The influence of hormone background on post-traumatic stress disorder and alcohol addiction in combat participants

The literature data about the role of cortisol and testosterone levels in post-traumatic stress disorder (PTSD) in combination with alcohol addiction (AA) in combatants is not detected clearly. This obstacle made our study relevant and appropriate. Objective: to determine the content of cortisol and testosterone in post-traumatic stress disorder and alcohol addiction in combatants. Materials and methods. 585 men aged 20-56 were examined. They were divided into 2 main groups (MG1 n=150 with PTSD; MG2 n=124; with PTSD and RVA); comparison group (CG0 n=156 with RVA) and 2 control groups (CG1 n=105 — military personnel who were not in the combat zone; CG2 n=50 with healthy civilians). Psychological examination and diagnosis of PTSD were conducted according to the order of the Ministry of Health of Ukraine No.121 dated February 23, 2016; AA diagnosis — according to the CAGE and AUDIT; anxiety diagnosis — according to the Spielberger — Khanin self-assessment scale; adaptability — according to the «Adaptivity-200» military questionnaire. Serum serotonin and testosterone were measured. Salivary cortisol was determined by enzyme-linked immunosorbent assay. The results were statistically processed, checked for normality of distribution. The results are presented as M±m. Correlation analysis was performed using Spearman-Pearson method (r). The significance level was set at p<0.05. Results. In combatants with PTSD salivary cortisol levels were significantly higher than in controls (17.70 vs. 1.01 nmol/L; p<0.0001) and it correlated with serotonin levels (p<0.0001). The saliva cortisol level elevation correlated with decreased RVA, lower total bilirubin level, activation of systemic inflammation, increased reactive anxiety, and decreased adaptability. Testosterone levels among PTSD combatants were significantly lower than in healthy individuals (7.90 vs. 22.10 nmol/L; p<0.001). In combatants with RVA testosterone levels increased significantly (from 7.70 to 8.98 nmol/l; p<0.05). In combatants with a combined course of PTSD and RVA, suppression of testosterone production was associated with the development of anemic syndrome. An increase in normal levels of testosterone was accompanied with a tendency to increase alcohol dependence, with an activation of systemic inflammation, and a decrease in platelets count. Conclusion. Salivary cortisol content significantly increased and blood testosterone levels decreased in combatants with post-traumatic stress disorder and alcohol addiction.

References

1. Miller L.N., Forbes D., McFarlane A.C. et al. (2023) Cumulative trauma load and timing of trauma prior to military deployment differentially influences inhibitory control processing across deployment. Sci. Rep., 13(1): 21414. doi: 10.1038/s41598-023-48505-7.
2. Palgi Y., Greenblatt-Kimron L., HoffmanY. et al. (2024) PTSD symptoms and subjective traumatic outlook in the Israel-Hamas war: Capturing a broader picture of posttraumatic reactions. Psychiatry Research, 339: 116096. PMID: 39067235.
3. Anjum G., Aziz M., Hamid H.K. (2023) Life and mental health in limbo of the Ukraine war: How can helpers assist civilians, asylum seekers and refugees affected by the war? Front Psychol., 14: 1129299. doi: 10.3389/fpsyg.2023.1129299.
4. Merians A.N., Spiller T., Harpaz-Rotem I. et al. (2023) Post-traumatic Stress Disorder. Med. Clin. North Am., 107(1): 85–99. doi: 10.1016/j.mcna.2022.04.003.
5. Handelsman D.J., Wittert G.A. (2024) Testosterone and Depression Symptoms in Aging Men. J. Clin. Endocrinol. Metab., 109(9): e1798–e1799. doi: 10.1210/clinem/dgae093.
6. Al-Kufaishi A.M.A., Al-Musawi N.J.T. (2024) Hypothalamus-pituitary-adrenal axis in patients with post-traumatic stress disorders and related to oxidative stress. Horm. Mol. Biol. Clin. Investig. doi: 10.1515/hmbci-2024-0017.
7. Tait L.J., Bulmer M.S., Drake M.J. et al. (2024) Impact of 12 weeks of basic military training on testosterone and cortisol responses BMJ Mil. Health, 170(4): 325–330. doi: 10.1136/military-2022-002179.
8. Karlović D., Serretti А., Marčinko D. et al. (2012) Serum testosterone concentration in combat-related chronic posttraumatic stress disorder. Neuropsychobiology, 65(2): 90–5. doi: 10.1159/000329556.
9. Schoissengeier V., Maqboul L., Weber D. et al. (2024) Association between bilirubin and biomarkers of metabolic health and oxidative stress in the MARK-AGE cohort. iScience, 27(7): 110234. doi: 10.1016/j.isci.2024.110234.
10. Rossini Gajšak L., Vogrinc Ž., Čelić Ružić M. et al. (2021) Salivary cortisol response to psychosocial stress in patients with first-episode psychosis. Croat Med. J., 62(1): 80–89. doi: 10.3325/cmj.2021.62.80.
11. Schumacher S., Engel S., Niemeyer H. et al. (2022) Salivary Cortisol and Alpha-Amylase in Posttraumatic Stress Disorder and Their Potential Role in the Evaluation of Cognitive Behavioral Treatment Outcomes. J. Trauma Stress, 35(1): 78–89. doi: 10.1002/jts.22683.
12. Budala D.G., Luchian I., Virvescu D.I. et al. (2025) Salivary Biomarkers as a Predictive Factor in Anxiety, Depression, and Stress. Curr. Issues Mol. Biol., 47(7): 488. doi: 10.3390/cimb47070488.
13. Panneh M., Ding Q., Kabuti R. et al. (2024) Associations of hair cortisol levels with violence, poor mental health, and harmful alcohol and other substance use among female sex workers in Nairobi, Kenya Discov. Ment Health, 4(1): 29. doi: 10.1007/s44192-024-00086-1.
14. Bijjal S., Huchegowda R., Gowda S.H. et al. (2024) A comparative study on hair cortisol concentration among generalized anxiety disorder patients with and without alcohol dependence syndrome presenting to a tertiary care center: A pilot study Indian J. Psychiatry, 66(9): 838–845. doi: 10.4103/indianjpsychiatry.indianjpsychiatry_520_24.
15. Flinn M.V., Thum E., Lau I. et al. (2025) Cortisol and psychological responses to natural disasters. Psychoneuroendocrinology, 177: 107474. doi: 10.1016/j.psyneuen.2025.107474.
16. AlSahman L., AlBagieh H., AlSahman R. (2025) Stress and salivary cortisol levels among temporomandibular disorders: a case-control study. J. Oral. Facial. Pain Headache, 39(2): 202–209. doi: 10.22514/jofph.2025.039.
17. Blalock Z.N., Wu G.W.Y., Lindqvist D. et al. (2024) Circulating cell-free mitochondrial DNA levels and glucocorticoid sensitivity in a cohort of male veterans with and without combat-related PTSD. Transl. Psychiatry, 14(1): 22. doi: 10.1038/s41398-023-02721-x.
18. He D., Gou Y., Wei W. et al. (2026) The complex relationship between testosterone imbalance and the risk of depression and anxiety in men. J. Affect. Disord., 407: 121815. doi: 10.1016/j.jad.2026.121815.
19. Indirli R., Lanzi V., Arosio M. et al. (2023) The association of hypogonadism with depression and its treatments. Front Endocrinol (Lausanne), 14: 1198437. doi: 10.3389/fendo.2023.1198437.
20. Genchi V.A., Cignarelli A., Sansone A. et al. (2024) Understanding the Role of Alcohol in Metabolic Dysfunction and Male Infertility Metabolites, 14(11): 626. doi: 10.3390/metabo14110626.
21. Cusack S.E., Maihofer A.X., Bustamante D. et al. (2024) Genetic influences on testosterone and PTSD. J. Psychiatr. Res., 174: 8–11. doi: 10.1016/j.jpsychires.2024.04.002.
22. Waller C., Ho A., Batzler A. et al. (2024) Genetic correlations of alcohol consumption and alcohol use disorder with sex hormone levels in females and males Res Sq [Preprint]: rs.3.rs-3944066. doi: 10.21203/rs.3.rs-3944066/v1.
23. Ho A.M., Pozsonyiova S., Waller T.C. et al. (2023) Associations of sex-related steroid hormones and proteins with alcohol dependence: A United Kingdom Biobank study Drug Alcohol Depend., 244: 109781. doi: 10.1016/j.drugalcdep.2023.109781.
24. Shen H., Stafford C., Meijsen J. et al. (2025) Associations between testosterone and future PTSD symptoms among middle age and older UK residents. Transl. Psychiatry, 15(1): 268. doi: 10.1038/s41398-025-03482-5.