title: Adverse effects of androgen deprivation therapy and strategies to mitigate them.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  RESULTS
  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.affiliation: Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA. Electronic address: pnguyen@LROC.harvard.edu.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Nguyen
authors.affiliation: Department of Medicine, University Health Network, Toronto, Canada.
authors.forename: Shabbir M H
authors.initials: SM
authors.lastname: Alibhai
authors.affiliation: Section on Men's Health, Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Shehzad
authors.initials: S
authors.lastname: Basaria
authors.affiliation: Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA.
authors.forename: Anthony V
authors.initials: AV
authors.lastname: D'Amico
authors.affiliation: Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
authors.affiliation: 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.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Keating
authors.affiliation: 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.
authors.forename: David F
authors.initials: DF
authors.lastname: Penson
authors.affiliation: Academic Urology Unit, Department of Oncology, Royal Hallamshire Hospital, University of Sheffield, Sheffield, UK.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Rosario
authors.affiliation: Division of Urology, Cliniques Universitaires Saint Luc, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tombal
authors.affiliation: Department of Hematology-Oncology, Massachusetts General Hospital Cancer Center, Boston, MA, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Smith
mesh_terms: D000726:Androgen Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects* / Q000627:therapeutic use; D001823:Body Composition / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000139:chemically induced; D002318:Cardiovascular Diseases / Q000139:chemically induced; D006177:Gynecomastia / Q000139:chemically induced; D019584:Hot Flashes / Q000139:chemically induced; D006801:Humans; D008297:Male; D008659:Metabolic Diseases / Q000139:chemically induced; D009124:Muscle Proteins / Q000187:drug effects; D017410:Practice Guidelines as Topic; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011788:Quality of Life / Q000523:psychology*
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D009124:Muscle Proteins
keywords: Androgen deprivation therapy; Prostate cancer