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Estrogen Boosts Memory In Men With Prostate Cancer

   Portland, Ore.

New study shows estrogen counteracts some side effects of standard prostate cancer treatment

High doses of estrogen improve long-term memory and decrease feelings of confusion in men whose testosterone levels have been lowered to treat advanced prostate cancer, according to a study conducted by Oregon Health & Science University Cancer Institute scientists.

Testosterone is often responsible for making prostate cancer grow. Shutting testosterone down is a standard treatment for advanced prostate cancer and is known as hormone deprivation therapy. Men receiving this treatment are considered androgen-deprived.

"This is encouraging news for men as our study also shows that decreasing men's testosterone significantly increases depression and feelings of confusion," said Tomasz M. Beer, M.D., director of the Prostate Cancer Program in the OHSU Cancer Institute and principal investigator of the study.

Joined by OHSU School of Medicine researcher Jeri Janowsky, Ph.D., Beer and colleagues examined both the cognitive effects of hormone deprivation and the effects of high dose estrogen given in combination with hormone deprivation to men with advanced prostate cancer. Beer presented the study on June 6, 2004, at the American Society for Clinical Oncology annual meeting in New Orleans, La.

"We pursued this study because while we know that estrogen replacement improves women's long-term memory and testosterone supplementation in older men produces improved short-term memory, very little is known about the neural and cognitive effects of depriving prostate cancer patients of testosterone," Beer said.

In the study, researchers compared long-term memory and short-term memory in androgen-deprived men before and after the addition of estrogen to the same measures in androgen-deprived men who did not receive estrogen and to healthy age-matched men. Long-term -- or verbal -- memory is a function of the brain's hippocampus. Short-term -- or working -- memory is a function of the brain's prefrontal cortex.

Researchers evaluated working memory with the trails test, which involves study subjects connecting dots in an illustration, alternating between letters and numbers. Verbal memory was tested through paragraph recall. Subjects heard a short story and then were asked to recall it from memory twice - immediately after hearing it and then 30 minutes later.

Nineteen androgen-deprived men were tested before being receiving estrogen. They were tested again one month after beginning treatment with six 7.6 milligram estrogen patches (45.6 mg total) applied every seven days. Seventeen androgen-deprived men were tested without a change in their treatment regimen. Seventeen healthy men were tested as part of a control group.

Results suggest that hormone deprivation, prostate cancer or a combination of the two significantly impair verbal memory, while estrogen therapy significantly improves verbal memory performance. Hormone deprivation slows working memory performance, but does not affect accuracy. Supplementation with estrogen does not affect working memory.

"Estrogen replacement improves verbal memory but not working memory, suggesting that specific actions of hormones affect cognitive function in men with prostate cancer," Beer said.

Researchers also measured negative mood, depression and confusion in the same groups of men using a standard mood test over the course of two separate visits. They found that androgen-deprived men with prostate cancer show significantly increased depression and confusion. Those receiving estrogen therapy reported decreased confusion.

"Though the source of beneficial effects from estrogen remains unclear, the overall outcome of estrogen therapy seems promising for men with prostate cancer," Beer said. "Further studies using additional cognitive measures and control subjects are necessary to develop a better understanding of estrogen's effects on the cognitive functions of prostate cancer patients." Prostate cancer is the most common cancer in men and the second leading cause of cancer-related death in American men. Overall, one in six men will develop prostate cancer during his lifetime.

Particulars: ASCO Abstract No. 4650, High dose estrogen may enhance memory in men with prostate cancer. This study was funded in part by the National Cancer Institute, a component of the National Institutes of Health.

Tomasz M. Beer, M.D., assistant professor of medicine (hematology and medical oncology) in the OHSU School of Medicine and director of the Prostate Cancer Program in the OHSU Cancer Institute.

Jeri Janowsky, Ph.D., professor of behavioral neuroscience and of neurology in the OHSU School of Medicine.

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