Stratification by Sex and Hormone Level When Contrasting Men and Women in Schizophrenia Trials Will Improve Personalized Treatment

Background: Sex and gender differences have been reported in the prevalence, expression, treatment response, and outcome of schizophrenia, but most reports are based on relatively small samples that have not been stratified for the impact of sex hormone levels. This literature review aims to show how women’s hormone levels can impact the results of male/female comparisons. Methods: This is a narrative review of data from publications of the last decade. Results: Epidemiologic evidence, reports of the impact of hormones on cognition, results of sexually dimorphic responses to treatment, and male/female trajectories of illness over time all suggest that female hormone fluctuations exert major effects on male/female differences in schizophrenia. Conclusions: Information on hormonal status in women participants is rarely available in clinical studies in schizophrenia, which makes male/female comparisons largely uninterpretable. These are the current challenges. Opportunities for individualized treatment are growing, however, and will undoubtedly result in improved outcomes for both women and men in the future