Hormones and Schizophrenia

Jayashri Kulkarni; Emily Hayes; Emmy Gavrilidis


Curr Opin Psychiatry. 2012;25(2):89-95. 

In This Article

Abstract and Introduction


Purpose of review It is a well established fact that many serious mental illnesses, in particular psychoses such as schizophrenia, may have a significant hormonal aetiological component. This study aims to discuss the oestrogen protection hypothesis of schizophrenia in particular, with an emphasis on findings from the recent literature in support of this theory.
Recent findings Epidemiological and life-cycle data point to significant differences in the incidence and course of schizophrenia between men and women, suggesting a protective role of oestrogen. In-vitro and in-vivo preclinical research has confirmed oestradiol's interactions with central neurotransmitter systems implicated in the pathogenesis of schizophrenia, whereas results from randomized controlled trials investigating the antipsychotic potential of oestrogen have been promising. Research into other neuroactive hormones with possible effects on mental state is a field still in its infancy but is evolving rapidly.
Summary Schizophrenia and related psychoses are pervasive and debilitating conditions, for which currently available treatments are often only partially effective and entail a high risk of serious side effects. Thus, new therapeutic strategies are needed, and the literature reviewed here suggests that hormones such as oestrogen could be a viable option. It is hoped that, with further research and larger trials, the oestrogen hypothesis can be translated into effective clinical practice.


Over a century ago, the father of modern psychiatry Emil Kraepelin first proposed that 'dementia praecox' could be partly the result of an imbalance of sexual hormones,[1] and reports of gonadal dysfunction and hypoestrogenism in psychotic patients have also been documented since that time.[2••] Despite these early observations, it is only during the last two decades that sound scientific evidence has come to light demonstrating the profound effects reproductive hormones such as oestrogen can have on central nervous system (CNS) functioning and mental health. Such evidence has led multiple researchers to suggest an 'oestrogen protection hypothesis' for schizophrenia,[3–6] which postulates that oestrogen helps protect women from developing severe mental illnesses at such an early age as men, and fluctuating and ultimately declining levels of oestrogen during the menopause can lead to a relapse or late onset of schizophrenia in predisposed women.[7]

This review will summarize and appraise recent epidemiological, preclinical and clinical findings to highlight the plausibility and clinical importance of the oestrogen protection model in psychotic illness.