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A validated age-related normative model for male total testosterone shows increasing variance but no decline after age 40 years.

ABSTRACT: The diagnosis of hypogonadism in human males includes identification of low serum testosterone levels, and hence there is an underlying assumption that normal ranges of testosterone for the healthy population are known for all ages. However, to our knowledge, no such reference model exists in the literature, and hence the availability of an applicable biochemical reference range would be helpful for the clinical assessment of hypogonadal men. In this study, using model selection and validation analysis of data identified and extracted from thirteen studies, we derive and validate a normative model of total testosterone across the lifespan in healthy men. We show that total testosterone peaks [mean (2.5-97.5 percentile)] at 15.4 (7.2-31.1) nmol/L at an average age of 19 years, and falls in the average case [mean (2.5-97.5 percentile)] to 13.0 (6.6-25.3) nmol/L by age 40 years, but we find no evidence for a further fall in mean total testosterone with increasing age through to old age. However we do show that there is an increased variation in total testosterone levels with advancing age after age 40 years. This model provides the age related reference ranges needed to support research and clinical decision making in males who have symptoms that may be due to hypogonadism.

SUBMITTER: Kelsey TW

PROVIDER: S-EPMC4190174 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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A validated age-related normative model for male total testosterone shows increasing variance but no decline after age 40 years.

Kelsey Thomas W TW Li Lucy Q LQ Mitchell Rod T RT Whelan Ashley A Anderson Richard A RA Wallace W Hamish B WH

PloS one 20141008 10

The diagnosis of hypogonadism in human males includes identification of low serum testosterone levels, and hence there is an underlying assumption that normal ranges of testosterone for the healthy population are known for all ages. However, to our knowledge, no such reference model exists in the literature, and hence the availability of an applicable biochemical reference range would be helpful for the clinical assessment of hypogonadal men. In this study, using model selection and validation a ...[more]

PMID: 25295520

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Project description:IntroductionAge-related decline in testosterone is associated with Leydig cell aging with impaired testosterone synthesis in aging. Obesity accelerates the age-related decline in testosterone. However, the mechanisms underlying the Leydig cell aging and the effects of obesity on Leydig cell aging remain unclear.MethodNatural aging mice and diet-induced obese mice were used to assess the process of testicular Leydig cell senescence with age or obesity. Bioinformatic analysis of the young and aged human testes was used to explore key genes related Leydig cell aging. Leydig cell-specific p38 MAPK knockout (p38LCKO) mice were used to further analyze the roles of p38 MAPK in Leydig cell aging. The levels of testosterone and steroidogenic enzymes, activity of p38 MAPK, aging status of Leydig cells, and oxidative stress and inflammation of testes or Leydig cells were detected by ELISA, immunoblotting, immunofluorescence, and senescence-associated β-galactosidase (SA-β-Gal) staining analysis, respectively.ResultThe serum testosterone level was significantly reduced in aged mice compared with young mice. In the testis of aged mice, the reduced mRNA and protein levels of LHCGR, SRB1, StAR, CYP11A1, and CYP17A1 and the elevated oxidative stress and inflammation were observed. KEGG analysis showed that MAPK pathway was changed in aged Leydig cells, and immunoblotting displayed that p38 MAPK was activated in aged Leydig cells. The intensity of SA-β-Gal staining on Leydig cells and the number of p21-postive Leydig cells in aged mice were more than those of young mice. Similar to aged mice, the testosterone-related indexes decreased, and the age-related indexes increased in the testicular Leydig cells of high fat diet (HFD) mice. Aged p38LCKO mice had higher levels of testosterone and steroidogenic enzymes than those of age-matched wild-type (WT) littermates, with reduced the intensity of SA-β-Gal staining and the expression of p21 protein.ConclusionOur study suggested that obesity was an important risk factor for Leydig cell aging. p38 MAPK was involved in Leydig cell aging induced by age and obesity. The inhibition of p38 MAPK could delay Leydig cell aging and alleviate decline in testosterone.

Project description:BackgroundFunctional neuroimaging has great potential to inform clinical decisions, whether by identifying neural biomarkers of illness progression and severity, predicting therapeutic response, or selecting suitable patients for surgical interventions. Yet a persisting barrier to functional neuroimaging's clinical translation is our incomplete understanding of how normative variance in cognition, personality, and behavior shape the brain's structural and functional organization. We propose that modeling individual differences in these brain-behavior relationships is crucial for improving the accuracy of neuroimaging biomarkers for neurologic and psychiatric disorders.MethodsWe addressed this goal by initiating the Cognitive Connectome Project, which bridges neuropsychology and neuroimaging by pairing nine cognitive domains typically assessed by clinically validated neuropsychological measures with those tapped by canonical neuroimaging tasks (motor, visuospatial perception, attention, language, memory, affective processing, decision making, working memory, and executive function). To date, we have recruited a diverse sample of 53 participants (mean [SD], age = 32 [9.7] years, 31 females).ResultsAs a proof of concept, we first demonstrate that our neuroimaging task battery can replicate previous findings that task performance recruits intrinsic brain networks identified during wakeful rest. We then expand upon these previous findings by showing that the extent to which these networks are recruited by task reflects individual differences in cognitive ability. Specifically, performance on the Judgment of Line Orientation task (a clinically validated measure of visuospatial perception) administered outside of the MRI scanner predicts the magnitude of task-induced activity of the dorsal visual network when performing a direct replication of this task within the MRI scanner. Other networks (such as default mode and right frontoparietal) showed task-induced changes in activity that were unrelated to task performance, suggesting these networks to not be involved in visuospatial perception.ConclusionThese findings establish a methodological framework by which clinical neuropsychology and functional neuroimaging may mutually inform one another, thus enhancing the translation of functional neuroimaging into clinical decision making.

Project description:OBJECTIVES:Two processes generate total variance in age at death: heterogeneity (between-group variance) and individual stochasticity (within-group variance). Limited research has evaluated how these two components have changed over time. We quantify the degree to which area-level deprivation contributed to total variance in age at death in Scotland between 1981 and 2011. DESIGN:Full population and mortality data for Scotland were obtained and matched with the Carstairs score, a standardised z-score calculated for each part-postcode sector that measures relative area-level deprivation. A z-score above zero indicates that the part-postcode sector experienced higher deprivation than the national average. A z-score below zero indicates lower deprivation. From the aggregated data we constructed 40 lifetables, one for each deprivation quintile in 1981, 1991, 2001 and 2011 stratified by sex. PRIMARY OUTCOME MEASURES:Total variance in age at death and the proportion explained by area-level deprivation heterogeneity (between-group variance). RESULTS:The most deprived areas experienced stagnating or slightly increasing variance in age at death. The least deprived areas experienced decreasing variance. For males, the most deprived quintile life expectancy was between 7% and 11% lower and the SD is between 6% and 25% higher than the least deprived. This suggests that the effect of deprivation on the SD of longevity is comparable to its effect on life expectancy. Decomposition analysis revealed that contributions from between-group variance doubled between 1981 and 2011 but at most only explained 4% of total variance. CONCLUSIONS:This study adds to the emerging body of literature demonstrating that socio-economic groups have experienced diverging trends in variance in age at death. The contribution from area-level deprivation to total variance in age at death, which we were able to capture, has doubled since 1981. Area-level deprivation may play an increasingly important role in mortality inequalities.

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A validated age-related normative model for male total testosterone shows increasing variance but no decline after age 40 years.

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A validated age-related normative model for male total testosterone shows increasing variance but no decline after age 40 years.

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