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Prostate cancer drugs increase dementia risk, study finds

Men who receive testosterone-lowering drugs for certain forms of prostate cancer are twice as likely to develop dementia, medical investigators have found in a study of patients’ medical records.

For years doctors have known that testosterone can drive the growth of prostate tumors. They also have known since the 1940s that androgen-deprivation therapy — lowering testosterone — can shrink them.

But researchers reporting in Thursday’s issue of JAMA Oncology, said drugs that lower testosterone levels raise the risk of dementia about five years after treatment. “The risk is real and, depending on the prior dementia history of the patient, we may want to consider alternative treatment,” Dr. Nigam Shah, a co-investigator in the research project at Stanford University, said.

Shah and Dr. Kevin Nead of the University of Pennsylvania, analyzed the medical records of 9,272 men with prostate cancer, 1,862 of whom were treated with androgen deprivation therapy.

The statistical research did not involve individual patients treated by the doctors. However, a so-called prospective study of actual patients reported recently in the New England Journal of Medicine, similarly drew the same conclusion: androgen-deprivation therapy raises the dementia risk.

Doctors on Long Island say the current study’s design does not answer enough questions.

“Androgen deprivation therapy has been around for a very long time,” said Dr. Louis Kouvassi, who chairs the Arthur Smith Institute for Urology at Northwell Health in New Hyde Park. “A Nobel Prize was awarded for showing that androgen deprivation therapy can control prostate cancer.

“So whenever you have something that’s been around a long time and suddenly there is clamoring that it’s causing X, Y and Z, these studies are suspect,” Kouvassi said. “It’s the same as vaccines causing autism. You may get people not acting in their best interest.”

Dr. Deepak Kapoor, president of Advanced Urology Centers, with offices on Long Island and New York City, said the analysis doesn’t take into account how androgen-deprivation medications are used.

“We use these drugs for people who have metastatic cancer,” Kapoor said. “These drugs should not be used as first-line agents. This is for people who have disease that has spread outside of the prostate.

“Without these drugs these patients would have very short survival,” Kapoor said. “If you don’t treat these people, you are risking death.”

Androgen deprivation therapy can involve any one of several types of medications, from the class of drugs known as “luteinizing hormone-releasing hormone agonists,” or LHRH agonists. These medications include Lupron, Eligard, Zoladex, Trelstar and Vantas.

Drug treatment is sometimes called chemical castration because the testosterone decline is similar to the drop occurring with surgical castration.

Patients have disliked the drugs because of side-effects, such as loss of libido. The medications also raise levels of the bad form of cholesterol.

The new research showed that men who underwent androgen deprivation therapy for at least 12 months had the greatest absolute increase in dementia risk. Men 70 or older who underwent treatment were the least likely to remain dementia-free.

Dr. Raymond Sultan, a urologist at St. Francis Hospital in Roslyn, said patients should talk to their urologists before drawing conclusions.

“It’s a good study. The numbers look impressive,” Sultan said, but the researchers “were mining databases and there are limits to these quantitative studies. We learned in biostatistics that correlation does not mean causation.”

Just because the statistics suggest androgen-deprivation therapy causes dementia, doesn’t mean the drugs actually cause cognitive decline, Sultan said.

Dr. Paul Wright, chairman of neurology at North Shore University Hospital in Manhasset, said the research isn’t clear about dementia. The term can refer to cognitive decline caused by any number of conditions, including neurological disorders, such as Alzheimer’s disease, and vascular dementia that can occur after a stroke.

The mechanisms underlying Alzheimer’s and vascular dementia differ and the Stanford team didn’t make note of that, Wright said.

“People who are diagnosing Alzheimer’s are not always correct,” he said, adding that patients can help prevent vascular dementia by modifying certain risk factors, which includes lowering blood pressure; avoiding cigarettes and controlling body weight.


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