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Combining Behavioral Endocrinology and Experimental Economics: Testosterone and Social Decision Making
Published on: March 2, 2011
Sex-divergent association of testosterone with suicidal risk in late-life depression
Han Wang1, Nan Lyu1, Juan Huang2
1Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders, National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, China; Laboratory for Clinical Medicine, Capital Medical University, Beijing, 100069, China.
Objective:
Suicidality in late-life depression (LLD) poses a significant public health challenge. While testosterone dysregulation is linked to suicide risk, its sex-specific role in LLD remains unclear. This study investigated sex-stratified associations between serum testosterone and suicidality, evaluating testosterone's clinical impact relative to modifiable risk factors.
Methods:
This study included 805 elderly inpatients with severe major depressive episodes (382 with suicidal ideation/behavior [MDS], 423 non-suicidal [MDNS]; mean age 66.0 years, range: 60-89; 281 males, 524 females) from 1884 screened. Serum total testosterone was measured via chemiluminescent immunoassay. Sex-specific standardization (mean-centering, z-scoring) addressed baseline hormonal differences. Staged logistic regression, adjusting for demographic, clinical, and stress-related confounders, analyzed associations.
Results:
MDS patients exhibited higher male prevalence, alcohol use, stress exposure, earlier depression onset, longer duration, and higher comorbidity burden and testosterone levels than MDNS (all p < 0.05). Multivariable analysis confirmed a significant interaction between sex-standardized testosterone and sex (p = 0.016). Stratified analyses revealed opposite effects: higher testosterone conferred protection against suicidality in males (OR = 0.81 per SD, AME = -7.6 % absolute risk reduction, p = 0.009) but increased risk in females (OR = 3.68 per SD, AME = +4.5 % absolute risk elevation, p = 0.039). Significant modifiable risk factors included physical comorbidities (stronger effect in females) and alcohol use (stronger effect in males), while stress events consistently elevated risk across sexes.
Conclusion:
This study demonstrates a critical sex-dependent dichotomy: higher sex-normalized testosterone protects elderly depressed males against suicidality but elevates risk in females, warranting longitudinal validation.
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