Hormone therapy for prostate cancer may raise dementia risk

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Men with prostate cancer who are treated with a form of hormone therapy may be at much higher risk of dementia, according to new research published in JAMA Oncology.

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The study found that men with prostate cancer who underwent androgen deprivation therapy (ADT) were almost twice as likely to be diagnosed with dementia in the 5 years after treatment than men who did not receive ADT.

Used since the 1940s, ADT is a treatment that reduces levels of androgens, which are male hormones – such as testosterone and dihydrotestosterone (DHT) – that can stimulate the growth of prostate cancer cells.

According to the American Cancer Society, ADT may be used for prostate cancer if the cancer is no longer treatable with surgery or radiation, if the cancer returns following surgery or radiation, or before or alongside radiation in order to boost treatment efficacy.

Lead study author Dr. Kevin T. Nead, of the Department of Radiation Oncology at the Perelman School of Medicine at the University of Pennsylvania, and colleagues note that each year, more than half a million men in the United States are treated with ADT.

While ADT has shown significant benefits for prostate cancer survival, some studies have shown the treatment may have negative implications for cognitive function.

Last year, for example, another study by the same research team uncovered a link between ADT and Alzheimer’s disease – the most common form of dementia.

The new study builds on those results, suggesting that ADT may have even broader implications for cognitive functioning.

Dementia risk doubled for men treated with ADT

The researchers came to their latest findings by using a “text processing” tool to analyze the medical records of 9,272 men of an average age of 67 who were treated for prostate cancer between 1994-2013. Of these, 1,826 were treated with ADT.

The team assessed dementia incidence among the men in the 5 years after treatment, including incidence of Alzheimer’s disease, vascular dementia, and frontotemporal dementia.

Compared with men who were not treated with ADT, those who did receive the treatment were more than twice as likely to be diagnosed with dementia over 5 years; ADT-treated men had an absolute dementia risk of 7.9 percent, compared with 3.5 percent for men not treated with ADT.

The team found that regardless of age, the risk of dementia with ADT was still doubled.

Among men aged 70 and older, the absolute risk of developing dementia was 13.7 percent for those treated with ADT, compared with 6.6 percent for those who did not receive the treatment. For men younger than 70, men treated with ADT had a 2.3 percent risk of dementia, compared with 1 percent for those not treated with the therapy.

While the study was not designed to pinpoint the mechanisms by which ADT might raise dementia risk, the authors point to previous studies that suggest testosterone protects brain cells. As such, reducing levels of this hormone with ADT may eliminate some of the ways in which the brain staves off dementia.

“Low testosterone and androgen deprivation therapy have also been shown to increase cardiometabolic disease, which is an independent risk factor for dementia by impacting neurovascular function,” Dr. Nead told Medical News Today. “Through these mechanisms, androgen deprivation therapy may globally decrease neurovascular function, thereby increasing the risk of dementia.”

‘Doctors should talk to patients about possible cognitive risks of ADT’

Given that Dr. Nead and colleagues have now produced two studies suggesting a link between ADT and dementia, they say further research into the cognitive effects of this cancer therapy is warranted.

“As the population of older, long-term cancer survivors continues to rise, the health issues that cancer therapies can leave in their wake will become increasingly important.

Further studies are needed to investigate the association between this therapy and dementias, given the significant patient and health system impacts if there are higher rates among the large group of patients undergoing ADT today.”

Dr. Kevin T. Nead

MNT asked Dr. Nead whether healthcare providers should warn prostate cancer patients about the possible cognitive risks of ADT.

“All men should have a detailed discussion with their doctors regarding the risks and benefits of ADT. Based on the body of literature that now exists, it would be reasonable to counsel patients regarding potential cognitive risks as this has been shown in multiple retrospective and prospective studies,” he replied.

“We would, however, not recommend specific changes to clinical practice based on this study alone, given that androgen deprivation therapy is a life-extending treatment in some men with prostate cancer.”

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