Leo Sher, M.D.

Our research work, “Progesterone and suicidality in male combat veterans” has been published in the QJM: An International Journal of Medicine online ahead of print (1).

Studies suggest that progesterone may influence mood and behavior in men. Neurosteroids including progesterone have relaxing, sedating, mood-enhancing, and anxiety decreasing effects on men. We hypothesized that higher progesterone levels in men are associated with lower suicidality. We examined morning baseline progesterone levels and the effect of dexamethasone administration on progesterone levels in male combat veterans with or without a history of suicide attempt.

Demographic and clinical parameters of the study participants were assessed and recorded. Study 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 to determine progesterone levels were collected in the morning on the day prior to and following dexamethasone ingestion.

Baseline progesterone levels were higher in suicide non-attempters in comparison to attempters. In the whole sample, higher baseline progesterone levels were associated with lower suicidal ideation, lower depression and more reasons not to die by suicide. Progesterone levels decreased after dexamethasone administration among non-attempters but not among attempters. Progesterone levels before and after dexamethasone administration positively correlated with aggression among non-attempters but not among suicide attempters. In the whole sample, progesterone levels before and after dexamethasone administration negatively correlated with the MADRS Reduced sleep item scores, i.e., higher progesterone levels were associated with better sleep.

Our study is the first demonstration of progesterone non-suppression by dexamethasone in suicide attempters. The results of our study underline the significant role of neurobiological mechanisms in the pathophysiology of suicidal behavior in combat veterans. Studies of the relation between neurosteroid function and suicidal behavior may lead to the development of biomarkers for suicidality and facilitate identification of individuals at high suicide risk.

Reference

1. Sher L, Bierer LM, Makotkine I, Yehuda R. Progesterone and suicidality in male combat veterans. QJM. 2025 Mar 24:hcaf082. doi: 10.1093/qjmed/hcaf082. Epub ahead of print.