Androgen deprivation therapy: evidence-based management of side effects.
WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The benefits of androgen deprivation therapy (ADT) are well recognized and a multitude of studies have documented the benefits of ADT in conjunction with other therapies. Given the widespread use of ADT due to its important clinical implications, it is imperative that clinicians understand the side effects to limit treatment-related morbidity. There are numerous well recognized adverse effects of ADT, including vasomotor flushing, loss of libido and impotence, fatigue, gynaecomastia, anaemia, osteoporosis and metabolic complications, as well as effects on cardiovascular health and bone density. Present study focuses on the most recent evidence-based treatment options for various side effects of ADT.


OBJECTIVE
To familiarize clinicians with the various side effects of androgen deprivation therapy (ADT). The present study focuses on the most recent evidence-based treatment strategies for the common side effects of ADT.


METHODS
A PubMed database search was conducted from 2000 to 2012. All prospective clinical studies were selected, including randomized and non-randomized clinical trials, as well as meta-analysis studies concerning preventive and therapeutic interventions for various side effects of ADT. 'The Oxford 2011 Levels of Evidence' classification system for treatment benefits was used to categorize selected studies.


RESULTS
Gabapentin shows moderate efficacy for the long-term treatment of hot flashes in a dose-dependent manner. A combined resistance/aerobic exercise programme leads to significant improvement in fatigue, sexual function and cognitive function. A home-based/group exercise programme also improves fatigue and unfavourable metabolic changes. Denosumab increases lumbar spine, hip and radius bone mass density, and also reduces the risk of vertebral fractures in men receiving ADT for non-metastatic prostate cancer. Metformin coupled with lifestyle intervention is a safe, well-tolerated intervention for adverse metabolic changes. Toremifene improves the lipid profile. Intermittent ADT improves early side effects, such as hot flashes, sexual activity, fatigue, and quality of life, although its effect on long-term side effects remains inconclusive.


CONCLUSIONS
Despite significant improvement in management strategies for the side effects of ADT, the best way of preventing side effects is to use ADT only when it is absolutely indicated.
USC Institute of Urology, USC/Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089-2211, USA.
Hamed
H
Ahmadi
Siamak
S
Daneshmand
D000368:Aged; D000726:Androgen Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000453:epidemiology; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000209:etiology*; D007172:Erectile Dysfunction / Q000139:chemically induced / Q000453:epidemiology; D019317:Evidence-Based Medicine; D005483:Flushing / Q000139:chemically induced / Q000453:epidemiology; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007989:Libido / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000139:chemically induced / Q000453:epidemiology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal