THE IMPACT OF SEX HORMONE LEVELS ON COGNITIVE FUNCTIONING IN WOMEN WITH SCHIZOPHRENIA - SCOPING REVIEW.

Background: Cognitive impairment is a core and disabling feature of schizophrenia, with a profound impact on functional outcomes. Female patients often demonstrate better cognitive profiles than males, suggesting a potential modulatory role of sex hormones. Estrogens, particularly estradiol, have been hypothesized to exert neuroprotective effects via modulation of neurotrophic, neurotransmitter, and inflammatory pathways. However, evidence regarding the relationship between sex hormone levels and cognition in schizophrenia remains scattered and inconclusive.

Methods: This scoping review synthesized evidence from clinical and preclinical studies examining the association between endogenous estrogen levels or estrogen-based treatments and cognitive functioning in women with schizophrenia. We included peer-reviewed literature addressing hormonal fluctuations across the menstrual cycle, menopause, and in response to antipsychotic treatment, with specific focus on estradiol and selective estrogen receptor modulators.

Results: Findings suggest that low estrogen levels may be linked to more severe negative symptoms and poorer cognitive performance in female patients. Studies investigating menstrual cycle phases report mixed results, while evidence from animal models indicates potential cognitive benefits of estrogenic compounds. Raloxifene has shown promise in mitigating cognitive deficits when administered during sensitive developmental periods. However, large-scale hormonal interventions in postmenopausal women have produced inconsistent results, likely due to differences in timing, dosage, and individual neurobiological context.

Conclusions: Sex hormone levels, especially estradiol, appear to influence cognitive outcomes in women with schizophrenia, though findings are heterogeneous. Future research should address methodological inconsistencies and explore phase-specific, personalized hormonal strategies. A deeper understanding of hormonal-cognitive interactions may inform more effective, sex-sensitive treatment approaches in schizophrenia.