Menstrual cycle irregularity and menopause status influence cognition in women with schizophrenia

•Cognitive impairments are a core feature of schizophrenia and contribute significantly to functional complications.•The current study investigated the influence of menstrual cycle irregularity and menopause status on cognitive functioning in 240 females with schizophrenia.•Results found that menstrual cycle irregularity predicted significantly poorer cognitive performance in the areas of psychomotor speed, verbal fluency and verbal memory, as compared to women with a regular cycle.•The post-menopausal period was associated with poorer visuospatial performance.•These results associate reproductive hormones with cognitive dysfunction in schizophrenia. Cognitive impairments are a core feature of schizophrenia and contribute significantly to functional complications. Current pharmacological treatments do not ameliorate cognitive dysfunction and the aetiology of cognitive impairments are poorly understood. Hormones of the hypothalamic-pituitary-gonadal (HPG) axis that regulate reproductive function have multiple effects on the development, maintenance and function of the brain and have been suggested to also influence cognition. The aim of the current study was to investigate how HPG axis hormones effect cognition, specifically exploring the influence of menopause status and menstrual cycle irregularity on cognitive performance in women with schizophrenia. The data for the present study represents pooled baseline data from three clinical trials. Two hundred and forty female participants with a diagnosis of schizophrenia or schizoaffective disorder were included in the analysis. Cognition was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status. Hormone assays for serum sex steroids and pituitary hormones (including estradiol, progesterone, luteinising hormone and follicle-stimulating hormone) were conducted and women were classified as postmenopausal; perimenopausal; premenopausal/reproductive, further classified into regular and irregular menstrual cycles. To model a comparison of cognitive performance for i) perimenopausal; ii) post-menopausal women and iii) reproductive aged women with irregular cycles to reproductive aged women with regular cycles a semiparametric regression model (generalised additive mode) was fitted. The results revealed that in females with schizophrenia, menstrual cycle irregularity predicted significantly poorer cognitive performance in the areas of psychomotor speed, verbal fluency and verbal memory.