Men with prostate cancer and their doctors already have tough decisions to make. Do they go with watchful waiting? Surgery? Radiation?

Now a new, large study from Penn Medicine makes decisions about a level of treatment often added for men with aggressive or metastatic prostate cancer even harder. It adds to evidence that hormone therapy is associated with higher rates of Alzheimer's disease and dementia.

The lead author of the study, Ravishanka Jayadevappa, said the decision about whether to use androgen deprivation therapy (ADT) will be most difficult for men with cancer that has not yet spread beyond the prostate but is known to be a more virulent type.

Previous work, including some done at Penn, has found a connection between ADT and higher rates of dementia. There also are studies that do not support the hypothesis. Jayadevappa said this study, which followed 154,000 men 65 and up with prostate cancer over an average of eight years, was larger than others and did a better job of adjusting for other illnesses. It also found that the association with dementia grew stronger the more ADT men had taken.

The study was published this month in the Journal of the American Medical Association.

Ravishankar Jayadevappa is a research professor of geriatrics and senior fellow in the Leonard Davis Institute of Health Economics at the Perelman School of Medicine at the University of Pennsylvania.
Courtesy of Ravishankar Jayadevappa
Ravishankar Jayadevappa is a research professor of geriatrics and senior fellow in the Leonard Davis Institute of Health Economics at the Perelman School of Medicine at the University of Pennsylvania.

Thirteen percent of men in the study who received hormone therapy were diagnosed with Azheimer's disease compared with nine percent who did not get ADT. The study also looked at dementia, an umbrella term for cognitive decline that includes Alzheimer's and several other forms of dementia. Twenty-two percent of the men who took ADT got that diagnosis, compared to 16 percent who didn't take it. No one was counted in both categories. After controlling for disease severity and other medical and socioeconomic factors, the research team found that men who had taken ADT had a 14 percent higher risk of developing Alzheimer's and 20 percent increased risk for dementia. The increases were consistent for patients who received surgery or radiation or decided on watchful waiting, although they were slightly higher in the radiation group, said Jayadevappa, who has Ph.D. in public policy and management and is a senior fellow at the Leonard Davis Institute of Health Economics.

Androgen deprivation therapy suppresses the amount of androgens, or male hormones in a man’s body, which fuel prostate cancer cell growth. Surgical castration is one form of hormone therapy, but there are multiple drugs that lower the amount of testosterone a man’s body makes or that stop androgens from working.

Hormone therapy can cause reduced sexual desire, impotence, hot flashes, osteoporosis, loss of muscle mass and several other negative side effects.

Jayadevappa said there are times when ADT may be "life-saving," but doctors may want to limit doses in patients with intermediate disease. "After this study, I think they'll all be a bit more mindful or cautious of overexposure with ADP," he said. He thinks there should be more research on ADT and its biological mechanisms, not just against cancer but within the brain.

Ravi Parikh is an oncologist who specializes in prostate cancer.
Courtesy of Ravi Parikh
Ravi Parikh is an oncologist who specializes in prostate cancer.

Ravi Parikh, an oncologist and prostate cancer specialist on the research team, said hormone therapy clearly lengthens life for men with Stage 4 or metastatic prostate cancer. While such cancer is often fatal, men with it can survive up to 10 years, although most live less than five years.

Among patients with localized, high-risk cancer, Parikh, who practices at the Corporal Michael J. Crescenz Medical Center in Philadelphia, said ADT is most beneficial for younger men who are healthy enough to live many years. About 80 percent of men with localized, aggressive cancer survive five years when hormone therapy is part of their treatment, compared to 60 percent who do not get ADT, he said.

Some men with localized cancer currently get hormone therapy for as long as two years. "Those are the men that I worry about," he said.

Another group that could need extra consideration is older men who already have signs of cognitive dysfunction, Parikh said.

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