Memory Matters: Hormone Therapy for Prostate Cancer and Cognitive Health

If you have metastatic prostate cancer, the current standard of care is androgen deprivation therapy (ADT). It is a type of hormone therapy that works by reducing the levels of male hormones, particularly testosterone, to slow down the growth of prostate cancer cells. While ADT is effective in treating prostate cancer, it may have side effects. Its impact on memory and cognitive function is one such area of concern.

This article looks at the association between ADT and cognitive dysfunction. The information here, hopefully, can help your decision-making on when to initiate ADT to treat prostate cancer.

Prostate cancer is a hormone-driven disease. Prostate cancer cells, in many cases, rely on testosterone for growth and proliferation. ADT aims to

• Inhibit the production of testosterone in testicles
• Inhibit the uptake of testosterone by prostate cancer cells

The inhibition of testosterone production by ADT hampers the energy source that fuels cancer progression. This therapeutic approach is particularly effective against hormone-sensitive prostate cancer.

Of the many side effects of ADT, mild cognitive impairment is one of them. It is often referred to as “fogginess” by individuals undergoing ADT who experience changes in their thinking and memory. It is comparable to the “chemo brain” associated with chemotherapy.

ADT-related mild cognitive impairment may seem like occasional forgetfulness, such as

• forgetting words during a sentence
• struggling to remember a list of items

These changes are typically subtle and do not affect every individual consistently. For many people, these cognitive changes tend to improve after the completion of hormone therapy.

While mild cognitive impairment is a recognized side effect of ADT, it is distinct from dementia. Dementia is a more severe and persistent decline in cognitive function that significantly interferes with daily life. The cognitive changes associated with ADT are generally temporary and reversible, distinguishing them from the more persistent and progressive nature of dementia.

Circulating testosterone levels are known to influence human behavior and neurologic functions. In normal aging, both testosterone concentration and neurocognitive function tend to decrease in men, complicating the efforts to associate ADT with neurocognitive dysfunction. However, more evidence is emerging to suggest a connection between the two:

1. A comprehensive study, spanning more than eight years and following 154,089 prostate cancer patients has shown that 13% of ADT recipients were later diagnosed with Alzheimer's disease (the most common type of dementia), compared to 9 percent without ADT. The gap widened for dementia (an overarching term to cover a range of neurocognitive disorders), with 22% of ADT recipients developing dementia, compared to 16% without the therapy. The risk remained significantly high after taking factors like age at diagnosis and ethnicity into account. They also found that the risk is higher if the individuals were exposed to ADT for a longer duration.
2. A recent study by Case Western Reserve University and Johns Hopkins University analyzed data from the electronic health record database in the U.S. that included 600,000 prostate cancer patients. The study revealed that ADT was linked to a 60% higher chance of developing dementia, encompassing Alzheimer's disease, vascular dementia, and other types of dementia. Interestingly, the elevated risk of dementia was observed among Caucasian individuals, but not among African Americans.

The evidence of association between ADT and neurocognitive dysfunction remains unclear. As of now, the benefit of ADT in treating metastatic hormone-sensitive prostate cancer outweighs the potential risk of neurocognitive dysfunction.

Dr Alicia Morgans, a medical oncologist at Vanderbilt University Medical Center has several pieces of advice to cover the uncertainties around ADT and its potential risk:

• Undergo ADT only if you really need it. Talk to your doctor and consider the risks and benefits during the shared decision-making process. Get a second opinion if you feel that you need to.
• Explore personalized treatment options, if possible. You may also be eligible for a clinical trial of alternative treatment.
• When used in combination with other drugs, the cognitive issues of ADT may be worsened. Inform your doctor about your symptoms and check if an intermittent ADT schedule is possible for your case.
• You may not be aware of changes in your cognitive functions, especially when they are very subtle. Your family and friends can help to observe any worrisome symptoms and bring them to the doctors’ and your attention.

If you are undergoing ADT, it is important to pay attention to changes in your thinking and memory. Keeping a diary to record daily tasks and responsibilities can be a practical strategy to manage memory changes. This practice may assist in organizing thoughts and activities, minimizing the impact of cognitive alterations on daily life. Communicate any concerns with your cancer care team.