and elderly men and the significance of comorbidity and fat mass on sex hormones in elderly men. DESIGN: Cross-sectional. PATIENTS: Seven hundred and eighty-three men aged 20-29 years and 600 men aged 60-74 years randomly recruited from the background population. MEASUREMENTS: Sex hormones and sex hormone-binding globulin (SHBG) were measured, and reference intervals were determined in healthy individuals in both groups and in elderly men stratified according to whether they were obese or lean (waist circumference ≥102 cm). RESULTS: Sex hormones were lower and SHBG higher in elderly men compared with the young cohort. Lower cut-offs for total testosterone (TT) in healthy, young and elderly men were similar [Lower cut-off (95% CI): Young: 11·7 (11·2-12·1) vs elderly: 11·2 (10·3-12·1) nmol/l], but lower and higher cut-offs of bioavailable testosterone (BT) and free testosterone (FT) were higher in young men. Higher levels of androgens were found in healthy elderly men compared with those with a chronic disease or obesity. Androgens were inversely associated with central fat mass (CFM), whereas SHBG was inversely and directly associated with CFM and lower extremity fat mass, respectively, in both young and elderly men. CONCLUSION: Reference intervals for TT were comparable in healthy young and elderly men, but reference intervals for FT and BT were lower in elderly men due to higher levels of SHBG. Androgens and SHBG were lower in elderly men with chronic disease and inversely associated with CFM.

Polymorphisms in the endocannabinoid receptor 1 in relation to fat mass distribution.

OBJECTIVE: Both animal and human studies have associated the endocannabinoid system with obesity and markers of metabolic dysfunction. Blockade of the cannabinoid receptor 1 (CB1) caused weight loss and reduction in waist size in both obese and type II diabetics. Recent studies on common variants of the CB1 receptor gene (CNR1) and the link to obesity have been conflicting. The aim of the present study was to evaluate whether selected common variants of the CNR1 are associated with measures of obesity and fat distribution. DESIGN AND METHODS: The single nucleotide polymorphisms (SNPs) rs806381, rs10485179 and rs1049353 were genotyped, and body fat and fat distribution were assessed by the use of dual-energy X-ray absorptiometry and magnetic resonance imaging in a population-based study comprising of 783 Danish men, aged 20-29 years. RESULTS: The rs806381 polymorphism was significantly associated with visceral fat mass (FM) only, whereas the rs1049353 was significantly and directly associated with visceral and intermuscular FM. None of the SNPs analysed were associated with total body FM or subcutaneous FM. CONCLUSION: The results point towards a link between common variants of the CNR1 and fat distribution in young men.

Subcutaneous rather than visceral adipose tissue is associated with adiponectin levels and insulin resistance in young men.

INTRODUCTION: Studies on the association between adiponectin, body composition, and insulin resistance (IR) have been conflicting. AIM: Our aim was to evaluate the impact of body composition on adiponectin and IR determined by homeostasis model assessment (HOMA) in a population-based study on relatively healthy young men, minimizing the possible effects of age, obesity, and severe comorbidity. DESIGN, METHODS, AND SUBJECTS: A population-based, cross-sectional study of 783 men aged 20-29 yr, randomly drawn from the Danish Central Personal Registry. Adiponectin was assessed using an in-house assay, and IR was determined using HOMA. Central fat mass (CFM) and lower extremity fat mass (LEFM) was measured by dual-energy x-ray absorptiometry, and visceral adipose tissue (VAT), sc adipose tissue (SAT), and thigh fat area (TFA) were assessed by magnetic resonance imaging. RESULTS: Using multiple linear regression analysis, adiponectin correlated negatively with CFM (r = -0.27; P < 0.001) and SAT (r = -0.20; P < 0.001) and positively with LEFM (r = 0.19; P < 0.001) and TFA (r = 0.18; P < 0.001), whereas VAT did not associate significantly. In multiple linear regression analysis, HOMA-IR (dependent variable), correlated significantly with CFM (r = 0.27; P < 0.001) and SAT (r = 0.15; P < 0.001), whereas LEFM, VAT, or TFA did not correlate. Adiponectin was an independent predictor of HOMA-IR in both analyses (r = -0.14; P < 0.001). CONCLUSION: SAT rather than VAT was inversely associated with adiponectin levels, and, interestingly, fat on the lower extremities was positively associated with adiponectin. Focusing on insulin resistance, SAT rather than VAT and TFA independently predicted a higher HOMA-IR. The observation that adiponectin was independently associated with lower HOMA-IR must be repeated in other populations.

Radiographic absorptiometry as a screening tool in male osteoporosis: results from the Odense Androgen Study.

BACKGROUND: Osteoporosis screening with dual-energy absorptiometry (DXA) is not recommended due to low diagnostic utility and costs. Radiographic absorptiometry (RA) determines bone mineral density (BMD) of the phalangeal bones of the hand and is a potential osteoporosis pre-screening tool. PURPOSE: To determine the ability of RA to identify patients with osteoporosis in a male population. MATERIAL AND METHODS: As part of the Odense Androgen Study, we measured BMD of the intermediate phalanges of the second to fourth finger, lumbar spine (L2-L4), and total hip in 218 men aged 60-74 years (mean 68.8 years), randomly invited from the population, using RA (MetriScan) and DXA (Hologic 4500-A). Osteopenia and osteoporosis were defined as a T-score of less than -1.0 and -2.5, respectively, in the hip and/or lumbar spine. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were computed. RESULTS: BMD(RA) of the phalanges correlated significantly with BMD(DXA) of the hip (R=0.47, P<0.001) and lumbar spine (R=0.46, P<0.001). A total of 105 men (48.2%) were osteopenic and 15 (6.9%) osteoporotic. The AUC (SE) value for detecting osteoporosis was 0.75 (0.06). The sensitivity and specificity of RA in identifying osteoporosis were 0.93 and 0.50, respectively. CONCLUSION: BMD(RA) correlated weakly with BMD(DXA) of the lumbar spine and total hip, and RA has a moderate ability to identify osteoporotic individuals. Nevertheless, RA may be used as a pre-screening tool in men, since the diagnosis may be ruled out in half the population at little cost.

Polymorphisms in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with peak bone mass in non-sedentary men: results from the Odense androgen study.

PURPOSE: To investigate the impact of the Ala1330Val (rs3736228, exon 18) and Val667Met (rs4988321, exon 9) polymorphisms of the low-density lipoprotein receptor-related protein 5 (LRP5) gene on peak bone mass in young men. METHODS: The Odense Androgen Study (OAS) is a population-based study comprising 783 Caucasian men aged 20-30 years. Genotyping was performed using real-time polymerase chain reaction (PCR) or fluorescence polarization. Bone mineral density (BMD) measurements were performed using dual-energy X-ray absorptiometry. RESULTS: The CC, CT, and TT genotypes in Ala1330Val were found in 75.6%, 21.8%, and 2.6% of the participants, respectively. Similarly, the GG, GA, and AA genotypes of Val667Met were found in 89.7%, 9.8%, and 0.5%, respectively. For the Ala1330Val polymorphism, no significant differences between the genotypes were found regarding BMD in the overall study population. However, when analysis was restricted to non-sedentary men (n = 589), a significant association between the number of T-alleles and BMD in the spine and whole body were found. Each copy of the T-allele changed the Z-score of the spine by (median and 95% confidence interval) -0.21 [95% CI: -0.40; -0.03] (p < 0.02). Analysis suggested an association between the AA genotype in the Val667Met polymorphism and increased body height and decreased BMD of the femoral neck; however, no significant gene-dose effect of the A-allele could be demonstrated in the whole population. When the analysis was restricted to non-sedentary subjects, however, each number of A-alleles was associated with a change in Z-score of -0.26 [95% CI: -0.51; -0.01] (p = 0.04). No further significant results emerged with haplotype analysis. CONCLUSION: The Ala1330Val and Val667Met polymorphisms in the LRP5 gene are significantly associated with peak bone mass in physically active men.

Population-based reference values for bone mineral density in young men.

UNLABELLED: Population-based reference values for peak bone mass density in Danish men. BMD of total hip (1.078 +/- 0,14 g/cm2) differed significantly from values from National Health and Nutrition Examination Survey III and of total lumbar spine ((1.073 +/- 0.125 g/cm2) differed significantly from Hologic values. INTRODUCTION: Geographic, ethnic, and socio-economic factors are known to affect bone mineral density (BMD) and peak bone mass significantly. Reference values for male peak bone mass are scarce, and the diagnosis of male osteoporosis often relies on values provided by producers of dual-energy X-ray absorptiometry (DXA) equipment. METHODS: The aim of the present study was 1) to establish population-based reference values for BMD in young men and 2) to study subgroups based on variables with suspected impact on bone metabolism. We included 783 young Caucasian men aged 20 to 30 years in the Odense Androgen Study (OAS). RESULTS: Peak BMD was attained within the third decade. Obesity (BMI > 30 kg/m2) was associated with higher BMD. Abuse of anabolic steroids as well as chronic illness was associated with lower BMD. Our population-based reference values for BMD of the total hip (1.078 +/- 0.14 g/cm2) differed significantly from published values from National Health and Nutrition Examination Survey III for non-Hispanic white men, while BMD of total lumbar spine (1.073 +/- 0.125 g/cm2) differed significantly from Hologic reference values. CONCLUSIONS: Locally derived reference values are important to avoid false positive or false negative findings during work-up in patients evaluated for osteoporosis.

Prevalence of overweight, obesity and physical inactivity in 20- to 29-year-old, Danish men. Relation to sociodemography, physical dysfunction and low socioeconomic status: the Odense Androgen Study.

OBJECTIVE: To assess the prevalence of overweight, obesity and physical inactivity in 20- to 29-year-old men and to analyze whether sociodemography, physical dysfunction and low socioeconomic status are independent correlates of obesity and physical inactivity. DESIGN: Population-based, cross-sectional study. SUBJECTS: Seven hundred and eighty-three Caucasian, Danish men, aged 20-29 years recruited from 2042 respondents in a questionnaire survey of 3000 men, randomly drawn from the Danish Civil Registration System. METHODS: Questionnaire, interview and physical examination. RESULTS: The 783 included men and the 2042 questionnaire respondents matched the background population demographically. The 783 men matched the questionnaire respondents as regards BMI, physical activity, chronic disease, medication, smoking, sociodemography and socioeconomic status. The prevalence of overweight and obesity was 31.7 and 7.9%, respectively (World Health Organization criteria). Using waist circumference (WC) cutoffs of 94 and 102 cm, the prevalence was 16.2 and 10.6%, respectively; 24.4% were physically inactive. BMI and WC increased significantly from age 20 to 29 years. Physical activity decreased significantly with age and correlated inversely with WC, but not with BMI. Occupation, geography, partner status, fatherhood and tobacco exposure were independently related with obesity and physical inactivity. Obesity was also related to musculoskeletal complaints, whereas chronic diseases and low educational level were associated with physical inactivity. Age was not independently related with either outcome. CONCLUSION: In affluent societies, sociodemographic changes may partly explain the age-related decrease in physical activity and the parallel increase in WC and BMI.