The effects of treatment with a longacting parenterally administered estrogenic substance were studied in 90 men, between the ages of 55 and 75 years, suffering from psychosis with cerebral atherosclerosis or senile psychosis. Of the 77 patients who were in the study more than three months, 37 received a placebo and 40 received estradiol valerate intramuscularly in doses of 25 mg. once every two weeks. The estrogen in this dosage produced gynecomastia in every patient who received it for 6 months or more. In the test group, there were 17 deaths at the end of 20 months of observation; in the placebo group there were 8 deaths. The difference in mortality was the only significant difference found (0.05 level), and no evidence of favorable effects on mental functioning was found.
Lifshitz K, Kline NS. Use of an Estrogen in the Treatment of Psychosis with Cerebral Atherosclerosis. JAMA. 1961;176(6):501-504. doi:10.1001/jama.1961.03040190023007