Oestrogen-A Protective Factor in Schizophrenia?

Gender differences in schizophrenia, in the age of onset, course, lifetime risk, age distribution of onsets over the life cycle and clinical symptoms will be reviewed from the literature and our own studies. Also, the pre- and postmenopausal course of illness in women will be explored. Explanations for the gender differences using "normal" behavioural sex differences and the protective oestrogen hypothesis will be discussed. The hypothesis of the "protective" effect of oestrogen is based on findings from animal experiments, epidemiological and clinical studies. Oestrogen acts similarly on D2, 5-HTA2 and NMDA receptors in both the neurochemical and genomic domains. The neuroprotective effects of oestrogen on a genomic and cellular level might also favourably affect degenerative processes in schizophrenia. The lack of a gender difference in age of onset in familial schizophrenia due to a lower age of onset in pre-menopausal, genetically predisposed women strongly suggests an antagonistic balance between predisposition to the illness and the oestrogen effect. Oestrogen treatment plus antipsychotic therapy, compared with antipsychotic therapy alone, accelerates symptom remission in both women and men, thus corroborating the antipsychotic properties of oestrogen. Oestrogen is the only known substance with preventive potential in schizophrenia. However, health risks associated with long-term oestrogen treatment require careful weighing up of risks and benefits for patients. Future efforts to develop oestrogen-like compounds which do not affect breast and uterine tissue must be strongly encouraged.