This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Prostate cancer is primarily a disease of older men. The average age at which patients are diagnosed is 72 and the incidence increases with age. The primary treatment options for patients with prostate cancer include surgery, radiation, and hormone therapy. As prostate cancer tends to grow rapidly in the presence of male sex hormones (androgens), hormonal treatment for prostate cancer is designed to suppress the production of these hormones, producing a state of androgen deprivation, which leads to a reduction in tumor size.Continuous androgen deprivation therapy, in which the production of androgens is suppressed on a constant basis, is a widely used hormone treatment for prostate cancer. However, this therapy is associated with a number of side effects that have a negative influence on quality of life, such as fatigue, emotional distress, and impotence. The adverse effects of continuous androgen deprivation have led to the use of intermittent androgen deprivation, in which hormone therapy is discontinued once a patient's prostate specific antigen level (a marker of tumor activity) is completely suppressed, and is subsequently resumed when the patient's androgen levels and prostate specific antigen rise, or his cancer begins to grow. Patients treated with intermittent androgen deprivation tend to experience fewer side effects than those treated with continuous androgen deprivation.In addition to the side effects commonly reported, anecdotal evidence suggests that androgen deprivation therapy may have a negative effect on cognitive abilities such as concentration and memory. Previous research indicates that sex hormones have a strong impact on certain aspects of cognitive function. Specifically, higher levels of female sex hormones are associated with superior verbal fluency, and verbal learning and memory, whereas androgen levels are related to spatial ability and working memory for visual information.Although it is clear that sex hormones affect certain cognitive abilities, no research has specifically explored the impact of androgen deprivation therapy on cognitive function. In this project we will examine the nature and severity of cognitive impairments experienced by men undergoing continuous androgen deprivation or intermittent androgen deprivation treatment. The cognitive abilities of androgen deprivation patients will be compared with those of a sample of healthy men. We expect that patients undergoing androgen deprivation therapy will experience impairments in those cognitive abilities related to androgen levels (e.g., spatial ability, working memory for visual information). In addition, because testosterone (an androgen) is transformed into estrogen (a female sex hormone) in the body, we anticipate that androgen deprivation also will result in diminished performance on cognitive tasks enhanced by the presence of female sex hormones (e.g., verbal fluency, verbal learning and memory).This project also will explore the differential impact of the two types of androgen deprivation therapy on cognitive function. We expect that patients treated with continuous or intermittent androgen deprivation therapy will perform equally well on the cognitive tests during conditions of androgen suppression. However, intermittent androgen deprivation patients should exhibit superior cognitive function during periods of normal androgen production. The findings of this study will contribute not only to knowledge of the impact of sex hormones on cognitive function in general, but also to knowledge of the impact of continuous androgen deprivation and intermittent androgen deprivation therapies on prostate cancer patients. These findings will allow us to attempt to improve quality of life by providing prostate cancer patients with interventions specifically intended to improve cognitive performance.
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