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

Research output: Research - peer-reviewArticle

  • External authors:
  • Robert J.A.H. Eendebak
  • Ilpo Huhtaniemi
  • Tomas Ahern
  • Georgy Bartfai
  • Felipe Casanueva
  • Mario Maggi
  • Gianni Forti
  • Aleksander Giwercman
  • Thang S Han
  • Krzysztof Kula
  • Michael E J Lean
  • Margus Punab
  • Brian Keevil
  • Dirk Vanderschueren
  • Royston Goodacre
  • Frederick Wu


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 which are influenced by testosterone (T) levels in middle-aged and elderly European men.

Design: Multinational European observational prospective cohort study

Participants: 1887 men (mean±sd age: 63±11 years; median follow-up: 4.3 years) from centres of 8 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 both as a continuous and 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 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 timeframe, variations in the AR CAG repeat do not contribute to the rate of phenotypic ageing, over and above, that, which might be associated with the age-related decline in T levels.

Bibliographical metadata

Original languageEnglish
Pages (from-to) 583-593
JournalEuropean Journal of Endocrinology
Early online date15 Sep 2016
StatePublished - 1 Dec 2016

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