Testosterone is the major circulating androgen in men but exhibits an age-related decline in the ageing male. Late-onset hypogonadism or androgen deficiency syndrome (ADS) is a ‘syndromic’ disorder ...including both a persistent low testosterone serum concentration and major clinical symptoms, including erectile dysfunction, low libido, decreased muscle mass and strength, increased body fat, decreased vitality or depressed mood. Given its unspecific symptoms, treatment goals and monitoring parameters, this review will outline the various uncertainties concerning the diagnosis, therapy and monitoring of ADS to date. Literature was identified primarily through searches for specific investigators in the PubMed database. No date or language limits were applied in the literature search for the present review. The current state of research, showing that metabolomics is starting to have an impact not only on disease diagnosis and prognosis but also on drug treatment efficacy and safety monitoring, will be presented, and the application of metabolomics to improve the clinical management of ADS will be discussed. Finally, the scientific opportunities presented by metabolomics and other -omics as novel and promising tools for biomarker discovery and individualised testosterone replacement therapy in men will be explored.
The aim of the present study was to investigate the association of serum gamma‐glutamyltransferase (GGT) levels with all‐cause mortality and to assess the impact of ultrasonographic findings of ...hepatic hyperechogenicity in that association. We used data from 4,160 subjects (2,044 men and 2,116 women) recruited for the population‐based Study of Health in Pomerania (SHIP) without baseline hepatitis B and C infections or liver cirrhosis. GGT was divided into age‐ and sex‐dependent quintiles to calculate overall and sex‐specific crude incidence mortality rates. Hepatic steatosis was defined by elevated GGT levels (>80%) and the presence of hyperechogenic liver ultrasound. We used multiple‐adjusted Cox proportional hazards regression models, first, to assess the direct effect of GGT on all‐cause mortality, second, to stratify according to the ultrasonographic finding, and third, to investigate potential mediating effects of cardiometabolic risk factors. During 29,810 person‐years (7.3 years, median) of follow‐up, 307 individuals (7.5%) died, resulting in a death rate of 0.86 deaths per 1000 person‐years. Elevated GGT levels were associated with increased risk of mortality in men (hazard ratio HR 1.49; 95% confidence interval CI, 1.08–2.05), but not in women (HR 1.30; 95% CI, 0.80–2.12). This association was even stronger in men with hepatic steatosis (HR 1.98; 95% CI, 1.21–3.27). Cause‐specific mortality analysis by cardiovascular disease deaths confirmed the sex‐specific association. Adjustment for cardiometabolic risk factors did not affect the estimates. Conclusion: In the case of increased GGT levels, liver ultrasound should be performed, not only for diagnosis, but also for further risk stratification. (HEPATOLOGY 2009.)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Obesity in men is associated with low serum testosterone and both are associated with several diseases and increased mortality.
Examine the direction and causality of the relationship between body ...mass index (BMI) and serum testosterone.
Bi-directional Mendelian randomization (MR) analysis on prospective cohorts.
Five cohorts from Denmark, Germany and Sweden (Inter99, SHIP, SHIP Trend, GOOD and MrOS Sweden).
7446 Caucasian men, genotyped for 97 BMI-associated SNPs and three testosterone-associated SNPs.
BMI and serum testosterone adjusted for age, smoking, time of blood sampling and site.
1 SD genetically instrumented increase in BMI was associated with a 0.25 SD decrease in serum testosterone (IV ratio: -0.25, 95% CI: -0.42--0.09, p = 2.8*10-3). For a body weight reduction altering the BMI from 30 to 25 kg/m2, the effect would equal a 13% increase in serum testosterone. No association was seen for genetically instrumented testosterone with BMI, a finding that was confirmed using large-scale data from the GIANT consortium (n = 104349).
Our results suggest that there is a causal effect of BMI on serum testosterone in men. Population level interventions to reduce BMI are expected to increase serum testosterone in men.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aim of this study was to evaluate the association of sex hormones with anthropometry in a large population-based cohort, with liquid chromatography-mass spectrometry (LCMS)-based sex hormone ...measurements and imaging markers.
Cross-sectional data from 957 men and women from the population-based Study of Health in Pomerania (SHIP) were used. Associations of a comprehensive panel of LCMS-measured sex hormones with anthropometric parameters, laboratory, and imaging markers were analyzed in multivariable regression models for the full sample and stratified by sex. Sex hormone measures included total testosterone (TT), free testosterone (fT), estrone and estradiol, androstenedione (ASD), dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin (SHBG). Domains of anthropometry included physical measures (body-mass-index (BMI), waist circumference, waist-to-height-ratio, waist-to-hip-ratio, and hip circumference), laboratory measures of adipokines (leptin and vaspin), and magnet resonance imaging-based measures (visceral and subcutaneous adipose tissue).
In men, inverse associations between all considered anthropometric parameters with TT were found: BMI (β-coefficient, standard error (SE): -0.159, 0.037), waist-circumference (β-coefficient, SE: -0.892, 0.292), subcutaneous adipose tissue (β-coefficient, SE: -0.156, 0.023), and leptin (β-coefficient, SE: -0.046, 0.009). In women TT (β-coefficient, SE: 1.356, 0.615) and estrone (β-coefficient, SE: 0.014, 0.005) were positively associated with BMI. In analyses of variance, BMI and leptin were inversely associated with TT, ASD, and DHEAS in men, but positively associated with estrone. In women, BMI and leptin were positively associated with all sex hormones.
The present population-based study confirmed and extended previously reported sex-specific associations between sex hormones and various anthropometric markers of overweight and obesity.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We present a genome-wide association study of metabolic traits in human urine, designed to investigate the detoxification capacity of the human body. Using NMR spectroscopy, we tested for ...associations between 59 metabolites in urine from 862 male participants in the population-based SHIP study. We replicated the results using 1,039 additional samples of the same study, including a 5-year follow-up, and 992 samples from the independent KORA study. We report five loci with joint P values of association from 3.2 × 10(-19) to 2.1 × 10(-182). Variants at three of these loci have previously been linked with important clinical outcomes: SLC7A9 is a risk locus for chronic kidney disease, NAT2 for coronary artery disease and genotype-dependent response to drug toxicity, and SLC6A20 for iminoglycinuria. Moreover, we identify rs37369 in AGXT2 as the genetic basis of hyper-β-aminoisobutyric aciduria.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Associations between androgens and depressive symptoms were mostly reported from cross-sectional and patient-based studies.
Longitudinal data from 4,110 participants of the Study of Health in ...Pomerania were used to assess sex-specific associations of baseline total and free testosterone, androstenedione and sex hormone-binding globulin with incident depressive symptoms and cognitive status at 5- and 10-year follow-up.
Despite sex-specific differences in depressive symptoms prevalence at baseline (women: 17.4%, men: 8.1%), cross-sectional analyses showed no associations between sex hormones and depressive symptoms. In age-adjusted longitudinal analyses, total testosterone was associated with incident depressive symptoms (relative risk at 5-year follow-up: 0.73, 95% confidence interval: 0.58-0.92). Similarly, age-adjusted analyses showed a positive association between sex hormone-binding globulin and cognitive status in men (β-coefficient per standard deviation: 0.44, 95% confidence interval: 0.13-0.74). In women, age-adjusted associations of androstenedione with baseline depressive symptoms (relative risk: 0.88, 95% confidence interval: 0.77-0.99) were found. None of the observed associations remained after multivariable adjustment.
The present population-based, longitudinal study revealed inverse associations between sex hormones and depressive symptoms. However, the null finding after multivariable adjustment suggests, that the observed associations were not independent of relevant confounders including body mass index, smoking and physical inactivity. Furthermore, the low number of incident endpoints in our non-clinical population-based sample limited the statistical power and reduced the chance to detect a statistically significant effect.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Associations between thyroid function and hepatic steatosis defined by enzymatic and sonographic criteria are largely unknown in the general population. Thus, the aim of the present study was to ...investigate the association between thyroid function tests and sonographic as well as enzymatic criteria of liver status in a large population-based study, the Study of Health in Germany (SHIP).
Data from 3661 SHIP participants without a self-reported history of thyroid or liver disease were analyzed. Hepatic steatosis was defined as the presence of a hyperechogenic ultrasound pattern of the liver and increased serum alanine transferase concentrations. Serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) concentrations were associated with hepatic steatosis using multinomial regression models adjusted for sex, age, physical activity, alcohol consumption, waist circumference, and food intake pattern.
We detected no consistent association of serum TSH and FT3 concentrations with hepatic steatosis. In contrast, serum FT4 concentrations were inversely associated with hepatic steatosis in men (odds ratio (OR)=0.04 95% confidence interval (CI)=0.01; 0.17) and women (OR=0.06 95% CI=0.01; 0.42).
Results from the present cross-sectional study suggest that low FT4 concentrations are associated with hepatic steatosis. Longitudinal and intervention studies are warranted to investigate whether hypothyroidism increases the risk of hepatic steatosis or vice versa.
Background: Previous studies provided conflicting results regarding the association of serum IGF-I or IGF-binding protein-3 (IGFBP-3) and mortality. The aim of this study was to assess the relation ...of IGF-I and IGFBP-3 levels with mortality from all causes, cardiovascular disease (CVD), and cancer in a prospective population-based study.
Methods: From the Study of Health in Pomerania (SHIP) 1988 men and 2069 women aged 20–79 yr were followed up on average 8.5 yr. Causes of deaths were coded according to the International Classification of Diseases, 10th revision. Serum IGF-I and IGFBP-3 levels were determined by chemiluminescence immunoassays and categorized into three groups (low, normal, high) according to the sex- and age-specific 10th and 90th percentiles.
Results: Adjusted analyses revealed that men with low but not high IGF-I levels had an almost 2-fold higher risk of all-cause mortality hazard ratio (HR) 1.92 (95% confidence interval CI 1.35; 2.73), CVD mortality HR 1.92 (95% CI 1.00; 3.71), and cancer mortality HR 1.85 (95% CI 1.00; 3.45) compared with men with normal IGF-I levels. In women, no association between IGF-I and mortality was found. Moreover, low IGFBP-3 levels were associated with higher all-cause mortality in men HR 1.87 (95% CI 1.31; 2.64) and women HR 1.63 (95% CI 0.96; 2.76).
Conclusions: The present study found inverse associations between IGF-I or IGFBP-3 levels and mortality from all causes, CVD, or cancer in men and between IGFBP-3 and all-cause mortality in women.
Low insulin-like growth factor-I (IGF-1) or IGF-binding protein 3 levels were associated with increased mortality in men.
Abstract Background A dentition of at least 20 teeth is associated with sufficient masticatory efficiency and is a stated health goal of the World Health Organisation. We examined whether subjects ...with missing, unreplaced teeth had an increased mortality risk. Methods We used data prospectively collected from those participants in the population-based Study of Health in Pomerania who had fewer than 20 remaining teeth, resulting in a sample of 1803 participants with a median age of 64 years. Of those, 188 subjects had 9 or more unreplaced teeth. During a median follow-up period of 9.9 years, 362 subjects died, 128 of whom of cardiovascular causes. Results We found that having 9 or more unreplaced teeth was related to all-cause mortality (rate ratio 1.53, 95% CI: 1.11–2.10; adjusted for variables according to causal diagrams: remaining teeth, age, sex, education, income, marital status, partnership, and oral health behaviour) and cardiovascular mortality (rate ratio 1.94, 95% CI: 1.15–3.25). When adjusting not only for the variables according to causal diagrams but also for smoking, alcohol consumption, physical activity, obesity, hypertension, diabetes, and dyslipidemia, the rate ratio was 1.43 (95% CI: 1.05–1.96) for all-cause mortality and 1.88 (95% CI: 1.10–3.21) for cardiovascular mortality. Conclusions A reduced, unrestored dentition is associated with increased mortality risk. Thus, clinicians and dietitians have a responsibility to consider individual chewing ability in nutritional recommendations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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