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      No increased risk of dementia in patients receiving androgen deprivation therapy for prostate cancer: a 5-year follow-up study

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          Abstract

          Prior studies suggested that the use of androgen deprivation therapy (ADT) in patients with prostate cancer (PC) might cause the impairment of cognitive function which is one of the common symptoms of dementia; however, the association between ADT and cognitive impairment still remains controversial. This retrospective cohort study aimed to investigate the relationship between ADT and subsequent risk of dementia using a population-based dataset. Data for this study were taken from the Taiwan (China)Longitudinal Health Insurance Database 2005. We included 755 PC patients who received ADT in the study cohort and 559 PC patients who did not receive ADT in the comparison cohort. Each patient was individually tracked for a 5-year period to define those who subsequently received a diagnosis of dementia. Results show that the incidence rates of dementia per 100 person-years were 2.35 (95% confidence interval [95% CI]: 1.82–2.98) and 1.85 (95% CI: 1.35–2.48) for PC patients who received ADT and those who did not receive ADT, respectively. The adjusted hazard ratio (HR) for dementia for PC patients who received ADT was 1.21 (95% CI: 0.82–1.78, P = 0.333) compared to those who did not receive ADT. In addition, the adjusted HRs for dementia for PC patients receiving ADT with gonadotropin-releasing hormone (GnRH) agonists and without GnRH agonists were 1.39 (95% CI: 0.80–2.40, P = 0.240) and 1.13 (95% CI: 0.75–1.71, P = 0.564), respectively, compared to PC patients not receiving ADT. We concluded that there was no difference in the risk of subsequent dementia between PC patients who did and those who did not receive ADT.

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          Most cited references23

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          Androgen deprivation therapy: progress in understanding mechanisms of resistance and optimizing androgen depletion.

          Androgen deprivation therapy remains a critical component of treatment for men with advanced prostate cancer, and data support its use in metastatic disease and in conjunction with surgery or radiation in specific settings. Alternatives to standard androgen deprivation therapy, such as intermittent androgen suppression and estrogen therapy, hold the potential to improve toxicity profiles while maintaining clinical benefit. Current androgen deprivation strategies seem to incompletely suppress androgen levels and androgen-receptor-mediated effects at the tissue level. Advances in the understanding of mechanisms that contribute to castration-resistant prostate cancer are leading to rationally designed therapies targeting androgen metabolism and the androgen receptor. The results of large trials investigating the optimization of primary androgen deprivation therapy, including evaluation of intermittent androgen suppression and phase III studies of novel androgen synthesis inhibitors, such as abiraterone acetate, are eagerly awaited.
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            Review of major adverse effects of androgen-deprivation therapy in men with prostate cancer.

            Androgen-deprivation therapy (ADT) is a common treatment for men with prostate cancer. Although ADT is effective at suppressing prostate-specific antigen (PSA), stabilizing disease, alleviating symptoms in advanced disease, and potentially prolonging survival, it is not without serious side effects. However, to the authors' knowledge, there is lack of a systematic review of its major adverse effects to date. The authors of this report systematically reviewed and quantitatively assessed the literature on skeletal and cardiac side effects associated with ADT in men with prostate cancer. The PubMed database was searched for relevant published articles from 1966 to May 2008, and 683 articles were reviewed systematically from an original 20 different Medical Subject Heading search combinations. The focus of the review was on bone-related and cardiovascular-related outcomes. When appropriate, results were pooled from articles on specific adverse outcomes, summary risk estimates were calculated, and tests of heterogeneity were performed. Fourteen articles were identified that met inclusion criteria from the original 683 studies. Men who underwent ADT for prostate cancer had a significantly increased risk of overall fracture of 23% (summary relative risk, 1.23; 95% confidence interval [95% CI], 1.10-1.38) compared with men who had prostate cancer but who did not undergo ADT. Furthermore, men who underwent ADT had a 17% increase in cardiovascular-related mortality compared with men who did not undergo with ADT (summary hazards ratio, 1.17; 95% CI, 1.07-1.29). Significant elevations in the risk of diabetes also were observed from 2 large studies. ADT was associated with an increased risk of skeletal fracture, incident diabetes, and cardiovascular-related mortality, although the absolute risk of these events was low. Preventive measures against these adverse effects and careful assessment of patient's baseline health status should be considered. (c) 2009 American Cancer Society.
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              Cognitive function in breast cancer patients prior to adjuvant treatment.

              To compare the neuropsychological functioning of breast cancer patients with invasive cancer and noninvasive cancer prior to adjuvant treatment. Breast cancer patients (N = 132) with invasive (Stages 1-3, N = 110, age = 54.1 +/- 8.1) or noninvasive (Stage 0, N = 22, age = 55.8 +/- 8.0) disease completed a battery of neuropsychological and psychological instruments following surgery but prior to initiation of chemotherapy, radiation or hormonal therapy. Matched healthy controls (N = 45, age = 52.9 +/- 10.0) completed the same battery of instruments. For the patients, data on menstrual status, type of surgery, time of general anesthesia, CBC and platelets, nutritional status (B12 and folate), and thyroid function were collected. Comparison of mean neuropsychological test scores revealed that all groups scored within the normal range; however, patients with Stage 1-3 cancer scored significantly lower than healthy controls on the Reaction Time domain (p = 0.005). Using a definition of lower than expected cognitive performance that corrected for misclassification error, Stage 1-3 patients were significantly (p = 0.002) more likely to be classified as having lower than expected overall cognitive performance (22%) as compared to Stage 0 patients (0%) and healthy controls (4%). No differences were observed between patients classified as having lower than expected cognitive performance compared to those classified as normal performance on measures of depression, anxiety, fatigue, menstrual status, surgery/anesthesia or any of the blood work parameters. Patients with Stage 1-3 breast cancer were more likely to be classified as having lower than expected cognitive performance prior to adjuvant treatment as compared to Stage 0 patients and healthy controls, although correction for misclassification error produced a lower rate than previously reported.
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                Author and article information

                Journal
                Asian J Androl
                Asian J. Androl
                AJA
                Asian Journal of Andrology
                Medknow Publications & Media Pvt Ltd (India )
                1008-682X
                1745-7262
                Jul-Aug 2017
                27 May 2016
                : 19
                : 4
                : 414-417
                Affiliations
                [1 ]Graduate Institute of Life Science, National Defense Medical Center, Taipei 110, Taiwan, China
                [2 ]Sleep Research Center, Taipei Medical University Hospital, Taipei 110, Taiwan, China
                [3 ]Division of Urology, Department of Surgery, Far Eastern Memorial Hospital, Taipei 110, Taiwan, China
                [4 ]Graduate Program in Biomedical Informatics, College of Informatics, Yuan-Ze University, Chung-Li 320, Taiwan, China
                [5 ]Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei 110, Taiwan, China
                [6 ]School of Public Health, Taipei Medical University, Taipei 110, Taiwan, China
                Author notes
                Correspondence: Dr. CY Huang ( cyh540909@ 123456gmail.com )
                [*]

                These authors contributed equally to this work.

                Article
                AJA-19-414
                10.4103/1008-682X.179528
                5507085
                27232853
                676074af-f314-4333-96e1-d6ab05a05ff8
                Copyright: © The Author(s)(2017)

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                : 23 August 2015
                : 11 November 2015
                : 18 March 2016
                Categories
                Original Article

                androgen deprivation therapy,dementia,epidemiology,prostate cancer

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