The study found that men who were on the testosterone-lowering therapy the longest were the ones most likely to be diagnosed with Alzheimer's disease in the years that followed the start of the treatment.
This was the conclusion of a new Journal of Clinical Oncology study led by the University of Pennsylvania (UPenn) that analyzed the medical records of two large US hospital systems.
The study also found the longer the men were on ADT, the more likely they were to be diagnosed with Alzheimer's disease in the years that followed.
The researchers say their investigation - the first to look at the link between ADT and Alzheimer's disease - is consistent with other evidence that low levels of testosterone may weaken resistance to the neurodegenerative disease in the older brain.
They say while their findings do not prove ADT causes Alzheimer's, they clearly point to the possibility and call for more research to investigate the link further.
Lead author Dr. Kevin T. Nead, a radiation oncologist in UPenn's Perelman School of Medicine, says their aim is to contribute to the discussion about the risks and benefits of ADT, and:
"Based on the results of our study, an increased risk of Alzheimer's disease is a potential adverse effect of ADT, but further research is needed before considering changes to clinical practice."
At any given time, there are around half a million men in the US taking ADT, a common treatment for prostate tumors. The therapy suppresses production of androgens, male hormones that normally help stimulate the growth of prostate cells, including cancerous ones.
However, dramatic reduction of male hormone levels can also lead to adverse side effects. There is evidence that low levels of androgens - primarily testosterone levels - are linked to obesity, diabetes, depression, impotence, heart disease and high blood pressure.
Men on ADT the longest had double risk of Alzheimer's
More recent studies have also linked low testosterone to problems with thinking and memory. There is also evidence that men who develop Alzheimer's disease tend to have lower levels of testosterone, compared with counterparts who do not develop the disease.
Fast facts about prostate cancer
- Other than skin cancer, prostate cancer is the most common cancer in American men
- About 1 in 7 men will be diagnosed with prostate cancer during their lifetime
- The average age at the time of diagnosis is about 66.
The new study analyzes data from two large sets of medical records: one covering 1.8 million patients from the Stanford health system and the other covering 3.7 million patients from Mt. Sinai Hospital in New York City.
From this large pool of over 5 million patient records, the researchers found around 18,000 prostate cancer patients, including 16,888 whose cancer was not metastatic - that is had not begun to spread. Within this pool, they also found 2,397 patients who had been treated with ADT.
Such a large data set allowed the researchers to compare the ADT patients with a matched control group of patients who did not have ADT but were similar in age and other factors.
Their analysis showed that compared to counterparts who did not have the therapy, the men who underwent ADT were significantly more likely to be diagnosed with Alzheimer's disease in the years following the start of their hormone-lowering therapy.
The researchers found the men on ADT were about 88% more likely to be diagnosed with Alzheimer's disease than men who did not have the therapy.
They also found a dose-response effect in that the longer the ADT lasted, the higher the likelihood of being diagnosed with Alzheimer's, to the point where the patients who were on ADT the longest had double the risk of Alzheimer's than those who did not have ADT.
Dr. Nead concludes:
"It's hard to determine the precise amount of increased risk in just one study and important to note that this study does not prove causation. But considering the already-high prevalence of Alzheimer's disease in older men, any increased risk would have significant public health implications."
The researchers are planning to look more closely at the link between ADT and Alzheimer's disease using much larger collections of cancer patient records.
Testosterone protects brain cells
The researchers did not investigate how ADT, by lowering testosterone, can lead to Alzheimer's disease.
However, there is evidence that testosterone helps protect brain cells, suggesting lower levels of the hormone could lower resistance to the processes that lead to Alzheimer's disease.
Other studies have suggested lower levels of testosterone may take the brakes off the production of amyloid beta, a faulty protein that develops in the brain of people with Alzheimer's disease.
There is also the possibility of an indirect effect in that low testosterone promotes diabetes, atherosclerosis and other conditions linked to higher Alzheimer's risk.
The American Cancer Society estimate that in 2015 there will be around 220,800 new cases of prostate cancer and 27,540 deaths from the disease, which occurs mainly in older men. Around 60% of cases are diagnosed in men aged 65 and older.
Meanwhile, in another example of where a treatment for one condition can affect the risk of another, Medical News Today recently learned risk of stroke is higher in older men who take alpha-blockers, a type of drug that is typically used in the treatment of high blood pressure and to improve urine flow in older men with enlarged prostates.