Association Between Serum Testosterone and Related Hormones and Risk of Symptomatic Abdominal Aortic Aneurysm in Male Participants from UK Biobank.

Background: Ruptured abdominal aortic aneurysm (AAA) is associated with high mortality risk. Few studies found a relationship between testosterone levels and AAA development but were limited by small event numbers and single-center design.

Objective: To assess the associations of serum testosterone and sex hormone-binding globulin (SHBG) levels with symptomatic AAA risk in male participants from the UK biobank.

Methods: Study exposures included baseline serum total testosterone (TT), free testosterone (cFT and FTZ), bioavailable testosterone (BioT), and SHBG. Multivariable Cox proportional-hazards regression models were employed for outcome analyses. The joint association of male hormones and AAA polygenetic risk score (PRS) was further investigated with AAA risk.

Results: This study followed 190,627 males over 15 years, with 1,903 symptomatic AAA cases identified. Compared to those in higher quartiles, individuals in the lowest quartile of TT, FTZ, cFT and BioT had a 19% (95%CI, 1.07-1.33), 16% (1.05-1.28), 8% (0.98-1.19), and 13% (1.03-1.25) higher risk of AAA, respectively. For SHBG, individuals in the highest quartile had a 20% (1.07-1.34) greater risk of AAA compared to those in lower quartiles. Stratified analysis by AAA PRS found that individuals with higher PRS and either lower testosterone levels or higher SHBG levels, had a greater risk of developing AAA.

Conclusion: This large population-based cohort study found that higher PRS and either lower testosterone or highest SHBG were associated with a greater risk of symptomatic AAA among male individuals. Due to the observational nature of this study, further research is warranted to establish whether or not a causal relationship exists between lower testosterone and development or growth of AAA, and whether testosterone treatment might reduce the risk of AAA.