Steroid hormones are implicated in many neural functions in the brain. A significant amount of research has pointed to the role of hormones as potential biomarkers of diagnosis and symptom severity in psychotic illness. Hormone biomarkers of treatment response have not, however, been sufficiently investigated, especially not in postmenopausal women with schizophrenia. Thus, the main goal of this review is to summarize the current evidence on adrenal and gonadal hormones as candidate biomarkers of treatment response in this specific population. The review focuses on the potential role of the hypothalamic-pituitary-gonadal (HPG) axis, and adrenal hormones as markers of treatment response. Dehydroepiandrosterone (DHEA) and its sulphate metabolite (DHEAs) have been reported to exert modulatory effects on neural excitability and synaptic plasticity. Production of DHEA and DHEAs in the adrenal gland decreases as people age, particularly in the context of schizophrenia. This decline has been associated with worsening of psychotic symptoms and a progressively poorer response to medications. With respect to gonadal hormones, their level drops significantly in women at the time of menopause. Many studies strongly suggest that it is the loss of estrogen’s neuroprotective effect that explains the relatively poor response to antipsychotic medications in postmenopausal women and the need for higher doses starting at this age. Estrogen neuroprotection is supported by clinical evidence of the benefits of adjunctive estrogen and of the selective estrogen receptor modulator, raloxifene, on schizophrenia symptoms. The potential therapeutic effect of adrenal compounds, whether agonists or antagonists, is still being investigated.
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