Androgen deprivation therapy (ADT) for prostate cancer is associated with an increased risk of dementia, according to a systematic review of largely observation studies.
"This study adds to a growing body of literature that androgen deprivation therapy may impact neurocognitive function,” Dr. Kevin T. Nead from the University of Pennsylvania Perelman School of Medicine, in Philadelphia, told Reuters Health by email. “Deficits in neurocognitive function, in addition to other well-defined adverse effects of androgen deprivation therapy, underscore the importance of appropriate patient selection.”
An estimated 50% of men with prostate cancer will ultimately undergo ADT, which has been linked to cognitive impairment as early as six months following its initiation. Recent studies investigating the possible link between ADT and dementia have yielded inconsistent results.
Dr. Nead’s team found nine studies, seven of which were retrospective, that compared risks of dementia among prostate-cancer patients who had or had not been exposed to ADT. The studies included more than 50,000 men in total.
In a primary meta-analysis of six studies, the risk of dementia was 47% higher following ADT than following another type of management (p=0.02), the researchers report in Prostate Cancer and Prostatic Diseases, online March 28.
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There was significant heterogeneity, however: 76% for the primary analysis, 81% for all-cause dementia and 40% for Alzheimer's disease.
“We currently do not have evidence that androgen deprivation therapy causes dementia,” Dr. Nead said. “What we know is that, taken together, the existing literature supports an association between androgen deprivation therapy and dementia.”
It is possible, the researchers concede, that their results are confounded by other factors.
“In general, individuals in the general population undergoing ADT are older and have a greater burden of medical comorbidities,” they write. “All of the studies included in our quantitative meta-analysis, except one, were retrospective population-based analyses.”
Dr. Nead said it was “reasonable for patients to be made aware of this association” between ADT and dementia, “but also important to acknowledge that in appropriately selected patients androgen deprivation therapy is a life-extending treatment.”
Dr. Laurent Azoulay from McGill University in Montreal, Canada, who earlier reported a lack of association between ADT and dementia risk in his population-based study of men with prostate cancer, told Reuters Health by email, "The authors’ finding that ADT is associated with an increased risk of dementia is not surprising, because their meta-analysis is dominated by the studies that suffered from important methodological shortcomings (such as immortal-time bias). Thus, the inclusion of such studies likely lead to an overall biased estimate and the results need to be interpreted with caution.”
“This study nicely summarizes the studies conducted to date on the subject,” he concluded. “But it is too early at this stage to claim that there is conclusive evidence that ADT increases the risk of dementia.”