scholarly journals Endogenous hormones, androgen receptor CAG repeat length and fluid cognition in middle-aged and older men: results from the European Male Ageing Study

2010 ◽  
Vol 162 (6) ◽  
pp. 1155-1164 ◽  
Author(s):  
David M Lee ◽  
Aslan Ulubaev ◽  
Abdelouahid Tajar ◽  
Stephen R Pye ◽  
Neil Pendleton ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Free Testosterone ◽  
Community Dwelling ◽  
Repeat Length ◽  
Cag Repeat ◽  
Sex Hormone Binding Globulin ◽  
Gas Chromatography Mass Spectrometry ◽  
Total Testosterone ◽  
Endogenous Hormones ◽  
Health Lifestyle

ObjectiveData remain divergent regarding the activational effects of endogenous hormones on adult cognitive function. We examined the association between cognition, hormones and androgen receptor (AR) CAG repeat length in a large cohort of men.DesignCommunity-based, cross-sectional study of 3369 men aged 40–79 years.MethodsCognition tests were the Rey-Osterrieth Complex Figure, Camden Topographical Recognition Memory and Digit-Symbol Substitution. A fluid cognition (FC) z-score was computed from the individual tests. Testosterone, oestradiol (OE2) and 5α-dihydrotestosterone were measured by gas chromatography–mass spectrometry; DHEAS, LH, FSH and sex hormone-binding globulin (SHBG) by electrochemiluminescence. Free testosterone and OE2 were calculated from total hormone, SHBG and albumin. CAG repeat lengths were assayed by PCR genotyping.ResultsTotal testosterone and free testosterone were associated with higher FC z-scores, LH and FSH with lower FC z-scores in age-adjusted linear regressions. After adjusting for health, lifestyle and centre, a modest association was only observed between DHEAS and a lower FC z-score (β=−0.011, P=0.02), although this was driven by subjects with DHEAS levels >10 μmol/l. Locally weighted plots revealed no threshold effects between hormones and FC. There was no association between CAG repeat length and FC z-score after adjustment for age and centre (β=−0.007, P=0.06), nor any interaction effect between CAG repeat length and hormones.ConclusionOur results suggest that endogenous hormones are not associated with a vision-based measure of FC among healthy, community-dwelling men. Further studies are warranted to determine whether ‘high’ DHEAS levels are associated with poorer performance on a broader range of neuropsychological tests.

scholarly journals Is the effect of testosterone on body composition modulated by the androgen receptor gene CAG repeat polymorphism in elderly men?

2007 ◽  
Vol 156 (3) ◽  
pp. 395-401 ◽  
Author(s):  
B Lapauw ◽  
S Goemaere ◽  
P Crabbe ◽  
J M Kaufman ◽  
J B Ruige
Keyword(s):  
Body Composition ◽  
Androgen Receptor ◽  
Effect Modification ◽  
Community Dwelling ◽  
Repeat Length ◽  
Fat Free Mass ◽  
Cag Repeat ◽  
Repeat Polymorphism ◽  
Elderly Men ◽  
Body Composition Assessment

Objective: The androgen receptor (AR) gene contains a CAG repeat polymorphism coding for a polyglutamine chain, the length of which is inversely correlated with AR transcriptional activity. We explored whether this polymorphism modulates the activities of testosterone (T) related to body composition in elderly men. Design: We performed cross-sectional analyses using data from a 4-year follow-up study in community-dwelling men aged 75–89 years (n=159). Methods: Body composition was assessed by dual-energy X-ray absorptiometry and its relation with T and the AR gene CAG repeat length was assessed by multiple linear regression analyses, adjusting for confounding and exploring effect modification. Results: AR gene CAG repeat length was not directly related to body composition, either with or without adjustment for confounding variables like age, weight, total T or sex hormone binding globulin (SHBG) levels. However, exploration of effect modification showed that CAG repeat length modulated the relation between T and body composition (standardized regression coefficients of interaction term: β=0.12, P<0.01 and β=−0.09, P<0.05 for fat-free mass and fat mass respectively). These results were confirmed using similar models and data of mean T, SHBG and weight of the 2 years’ preceding body composition assessment instead of data of the same year (β=0.09, P<0.05 and β=−0.09, P<0.05 respectively). Conclusion: These findings suggest that the AR gene CAG polymorphism contributes, albeit modestly, to the between-subject variation of T action on body composition in community-dwelling elderly men.

scholarly journals Testosterone, androgen receptor gene CAG repeat length, mood and behaviour in adolescent males

2010 ◽  
Vol 163 (2) ◽  
pp. 319-328 ◽  
Author(s):  
Hans Vermeersch ◽  
Guy T'Sjoen ◽  
Jean Marc Kaufman ◽  
John Vincke ◽  
Mieke Van Houtte
Keyword(s):  
Depressive Symptoms ◽  
Androgen Receptor ◽  
Receptor Gene ◽  
Positive Association ◽  
Free Testosterone ◽  
Self Esteem ◽  
Androgen Receptor Gene ◽  
Repeat Length ◽  
Cag Repeat ◽  
Inverse Association

ObjectivesAndrogen activity has been implicated in a range of traits and behaviours that have well-documented sex differences. However, the results of the studies on the relationship between testosterone and these traits and behaviours are inconsistent. This study has analyzed i) whether CAG repeat length, a presumed modulator of androgen receptor sensitivity, is associated with sex-dimorphic traits and behaviours (aggressive and non-aggressive risk-taking (ART and NART), dominance, depressive symptoms and self-esteem), and ii) whether CAG repeat length interacts with free testosterone (FT) with respect to these traits and behaviours.Design and methodsData obtained from a group of adolescent boys (n=301; mean age: 14.4 years) were analyzed using multivariate general linear modelling (SPSS, Chicago, IL, USA 15.0).ResultsWe found no direct correlation between CAG repeat length and dependent variables. We found significant interactions between CAG repeat length and testosterone, indicating that FT was more positively related to ART and NART with a shorter repeat length, and that an inverse association of FT with depressive symptoms and a positive association with self-esteem were stronger in boys with a longer CAG repeat length.ConclusionOur findings indicate the importance of studying FT and CAG repeat length simultaneously with respect to sex-dimorphic traits, taking into account the possible interactions between the two.

scholarly journals Lower sex hormone-binding globulin is more strongly associated with metabolic syndrome than lower total testosterone in older men: the Health in Men Study

2008 ◽  
Vol 158 (6) ◽  
pp. 785-792 ◽  
Author(s):  
S A Paul Chubb ◽  
Zoë Hyde ◽  
Osvaldo P Almeida ◽  
Leon Flicker ◽  
Paul E Norman ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Free Testosterone ◽  
Older Men ◽  
Community Dwelling ◽  
Sex Hormone ◽  
Mass Action ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Hormone Binding ◽  
Cross Sectional

BackgroundReduced circulating testosterone and sex hormone-binding globulin (SHBG) are implicated as risk factors for metabolic syndrome. As SHBG increases with age while testosterone declines, we examined the relative contributions of SHBG and testosterone to the risk of metabolic syndrome in older men.MethodsWe conducted a cross-sectional study of 2502 community-dwelling men aged ≥70 years without known diabetes. Metabolic syndrome was defined using the National Cholesterol Education Program-Third Adult Treatment Panel (NCEP-ATPIII) criteria. Early morning fasting sera were assayed for total testosterone, SHBG and LH. Free testosterone was calculated using mass action equations.ResultsThere were 602 men with metabolic syndrome (24.1%). The risk of metabolic syndrome increased for total testosterone <20 nmol/l, SHBG <50 nmol/l and free testosterone <300 pmol/l. In univariate analyses SHBG was associated with all five components of metabolic syndrome, total testosterone was associated with all except hypertension, and free testosterone was associated only with waist circumference and triglycerides. In multivariate analysis, both total testosterone and especially SHBG remained associated with metabolic syndrome, with odds ratios of 1.34 (95% confidence interval (CI): 1.18–1.52) and 1.77 (95% CI: 1.53–2.06) respectively. Men with hypogonadotrophic hypogonadism (total testosterone <8 nmol/l, LH ≤12 IU/l) had the highest prevalence of metabolic syndrome (53%,P<0.001).ConclusionsLower SHBG is more strongly associated with metabolic syndrome than lower total testosterone in community-dwelling older men. SHBG may be the primary driver of these relationships, possibly reflecting its relationship with insulin sensitivity. Further studies should examine whether measures that raise SHBG protect against the development of metabolic syndrome in older men.

scholarly journals The androgen receptor gene CAG repeat 
in relation to 4-year changes in 
androgen-sensitive endpoints in 
community-dwelling older European men

2016 ◽  
Vol 175 (6) ◽  
pp. 583-593 ◽  
Author(s):  
Robert J A H Eendebak ◽  
Ilpo T Huhtaniemi ◽  
Stephen R Pye ◽  
Tomas Ahern ◽  
Terence W O’Neill ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Receptor Gene ◽  
Time Frame ◽  
Androgen Receptor Gene ◽  
Community Dwelling ◽  
Repeat Length ◽  
Cag Repeat ◽  
Medical Conditions ◽  
Longitudinal Changes ◽  
Age Related

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. Conclusion Within a 4-year time frame, variations in the AR CAG repeat do not contribute to the rate of phenotypic ageing, over and above, which might be associated with the age-related decline in T levels.

Interactions among impulsiveness, testosterone, sex hormone binding globulin and androgen receptor gene CAG repeat length

2015 ◽  
Vol 147 ◽  
pp. 91-96 ◽  
Author(s):  
Anton Aluja ◽  
Luís F. García ◽  
Maite Martí-Guiu ◽  
Eduardo Blanco ◽  
Oscar García ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Receptor Gene ◽  
Androgen Receptor Gene ◽  
Sex Hormone ◽  
Repeat Length ◽  
Cag Repeat ◽  
Sex Hormone Binding Globulin ◽  
Hormone Binding

scholarly journals Evidence that the CAG repeat in the androgen receptor gene is associated with the age-related decline in serum androgen levels in men

1999 ◽  
Vol 162 (1) ◽  
pp. 137-142 ◽  
Author(s):  
K Krithivas ◽  
SM Yurgalevitch ◽  
BA Mohr ◽  
CJ Wilcox ◽  
SJ Batter ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Repeat Length ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Sex Hormone Binding Globulin ◽  
Sample Survey ◽  
Hormone Levels ◽  
Age Related ◽  
Androgen Levels

In men over 30 years old, serum levels of testosterone (T) decrease with age. A shorter polymorphic CAG repeat length in exon 1 of the androgen receptor (AR) gene is associated with higher transcription activation by the AR. We determined the number of CAG repeats for 882 men aged between 40 and 70 years from the Massachusetts Male Aging Study (MMAS). MMAS is a population-based random sample survey of men for whom baseline (1987-1989, mean age 53+/-8 years) and follow-up (1995-1997, mean age 61+/-8 years) serum hormone levels were available. Multiple linear regression was used to determine if CAG repeat length would be predictive of hormone levels at follow-up. Hormone levels measured included T, free T, albumin-bound T, dihydrotestosterone (DHT), sex hormone-binding globulin (SHBG) and luteinizing hormone (LH). The CAG repeat length was significantly associated with T (P=0.041), albumin-bound T (P=0.025) and free T (P=0.003) when controlled for age, baseline hormone levels and anthropometrics. Follow-up levels of T decreased by 0.74%+/-0.36 per CAG repeat decrement. Likewise, the percentages of free and albumin-bound T decreased by 0.93%+/-0.31 and 0.71%+/-0.32 per CAG repeat decrement respectively. These results suggest that androgen levels may be modulated by AR genotype.

scholarly journals Androgen receptor CAG repeat length polymorphism modifies the impact of testosterone on insulin sensitivity in men

2011 ◽  
Vol 164 (6) ◽  
pp. 1013-1018 ◽  
Author(s):  
Matthias Möhlig ◽  
Ayman M Arafat ◽  
Martin A Osterhoff ◽  
Frank Isken ◽  
Martin O Weickert ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Androgen Receptor ◽  
Length Polymorphism ◽  
Free Testosterone ◽  
Repeat Length ◽  
Cag Repeat ◽  
Model Assessment ◽  
Multiplicative Interaction ◽  
Interaction Term ◽  
The Impact

ObjectiveLow circulating testosterone concentrations have been associated with insulin resistance (IR). Androgen action is mediated by the androgen receptor (AR) whose activity is modulated by a polymorphic CAG repeat sequence within exon 1. An interaction between testosterone and CAG repeat length (CAG length) with respect to IR has been described in women.ObjectiveWe investigated such a putative interaction between testosterone and the CAG length with respect to IR in men with normal glucose tolerance.DesignCross-sectional study.MethodsIn 113 non-diabetic men calculated free testosterone, the CAG length, and a multiplicative interaction term were investigated by multiple linear regression analysis for an association with IR, as indicated by homeostasis model assessment (HOMA %S).ResultsIn a multivariate regression analysis adjusted for age and body mass index, free testosterone, CAG length, and a multiplicative interaction term were significantly associated with IR (P=0.001, P=0.001, P=0.01 respectively). The model explained 36.6% of the variation of IR and predicted that in carriers with a CAG length of 23, changes in testosterone would only minimally affect IR. For CAG lengths longer than 23, however, an increase in testosterone would improve IR, namely the longer the CAG length, the greater the effect. In contrast, in the case of CAG lengths shorter than 23, the effect of increasing testosterone would be the opposite.ConclusionsIn men, testosterone and the AR CAG repeat length polymorphism interacted with respect to IR. The interpretation of the association between testosterone and IR seems to require consideration of the AR CAG repeat polymorphism.

Androgen receptor CAG repeat length as a moderator of the relationship between free testosterone levels and cognition

2021 ◽  
Vol 131 ◽  
pp. 104966
Author(s):  
Sherilyn Tan ◽  
Tenielle Porter ◽  
Romola S. Bucks ◽  
Michael Weinborn ◽  
Lidija Milicic ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Free Testosterone ◽  
Repeat Length ◽  
Cag Repeat ◽  
Testosterone Levels ◽  
The Relationship

scholarly journals Hypogonadism and liver fibrosis in HIV-infected patients

2021 ◽  
Author(s):  
E. Quiros-Roldan ◽  
T. Porcelli ◽  
L. C. Pezzaioli ◽  
M. Degli Antoni ◽  
S. Paghera ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Univariate Analysis ◽  
Free Testosterone ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Cross Sectional ◽  
Pituitary Dysfunction ◽  
Consequent Reduction ◽  
Secondary Hypogonadism ◽  
The Relationship

Abstract Purpose Hypogonadism is frequent in HIV-infected men and might impact on metabolic and sexual health. Low testosterone results from either primary testicular damage, secondary hypothalamic-pituitary dysfunction, or from liver-derived sex-hormone-binding-globulin (SHBG) elevation, with consequent reduction of free testosterone. The relationship between liver fibrosis and hypogonadism in HIV-infected men is unknown. Aim of our study was to determine the prevalence and type of hypogonadism in a cohort of HIV-infected men and its relationship with liver fibrosis. Methods We performed a cross-sectional retrospective study including 107 HIV-infected men (median age 54 years) with hypogonadal symptoms. Based on total testosterone (TT), calculated free testosterone, and luteinizing hormone, five categories were identified: eugonadism, primary, secondary, normogonadotropic and compensated hypogonadism. Estimates of liver fibrosis were performed by aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) scores. Results Hypogonadism was found in 32/107 patients (30.8%), with normogonadotropic (10/107, 9.3%) and compensated (17/107, 15.8%) being the most frequent forms. Patients with secondary/normogonadotropic hypogonadism had higher body mass index (BMI) (p < 0001). Patients with compensated hypogonadism had longer HIV infection duration (p = 0.031), higher APRI (p = 0.035) and FIB-4 scores (p = 0.008), and higher HCV co-infection. Univariate analysis showed a direct significant correlation between APRI and TT (p = 0.006) and SHBG (p = 0.002), and between FIB-4 and SHBG (p = 0.045). Multivariate analysis showed that SHBG was independently associated with both liver fibrosis scores. Conclusion Overt and compensated hypogonadism are frequently observed among HIV-infected men. Whereas obesity is related to secondary hypogonadism, high SHBG levels, related to liver fibrosis degree and HCV co-infection, are responsible for compensated forms.

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