Low testosterone levels increase dementia risk

In a retrospective study of medical records, researchers from Stanford University and the University of Pennsylvania concluded that lowering testosterone levels in men with prostate cancer could be associated with an increased risk of developing dementia. These findings, if confirmed by future clinical trials, could alter the way doctors treat prostate cancer in the near future.

A common component of current prostate cancer treatments involves androgen deprivation therapy (ADT), which lowers patients’ testosterone levels. Since the 1940s, doctors have considered this treatment an effective preventative method for halting the progression of prostate cancer because testosterone promotes the growth of prostate tumors. The therapy is particularly common in men whose cancer is untreatable with radiotherapy or surgery alone.

However, this new study, published online in JAMA Oncology on Oct. 13, stated that ADT could put patients with a history of dementia at risk of further complications. In fact, the study stated that men who received ADT were “twice as likely to develop dementia within five years than patients whose treatments [didn’t] include lowering testosterone.”

The surprising conclusion aligns with previous studies linking androgens like testosterone to neuron growth and protection against certain types of cognitive deficits. Therefore, lowering testosterone levels could inhibit brain signals.

The implications of this study are not new; The study’s co-authors Dr. Kevin Nead, a resident at the University of Pennsylvania, and Nigam Shah, an associate professor at Stanford University published results of a similar study in 2015 linking ADT and Alzheimer’s disease. However, researchers decided to expand the scope of the study.

“When we published our last paper, a letter to the editor pointed out that Alzheimer’s is often confused with vascular dementia,” Shah said in a press release. “So instead of looking for Alzheimer’s and dementia separately, we decided to aggregate them into a higher-level category — all dementias and cognitive decline.”

In the new study, researchers increased their sample size to decrease random error, analyzing 10,000 de-identified patient records from Stanford Medicine’s clinical research data warehouse. The study found that, of the 1,829 men who had undergone ADT, 7.9 percent developed dementia within five years. Only 3.5 percent of the patients who did not receive ADT developed dementia.

However, Nead and Shah emphasized that patients with prostate cancer should not change treatments without consulting their doctor first. Like all retrospective studies, researchers could not firmly establish a cause-and-effect relationship between ADT and dementia. Without randomization in health record studies, researchers stated, the conclusions drawn could be inaccurate.

Still, studies like Nead and Shah’s are cost and time-effective; the study spanned a few weeks rather than the few years needed for a clinical study. In addition, millions of dollars are usually required for randomized clinical studies. Regardless, retrospective studies like Nead and Shah’s may help uncover unexpected relationships between treatments and side effects and can often drive researchers to conduct future clinical trials.

Nead added that a prospective, randomized clinical trial would help more firmly establish a connection between ADT and an increased risk of dementia. He also hopes to identify what types of patients might be vulnerable to that increased risk.

The study’s implications may have lasting effects on the way doctors treat prostate cancer, which affects one in seven men, according to the Prostate Cancer Foundation. If clinical trials confirm hypotheses of a positive correlation between ADT and development of dementia, doctors may begin recommending alternative treatments for patients, especially those with a history of dementia.