¹Icahn School of Medicine at Mount Sinai, Psychiatry, New York, United States, ²U.S. Department of Veterans Affairs James J. Peters Medical Center, Mental Health, New York, United States

Background: Prior research indicates that progesterone may play a role in modulating mood and behavior in men. Neurosteroids, including progesterone, are known to exert relaxing, sedative, mood-enhancing, and anxiolytic effects. These effects—namely improved mood, reduced anxiety, and increased relaxation and sedation—are generally associated with reduced suicidality.

Aims & Objectives: We hypothesized that higher progesterone levels in men would be associated with lower suicidality. To test this, we examined morning baseline progesterone levels and the effect of dexamethasone administration on progesterone in male combat veterans with and without a history of suicide attempt.

Method: Demographic and clinical characteristics of participants were assessed and recorded. Participants were interviewed by a trained clinician using the Mini-International Neuropsychiatric Interview, the Montgomery–Åsberg Depression Rating Scale (MADRS), the Scale for Suicidal Ideation, the Brown–Goodwin Aggression Scale, and the Reasons for Living Inventory. Blood samples for the determination of progesterone levels were collected in the morning, both on the day prior to and on the day following dexamethasone administration.

Results: Baseline progesterone levels were higher in non-attempters compared with suicide attempters. In the overall sample, higher baseline progesterone levels were associated with lower suicidal ideation, lower depressive symptom severity, and a greater number of reasons for living. Progesterone levels decreased following dexamethasone administration among non-attempters but not among attempters. Among non-attempters, progesterone levels before and after dexamethasone administration were positively correlated with aggression, a relationship not observed in attempters. In the entire sample, progesterone levels before and after dexamethasone administration were negatively correlated with the MADRS “Reduced Sleep” item scores, indicating that higher progesterone levels were associated with better sleep.

Discussion & Conclusions: This study provides the first evidence of progesterone non-suppression by dexamethasone in individuals with a history of suicide attempt. These findings highlight the important role of neurobiological mechanisms in the pathophysiology of suicidal behavior among combat veterans. Further investigation of neurosteroid function in relation to suicidal behavior may contribute to the identification of potential biomarkers of suicide risk and support earlier identification of individuals at elevated risk.