Adverse effects of androgen deprivation therapy and strategies to mitigate them.

Paul L Nguyen, Shabbir M H Alibhai, Shehzad Basaria, Anthony V D'Amico, Philip W Kantoff, Nancy L Keating, David F Penson, Derek J Rosario, Bertrand Tombal, Matthew R Smith

Journal: European urology 2016;67(5):825-36

PMID: 25097095

Full Text on Elsevier Science View on PubMed

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.

Address: Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA. Electronic address: [email protected].; Department of Medicine, University Health Network, Toronto, Canada.; Section on Men's Health, Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA.; Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; 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.; 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.; Academic Urology Unit, Department of Oncology, Royal Hallamshire Hospital, University of Sheffield, Sheffield, UK.; Division of Urology, Cliniques Universitaires Saint Luc, Université Catholique de Louvain, Brussels, Belgium.; Department of Hematology-Oncology, Massachusetts General Hospital Cancer Center, Boston, MA, USA.

DOI: 10.1016/j.eururo.2014.07.010

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MeSH Terms: Androgen Antagonists, Antineoplastic Agents, Hormonal, Body Composition, Bone Diseases, Metabolic, Cardiovascular Diseases, Gynecomastia, Hot Flashes, Humans, Male, Metabolic Diseases, Muscle Proteins, Practice Guidelines as Topic, Prostatic Neoplasms, Quality of Life