Introduction: Gender diferences in schizophrenia include the age of onset, better treatment response, a better out- come, and the peak of the disease in postmenopausal women. Some evidence indicates that these variations are due to estrogen’s efect. he intention of this study was to evaluate the efectiveness of estrogen as an adjuvant agent in the treatment of women with chronic schizophrenia. Methods: Study participants were 32 women of childbearing age with chronic schizophrenia. hese patients were hospitalized in an institute for the chronically mentally ill. Participants were randomized into two groups: the irst group (16 cases) received conjugated estrogens 0.625 mg/day 4 weeks with their previous antipsychotic treatment, while the second group (16 cases) received placebo booster and antipsychotics. he Positive and Negative Syndrome Scale (PANSS) was used as a measurement tool for assessing psychopathology. Results: he combination of conjugated estrogens with antipsychotic treatment showed a signiicant decrease in positive (p=0.003), negative (p<0.001), general (p<0.001) and total (p<0.001) PANSS scores over 4 weeks. Conclusions: Estro- gen may be an efective adjuvant agent in the treatment of women with chronic schizophrenia. Original Contributions Combination of Estrogen and Antipsychotics in the Treatment of Women with Chronic Schizophrenia: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial ¹ Faculty of Medicine, Yasouj University of Medical Sciences, Yasouj, Iran ² Department of Epidemiology, Yasouj University of Medical Sciences, Yasouj, Iran ³ Department of Biostatistics, Yasouj University of Medical Sciences, Yasouj, Iran ⁴ Department of Agricultural, Food and Nutritional Sciences, University of Alberta, Edmonton, Canada ⁵ Department of Internal Medicine, Shiraz University of Medical Sciences, Shiraz, Iran 6 Department of Psychiatry, Yasouj University of Medical Sciences, Yasouj, Iran Address for correspondence: Ali Mohammadi, MD, Department of Psychiatry, Yasouj University of Medical Sciences, Motahari Street, Yasouj, Iran Phone: +98-9171198320; Fax: +98-7412230290; E-mail: amohammadi@hotmail.com Submitted: November 27, 2010; Revised: January 25, 2011; Accepted: January 29, 2011 Emel Ghafari ¹, Mohammad Fararouie ², Hamidreza Ghafarian Shirazi ³, Arazm Farhangfar ⁴, Fateme Ghaderi ⁵, Ali Mohammadi 6 Key Words: Schizophrenia, Estrogen, PANSS Abstract Introduction For the century since Kraepelin proposed gender dif- ferences in schizophrenia (1, 2), several epidemiological and clinical studies have supported this theory. he irst episode of schizophrenia begins at a later age in women than in men (3-5) and the rate of relapse of the disease increases in postpartum (6) and during postmenopause (3, 7, 8), which may require higher doses of antipsychotic medication (8). Antipsychotic response and prognosis of the disease among women of childbearing age is generally better than men (8, 9), and estrogen was reported to reduce psychotic symptoms in women with schizophrenia during the luteal phase of menstruation, when estrogen is at its highest level (10, 11). he cause of these variations of sex has been attributed to the efect of estrogen (12). 172 • Clinical Schizophrenia & Related Psychoses January 2013