Do estradiol levels influence on the cognitive function during antidepressant treatments in post-menopausal women with major depressive disorder? A comparison with pre-menopausal women.

OBJECTIVES: A hypo-estrogenic status, as that occurring with menopause, has been proposed to negatively affect cognitive function in post-menopause women. Nevertheless, little is known about the improvement of cognitive functions during antidepressant treatment in post-menopausal women with major depressive disorder (MDD) and its relation with hormonal changes. Hence, this study aimed to investigate the role of menopausal status including the level of sex hormones on cognitive function during antidepressant treatment.

DESIGN AND SETTINGS: Thirty-nine female patients (n=17 in pre-menopause; n=22 in post-menopause) with MDD based on DSM-IV criteria and who were not on hormonal replacement therapies participated in a prospective, 6-week, open-label naturalistic study. All patients were recruited in a university-based hospital. The Hamilton rating scale for Depression (HAMD), Montgomery-Asberg Depression Rating Scale (MADRS) and the Cognitive Failure Questionnaire (CFQ) were administered at baseline, week 1, week 3, and week 6. Levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) were collected at baseline visit.

RESULTS: Cognitive functioning improved during antidepressant treatment in the overall sample (P=0.00001). In post-menopausal women, E2 levels were strongly correlated with CFQ scores at each measurement. After controlling for depression severity, E2 levels maintained a significant association with the baseline CFQ scores (regression analysis: beta= -0.55 P=0.010; correlation: R= -0.54). In addition, the reduction of CFQ scores during antidepressant treatment was significantly associated with E2 levels (P=0.021), independently from the improvement of depressive symptoms, which however had a strong effect (P=0.0003). Nevertheless, we failed to find any association of CFQ score with sex hormones in pre-menopausal women.

MAIN FINDINGS: In post-menopausal women, the CFQ scores were correlated with E2 levels and the reduction of CFQ score during antidepressant treatment was also dependent on E2 levels, even controlling for depressive symptoms severity.

CONCLUSION: The present study further supports a crucial role of E2 on the cognitive function in post-menopause women. Moreover, our results suggest that E2 may influence the improvement of cognitive function in post-menopause women with MDD, during treatment with antidepressants.