Past studies have suggested that estrogens may improve brain functioning, possibly by blocking neural cell death caused by oxidation. However, some studies have suggested that tamoxifen, which blocks estrogen’s stimulatory effects in breast cancer, may block estrogen’s beneficial effects on the brain and possibly contribute to cognitive decline.
To study tamoxifen’s effect on brain chemistry in elderly women, Ernst and his coworkers used a brain imaging technique to compare levels of myo-inositol, a chemical that increases in response to brain injury, among 16 breast cancer survivors who had been treated with tamoxifen for at least 2 years, 27 healthy women who had been treated with preventive estrogen replacement therapy for at least 2 years, and 33 healthy women who had not received any treatment. All of the women were between the ages of 65 and 80 and did not have any neurologic diseases.
The researchers found that women who had been treated with tamoxifen had lower levels of myo-inositol in the brain than the untreated women. Women who took estrogen also had lower levels of the chemical. Myo-inositol levels were lowest among women who had been treated with tamoxifen for longer periods of time.
The authors conclude from the lower levels of myo-inositol in women treated with tamoxifen or estrogen that “both [tamoxifen and estrogen] may be neuroprotective and may have favorable modulatory effects on aging.” They note, however, that future studies are necessary to look at the long-term effects of such therapies on cognitive function.
In an accompanying editorial, Patricia A. Ganz, University of California Los Angeles Jonsson Comprehensive Cancer Center, and her colleagues write that, “it is highly speculative to interpret [these findings] as indicative of neuroprotection.” They note that “it is important to consider alternative explanations for these results that take into account all of what we know about the physiologic effects of estrogen in women, as well as the relationship between lifelong exposure to estrogen and the risk for breast cancer.”
Ganz and her coworkers point out that two ongoing studies, the Women’s Health Initiative Memory Study trial and the Study of Tamoxifen and Raloxifene, may provide more definitive answers about the value of hormone replacement therapy as a neuroprotective agent. “In a few years, we may have reliable information about the neurocognitive effects of estrogen and tamoxifen on the brain,” the editorialists conclude.
Contact: Karen McNulty Walsh, Brookhaven National Laboratory, (631) 344-8350, fax: (631) 344-3368, kmcnulty@bnl.gov
Editorial: Kim Irwin, UCLA Jonsson Comprehensive Cancer Center, (310) 206-2805, fax: (310) 206-5553, kirwin@mednet.ucla.edu
Ernst T, Chang L, Cooray D, Salcador C, Jovichich J, Walot I, et al. The effects of tamoxifen and estrogen on brain metabolism in elderly women. J Natl Cancer Inst 2002;94:592–7.
Editorial: Ganz PA, Castellon SA, Silverman DHS. Estrogen, tamoxifen, and the brain. J Natl Cancer Inst 2002;94:547–9.
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