Relationship between estrogen and schizophrenia.

There is a wealth of historical and circumstantial evidence to suggest that female patients with schizophrenia may suffer from a deficit in estrogenic function. The prolactin-inducing properties of most antipsychotic drugs, and subsequent negative feedback on estrogen levels, is in keeping with this. The functions of estrogen, its complex receptor organization and its numerous actions are the focus of ongoing research activity. Of particular interest are its neuroprotective properties, particularly with regard to cognitive impairment, and its involvement with neurotransmitter systems, which are the substrate for psychotropic drugs. Estrogen has now been used as an adjunct to standard antipsychotic medication in quite a few studies of female schizophrenia patients. However, most of these are not double-blind, randomized, controlled trials. Only two relatively small double-blind, randomized clinical trials returned positive results: one long-term study that selected for hypoestrogenism reported negative findings. Furthermore, recent evidence of the risks of long-term hormone replacement therapy is of concern. The advent of specific estrogen receptor modulators, which may avoid excess risks of cancer and cardiovascular events, will have little to add to schizophrenia treatment if estrogen is, essentially, devoid of any specific antipsychotic or adjuvant mechanism of action relevant to the pathophysiology of this disorder.