Background: The loss of estrogens in the menopause may lead to increased vulnerability for psychotic relapse, poor clinical outcome, and a need for increased antipsychotic dose. However, confounders such as cumulative estrogen exposure and time since menopause have been inadequately studied. Our aim was to investigate potential variables capable of influencing antipsychotic response in a sample of postmenopausal women with schizophrenia. Methods: Sixty-four postmenopausal schizophrenic women were followed in a 12-week prospective treatment-by-clinical requirement study. Duration of reproductive years was considered an indirect measure of lifetime cumulative estrogens exposure. Psychopathological assessment included the following: Positive and Negative Syndrome Scale, Personal and Social Performance, and Clinical Global Impression-Schizophrenia Scale. Response was defined as a reduction of 30% or more of Positive and Negative Syndrome Scale total scores. Antipsychotic adherence was assessed by plasma level monitoring at 4 weeks. Regression analyses were performed to investigate the association between potential confounding factors and antipsychotic response. Results: Forty-two participants (66%) were found to be antipsychotic responders. Time since menopause was significantly and negatively associated with overall antipsychotic response, explaining almost 42% of the variance of the model used. Smoking and cumulative estrogen exposures were associated with improvement in negative symptoms. Smoking and time since menopause were associated with improvement in excitement symptoms, and smoking was positively associated with improvement in depressive and cognitive symptoms. Discussion: Time since menopause was significantly negatively associated with antipsychotic response in postmenopausal schizophrenic women, suggesting a decline in antipsychotic response after menopause. The neurobiological basis for antipsychotic response may include a role for estrogen and nicotine receptors.

Women with schizophrenia show sex-specific health needs that differ according to stage of life. The aim of this narrative review is to resolve important questions concerning the treatment of women with schizophrenia at different periods of their life—paying special attention to reproductive and post-reproductive stages. Review results suggest that menstrual cycle-dependent treatments may be a useful option for many women and that recommendations re contraceptive options need always to be part of care provision. The pregnancy and the postpartum periods—while constituting vulnerable time periods for the mother—require special attention to antipsychotic effects on the fetus and neonate. Menopause and aging are further vulnerable times, with extra challenges posed by associated health risks. Pregnancy complications, neurodevelopmental difficulties of offspring, cancer risk and cognitive defects are indirect results of the interplay of hormones and antipsychotic treatment of women over the course of the lifespan. The literature recommends that health promotion strategies need to be directed at lifestyle modifications, prevention of medical comorbidities and increased psychosocial support. Careful monitoring of pharmacological treatment has been shown to be critical during periods of hormonal transition. Not only does treatment of women with schizophrenia often need to be different than that of their male peers, but it also needs to vary over the course of life.

Neuroimaging studies of cognitive remediation in schizophrenia: A systematic and critical review