Raloxifene as a treatment for cognition in women with schizophrenia: the influence of menopause status

Cognitive impairments cause significant functional issues for people with schizophrenia, often emerging before the onset of hallucinations, delusions and other psychosis symptoms. Current pharmacological treatments do not target cognitive dysfunction. Several lines of evidence support the beneficial effects of estrogens on cognition. Raloxifene hydrochloride, a selective estrogen receptor modulator, has been associated with cognitive improvements in healthy postmenopausal women and in schizophrenia, although findings are inconsistent. Using pooled data from two clinical trials, the aim of the current study was to compare the efficacy of 120 mg/day adjunctive raloxifene to placebo for 12 weeks on cognitive performance in women with schizophrenia who were stratified by menopause status (pre-menopausal; peri-menopausal or post-menopausal). A total of sixty-nine participants with a diagnosis of schizophrenia or schizoaffective disorder were included. Cognition was assessed at baseline and study end using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Results indicated that after stratifying for menopause status (strata) and adjusting for endogenous hormone levels (estrogen, progesterone, follicle stimulating hormone and luteinising hormone), semantic fluency, picture naming and list recognition change from baseline scores for the raloxifene group differed significantly from the placebo group. The findings from the current study highlight the importance of considering menopause status when interpreting the effects of hormonal treatments.