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      Effect of androgen deprivation therapy on cognitive functioning in men with prostate cancer: A systematic review

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          Abstract

          The objective of this study was to review publications assessing cognitive functioning in patients with prostate cancer treated with androgen deprivation therapy. We conducted a systematic review of the literature published in PubMed, Embase, Web of Science, Cochrane Library, and PsycINFO up to February 2020. A total of 31 studies were included. Half of the studies ( n = 16) demonstrated that androgen deprivation therapy in patients with prostate carcinoma did not result in a negative effect on cognitive functioning, however, still a substantial proportion of the studies ( n = 11) reported a negative effect on cognitive functioning. In four studies the results were inconclusive. In the three studies using additional functional magnetic resonance imaging, no significant effect on neuropsychological tests was found, but grey matter volume, brain activity, and brain connectivity were affected. Given the substantial number of studies showing a significant negative effect of androgen deprivation therapy on cognitive functioning, clinicians should be aware of this side effect. Furthermore, future research should focus on the further examination of brain characteristics using functional magnetic resonance imaging, since these techniques might be more sensitive in detecting brain abnormalities as a result of androgen deprivation therapy.

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          Changes in neuronal activation patterns in response to androgen deprivation therapy: a pilot study

          Background A common treatment option for men with prostate cancer is androgen deprivation therapy (ADT). However, men undergoing ADT may experience physical side effects, changes in quality of life and sometimes psychiatric and cognitive side effects. Methods In this study, hormone naïve patients without evidence of metastases with a rising PSA were treated with nine months of ADT. Functional magnetic resonance imaging (fMRI) of the brain during three visuospatial tasks was performed at baseline prior to treatment and after nine months of ADT in five subjects. Seven healthy control patients, underwent neuroimaging at the same time intervals. Results ADT patients showed reduced, task-related BOLD-fMRI activation during treatment that was not observed in control subjects. Reduction in activation in right parietal-occipital regions from baseline was observed during recall of the spatial location of objects and mental rotation. Conclusions Findings, while preliminary, suggest that ADT reduces task-related neural activation in brain regions that are involved in mental rotation and accurate recall of spatial information.
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            Androgen-targeted therapy in men with prostate cancer: evolving practice and future considerations

            Background Androgen deprivation therapy (ADT) is foundational in the management of advanced prostate cancer (PCa) and has benefitted from a recent explosion in scientific advances. These include approval of new therapies that suppress testosterone (T) levels or inactivate its function, improvements in diagnostic and assay technologies, identification of lower therapeutic targets for T, discovery of the relevance of germline genetic mutations and identification of the benefits of sequential and combination therapies. Methods This review discusses the clinical profiles of the most up-to-date options for ADT, best practices for managing patients with advanced PCa and future directions in therapy. Results and conclusions Modern assay technologies reveal that bilateral orchiectomy results in a serum T level of approximately 15 ng/dL as compared to the historical definition of castration of T < 50 ng/dL. Evidence shows that lowering T levels to <20 ng/dL improves patient survival and delays disease progression. Routine monitoring of T in addition to prostate-specific antigen throughout treatment is important to ensure continuing efficacy of T suppression. New drugs that inhibit androgen signaling in combination with traditional ADT suppress T activity to near zero and have significantly improved patient survival. When personalizing ADT regimens physicians should consider a number of factors including initiation and duration of ADT, monitoring of T levels and PSA, the possibility of switching monotherapies if a patient does not achieve adequate T suppression, and consideration of intermittent vs. continuous ADT according to patients’ lifestyles, comorbidities, risk factors and tolerance to treatment.
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              Updated recommendations of the International Society of Geriatric Oncology on prostate cancer management in older patients

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                Author and article information

                Contributors
                c.d.andela@lumc.nl
                Journal
                Int J Urol
                Int J Urol
                10.1111/(ISSN)1442-2042
                IJU
                International Journal of Urology
                John Wiley and Sons Inc. (Hoboken )
                0919-8172
                1442-2042
                14 June 2021
                August 2021
                : 28
                : 8 ( doiID: 10.1111/iju.v28.8 )
                : 786-798
                Affiliations
                [ 1 ] Division of Endocrinology Department of Medicine Leiden University Medical Center Leiden The Netherlands
                [ 2 ] Department of Urology Leiden University Medical Center Leiden The Netherlands
                [ 3 ] Walaeus Library Leiden University Medical Center Leiden The Netherlands
                Author notes
                [*] [* ] Correspondence: Cornelie D Andela M.D., Ph.D., Division of Endocrinology, Department of Medicine, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Email: c.d.andela@ 123456lumc.nl

                Article
                IJU14596
                10.1111/iju.14596
                9545697
                34128263
                e80ab3b4-e855-4e67-8087-357ae9500c81
                © 2021 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 25 October 2020
                : 14 April 2021
                Page count
                Figures: 1, Tables: 3, Pages: 13, Words: 10308
                Categories
                Review Article
                Review Article
                Custom metadata
                2.0
                August 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.0 mode:remove_FC converted:07.10.2022

                Urology
                androgen deprivation therapy,cognitive functioning
                Urology
                androgen deprivation therapy, cognitive functioning

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