Hanyang Shen, Ciera Stafford, Joeri Meijsen, Lijin Zhang, Jacob Reiter, Rebecca B Lawn, Alicia K Smith, Mytilee Vermuri, Laramie E Duncan
{"title":"Associations between testosterone and future PTSD symptoms among middle age and older UK residents.","authors":"Hanyang Shen, Ciera Stafford, Joeri Meijsen, Lijin Zhang, Jacob Reiter, Rebecca B Lawn, Alicia K Smith, Mytilee Vermuri, Laramie E Duncan","doi":"10.1038/s41398-025-03482-5","DOIUrl":null,"url":null,"abstract":"<p><p>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<sub>males</sub> = 61,758, N<sub>females</sub> = 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<sup>-3</sup>) and females (beta = -0.23, p = 3.04 × 10<sup>-5</sup>). 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.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"268"},"PeriodicalIF":6.2000,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12328684/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41398-025-03482-5","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
引用次数: 0
Abstract
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 (Nmales = 61,758, Nfemales = 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.
期刊介绍:
Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.