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Androgen Deprivation Therapy for Prostate Cancer and Alzheimer’s Risk

Androgen deprivation therapy (ADT) has been a significant treatment of prostate cancer for decades. The aim of ADT is to lower male androgens, or hormones, specifically testosterone, in order to slow or stop the growth of prostate cancer, which can depend on these androgens to grow.1 As with any medical treatment, there are adverse effects of ADT. There are studies that show an association between ADT and subsequent risk of Alzheimer’s disease.

ADT and adverse effects

After ADT, most men receiving the treatment see a return of normal androgen levels, but 20 percent to 30 percent of men have prolonged androgen suppression.1 Low testosterone levels are associated with a variety of issues, including cardiovascular disease, diabetes, loss of lean body mass, depression, and bone health.1,2

In addition to the physical adverse effects associated with ADT, the therapy has been associated with an array of cognitive effects, including impairments in visuomotor and executive functioning, which are also main features of Alzheimer’s disease.1 There are lower levels of circulating brain testosterone in men diagnosed with Alzheimer’s disease, and it has been found that in those individuals, supplementation with testosterone improves visual and spatial memory.1 Hormone therapy can potentially affect cognitive function by interfering with neuron growth and axon regeneration.3 Low androgen levels, then, may be significantly associated with cognitive impairments and development of Alzheimer’s disease.

ADT and Alzheimer’s disease or dementia

In July 2019, a retrospective cohort study was published that used the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, looking at the potential association between ADT exposure and diagnosis of Alzheimer’s disease or dementia.2 It was the largest study on this topic yet. The individuals studied were age 66 and older and had at least 10 years of follow-up after the diagnosis of prostate cancer.

Those with prostate cancer treated with ADT were more likely to be diagnosed with Alzheimer’s disease, compared to those who did not receive ADT.2 Individuals who received ADT were also more likely to be diagnosed with dementia than those who were not treated with ADT.2 Percentage-wise, of the individuals who received ADT, 13 percent were later diagnosed with Alzheimer’s disease, compared to the 9 percent diagnosed with Alzheimer’s who did not have ADT.2,3 For dementia, those percentages were 22 percent and 16 percent, respectively.2,3 There appeared to be a dose-response relationship, meaning that the more doses of ADT received, the higher risk of developing Alzheimer’s or dementia.2

Things to consider

Because it is thought that there is a latency period before noticeable clinical symptoms of dementia and Alzheimer’s disease, in which changes are taking place and the disease process has started, but it cannot be seen, more research is needed. It may be that ADT magnifies the changes already taking place in these individuals; it is not known. Some individuals may receive ADT instead of surgical therapy because of things like cardiovascular disease, which is also a risk factor for Alzheimer’s disease.1 There are a variety of factors, all of which warrant further exploration.

If you have prostate cancer and are concerned about your risk of Alzheimer’s disease, or have multiple risk factors for Alzheimer’s disease, talk with your doctor. The decision about treatment is an individual one, and many times it depends on an individual’s medical history and the severity of disease.3 The risks that hormone therapy may have need to be examined, and the risks and benefits should be discussed with your treatment team.

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