Endocrine Abstracts

Introduction: The androgen receptor (AR) mediates the peripheral effects of testosterone. The main mechanism of action for the AR is direct regulation of gene transcription. Available evidence suggests that the number of CAG repeats in exon-1 of the AR gene is negatively correlated with transcriptional activity of the AR and that CAG repeat number links to mortality rate in T2DM men. The aim of this analysis was to determine the association between CAG repeat number and all cause mortality in a non-T2DM cohort.

Methods: Men aged between 40 and 79 years were recruited from primary care registers for participation in the UK arm of the European Male Aging Study. Baseline assessment included sex hormone levels and also CAG repeat determination. They were followed prospectively for up to 18 years. Cox proportional hazards model was used to determine the association between CAG repeat number/mortality with the results expressed as hazard ratios (HR) and 95% confidence interval (CI).

Results: 312 men contributed data to the analysis. The mean age at baseline was 59.5 years. At follow up 85 of the 312 (27%) men had died. The range of CAG repeat length varied between 14 and 39, with the highest proportion of CAG repeat number at 19 repeats (14.1%). Using men with CAG repeat numbers of 22-23 as a reference group, and after adjustment for age at recruitment, total testosterone level and also index of multiple deprivation, men with a lower number of CAG repeats (< 22) had a higher likelihood of dying in the follow-up period (HR 1.50; 95% CI 0.78, 2.89) as did men with higher number of repeats (>23) (HR = 1.31; 95% CI 0.62, 2.76).

Conclusions: Our data suggest that CAG repeat number may influence the risk of mortality in men. Further larger studies are required to confirm these findings.