title: The androgen receptor gene CAG repeat  in relation to 4-year changes in  androgen-sensitive endpoints in  community-dwelling older European men.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Multinational European observational prospective cohort study.
  
  
  METHODS
  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.
  
  
  METHODS
  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 E2levels.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Faculty of Medical and Human SciencesInstitute of Human Development, Centre for Endocrinology and Diabetes, Andrology Research Unit, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK roberteendebak@gmail.com.
authors.forename: Robert J A H
authors.initials: RJ
authors.lastname: Eendebak
authors.affiliation: Department of Surgery and CancerInstitute of Reproductive and Developmental Biology, Imperial College London, London, UK.
authors.forename: Ilpo T
authors.initials: IT
authors.lastname: Huhtaniemi
authors.affiliation: Arthritis Research UK Centre for EpidemiologyCentre for Musculoskeletal Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Pye
authors.affiliation: Faculty of Medical and Human SciencesInstitute of Human Development, Centre for Endocrinology and Diabetes, Andrology Research Unit, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.
authors.forename: Tomas
authors.initials: T
authors.lastname: Ahern
authors.affiliation: Arthritis Research UK Centre for EpidemiologyCentre for Musculoskeletal Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.
authors.forename: Terence W
authors.initials: TW
authors.lastname: O'Neill
authors.affiliation: Department of Obstetrics and Gynaecology and AndrologyAlbert Svent Gyorgy Medical University, Szeged, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Bartfai
authors.affiliation: Department of MedicineUniversity Santiago de Compostela, Santiago de Compostela, UK.
authors.forename: Felipe F
authors.initials: FF
authors.lastname: Casanueva
authors.affiliation: Department of Clinical PhysiopathologyAndrology Unit, University of Florence, Florence, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Maggi
authors.affiliation: Department of Clinical PhysiopathologyAndrology Unit, University of Florence, Florence, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Forti
authors.affiliation: Faculty of Medical and Human SciencesInstitute of Human Development, Centre for Endocrinology and Diabetes, Andrology Research Unit, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Alston
authors.affiliation: Department of UrologyScanian Andrology Centre, Malmo University Hospital, Lund University, Malmo, Sweden.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Giwercman
authors.affiliation: Department of EndocrinologyUniversity College London, London, UK.
authors.forename: Thang S
authors.initials: TS
authors.lastname: Han
authors.affiliation: Department of Andrology and Reproductive EndocrinologyMedical University Lodz, Lodz, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kula
authors.affiliation: Department of Human NutritionUniversity of Glasgow, Glasgow, UK.
authors.forename: Michael E J
authors.initials: ME
authors.lastname: Lean
authors.affiliation: United LabsAndrology Unit, Tartu University Clinic, Tartu, Estonia.
authors.forename: Margus
authors.initials: M
authors.lastname: Punab
authors.affiliation: Salford Royal NHS TrustSchool of Community Based Medicine, University of Manchester, Manchester, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Pendleton
authors.affiliation: Department of Clinical BiochemistryUniversity South Manchester Hospital, Manchester, UK.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Keevil
authors.affiliation: Department of Andrology and EndocrinologyCatholic University Leuven, Leuven, Belgium.
authors.forename: Dirk
authors.initials: D
authors.lastname: Vanderschueren
authors.affiliation: Manchester Diabetes CentreCentral Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre.|Faculty of Medical and Human SciencesInstitute of Human Development, Endocrinology and Diabetes Research Group.
authors.forename: Martin K
authors.initials: MK
authors.lastname: Rutter
authors.affiliation: Faculty of HumanitiesCathie Marsh Institute for Social Research.
authors.forename: Gindo
authors.initials: G
authors.lastname: Tampubolon
authors.affiliation: School of ChemistryManchester Institute for Biotechnology, University of Manchester, Manchester, UK.
authors.forename: Royston
authors.initials: R
authors.lastname: Goodacre
authors.affiliation: Faculty of Medical and Human SciencesInstitute of Human Development, Centre for Endocrinology and Diabetes, Andrology Research Unit, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.
authors.forename: Frederick C W
authors.initials: FC
authors.lastname: Wu
mesh_terms: D000368:Aged; D000728:Androgens / Q000097:blood* / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005060:Europe / Q000453:epidemiology; D005500:Follow-Up Studies; D006801:Humans; D057187:Independent Living / Q000639:trends*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011944:Receptors, Androgen / Q000097:blood* / Q000235:genetics*; D013997:Time Factors; D018911:Trinucleotide Repeats / Q000235:genetics*
chemical_list: D000728:Androgens; D015415:Biomarkers; D011944:Receptors, Androgen