Androgen deprivation, which can be accomplished via drug treatment using gonadotropin-releasing hormone (GnRH) agonists, antiandrogens, or both combined, is widely used in the treatment of prostate cancer. Androgen deprivation therapy (ADT) can delay cancer progression and be life-prolonging. As with almost all cancer treatments, ADT comes with side effects and one of the most concerning is the possibility of accelerated brain aging and cognitive decline. Patients and their friends and family may notice diminished memory, attention, and information processing. This is thought to be related to the neuroprotective supportive role that testosterone plays in the healthy brain. It enhances synaptic plasticity, improves mitochondrial function, and is anti-inflammatory. Reducing androgens to castration levels may mean loss of this protection.
Our purpose in writing this paper is to bring together the current information on the relationship between ADT and cognition while recognizing that there is controversy as to whether a causal link exists. It is our experience that patients and their families do notice these changes and are often distressed by their negative impact on quality of life. We hope to raise awareness among clinicians so that they will address the issue and among researchers so that more attention will be directed at finding ways to minimize these effects. We need better tools to evaluate the more subtle deficits that may be observed in prostate cancer patients on ADT without the need for an impractical extensive battery of neuropsychological testing. Our general lack of neuroprotective therapy leads to the question of how we can advise our patients right now.
As we note in our paper, optimizing lifestyle factors is important. Encouraging a nutritious diet, regular exercise and social engagement is good for overall health and brain health. Treating depression, fatigue, and sleep issues is also important. Of course, the risk-to-benefit ratio of ADT in each individual patient must be considered in designing therapy. There is a need to explore underlying mechanisms. Our team and others are pursuing this in an effort to develop ways to mitigate adverse ADT effects.
Written by: Allison B. Reiss, Usman Saeedullah, David J. Grossfeld, Amy D. Glass, Aaron Pinkhasov, and Aaron E. Katz, NYU Long Island School of Medicine, Mineola, NY, USA
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