Elsevier

European Urology

Volume 67, Issue 5, May 2015, Pages 825-836
European Urology

Platinum Priority – Collaborative Review – Prostate Cancer
Editorial by Fred Saad on pp. 837–838 of this issue
Adverse Effects of Androgen Deprivation Therapy and Strategies to Mitigate Them

https://doi.org/10.1016/j.eururo.2014.07.010Get rights and content

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.

Introduction

Androgen deprivation therapy (ADT) is a mainstay of prostate cancer treatment and has been shown in randomized trials to improve overall survival when used with radiation for intermediate- and high-risk localized disease [1], [2], as well as locally advanced [3], [4] and node-positive disease [5], and after surgery for node-positive disease [6]. Although ADT can improve survival, it can also cause significant morbidity and a decrement in quality of life (QOL). This narrative review describes the adverse consequences of ADT and provides an up-to-date summary of evidence-based interventions that can prevent or reduce these side effects (Table 1, Table 2).

Section snippets

Evidence acquisition

A Medline search was conducted to identify original articles and review articles published from January 1, 1966, to August 1, 2013, that focused on the side effects of ADT and methods to mitigate those side effects. Keywords included androgen deprivation therapy and side effects. The articles with the highest level of evidence within each of the side effect categories examined were identified with the consensus of all of the collaborative authors and were reviewed. For the treatment of

Impact of androgen deprivation therapy on bone health and strategies for prevention

ADT is associated with decreases in bone mineral density (BMD) and increased risk of fracture. Prospective studies suggest that BMD decreases by 5–10% in the first year after initiating ADT for prostate cancer [7], [8], [9], [10]. Two studies based on the Surveillance Epidemiology and End Results (SEER)–Medicare database reported an increased fracture risk with ADT that increased with longer duration of ADT. One study noted a 21% relative increase in clinical fractures with ADT use [11], and

Conclusions

Although ADT can improve survival for men in certain settings, ADT also has a variety of potential harms. Methods of preventing bone loss are now well established, and exercise may prove to be a good way to reduce the body composition changes and fatigue from ADT, but these results will require further confirmation. For several other side effects, there are presently no effective mitigating interventions. At this point, the only certain way to prevent many of the adverse effects is to avoid

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