Paul L Nguyen1, Shabbir M H Alibhai2, Shehzad Basaria3, Anthony V D'Amico4, Philip W Kantoff5, Nancy L Keating6, David F Penson7, Derek J Rosario8, Bertrand Tombal9, Matthew R Smith10. 1. Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA. Electronic address: pnguyen@LROC.harvard.edu. 2. Department of Medicine, University Health Network, Toronto, Canada. 3. Section on Men's Health, Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 4. Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA. 5. Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 6. Division of General Internal Medicine, Department of Medicine, Brigham and Women's Hospital, and Department of Health Care Policy, Harvard Medical School, Boston, MA, USA. 7. Department of Urologic Surgery and the Center for Surgical Quality and Outcomes Research, Vanderbilt University, and the VA Tennessee Valley Geriatric Research, Education, and Clinical Center, Nashville, TN, USA. 8. Academic Urology Unit, Department of Oncology, Royal Hallamshire Hospital, University of Sheffield, Sheffield, UK. 9. Division of Urology, Cliniques Universitaires Saint Luc, Université Catholique de Louvain, Brussels, Belgium. 10. Department of Hematology-Oncology, Massachusetts General Hospital Cancer Center, Boston, MA, USA.
Abstract
CONTEXT: Androgen-deprivation therapy (ADT) is a key component of treatment for aggressive and advanced prostate cancer, but it has also been associated with adverse effects on bone, metabolic, cardiovascular, sexual, and cognitive health as well as body composition. OBJECTIVE: To review the current literature on the adverse effects of ADT and strategies for ameliorating harm from ADT. EVIDENCE ACQUISITION: The Medline database (through PubMed) was searched from inception to August 1, 2013, for studies documenting the side effects of ADT and for randomized and prospective trials of interventions to mitigate those side effects. EVIDENCE SYNTHESIS: Adverse effects of ADT include decreases in bone mineral density; metabolic changes such as weight gain, decreased muscle mass, and increased insulin resistance; decreased libido and sexual dysfunction; hot flashes; gynecomastia; reduced testicle size; anemia; and fatigue. Several observational studies suggest an increased risk of diabetes and cardiovascular events, although most published studies report that ADT is not linked to greater cardiovascular mortality. Randomized trials have found value in treatments for some adverse effects including bone loss (bisphosphonates, denosumab, selective estrogen receptor modulators), markers of metabolic syndrome (exercise, diet, metformin), gynecomastia (tamoxifen, prophylactic radiation), muscle loss (resistance and aerobic exercise), and hot flashes (venlafaxine, medroxyprogesterone, cyproterone acetate, gabapentin). CONCLUSIONS: ADT is often a necessary component of the treatment of aggressive prostate cancer, yet it has known harms that can impair health and quality of life. Clinicians should be aware of interventions that can help mitigate these adverse effects. PATIENT SUMMARY: Androgen deprivation therapy is a critical component of the management of aggressive and advanced prostate cancer, but it causes adverse effects including bone loss, metabolic changes, gynecomastia, muscle loss, hot flashes, and possibly increased cardiovascular events. Clinicians should be aware of interventions that can help mitigate these adverse effects.
CONTEXT: Androgen-deprivation therapy (ADT) is a key component of treatment for aggressive and advanced prostate cancer, but it has also been associated with adverse effects on bone, metabolic, cardiovascular, sexual, and cognitive health as well as body composition. OBJECTIVE: To review the current literature on the adverse effects of ADT and strategies for ameliorating harm from ADT. EVIDENCE ACQUISITION: The Medline database (through PubMed) was searched from inception to August 1, 2013, for studies documenting the side effects of ADT and for randomized and prospective trials of interventions to mitigate those side effects. EVIDENCE SYNTHESIS: Adverse effects of ADT include decreases in bone mineral density; metabolic changes such as weight gain, decreased muscle mass, and increased insulin resistance; decreased libido and sexual dysfunction; hot flashes; gynecomastia; reduced testicle size; anemia; and fatigue. Several observational studies suggest an increased risk of diabetes and cardiovascular events, although most published studies report that ADT is not linked to greater cardiovascular mortality. Randomized trials have found value in treatments for some adverse effects including bone loss (bisphosphonates, denosumab, selective estrogen receptor modulators), markers of metabolic syndrome (exercise, diet, metformin), gynecomastia (tamoxifen, prophylactic radiation), muscle loss (resistance and aerobic exercise), and hot flashes (venlafaxine, medroxyprogesterone, cyproterone acetate, gabapentin). CONCLUSIONS:ADT is often a necessary component of the treatment of aggressive prostate cancer, yet it has known harms that can impair health and quality of life. Clinicians should be aware of interventions that can help mitigate these adverse effects. PATIENT SUMMARY: Androgen deprivation therapy is a critical component of the management of aggressive and advanced prostate cancer, but it causes adverse effects including bone loss, metabolic changes, gynecomastia, muscle loss, hot flashes, and possibly increased cardiovascular events. Clinicians should be aware of interventions that can help mitigate these adverse effects.
Authors: James Randall Patrinely; Arissa C Young; Henry Quach; Grant R Williams; Fei Ye; Run Fan; Leora Horn; Kathryn E Beckermann; Erin A Gillaspie; Jeffrey A Sosman; Debra L Friedman; Javid J Moslehi; Douglas B Johnson Journal: Eur J Cancer Date: 2020-06-27 Impact factor: 9.162
Authors: Douglas B Johnson; Debra L Friedman; Elizabeth Berry; Ilka Decker; Fei Ye; Shilin Zhao; Alicia K Morgans; Igor Puzanov; Jeffrey A Sosman; Christine M Lovly Journal: Cancer Immunol Res Date: 2015-02-03 Impact factor: 11.151
Authors: Tomasz Barelkowski; Peter Wust; David Kaul; Sebastian Zschaeck; Waldemar Wlodarczyk; Volker Budach; Pirus Ghadjar; Marcus Beck Journal: Strahlenther Onkol Date: 2019-12-23 Impact factor: 3.621
Authors: T Hasenoehrl; M Keilani; T Sedghi Komanadj; M Mickel; M Margreiter; M Marhold; R Crevenna Journal: Support Care Cancer Date: 2015-05-24 Impact factor: 3.603
Authors: Thiago Gagliano-Jucá; M Furkan Burak; Karol M Pencina; Zhuoying Li; Robert R Edwards; Thomas G Travison; Shehzad Basaria Journal: J Clin Endocrinol Metab Date: 2018-10-01 Impact factor: 5.958
Authors: Kagan Griffin; Ilona Csizmadi; Lauren E Howard; Gina-Maria Pomann; William J Aronson; Christopher J Kane; Christopher L Amling; Matthew R Cooperberg; Martha K Terris; Jennifer Beebe-Dimmer; Stephen J Freedland Journal: Cancer Causes Control Date: 2019-01-30 Impact factor: 2.506
Authors: J Uth; T Hornstrup; J F Christensen; K B Christensen; N R Jørgensen; J F Schmidt; K Brasso; M D Jakobsen; E Sundstrup; L L Andersen; M Rørth; J Midtgaard; P Krustrup; E W Helge Journal: Osteoporos Int Date: 2015-11-16 Impact factor: 4.507