In the past, some authors postulated that many women with schizophrenia showed signs of “hypoestrogenism”, suggesting that women became psychotic mainly before or during menstruation. Kraepelin created the diagnostic category “Menstrual Psychosis”.

Understand a possible relationship between menopause/estrogens and the development of schizophrenia.

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Several authors observed a relationship between estrogen levels and psychotic symptoms. Some facts contribute to this hypothesis like late-onset schizophrenia being more frequent in women, a second peak for onset of the disease, psychosis in temporal relationship with ovary surgery, puerperium and oscillations throughout the menstrual cycle, lower doses of antipsychotics during pregnancy.

For some authors, estrogens also exert a “protective” effect over psychotic symptoms, beyond other several known effects on various psychopathological aspects, namely through antidopaminergic actions as well as modulation of apoptosis and improvement of depressive and negative symptoms. Although some evidence confirms this theory, the estrogen hypothesis is not universally accepted, some authors claiming the existence of other biological, emotional and social factors that should be considered in menopause.

The etiology of the gender differences in schizophrenia is not yet well understood, but hormone-gene interactions may explain part of the mechanism. The psychiatric interview should explore menstrual irregularities or galactorrhoea, and, with increasing evidence, serum levels of prolactin and estrogens may become part of the routine tests. In the future, treatment with hormone replacement therapy may be a possibility for these patients.