Philadelphia—About a half-million men currently receive androgen deprivation therapy (ADT) in an effort to improve their survival with prostate cancer, a new study points out.

The problem, according to the analysis published in Prostate Cancer and Prostatic Diseases, is that the potentially life-saving therapy could also have a devastating downside: increasing their risk of dementia.

Researchers from the Perelman School of Medicine at the University of Pennsylvania point to previous studies—including some they conducted—suggesting that men on ADT therapy have an increased risk of dementia, including Alzheimer’s disease, compared to men not treated with the drug.

In this case, Penn researchers conducted a meta-analysis on the topic and found that the evidence supports the link. Included in the systematic review were nine studies, including seven that reported an adjusted effect estimate for dementia risk. The random-effects meta–analysis of studies reporting any dementia outcome, which included 50,541 patients, showed an increased risk of dementia among ADT users, with a hazard ratio (HR) of 1.47.

The researchers separately conducted meta-analyses studies reporting all-cause dementia (HR, 1.46) and Alzheimer’s disease (HR, 1.25).

“Since publishing our initial findings, there has been a lot of other research on this topic, and we wanted to see what that research was saying,” the study’s lead author Kevin Nead, MD, MPhil, said. “This analysis tells us that the composite message of existing studies is that androgen deprivation therapy is associated with dementia.”

“Research shows androgens play a key role in neuron maintenance and growth, so the longer you undergo this therapy to decrease androgens, the more it may impact the brain’s normal functions,” explained Nead, who emphasized that the statistics show correlation, not causation at this point.

The connection to Alzheimer’s was not as clearly defined as the link to dementia, study authors note, yet, Nead advised, “There’s enough evidence of these links that patients should know about them when considering their options.”

An earlier study involving Penn researchers found that the risk of developing Alzheimer’s disease increased in men treated with ADT for prostate cancer in certain situations, such as those who took testosterone-lowering medications for longer periods of time.

That analysis of medical records from two large hospital systems, published in the Journal of Clinical Oncology, revealed that patients using ADT were almost twice as likely to be diagnosed with Alzheimer’s disease in the years that followed, compared to those who didn’t undergo the therapy. In addition, the risk shot up with longer duration of treatment.

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