Reports suggest that 17-beta estradiol effectively neutralizes toxicity in rat and human neuronal cultures. However, other estrogens may be more effective and perhaps more relevant to neuropsychiatric diseases such as Alzheimer's and Parkinson's.

One such compound is the catecholestrogen 2-hydroxy-estradiol, which may protect against free radical-induced neurotoxicity, according to Dr. Vedder's studies of rat neuronal cell cultures.

Dr. Vedder and colleagues observed that pre-incubation with 2-hydroxy-estradiol had greater protective effects than did 17-beta-estradiol in reducing hydrogen peroxide-induced cell death in mouse hippocampal cells.

After four hours of incubation with 2-hydroxy-estradiol, researchers observed significantly higher cell survival compared with effects of other estrogens, prompting Dr. Vedder to speculate that catecholestrogens may exert potent neuroprotective effects.

Other findings by Dr. Vedder and his colleagues suggest that neuroprotective effects of catecholestrogens may derive from neutralization of free radicals. Exposing mouse neurons to iron and then measuring free radical formation with a fluorescence method, Dr. Vedder and colleagues found a significant reduction in fluorescence intensity after addition of 2-hydroxy-estradiol, but not 17-beta-estradiol.

Another neurotoxic mechanism may be lipid peroxidation, which is reduced in mouse hippocampal cells by both 2-hydroxy-estradiol and 17-beta-estradiol.

Dr. Vedder asserted that the in vitro neuroprotective effects of 2-hydroxy-estradiol that he and his colleagues observed may have important implications for treatment of neuropsychiatric disorders. Consistently, severity of psychopathology in schizophrenia has been correlated in some studies with blood estrogen concentrations; abnormalities of catecholestrogen metabolism have been reported in patients with major depression; and estrogen administration has been reported to improve response in models of Alzheimer's disease.