From the Desk of the Editor: Androgen deprivation therapy for prostate cancer and dementia risk

Hot flashes.  Loss of Libido.  Impotence.  Fatigue.  Osteoporosis. Weight gain. Diabetes. Loss of muscle mass.  Gain in fat mass. Testicular shrinkage. Cardiovascular disease (still controversial). What do these all have in common?  No, they are not the rare side effects that may occur from a drug that you hear on a TV commercial.  These are all real and common side effects of androgen deprivation therapy (ADT) for prostate cancer. 

Despite this, we know, in the right setting (men with metastatic prostate cancer and those with high-risk disease undergoing radiation), that hormonal therapy is life-prolonging.  The question is whether there are other, less common, side effects to ADT that we don’t currently know about. Specifically, questions have been raised recently about central nervous system side effects of ADT – dementia and Alzheimer’s disease.

To provide clarity out of the noise, Nead et al. performed a systematic review of the data linking ADT and dementia and Alzheimer’s risk. A systematic review is a special type of review wherein all relevant papers are systematically examined and included.  This differs from most reviews (called narrative reviews), where the authors are often given leeway to pick and choose the “best” articles, which invariably are the articles that best support their opinion.  Thus, a systematic review is considered a higher level of evidence. Nead et al. then performed a meta-analysis – essentially taking all the data and compiling together. When this was done, there was a strong signal that ADT is linked with dementia (47% higher risk).  Furthermore, there was a borderline significant suggestion that ADT may be linked with Alzheimer’s disease (25% increased risk). 

Based upon this article, we can conclude that the best evidence to date points to a link between ADT and dementia and Alzheimer’s.  However, a link does not mean causation. Thus, we cannot conclude that ADT causes these effects – rather they are linked. Linkage could be due to causation. However, other possibilities exist. ADT is often reserved for men who are “too sick” for radiation or surgery. As such, ADT treated patients may be more likely to be predisposed to dementia. ADT is reserved for men with more advanced disease who are at higher risk of brain metastases (albeit still low risk).  Perhaps this explains the link. Finally, men treated with ADT often have tumors that progress requiring other drugs (i.e. chemotherapy).  Perhaps this is the reason ADT is linked with dementia. While all plausible, the possibility that ADT actually causes dementia must give us pause. If true, this can then be added to the ever-growing list of side effects induced by ADT. Certainly, this is something worthy of more study as well as mentioning to patients with the full caveat that while a link had been shown – we don’t know yet the exact reason.

Written By: Stephen Freedland, MD
Editor-in-Chief, Prostate Cancer and Prostatic Diseases
Cedars-Sinai Medical Center, Los Angeles, CA

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