Prostate Cancer Hormone Therapy Tied To Dementia Depression In Younger Men
Androgen deprivation therapy in men aged 40 to 64 years with nonmetastatic prostate cancer is associated with an increased risk for dementia and depression, according to investigators.
In an observational study of 9117 men aged 40 to 64 years diagnosed with localized PCa, a team led by Quoc-Dien Trinh, MD, of Brigham and Womens Hospital in Boston, found that patients who received ADT had a significantly higher incidence of new-onset dementia and depression compared with those who did not .
The ADT group had a 1.7- and 2.0-fold increased risk for new-onset dementia and depression, respectively, compared with no-ADT, Dr Trinh and colleagues reported in European Urology Oncology. In addition, longer duration of ADT is associated with a higher risk for either outcome.
Our results add to the evidence that the receipt of ADT is associated with depression and dementia, and emphasize the importance of neurocognitive assessment in patients undergoing ADT, especially in younger patients, the authors wrote.
They added, In patients with advanced disease, who are likely to remain on ADT for the rest of their lives, it is crucial to screen them for these adverse outcomes, especially in the era of promising novel agents.
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Caution In Changing Treatment
A collaboration between prostate cancer and Alzheimers researchers could lead to benefits on both sides: Alzheimers researchers could learn more about the influence of low testosterone on the brain, and oncologists could learn strategies to allow them to continue ADT. Pike said that there are synthetic testosterone drugs, called selective androgen receptor modulators , in clinical trials that could be combined with ADT. They could provide the hormones protective benefits to the rest of the body, while letting the ADT influence the cancer growth.
Further, it appears that not every patient has the same risk when given ADT. Brian Gonzalez, an assistant professor at the Rutgers Cancer Institute in New Jersey, compared men receiving hormonal therapy for prostate cancer to men who were not and saw that a patients genetic makeup partially explained why some showed a greater risk of cognitive impairment than others.
Interview With An Expert: Cognitive Impairment And Adt
Alicia Morgans, M.D., M.P.H., Medical OncologistVanderbilt University Medical Center
Does ADT cause cognitive impairment?
This question seems simple, but really, its more like opening a medical can of worms. So lets ask a different question.
Do men on ADT get cognitive impairment? Yes, some do. But many dont.
It is hard to pin down definitive facts here like, how many men get it? Whats the risk at one year, two years, five years, and ten years?
Nobody knows the exact statistics, and there are several reasons why.
- There are probably many more men on ADT with cognitive impairment than we know about. But they dont spend enough time with their doctors, at 5- and 10-minute follow-up visits to renew their Lupron prescription, for their mental status to be evaluated. Cognitive impairment doesnt always show up in casual conversation.
- Scientists looking to answer this question arent using standardized criteria. For example, does hormonal therapy mean only ADT, or ADT plus another drug, like enzalutamide? Also, are we talking about actual Alzheimers disease here, or just an inability to find the right word quickly on a crossword puzzle?
Lets take yet another tack, and look at men who are actually showing signs of cognitive impairment. Thats not much easier there are still more questions:
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Testosterone Deprivation And Alzheimers Disease Pathogenesis In Small Animals
AD is characterized from a pathological point of view by two pathognomonic lesions: 1/extracellular plaques of insoluble -amyloid peptides and 2/neurofibrillary tangles composed of hyperphosphorylated tau protein in neural cytoplasm. Using preclinical experiments in rodents, testosterone has been shown to modulate A and potentially hyperphosphorylation of tau in the serum and the central nervous system.
The Role of Testosterone Depletion on A Accumulation
Ramsden et al., comparing gonadectomized and sham GDX male rats, were the first to show that depletion of endogenous sex steroid hormones via GDX caused a 25% increase in soluble brain levels of A40 and A42. They also revealed that injections of 5-dihydrotestosterone to GDX rats not only reversed the GDX-induced increase in A but significantly lowered brain levels of both A species compared to sham GDX animals. In contrast to the increase in soluble brain levels of A, no effect of GDX on plasma A was observed .
The effect of testosterone on the level of A peptides was also investigated by Wahjoepramono et al. in guinea pigs . In accordance with the previous studies, castrated guinea pigs exhibited lower cerebrospinal fluid A40 level that non castrated animals. But, unlike Ramsden et al., these authors showed also a decrease in plasma A40 level for GPX.
If the link between testosterone depletion in plasma and brain A accumulation has been pointed out, the underlying molecular mechanisms are still unclear.
New Study Downplays Potential Risk Of Dementia And Alzheimers Disease Among Elderly Men Treated With Hormonal Therapy For Prostate Cancer
- By Charlie Schmidt, Editor, Harvard Medical School Annual Report on Prostate Diseases
The male hormone testosterone contributes to normal brain function, and some research links memory loss in older men to testosterone declines that occur naturally with aging. However, testosterone is also like jet fuel for prostate tumors, causing them to grow faster, so during cancer treatment doctors will often give hormonal therapies that suppress its activities in the body. But do those therapies increase risks for dementia and Alzheimers disease? Some recent reports suggest that they might, although researchers have so far been unable to prove the connection, and other studies have found no link at all.
In October, researchers published the largest study yet of hormonal therapy as a possible risk factor for dementia and Alzheimers disease. The researchers scoured Medicare beneficiary data for 1.2 million men aged 67 or older with prostate cancer who were treated between 2001 and 2014. Of those men, 35% were treated with hormonal therapy. Published in the prestigious Journal of Clinical Oncology, the investigation found no convincing evidence that hormonal therapy poses a meaningful risk for either dementia or Alzheimers disease.
Charles Schmidt
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Doctors Should Talk To Patients About Possible Cognitive Risks Of Adt
Given that Dr. Nead and colleagues have now produced two studies suggesting a link between ADT and dementia, they say further research into the cognitive effects of this cancer therapy is warranted.
As the population of older, long-term cancer survivors continues to rise, the health issues that cancer therapies can leave in their wake will become increasingly important.
Further studies are needed to investigate the association between this therapy and dementias, given the significant patient and health system impacts if there are higher rates among the large group of patients undergoing ADT today.
Dr. Kevin T. Nead
MNT asked Dr. Nead whether healthcare providers should warn prostate cancer patients about the possible cognitive risks of ADT.
All men should have a detailed discussion with their doctors regarding the risks and benefits of ADT. Based on the body of literature that now exists, it would be reasonable to counsel patients regarding potential cognitive risks as this has been shown in multiple retrospective and prospective studies, he replied.
We would, however, not recommend specific changes to clinical practice based on this study alone, given that androgen deprivation therapy is a life-extending treatment in some men with prostate cancer.
How Hormone Therapy Affects Thinking And Memory
Memory and the way we process information is called cognition. Cognitive ability describes how well you can remember and concentrate. This includes how you manage doing more than one task at the same time.
Some people notice changes to how they think and remember after hormone treatment for prostate cancer. It may not affect you every day. You may forget a word during a sentence or struggle to remember a shopping list.
Doctors call this mild cognitive impairment. You may hear it described as chemo brain, or a general fogginess. It doesnt only happen after chemotherapy. It can also be a side effect of hormone treatment.
For many people the changes are very subtle and get better after treatment.
Researchers are trying to find out how hormone treatment affects memory.
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Biomarkers To Evaluate Androgen Deprivation Therapy For Prostate Cancer And Risk Of Alzheimers Disease And Neurodegeneration: Old Drugs New Concerns
- 1Division of Radiation Oncology, Department of Oncology, Geneva University Hospitals and Faculty of Medicine, Geneva University, Geneva, Switzerland
- 2Division of Nuclear Medicine and Molecular Imaging, Diagnostic Department, Geneva University Hospitals, and NimtLab, Faculty of Medicine, Geneva University, Geneva, Switzerland
- 3Division of Adult Psychiatry, Department of Psychiatry, Geneva University Hospitals and Faculty of Medicine, Geneva University, Geneva, Switzerland
- 4Memory Clinic, Department of Rehabilitation and Geriatrics, Geneva University and University Hospitals, Geneva, Switzerland
This Prostate Cancer Therapy May Up Dementia Risk
Study found chances doubled, but did not prove androgen deprivation caused damage to brain
HealthDay Reporter
THURSDAY, Oct. 13, 2016 — The risk of dementia might be doubled for prostate cancer patients who are treated with testosterone-lowering drugs, a new study suggests.
Men who underwent androgen-deprivation therapy had close to an 8 percent risk of developing dementia within five years of treatment, compared with a 3.5 percent risk for prostate cancer patients who didn’t receive the therapy, researchers discovered.
“People who got ADT in our study had twice the risk of developing dementia, compared to people who didn’t,” said lead researcher Dr. Kevin Nead. He is a radiation oncology resident at the University of Pennsylvania who conducted the research while at Stanford University in California.
But, the study only found an association between ADT and dementia risk, not cause and effect. And men undergoing androgen therapy shouldn’t stop the treatment based on these findings, the researchers said, because more studies are needed to verify this potential link.
Testosterone can promote the growth of prostate cancer, so one treatment option involves using drugs to reduce blood levels of male hormones, or androgens, the study authors explained in background information.
Even so, there’s a good chance your doctor will pursue a course of “watchful waiting” rather than androgen-deprivation therapy, surgery or some other treatment, the researchers noted.
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Does Hormone Therapy For Prostate Cancer Raise Dementia Risk
When men with prostate cancer have to take drugs that block the testosterone fueling their tumors, they can suffer a host of side effects that include impotence, bone loss, heart trouble and obesity.
But new research uncovers yet another possible downside to the treatment: These men may be at greater risk for dementia.
For any type of dementia, that risk increased 17% for Alzheimer’s disease, it increased 23%, the researchers said.
Common side effects of so-called androgen-deprivation therapy include hot flashes, unstable mood, trouble sleeping, headaches, high blood sugar, allergic reactions and impotence.
“Androgen-deprivation therapy may not only cause physical changes such as osteoporosis, cardiovascular disease or obesitybut may also cause changes in cognition,” said researcher Dr. Karl Tully, a research fellow at Brigham and Women’s Hospital in Boston.
But Tully cautioned that this study cannot prove that such hormone therapy caused dementia, only that the two are associated.
The investigators also found that men on this type of therapy had a 10% greater risk of seeking psychiatric services.
The risk for dementia increased as the length of therapy increased, the researchers noted. Men on androgen-deprivation therapy for six months had a 25% increased risk for any kind of dementia and a 37% increased risk for Alzheimer’s, the findings showed.
One urologist, however, doesn’t think patients need to be told about this tenuous association.
Explore further
Prostate Cancer Hormone Therapy Tied To Higher Dementia Risk
By Lisa Rapaport, Reuters Health
4 Min Read
– Men who take hormone therapy for prostate cancer may have a higher risk of dementia than patients who receive different treatment for these malignancies, a U.S. study suggests.
Prostate cancer cells need testosterone to grow and spread. Researchers focused on a common treatment known as androgen deprivation therapy , which works by depriving tumor cells of testosterone. Side effects can include sexual dysfunction, weight gain and fatigue.
Multiple studies now suggest that androgen deprivation therapy may be associated with cognitive changes, including dementia, and the current study certainly supports this, said lead study author Dr. Kevin Nead of the University of Pennsylvania in Philadelphia.
Patients with prostate cancer who received hormone therapy were more than twice as likely to develop dementia as men who received alternative treatments, Nead and his colleagues found.
There is certainly a concern that we may be over treating some men with prostate cancer and the current study reinforces the importance of appropriately and thoughtfully selecting patients for all treatments, Nead, who conducted the research at Stanford University, added by email.
To explore the link between hormone therapy and dementia, Neads team analyzed data on 9,272 men with prostate cancer treated at an academic medical center from 1994 to 2013.The study group included 1,826 men who were treated with ADT.
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Its Not Fair For Us Just To Look At The Benefits Of Treatment Anymore She Says Now That We Are Starting To Understanding The Risks Better
One easy place to start is to make sure that all men who are put on ADT really need it. Next, men on ADT need better follow-up to monitor their cognitive function. Morgans believes cognitive impairment in men on ADT is underreported, underappreciated, and underdiagnosed. In a PCF-funded study, Morgans patients are taking brief neuropsychological tests the tests look for changes in verbal memory, visual memory, attention, and executive function. She hopes to develop reliable tests that can be done online tests that could be given to many more patients in clinical trials, so that investigators can get an idea of the scope of the problem.
Family and friends can help: Someone who is having cognitive impairment may not be aware of changes, or may not be able to articulate them well. But his family and friends can help bring worrisome symptoms to the doctors attention.
Layers of medication: One of Morgans patients, a 76-year-old man, had been doing fine on Lupron for years. But when his PSA started to rise, Morgans added abiraterone, and then enzalutamide. For this man, enzalutamide might have been the tipping point, one thing on top of another thing, on top of another thing. He was experiencing confusion and forgetfulness, she says. The man, a minister, was not able to write or deliver sermons anymore. We decided, despite the fall in his PSA, to stop the enzalutamide. Four weeks later, his cognitive function had improved, and he continues to give sermons today.
Hormone Therapy For Prostate Cancer May Raise Risk Of Alzheimers Dementia
For patients with prostate cancer, treating the disease with androgen deprivation therapy is linked to a higher likelihood of being diagnosed with Alzheimers disease or dementia, compared to patients who do not receive the therapy, according to a study from researchers in the Perelman School of Medicine. The results were published this week in JAMA.
Of the 154,089 men sampled in the study, 62,330 received ADT within two years of their prostate cancer diagnosis and 91,759 did not. Of the patients with prostate cancer who received the hormone therapy, 13 percent were later diagnosed with Alzheimers disease, compared to 9 percent who did not receive ADT. For dementia, those numbers widened: 22 percent of prostate cancer patients who received ADT were diagnosed with dementia, compared to 16 percent who did not receive the therapy. This research builds on previous, smaller studies that showed similar correlations between hormone therapy and cognitive risks in patients with prostate cancer. The lifetime risk for Alzheimers and dementia for men overall is 12 percent, according to data from the Framingham Heart Study.
Read more at Penn Medicine News.
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Tips To Help With Changes To Thinking And Memory
- Keep a diary or calendar to help you remember what you need to do each day
- Write lists of jobs to do, things to buy or where you keep things you use every day
- Use post it notes to remind you to do tasks
- Write down people names with a description to remember them
- Repeat information back to people to check understanding
- Keep your mind active, you could try crosswords, sudoku or puzzles
Risk Of Dementia Rises With Prostate Cancer Hormone
5 Min Read
Prostate cancer patients who received hormone-lowering therapy were at higher risk of developing dementia and Alzheimers disease later on than men who didnt get this treatment, a large U.S. study finds.
Researchers who followed nearly 155,000 men with prostate cancer found that overall, those given so-called androgen-deprivation therapy were at a 20% higher risk of being diagnosed with dementia and at 14% higher risk of an Alzheimers diagnosis in the next 10 years. The risk continued to rise with increasing doses of androgen-deprivation drugs.
The results suggest that in cases where the prostate cancer is localized, androgen-deprivation therapy may not be a good choice, said the studys lead author, Ravishankar Jayadevappa, a research associate professor in the department of medicine at the University of Pennsylvanias Perelman School of Medicine in Philadelphia.
Even in patients at high risk, there needs to be a discussion about the elevated risk of dementia and Alzheimers disease during long-term follow-up, Jayadevappa said.
The most common androgens found in the male body are testosterone and dihydrotestosterone . According to the American Cancer Society, doctors may choose to prescribe androgen-lowering therapy because it can result in slower growth – or even shrinkage – of prostate tumors.
Studies on the cognitive impacts of androgen-deprivation therapy have had mixed results, Jayadevappa and his colleagues note in JAMA Network Open.
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