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

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 s...

Full description

Saved in:
Bibliographic Details
Main Authors: Hanyang Shen, Ciera Stafford, Joeri Meijsen, Lijin Zhang, Jacob Reiter, Rebecca B. Lawn, Alicia K. Smith, Mytilee Vermuri, Laramie E. Duncan
Format: Article
Language:English
Published: Nature Publishing Group 2025-08-01
Series:Translational Psychiatry
Online Access:https://doi.org/10.1038/s41398-025-03482-5
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849235699679625216
author Hanyang Shen
Ciera Stafford
Joeri Meijsen
Lijin Zhang
Jacob Reiter
Rebecca B. Lawn
Alicia K. Smith
Mytilee Vermuri
Laramie E. Duncan
author_facet Hanyang Shen
Ciera Stafford
Joeri Meijsen
Lijin Zhang
Jacob Reiter
Rebecca B. Lawn
Alicia K. Smith
Mytilee Vermuri
Laramie E. Duncan
author_sort Hanyang Shen
collection DOAJ
description 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.
format Article
id doaj-art-a9207bc8a7474a65a3ccd9d42ef4ae21
institution Kabale University
issn 2158-3188
language English
publishDate 2025-08-01
publisher Nature Publishing Group
record_format Article
series Translational Psychiatry
spelling doaj-art-a9207bc8a7474a65a3ccd9d42ef4ae212025-08-20T04:02:42ZengNature Publishing GroupTranslational Psychiatry2158-31882025-08-011511910.1038/s41398-025-03482-5Associations between testosterone and future PTSD symptoms among middle age and older UK residentsHanyang Shen0Ciera Stafford1Joeri Meijsen2Lijin Zhang3Jacob Reiter4Rebecca B. Lawn5Alicia K. Smith6Mytilee Vermuri7Laramie E. Duncan8Department of Psychiatry and Behavioral Sciences, Stanford UniversityDepartment of Psychiatry and Behavioral Sciences, Stanford UniversityDepartment of Psychiatry and Behavioral Sciences, Stanford UniversityGraduate School of Education, Stanford UniversityDepartment of Psychiatry and Behavioral Sciences, Stanford UniversityDepartment of Epidemiology at the Harvard T.H. Chan School of Public HealthDepartment of Gynecology and Obstetrics, Department of Psychiatry and Behavioral Sciences, Department of Human Genetics, Emory UniversityDepartment of Psychiatry and Behavioral Sciences, Stanford UniversityDepartment of Psychiatry and Behavioral Sciences, Stanford UniversityAbstract 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.https://doi.org/10.1038/s41398-025-03482-5
spellingShingle Hanyang Shen
Ciera Stafford
Joeri Meijsen
Lijin Zhang
Jacob Reiter
Rebecca B. Lawn
Alicia K. Smith
Mytilee Vermuri
Laramie E. Duncan
Associations between testosterone and future PTSD symptoms among middle age and older UK residents
Translational Psychiatry
title Associations between testosterone and future PTSD symptoms among middle age and older UK residents
title_full Associations between testosterone and future PTSD symptoms among middle age and older UK residents
title_fullStr Associations between testosterone and future PTSD symptoms among middle age and older UK residents
title_full_unstemmed Associations between testosterone and future PTSD symptoms among middle age and older UK residents
title_short Associations between testosterone and future PTSD symptoms among middle age and older UK residents
title_sort associations between testosterone and future ptsd symptoms among middle age and older uk residents
url https://doi.org/10.1038/s41398-025-03482-5
work_keys_str_mv AT hanyangshen associationsbetweentestosteroneandfutureptsdsymptomsamongmiddleageandolderukresidents
AT cierastafford associationsbetweentestosteroneandfutureptsdsymptomsamongmiddleageandolderukresidents
AT joerimeijsen associationsbetweentestosteroneandfutureptsdsymptomsamongmiddleageandolderukresidents
AT lijinzhang associationsbetweentestosteroneandfutureptsdsymptomsamongmiddleageandolderukresidents
AT jacobreiter associationsbetweentestosteroneandfutureptsdsymptomsamongmiddleageandolderukresidents
AT rebeccablawn associationsbetweentestosteroneandfutureptsdsymptomsamongmiddleageandolderukresidents
AT aliciaksmith associationsbetweentestosteroneandfutureptsdsymptomsamongmiddleageandolderukresidents
AT mytileevermuri associationsbetweentestosteroneandfutureptsdsymptomsamongmiddleageandolderukresidents
AT laramieeduncan associationsbetweentestosteroneandfutureptsdsymptomsamongmiddleageandolderukresidents