Context: Accumulating evidence suggests that estrogens may have therapeutic effects in severe mental illnesses, including schizophrenia, via neuromodulatory and neuroprotective activity.
Objective: To compare the efficacy of adjunctive transdermal estradiol with that of adjunctive placebo in the treatment of acute psychotic symptoms.
Design: Randomized, double-blind study.
Setting: Patients were recruited from inpatient acute hospital wards and outpatient clinics of 2 metropolitan Melbourne general hospitals.
Participants: One hundred two women of childbearing age with schizophrenia. All participants were in an acute or chronic phase of their illness; 73 participants were outpatients and the rest were inpatients. Intervention Patients were randomized to receive 100 microg of transdermal estradiol (n = 56) or transdermal placebo (n = 46) for 28 days.
Main outcome measures: Psychopathological symptoms were assessed weekly with the Positive and Negative Syndrome Scale.
Results: The addition of 100 microg of transdermal estradiol significantly reduced positive (P < .05) and general psychopathological (P < .05) symptoms during the 28-day trial period compared with women receiving antipsychotic medication alone.
Conclusion: Estradiol appears to be a useful treatment for women with schizophrenia and may provide a new adjunctive therapeutic option for severe mental illness.
Trial registration: clinicaltrials.gov Identifier: NCT00206570.