Improvement in depression with oestrogen treatment in women with schizophrenia.

Women with schizophrenia are often noted to suffer with comorbid depression. Many studies have shown associations between fluctuating oestrogen levels in the brain and mental illness. This study investigates the effect of oestradiol treatment on comorbid depressive symptoms in women with schizophrenia. This study is an 8-week, three-arm, double-blind, randomised-controlled trial. The 180 female participants were aged between 18 and 45, with schizophrenia and ongoing symptoms of psychosis Positive and Negative Syndrome Scale (PANSS) score > 60 despite a stable dose of antipsychotic medication. Depressive symptoms were assessed using Montgomery Asberg Depression Scale (MADRS) with a mean score of 73.77 at baseline. Participants received transdermal oestradiol 200 µg or transdermal oestradiol 100 µg or an identical placebo patch. The a priori outcome measure was the change in PANSS score measured at baseline and days 7, 14, 28 and 56, but in this study, we focused on the change in MADRS score at the same time points. Data were analysed by using Quade's rank analysis of covariance (ANCOVA) (Huitema 1980) with baseline MADRS score as a covariate. We found a fluctuating but overall trend towards improvement of comorbid depressive symptoms in women with schizophrenia taking transdermal oestrogen 200 mcg compared with oestrogen 100 mcg or placebo. The stronger 'antidepressant' effect of 200 mcg transdermal oestradiol was found at day 28 (p = 0.03). Our study suggests that adjunctive oestradiol treatment for depression may be a promising treatment for women with comorbid depression and schizophrenia.

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.

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. 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. Perimenopause was not associated with cognitive changes and the post-menopausal period was associated with poorer visuospatial performance. This study provides evidence to associate reproductive hormones with cognitive dysfunction in schizophrenia.