The People's Perspective on Medicine

Prostate Cancer Therapy and Dementia: The Link Gets Stronger

Determining the best treatment(s) for PCa is challenging. Hormone suppression is common. Is there a link between this prostate cancer therapy and dementia?

Prostate cancer is hard enough by itself. That’s because treatment often comes with unpleasant complications. Now, add the possibility of Alzheimer’s disease and/or dementia linked to testosterone suppression (androgen deprivation therapy or ADT). The latest research was published in JAMA Network Open (July 3, 2019). It means that men diagnosed with prostate cancer now face a difficult dilemma. Weigh the benefit of lowering testosterone levels, which delays prostate cancer progression, against the risk of developing Alzheimer’s disease. That decision sucks. Nevertheless, urologists and oncologists should now discuss the tradeoffs between prostate cancer therapy and dementia.

The Latest Research Linking Prostate Cancer Therapy and Dementia

Investigators at the University of Pennsylvania Perlman School of Medicine followed nearly 155,000 older men for at least 10 years. These gentlemen were included in a Medicare database. They were at least 66 years of age and had been “diagnosed with localized or advanced prostate cancer between 1996 and 2003.”

Over 62,000 of them received androgen deprivation therapy within two years of diagnosis. This involves the suppression of testosterone with anti-androgen medications. Roughly 92,000 did not receive hormone suppression treatment.

Exposure to androgen deprivation therapy was linked to an increased risk of both Alzheimer disease and dementia in these Medicare patients. Of those who received testosterone suppression, 21.6% were diagnosed with dementia over the decade of follow-up. Men who did not have their hormones blocked had a 15.8% risk of dementia.

What makes this research a little more convincing is the dosing data. The association between prostate cancer therapy and dementia was stronger depending upon the total ADT exposure.

Prostate Cancer Therapy and Dementia | The Number Needed to Harm:

One of the ways physicians judge the benefits and risks of medications is the number needed to treat and the number needed to harm. In plain English, how many people need to take a medicine for one to get measurable benefit? It often takes 20 or 30 individuals taking a drug for five years for one to see a benefit. In the case of statins it is even more than that. Doctors also like to know how many men will be harmed from a particular treatment.

The authors of the recent ADT study report that:

“The number needed to harm was 18 patients for Alzheimer disease and 10 patients for dementia.”

For many men those odds may be worth it. One out of 18 patients would be predicted to develop Alzheimer’s disease over a decade if testosterone were suppressed for several months or a year or two. Roughly one man out of 10 would be likely to develop dementia over a decade.

Other Research Linking Prostate Cancer Therapy and Dementia:

This is not the first study to suggest that depriving the body of testosterone can have an impact on the brain. A study conducted in Taiwan collected data on over 24,000 prostate cancer patients (Aging Male, March, 2017). Over four years the men who received ADT were 84% more likely to develop Alzheimer’s disease (AD) than men who did not have their hormones suppressed. The authors concluded:

“The present results suggest that ADT use is associated with an increased risk of developing AD.”

A meta-analysis and systematic review of the medical literature collected data on nine studies (Prostate Cancer and Prostate Disease, Sept. 2017).  The authors concluded:

“The currently available combined evidence suggests that ADT in the treatment of prostate cancer may be associated with an increased dementia risk. The potential for neurocognitive deficits secondary to ADT should be discussed with patients and evaluated prospectively.”

The Flip Side of Prostate Cancer Therapy and Dementia:

This is not a cut and dried conclusion. Another study involving the FDA’s database of adverse drug reactions came to a different conclusion (Journal of Alzheimer’s Disease Reports, June 30, 2018). The authors wrote:

“Our analysis of FDA MedWatch adverse event data reports does not support the idea that androgen deprivation therapy per se is associated with Alzheimer’s disease or cognitive dysfunction. Perhaps the prostate cancer itself, or the stress it imposes on the man who has it, may be detrimental to mood and intellect, increasing susceptibility to Alzheimer’s disease and cognitive disorder.”

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What Happens when Testosterone Levels are Lowered?

Testosterone is not an accident. Men and women rely on this hormone for a number of essential physiological processes. Although it is often referred to as a male hormone, women make testosterone too.

When the body is deprived of testosterone there is a greater risk for muscle wasting and weakness. This hormone is also important for good bone health. When testosterone levels are low, there is a greater risk for bone loss and osteoporosis.

Other side effects associated with testosterone deprivation include breast development (gynecomastia), erectile dysfunction (ED), difficulty concentrating, depression, hot flashes and possibly even heart disease (Journal of Clinical Oncology, June, 2007). 

The Benefits of ADT

For the record, let’s be very clear. Androgen deprivation therapy improves outcomes in prostate cancer patients. There is evidence that ADT and lower levels of testosterone are associated with “reduced risk of death and progression” (Clinical Genitourinary Cancer, June, 2018).

Balancing The Pros and Cons of ADT:

Prostate cancer is a leading killer of men. It is the second most common cause of cancer death in this population. Treatment is often very confusing. There are no easy answers and no perfect solutions.

ADT is one of the pillars of therapy, whether men receive radiation or some other approach. It is a sad commentary on current prostate cancer treatment that we do not have clear answers about the best approach to stave off this disease.

Men with PCa need to weigh the benefits and the risks of ADT. Physicians need to be honest about the pros and cons of androgen deprivation therapy so men can make informed decisions. Each man will have to decide for himself what the best path forward will be.

If you have had ADT, please share your experience in the comment section.

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.” .
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I had cancer diagnosis in August 1999. Surgery in December 1999. Cancer had spread to seminal vesicles. PSA after surgery was 5.8. Had 😕35 radiation treatments.

After several years PSA was up again. Started on Casodex for 15months. In the past 18+ years, I have been on Casodex for 5 years each time my PSA came back up. Just started it again July 2019. Hot flashes start again as well as constipation and fatigue.

I’m glad to be alive. I’ve lived 18+ years since my diagnosis of an aggressive prostate cancer.

I had radical prostate cancer surgery in December 2007 and radiation treatment together with two Lupron shots (ADT) in spring of 2017. I wonder if the drug interaction with the pitutiary gland in the brain is causing dementia in certain patients. It would be nice if they had conducted the same study on patients who opted for castration. I do have trouble remembering names sometimes, hopefully it’s not related to ADT. I am 79 years old.

Is the 6% difference in developing dementia when treated with ADT really that significant vs lowering the chances of getting cancer?

My husband was operated on for prostate cancer and bladder cancer in Dec 2015. He had radiation. Hormone therapy for 1 year.

He was already having memory problems but he has now in 2019 been diagnosed with Dementia-Alzheimers. Is now in stage 5-6.

May have happened anyway but also may be Lupron. Also in 2018 had to have a heart Stent.

I had ADT treatment for 13 months in 2005 after biopsy showed 5 out of 12 samples cancerous with a Gleeson level of 6. I have had very slow increased in my PSA during the following period as it rose to 2 within a year and it is about 3.3 at this time — 14 years later. I have no signs of
dementia or Alzheimer’s.

I underwent ADT therapy as well as radiation for 40 weeks in 2011.
I don’t REALLY see it, but my wife says I am very forgetful.

Testosterone suppression therapy changes a man into a eunuch, with all the eunuch’s miserable characteristics. It may increase survival by only a short time, and that parody of a man dies regretting that he chose the illusion of preserving erection by not having the prostate removed completely as a whole. At the same time penile implants function excellently, but they are mostly unknown and under-used.

Does this apply to radon seed implants. Cancer is cured, but patient now has dementia.

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