Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Dec;99(6):559-565.
doi: 10.1111/cen.14962. Epub 2023 Sep 18.

Number of CAG repeats and mortality in middle aged and older men

Adrian Heald  1   2 , Michael J Cook  3   4 , Leen Antonio  5   6 , Jos Tournoy  7   8 , Parisa Ghaffari  1 , Fahmida Mannan  2 , Helene Fachim  1   2 , Dirk Vanderschueren  5   6 , Ian Laing  9 , Geoff Hackett  10 , Felipe F Casanueva  11 , Ilpo T Huhtaniemi  12 , Mario Maggi  13 , Giulia Rastrelli  13 , Jolanta Slowikowska-Hilczer  14 , Fred Wu  2   15 , Terence W O'Neill  16   17
Affiliations

Number of CAG repeats and mortality in middle aged and older men

Adrian Heald et al. Clin Endocrinol (Oxf). 2023 Dec.

Abstract

Design: The androgen receptor (AR) mediates peripheral effects of testosterone. Previous data suggests an association between the number of CAG repeats in exon-1 of the AR gene and AR transcriptional activity. The aim of this analysis was to determine the association between the number of AR CAG repeats and all-cause mortality in men and the influence of testosterone level on the association.

Patients and measurements: Follow-up data to 27 January 2018 were available for men aged 40-79 years recruited across six countries of the European Male Aging Study between 2003 and 2005. Cox proportional hazards modelling was used to determine the association between CAG repeat number/mortality. Results were expressed as hazard ratios (HR)/95% confidence intervals (CI).

Results: One thousand nine hundred and seventy-seven men were followed up. Mean baseline age was 60 ± 11.1 years. Mean duration of follow-up was 12.2 years. At follow up 25.1% of men had died. CAG repeat length ranged from 6 to 39, with the highest proportion of CAG repeat number at 21 repeats (16.4%). In a multivariable model, compared to men with 22-23 AR CAG repeats: for men with <22 and >23 AR CAG HR, 95% CI for mortality were, <22 CAG repeats 1.17 (0.93-1.49) and >23 CAG repeats 1.14 (0.88-1.47). In a post-hoc analysis, the association was significant for men in the lowest tertile of baseline testosterone (<14.2 nmol/L) with >23 CAG repeats: in the adjusted model for <22 and >23 CAG repeats, respectively, 1.49 (0.97-2.27) and 1.68 (1.06-2.67) versus 22-23 repeats.

Conclusions: Our European-wide cohort data overall found no association of androgen receptor CAG repeat number and mortality in men. However, post hoc analysis suggested that an association might be present in men with lower baseline testosterone concentrations, which merits further investigation.

Keywords: CAG; EMAS; male; mortality; testosterone.

PubMed Disclaimer

References

REFERENCES

    1. Heald A, Cook M, Antonio L, et al. The number of androgen receptor CAG repeats and mortality in men. Aging Male. 2022;25:167-172.
    1. Heald AH, Yadegar Far G, Livingston M, et al. Androgen receptor-reduced sensitivity is associated with increased mortality and poorer glycaemia in men with type 2 diabetes mellitus: a prospective cohort study. Cardiovasc Endocrinol Metab. 2020;10:37-44.
    1. Pye SR, Huhtaniemi IT, Finn JD, et al. EMAS Study Group. Late-onset hypogonadism and mortality in aging men. J Clin Endocrinol Metab. 2014;99:1357-1366.
    1. Lee DM, O'Neill TW, Pye SR, et al. EMAS study group. The European Male Ageing Study (EMAS): design, methods and recruitment. Int J Androl. 2009;32:11-24.
    1. Ketha H, Kaur S, Grebe SK, Singh RJ. Clinical applications of LC-MS sex steroid assays: evolution of methodologies in the 21st century. Curr Opin Endocrinol Diab Obes. 2014;21:217-226.

LinkOut - more resources