Effect of high-dose estrogen on memory in men with prostate cancer

Abstract

4650 Background: Estrogen replacement in women, and in female animal models, improves memory and changes the structure and physiology of relevant brain regions. Estrogen replacement in women improves long term verbal memory (hippocampal function) but may not affect short term working memory (prefrontal cortex function). Gonadectomy in male rats decreases synapse density in the hippocampus, a region important for long term memory. Testosterone, but not estrogen, replacement restores hippocampal synapse spine density. Testosterone supplementation in older men produces improvements in short term working memory. Little is known about the neural and cognitive effects of androgen suppression or estrogen therapy in men with prostate cancer. Methods: We compared the long term verbal memory (using the immediate and delayed Paragraph Recall test), and working memory (using Subject Ordered and Trails tests) of androgen-deprived men with androgen-independent prostate cancer before and 1 month after starting second-line hormonal therapy with transdermal estradiol 45.6 mg (six 7.6 mg patches) applied every 7 days. Results: Androgen deprived men treated with estradiol had a significant improvement in their paragraph recall performance but no change in working memory. Conclusions: High dose estradiol may have had beneficial but specific effects on cognitive performance. The mechanism of this effect is not clear. Previous studies have shown beneficial effects of testosterone on the brain and performance in androgen deprived male rats, but effects of estradiol have only been found for recovery of function after brain injury. Thus, the beneficial effects of estradiol in this study may be due to its use in combination with androgen suppression, disease and/or an aging brain. Further studies using additional cognitive measures and control subjects will further elucidate the brain and cognitive effects of estradiol in prostate cancer patients. No significant financial relationships to disclose.