A growing body of evidence suggests cognitive problems can occur as a consequence of systemic cancer treatment. Although progress has been made in understanding these problems, several important gaps remain. One notable gap is the lack of research on men with prostate cancer, the most common cancer in U.S. men. Concern rests primarily with the estimated 50,000 men per year who are candidates for treatment with luteinizing hormone- releasing hormone (LHRH) agonists. The concern reflects the fact that these agents act against prostate cancer by blocking testosterone production. In addition to giving rise to side effects that can interfere with cognitive functioning (e.g., fatigue, depression, and hot flashes), LHRH agonists may have a direct effect on cognitive functioning. Evidence for this includes studies showing that lower levels of testosterone are associated with poorer cognitive functioning in healthy older men and that testosterone supplementation in men is associated with improvements in cognitive functioning. Additional evidence includes a small number of studies showing problems with cognitive functioning among prostate cancer patients receiving LHRH agonists. Most of these studies, however, have been characterized by methodological limitations (i.e., small sample sizes, use of cross-sectional research designs, and absence of appropriate comparison groups). In addition, there has been little effort to examine mechanisms that may underlie the impact of LHRH agonists on cognitive functioning or to identify patient characteristics that may moderate their impact on cognitive functioning. With these issues in mind, the aims of the current study are: 1) to identify the magnitude and features of changes in cognitive functioning attributable to treatment of prostate cancer with LHRH agonist therapy;2) to examine the relationship of changes in testosterone and estradiol to changes in cognitive functioning during treatment with LHRH agonist therapy;3) to identify whether genetic variations associated with cognitive functioning in other populations are predictive of changes in cognitive functioning related to receipt of LHRH agonist therapy;and 4) to identify whether cognitive difficulties during LHRH agonist therapy are part of a cluster of symptoms related to declines in testosterone that also includes hot flashes, fatigue, depressive symptoms, and loss of sexual desire.
These aims will be addressed through the study of men with prostate cancer receiving LHRH agonist therapy and matched comparison samples of men with prostate cancer not receiving LHRH agonist therapy and men with no history of cancer. Public Health Relevance Paragraph: By learning more about the cognitive problems experienced by men receiving hormonal therapy for prostate cancer, we hope to lay the groundwork for future efforts to improve the quality of life of these individuals.
This aim i s consistent with the strategic objective of improving the quality of life of cancer patients and survivors outlined in the National Cancer Institute's 2015 Challenge Goal of Eliminating the Suffering and Death Due to Cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA132803-02
Application #
7628543
Study Section
Behavioral Medicine, Interventions and Outcomes Study Section (BMIO)
Program Officer
O'Mara, Ann M
Project Start
2008-06-01
Project End
2012-04-30
Budget Start
2009-05-01
Budget End
2010-04-30
Support Year
2
Fiscal Year
2009
Total Cost
$404,858
Indirect Cost
Name
H. Lee Moffitt Cancer Center & Research Institute
Department
Type
DUNS #
139301956
City
Tampa
State
FL
Country
United States
Zip Code
33612
Gonzalez, Brian D; Small, Brent J; Cases, Mallory G et al. (2018) Sleep disturbance in men receiving androgen deprivation therapy for prostate cancer: The role of hot flashes and nocturia. Cancer 124:499-506
Donovan, Kristine A; Gonzalez, Brian D; Nelson, Ashley M et al. (2018) Effect of androgen deprivation therapy on sexual function and bother in men with prostate cancer: A controlled comparison. Psychooncology 27:316-324
Gonzalez, Brian D; Jim, Heather S L; Small, Brent J et al. (2016) Changes in physical functioning and muscle strength in men receiving androgen deprivation therapy for prostate cancer: a controlled comparison. Support Care Cancer 24:2201-2207
Cessna, Julie M; Jim, Heather S L; Sutton, Steven K et al. (2016) Evaluation of the psychometric properties of the PROMIS Cancer Fatigue Short Form with cancer patients. J Psychosom Res 81:9-13
Nelson, Ashley M; Gonzalez, Brian D; Jim, Heather S L et al. (2016) Characteristics and predictors of fatigue among men receiving androgen deprivation therapy for prostate cancer: a controlled comparison. Support Care Cancer 24:4159-66
Gonzalez, Brian D; Jim, Heather S L; Booth-Jones, Margaret et al. (2015) Course and Predictors of Cognitive Function in Patients With Prostate Cancer Receiving Androgen-Deprivation Therapy: A Controlled Comparison. J Clin Oncol 33:2021-7
Lee, Morgan; Jim, Heather S; Fishman, Mayer et al. (2015) Depressive symptomatology in men receiving androgen deprivation therapy for prostate cancer: a controlled comparison. Psychooncology 24:472-7
Gonzalez, Brian D; Jim, Heather S L; Donovan, Kristine A et al. (2015) Course and Moderators of Hot Flash Interference during Androgen Deprivation Therapy for Prostate Cancer: A Matched Comparison. J Urol 194:690-5
Mandelblatt, Jeanne S; Jacobsen, Paul B; Ahles, Tim (2014) Cognitive effects of cancer systemic therapy: implications for the care of older patients and survivors. J Clin Oncol 32:2617-26
McGinty, Heather L; Phillips, Kristin M; Jim, Heather S L et al. (2014) Cognitive functioning in men receiving androgen deprivation therapy for prostate cancer: a systematic review and meta-analysis. Support Care Cancer 22:2271-80

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