Gender related differential response to dexamethasone in endocrine and immune measures in depressed patients and healthy controls

Introduction: There is a substantial predominance of women with depressive episodes. Gonadal steroids have been shown to modulate the HPA-axis, which has repeatedly been implicated with major depression. Objective: Characterization of gender differences in HPA-axis regulation. Methods: Dex-CRH-test was applied in healthy controls and depressed patients. The sample comprised 133 depressed patients (38,35% women) and 172 healthy controls (30% women). Blood was collected at baseline at 6 pm and 3 hours as well as 21 hours after ingestion of 1.5 mg dexamethasone with measurement of cortisol, ACTH and differential white blood count. The Dex-CRH-test was performed in a subsample of 115 patients (36,52% women) and 116 controls (25,86% women). Results: ACTH tone was significantly higher in male compared to female controls, in cases there was no gender difference. Only in women ACTH levels 3 and 21 hours after dexamethasone intake were disease-dependently altered. The cortisol response in the Dex-CRH test was reduced in female patients compared to controls. Leucocytes showed a significantly stronger increase upon dexamethasone administration in controls compared to patients in both sexes. Discussion: These preliminary findings suggest substantial gender differences in GR sensitivity following in-vivo glucocorticoid stimulation. The gender-related differences in HPA-axis regulation and immune system function may in part be responsible for gender differences in the occurrence of MDD.