Effects of Androgen Blockade on Cognitive Function and Quality of Life in Men with Prostate Cancer

Funded by: Department of Defense
Project Period: 1/02 - 1/05

Abstract

Objective: Hormonal treatment of prostate cancer by means of androgen deprivation (AD) can be an effective means of inducing tumor regression and delaying progression of the disease. The treatment, however, adversely affects quality of life (QOL), causing fatigue, depression, impotence, and loss of libido. Anecdotal evidence suggests that cognitive function also may be negatively affected. Prostate cancer is predominantly a disease of older men, and impairment of cognitive function among older individuals can have a significant impact on QOL, everyday functioning, and independence. Because men with prostate cancer may survive for many years if the disease is suppressed, the identification of possible negative influences of life-prolonging treatment on QOL, and the development of means to treat such side effects, is of great importance. The research questions we are addressing concern: whether androgen suppression produces cognitive impairment among men with prostate cancer; the nature of such cognitive deficits; the relationship of the hypothesized deficits to serum levels of sex steroids (both testosterone and estrogen); and the relationship among cognitive functioning, testosterone/estrogen levels, and QOL. Our specific aims are to: 1) assess whether there is evidence of cognitive impairment among patients on AD therapy; 2) assess the nature and severity of that impairment; 3) use cognitive tests sensitive to fluctuations in levels of testosterone (T) or estrogen, and others unaffected by sex steroid levels, to determine if deficits observed are related to T suppression, decreased estrogen level, or both; 4) obtain serum levels of T, estradiol, estrone, and sex hormone binding globulin (SHBG) at each data collection time point to evaluate the relationships between performance on specific cognitive tests and levels of these sex steroids; and 5) examine the relationship among performance on cognitive measures, steroid levels, and QOL.

Methods: We are examining men on either continuous or intermittent AD, and a matched sample of healthy controls using tests of working memory, learning, verbal fluency, spatial perception, and verbal reasoning. Each subject is tested at baseline (unsuppressed), two to four weeks following start of suppression, and three months after the first follow-up. We obtain hormone levels at each time point, and assess QOL using the SF-36 and a depression scale. Mean comparisons will be made between suppressed and non-suppressed samples on all measures. We will examine the relationship between cognitive functioning and QOL.

Current Project Status: An important issue in prostate cancer treatment is to provide life-prolonging care while maximizing QOL. Anecdotal evidence and data on the link between sex steroids and cognition strongly suggest that the use of AD therapy may produce cognitive impairment. It is essential to determine whether such impairment exists, to identify its nature and relationship to the suppression of endogenous sex steroids, and to assess the strength of its relationship with QOL. This is our goal in this study. That having been accomplished, a next step might be to devise pharmacologic or other interventions that can reduce the negative impact of AD on cognition, thereby improving QOL.

Key Staff: Grigsby, Brega, Paulich, Glodé, Laudenslager

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