Associations between testosterone and future PTSD symptoms among middle age and older UK residents

Testosterone has been theorized to influence the development of post-traumatic stress disorder (PTSD). However, the relationship between testosterone level and PTSD is still not well understood. We evaluated the potential association between testosterone and subsequent development of PTSD symptoms using a large sample size, in a civilian context, inclusive of both males and females. Out of around 500,000 total UK Biobank participants, our sample had 130,471 participants who: had testosterone measures, completed the mental health questionnaire, and passed outlier exclusion. After adjusting for relevant covariates, we used linear regression to assess the relationship between testosterone level and future development of symptoms, in males and females separately (N_males = 61,758, N_females = 67,053). In both males and females, small but significant nonlinear (and oftentimes U-shaped) relationships were observed between testosterone levels and PTSD symptoms. When grouping participants into deciles of testosterone for both sexes, the strongest associations between testosterone levels and PTSD symptoms were observed in the central deciles. For example, for total testosterone, compared to decile 1: individuals in decile 7 had the lowest PTSD symptom scores in both males (beta = -0.16, p = 1.58 × 10^-3) and females (beta = -0.23, p = 3.04 × 10^-5). We also found that body mass index (BMI) moderated the relationship between testosterone and PTSD symptoms, such that the relationship was considerably stronger among individuals with higher BMI. Results were similar for depression and anxiety measures. Analyses using calculated free testosterone (cFT) and the free androgen index (FAI) were generally consistent with total testosterone (TT) results. These findings suggest that mid-range testosterone levels are associated with the lowest risk of PTSD symptoms in both sexes, and future work should seek to examine if this relationship is causal.