Alzheimer’s disease may be a risk for older prostate cancer patients given hormone-blocking treatment

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Alzheimer’s disease may be a risk for older prostate cancer patients given hormone-blocking treatment, a large, U.S. government-funded analysis found.

Previous evidence has been mixed on whether the treatment might be linked with mental decline.

But experts say the new results stand out because they’re from a respected national cancer database and the men were tracked for a long time – eight years on average.

Among 154,000 older patients, 13% who received hormone-blocking treatment developed Alzheimer’s, compared with 9% who had other treatment or chose no therapy, the study found.

The risk for dementia from strokes or other causes was higher: It was diagnosed in 22% of those who got hormone-blocking treatment, versus 16% of the other patients.

The results, using perhaps one of the largest and most reliable databases, suggests there truly may be a connection, said Dr. Sumanta Pal, a prostate cancer expert with the American Society of Clinical Oncology. Pal was not involved in the study.

The analysis from University of Pennsylvania researchers was published Friday in JAMA Network Open.

The results aren’t proof but experts say they underscore the importance of discussing potential risks and benefits when choosing cancer treatment.

The researchers analyzed data from a National Cancer Institute database of cancer cases and treatment and covers almost 30% of the U.S. population.

The study focused on men in their 70s, on average, with local or advanced prostate cancer diagnosed between 1996 and 2003.

They were followed until 2013.

Medicare records indicated dementia or Alzheimer’s diagnosis.

Hormone-blocking treatment can include testes removal to reduce levels of testosterone, which fuels prostate cancer growth.

But it more typically involves periodic drug injections or implants that achieve the same result.

Most U.S. men who receive this treatment are in their 70s or older.

It’s sometimes used in men who might not be healthy enough to tolerate other cancer treatments including surgery to remove the prostate and radiation.

It’s unclear how the treatment might be linked with mental decline.

The researchers noted that it can lead to diabetes, which also has been linked with dementia – perhaps because blood vessel damage from diabetes can restrict blood flow to the brain.

Hormone treatment also raises risks for heart disease and depression, which both have been linked with dementia.

Researcher Grace Lu-Yao of the Sidney Kimmel Cancer Center in Philadelphia, said the potential dementia risks from hormone-blocking treatment may outweigh any benefit for younger, healthier patients with longer expected life spans.

While the study doesn’t prove that the treatment causes dementia, she said, it is important to tell patients “because of the potential impact of Alzheimer’s disease or dementia on the quality of life of patients and their family.”

She was not involved in the study.


Postmenopausal women who received hormone replacement therapy (HRT) had a “small absolute increased risk” of developing Alzheimer disease in a nationwide case-control study from Finland.

“The present study indicates that the use of systemic hormone therapy, once claimed to be protective against Alzheimer’s disease, is accompanied with a 9–17% increase in the risk of the disease in postmenopausal women, whereas the exclusive use of vaginal estradiol shows no risk,” the researchers report in an article published online March 6 in the BMJ.

“Even though the absolute risk increase for Alzheimer’s disease is small, our data should be implemented into information for present and future users of hormone therapy,” Hanna Savolainen-Peltonen, MD, PhD, Department of Obstetrics and Gynecology, University of Helsinki, Finland, and colleagues conclude.

The findings showed that “particularly long-term exposure to hormone therapy is associated with an increased risk of Alzheimer’s disease,” they add. The increase in risk “is not dependent” on the age at which treatment starts.

Thus, the “evidence is reassuring for women needing a few years’ treatment for menopausal symptoms,” Pauline M. Maki, PhD, Departments of Psychiatry, Psychology, and Obstetrics and Gynecology, University of Illinois at Chicago, and colleagues observe in an editorial that accompanies the article.

“For women in early menopause with bothersome vasomotor symptoms, no compelling evidence exists of cognitive concern from randomized trials” of HRT, according to the editorialists, “and instead there is reassurance about cognitive safety.”

On the other hand, they too stress that “concerns about longer term use of estrogen plus progestin on cognitive outcomes remain.”

Does HRT Prevent or Promote Alzheimer Disease?

Observational studies have reported that HRT is associated with a reduced risk for Alzheimer disease, the authors note, but the studies lacked a placebo group, and the women who received HRT may have been healthier to start with.

This criticism “gained strong support” when the placebo-controlled Women’s Health Initiative Memory Study (WHIMS) reported that postmenopausal women who took estrogen had an increased risk for impaired cognition and probable dementia.

However, WHIMS was criticized because the women started taking HRT at age 65, long after menopause started and later than usual in clinical practice.

To investigate this issue further, the researchers conducted a case-control analysis, using data from national registries in Finland.

They identified 84,739 postmenopausal women who received a diagnosis of Alzheimer disease from a neurologist or geriatrician between 1999 and 2013.

The investigators matched these women with 84,739 women who were the same age and lived in the same area (hospital district) but who did not develop Alzheimer disease.

Alzheimer disease was mostly diagnosed when the women were aged 80 years or older (56%) or 70 to 79 years (37%), and rarely when they were younger than this (7%).

Of the women with Alzheimer disease, 69% had not used HRT, 13% had used vaginal estradiol, and 1% had used tibolone (multiple brands).

The remainder had used systemic HRT — more often, estrogen/progestin therapy (63%). The remainder took estradiol only.


More information: Ravishankar Jayadevappa et al. Association Between Androgen Deprivation Therapy Use and Diagnosis of Dementia in Men With Prostate Cancer, JAMA Network Open (2019). DOI: 10.1001/jamanetworkopen.2019.6562

Journal information: JAMA Network Open

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