The role of estrogen in schizophrenia: implications for schizophrenia practice guidelines for women.
OBJECTIVE
The objective of this paper is to integrate what is known about estrogen effects on symptoms and treatment response into a global understanding of schizophrenia. The aim is to expand Canadian schizophrenia guidelines to include the specific needs of women.


METHODS
We searched the Medline database; keywords included estrogen, estrogen replacement therapy, schizophrenia, psychosis, treatment, tardive dyskinesia (TD), and women. We examined reference lists from relevant articles to ensure that our review was complete. We review the evidence for the effects of estrogen in schizophrenia and we make recommendations for the next revision of official practice guidelines.


RESULTS
The epidemiologic evidence suggests that, relative to men, women show an initial delay in onset age of schizophrenia, with a second onset peak after age 44 years. This points to a protective effect of estrogen, confirming animal research that has documented both neurotrophic and neuromodulatory effects. Clinical research results indicate that symptoms in women frequently vary with the menstrual cycle, worsening during low estrogen phases. Pregnancy is often, though not always, a less symptomatic time for women, but relapses are frequent postpartum. Some work suggests that in the younger age groups women require lower antipsychotic dosages than men but that following menopause they require higher dosages. Estrogen has been used effectively as an adjunctive treatment in women with schizophrenia. Estrogen may also play a preventive role in TD.


CONCLUSIONS
Symptom evaluation and diagnosis in women needs to take hormonal status into account. Consideration should be given to cycle-modulated neuroleptic dosing and to careful titration during pregnancy, postpartum, and at menopause. We recommend that discretionary use of newer neuroleptic medication and adjuvant estrogen therapy be considered.
Grigoriadis
Sophie
S
University of Toronto, Centre for Addiction and Mental Health, Clarke Division, 250 College Street, Toronto, ON M5T 1R8. sophie_grigoriadis@camh.net
Seeman
Mary V
MV
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy; D015914:Estrogen Replacement Therapy; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D008297:Male; D017410:Practice Guidelines as Topic; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology
D014150:Antipsychotic Agents