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Does ADT Raise Your Risk of Alzheimer’s?

Part Four of Four

It’s challenging enough that you need to be on androgen deprivation therapy (ADT) in the first place.   Now, in addition to prostate cancer, you have to worry about the risk of dementia?

Some studies have shown an increased risk for Alzheimer’s disease, and cognitive impairment and depression are known problems that can go along with ADT. We’ll come back to those in a moment.

There is some reassuring news: a new study, the largest of its kind, published in the Journal of Clinical Oncology, suggests that your risk for Alzheimer’s disease does not go up with ADT.   The study was led by Clement Joseph McDonald, M.D., of the National Institutes of Health. It involves a massive database: the medical records of men with advanced prostate cancer – more than 1.2 million of them, age 67 and older, enrolled in Medicare.

Between 2001 and 2014, 35 percent of these men were treated with ADT (either through drugs such as Lupron or with surgical castration). Of these men, about 9 percent developed Alzheimer’s disease, nearly 19 percent developed dementia, and about a third died without developing either condition.

Now, here’s where it gets a little complicated: the unadjusted rates for dementia in men who were on ADT were slightly higher than for the men not on ADT – nearly 39 percent compared to nearly 33 percent. But when McDonald and colleagues accounted for factors such as other cancer treatment, other health conditions, and age, they found that the risk of Alzheimer’s was not significantly higher in the men on ADT. In fact, it was even slightly lower, but this “possibly was attributable to the high death rate.” In fact, the average time of follow-up was about five and a half years.

If you’re reading this and you think, “Oh, no, they didn’t live very long, and that’s why they didn’t get dementia,” well, you may be right. But treatment for advanced cancer is getting better all the time, and it’s not clear from this study whether these men went on to have second-line treatment, such as abiraterone, enzalutamide, taxotere, or any of the immunotherapy drugs currently being tested in clinical trials across the country.

So take heart: New and better treatments are here, and what happened to these men does not define what’s going to happen to you.

But here’s where the grain of salt comes in: Some of these men did develop dementia. So even if it wasn’t technically Alzheimer’s, the name of the problem doesn’t really matter if you’re the one who’s got it. What do we make of this?

As we’ve discussed before, ADT can cause metabolic syndrome: it can raise your blood pressure, your blood sugar level, your cholesterol and triglycerides, and it’s very easy to gain weight – particularly right in the belly, which raises your risk for diabetes, heart attack, and stroke. You need to burn more calories than you’ve ever had to in your life just to lose a pound. That doesn’t mean it can’t be done – it can. You just have to work harder. But you can do this, and it helps if you don’t eat a lot of carbs.

If you are on ADT, you also need to do your best to help out your cardiovascular system with exercise. It doesn’t have to be anything more strenuous than walking; just keep that blood flowing and the heart pumping, and what’s good for the heart is good for the brain. Which means, you can help prevent cognitive damage by staying active. Many men with ADT also have temporary depression. This also is improved by exercise – but if you need it, medication can help these symptoms, too.

 

More of this story and much more about prostate cancer are on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.” The PCF is funding the research that is going to cure this disease, and they have a new movement called MANy Versus Cancer that aims to crowd-fund the cure, and also empower men to find out their risks and determine the best treatment. As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

Regular disclaimer: This is a blog. It is not an encyclopedia article or a research paper published in a peer-reviewed journal. If a relevant publication is involved in the story, I mention it. Otherwise, don’t look for a lot of citations, especially if I’m quoting from a medical professional.

 

 

ADT and Cognitive Impairment

Part Three of Four

Does ADT cause cognitive impairment? This question seems simple, but really, it’s more like opening a medical can of worms. So let’s ask a different question. Do men on ADT get cognitive impairment? Yes, some do. But many don’t. It is hard to pin down definitive facts here – like, how many men get it? What’s 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 don’t 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 doesn’t always show up in casual conversation.
  • Scientists looking to answer this question aren’t using standardized criteria. For example, does hormonal therapy mean only ADT, or ADT plus another drug, like enzalutamide? Also, are we talking about actual Alzheimer’s disease here, or just an inability to find the right word quickly on a crossword puzzle?

Well, what about men who are actually showing signs of cognitive impairment? That’s not much easier; there are still more questions:

  • Would they have gotten it anyway?
  • Did they start ADT with some risk factors for dementia already on board?
  • If they are showing signs of dementia, is it because when they got on ADT they stopped exercising, gained weight, and experienced depression – and could one of those those factors actually be the tipping point?

I recently interviewed medical oncologist Jonathan Simons, M.D., CEO of the Prostate Cancer Foundation (PCF), and medical oncologist Alicia Morgans, M.D., of Northwestern University, about ADT for the PCF’s website.  “We have reached a crossroads, and in some ways, it’s actually a sign of progress,” notes Simons. Long, long ago, heart disease wasn’t a big health problem – because people died of other things, like accidents and infections, and diseases that we now get routinely vaccinated for. Diabetes wasn’t a huge risk for many people; sugar wasn’t widely available, there was no such thing as soda, obesity was rare, and people were more physically active. Prostate cancer wasn’t that big a deal, either, because most men didn’t live long enough to get it.  “Not too long ago, men with metastatic cancer died within months or a few years of their diagnosis. Today, men with metastatic prostate cancer are living long enough to develop other problems, and doctors – who previously had just been focused on keeping these patients alive – are trying to figure out how best to keep them alive and well.”

What we have here is an issue of survivorship – living with metastatic prostate cancer, and dealing with the side effects and challenges of treatment.   Medical oncologist Alicia Morgans, M.D., M.P.H., of Northwestern University, is a pioneer in studying survivorship. Cognitive issues have not been much studied in prostate cancer, and scientists are playing catch-up. “It’s 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 doctor’s 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.”

For this man, the key to cognitive issues seemed to be enzalutamide. For another man, it could be something different. It could be a different kind of domino effect – the higher risk of diabetes and cardiovascular disease, for instance; maybe these other health problems, in turn, affect the vitality of the brain. “There may be subclinical strokes or cerebrovascular disease that we don’t know about,” Morgans says.

Loss of estrogen? Morgans suspects that a change in cognitive function might also have something to do with a man’s estrogen levels. Women aren’t the only ones who make estrogen; men make it, too, at lower levels. But ADT causes men to have “very low levels of estrogens, lower than postmenopausal women have.”  In studies of women with breast cancer, she points out, “low estrogen levels on their own can be associated with cognitive decline. It’s not ‘chemo brain,’ it’s something different.”

Men with prostate cancer don’t need to have low estrogen levels in order for their cancer to be treated; it just happens as a byproduct. Normally, men need some level of testosterone in order to make estrogens. “Estrogen doesn’t have to fall for us to treat prostate cancer, but it does fall with the method we use – we know testosterone drops to a place it’s never been since puberty.” Would giving some type of estrogen along with the ADT be helpful? No one knows.

Depression is a risk factor for dementia; big changes in sleep habits can also be a risk factor. It may be that addressing each of these separately – with an antidepressant, with exercise, and with melatonin to help with sleeping – could help keep the brain working better.

What about changes in the way ADT is given? Intermittent therapy may be an option. This could mean giving ADT, stopping it for a few months, and then starting back up again. “When men go off ADT, their testosterone comes back, they feel better, think better, their executive function is better – their ability to do a crossword puzzle, or find a synonym, or find the word they’re searching for – and they feel more like themselves again.” Another approach, as investigator Samuel Denmeade is testing at Johns Hopkins, is “bipolar” hormonal therapy: alternating ADT with its polar opposite – high-dose testosterone.

Could “brain exercise” help? Maybe. Crossword puzzles and mind-challenging games may indeed act as mental push-ups and sit-ups, says Simons.

The ultimate goal for treatment, scientists and doctors agree, is to find a way around ADT altogether, or to change it somehow so that the prostate cancer is affected, but the brain is not. Until then, it’s up to doctors to use ADT wisely, only when it is medically appropriate. “Using hormonal therapy has to be more than just a reflex, like giving people penicillin for a head cold,” Simons states. “The PCF, in fact, is actively funding research for other ways to treat metastatic cancer that don’t involve hormones at all.”

It’s also up to you, too, to make sure you start ADT only if and when you need it. If you are at intermediate- to high-risk of recurrence, or if you have a rising PSA but no evidence of metastatic disease and your doctor wants to put you on ADT, get a second opinion. You may also be eligible for a clinical trial of a different kind of therapy that does not affect your hormones, including treatment for oligometastasis — SBRT radiation to a few spots of cancer in your bones, or surgery to remove cancer that is just in one lymph node.

If you do have metastatic disease, right now ADT is the standard of care, and it could put your cancer into remission for many years. There is a lot you can do to help mitigate the side effects – which, in turn, may help protect your brain.

———

More of this story and much more about prostate cancer are on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.” The PCF is funding the research that is going to cure this disease, and they have a new movement called MANy Versus Cancer that aims to crowd-fund the cure, and also empower men to find out their risks and determine the best treatment. As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

Regular disclaimer: This is a blog. It is not an encyclopedia article or a research paper published in a peer-reviewed journal. If a relevant publication is involved in the story, I mention it. Otherwise, don’t look for a lot of citations, especially if I’m quoting from a medical professional.

 

ADT and Metabolic Syndrome

Part Two of Four

Metabolic syndrome includes an unholy cluster of bad things that can lead to a heart attack or stroke. Elevated blood pressure; unhealthy levels of blood sugar, cholesterol, and triglycerides; and abdominal fat – a big jelly donut of visceral fat, also known as “heart attack fat,” right around your belly, a cardiac spare tire. A big gut equals a bigger risk for diabetes, heart attack and stroke.  All of this is magnified with ADT, androgen deprivation therapy for prostate cancer.

Maybe you already have some of these risk factors; maybe you’ve already had a heart attack, or you’ve got diabetes. If you need ADT, you need it.

But hear these words: You will need to fight what it’s doing to do to the rest of your body, even as it saves you from your prostate cancer.

You will need to get mad at it. Work hard to take back your life – work doubly hard, because not only will it try to turn you into a tub of butter, but you might get mildly depressed. Your brain will tell you that you’re too tired to exercise. It’s deceiving you. You must not listen to it. Exercise anyway.

Here’s what you’re up against: Normally, if a man wants to lose a pound, he needs to burn 3,500 calories. A man on ADT who wants to lose that same pound needs to burn 4,500 calories. He’s slogging upstream with ankle weights. His metabolism is slower, his sugar metabolism is messed up, his blood pressure may be higher, and for many reasons, he probably feels like crap. Maybe he stops taking care of himself.   This is the worst thing he can do.

You need to be aware of this, because it might not be on your doctor’s radar.

Just as important, you need to enlist your family and friends, NOT ONLY to help push you to exercise and eat right – cut way down on the carbs and sugar, especially – but to tell you if you seem depressed, because depression might have snuck up on you, and you might not have noticed it.

I recently interviewed medical oncologist Jonathan Simons, M.D., CEO of the Prostate Cancer Foundation, and medical oncologist Alicia Morgans, M.D., of Northwestern University, about ADT for the Prostate Cancer Foundation’s website.

All of these things can be fought, both doctors say. However, “if you just go back to the urologist or oncologist for a 5-minute appointment and another Lupron shot, you are probably not getting the monitoring you need,” says Simons. Depression may not show up in a brief doctor’s visit. Even if the scale shows that you’ve put on weight, your doctor might say, “Well, that’s common with ADT.”

Years ago, when doctors first started using ADT, “men didn’t live that long,” Morgans notes. “Now, men are living for years or even decades on ADT, and if that stops working, there are other drugs that can help, and exciting new types of drugs showing amazing results for some men in clinical trials.” This is very good news; however, the downside is that doctors might just think, “hey, it’s great, he’s still alive and his PSA is not moving up.”

But we know that weight gain is not only a common side effect of ADT; it’s bad. It’s also something you can help prevent. You need to exercise, with cardio (walking, swimming, riding a bike, aerobics, jogging, etc.,) plus weights for strength. These can be light weights; you don’t need to turn into Arnold Schwarzenegger and bench-press a Volkswagon Beetle or anything like that. You just need to keep your muscles working. Exercise will help with depression, with the cardiac risks, and with the risk to your brain. As University of Colorado radiation oncologist E. David Crawford, M.D., recently put it, “What’s heart healthy is usually prostate-cancer healthy… I’ve got a number of (patients on ADT) who are in great shape and they’re tolerating [treatment] quite well. These are the people who are out there, who continue to lift weights, they continue to exercise, they watch their diet.”

The metabolic syndrome that ADT causes may be a major reason – nobody knows for certain yet – why some men who are on ADT have cognitive impairment.

Coming up next:  ADT and cognitive impairment.

More of this story and much more about prostate cancer are on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.” The PCF is funding the research that is going to cure this disease, and they have a new movement called MANy Versus Cancer that aims to crowd-fund the cure, and also empower men to find out their risks and determine the best treatment. As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

Regular disclaimer: This is a blog. It is not an encyclopedia article or a research paper published in a peer-reviewed journal. If a relevant publication is involved in the story, I mention it. Otherwise, don’t look for a lot of citations, especially if I’m quoting from a medical professional.

ADT and Prostate Cancer: Who Really Needs It?

Part One of Four

The only people who really like androgen  deprivation therapy (also called ADT, or hormonal therapy) are the drug companies that make billions of dollars a year selling the drugs.   Doctors don’t like it, and men don’t like being on these drugs.  So why do it?   There are few specific situations when ADT therapy is the right thing to do. These are the most common:

* Intermediate-risk men who are given six months of ADT plus external-beam radiation;

 * High-risk men who are getting radiation therapy. This is a finite course of ADT, and this combination – two or three years of ADT plus external-beam radiation – has been proven to cure cancer in many men.

* Men with metastatic prostate cancer. ADT can make a big difference in these men, in relieving their symptoms and dramatically improving their quality of life. It can also extend life – some men have been on ADT for 20 years and are still going strong.

Who should not get ADT? Anybody else with prostate cancer. If you just have a rising PSA after radiation therapy or radical prostatectomy, that is not a good enough reason for a doctor to put you on ADT. If your doctor wants to put you on ADT to “shrink your prostate” before brachytherapy, that’s not a good enough reason.

ADT has never been shown to extend life if it’s given too soon, as opposed to taking it when you need it. Johns Hopkins urologist Patrick Walsh, M.D., with whom I have written several books on prostate cancer, has been saying this for many years.

Why not just start ADT? At least it’s doing something, rather than sitting around waiting for the cancer to spread. Well, that sounds good. Please refer to the previous paragraph, and read that first sentence again. Now, if you have a rising PSA, there are other things you can do that may help a lot. These include:

  • Salvage surgery or radiation, if your doctor thinks the cancer is still confined to the “prostate bed,” the area around the prostate.   (Note: In this case, if you get salvage radiation, your radiation oncologist may want to put you on a limited course of ADT, which is one of the two specific acceptable situations for ADT; see above.)
  • Immunotherapy; a vaccine such as Provenge, designed to boost your body’s ability to fight off the cancer.
  • Early chemotherapy.
  • A clinical trial testing a promising new drug.
  • Treatment for oligometastasis. Cancer may only be in a lymph node or in a few spots in the bone, and doctors are now treating this. It may still be possible to cure your cancer. I will be writing more about this in future posts.

Don’t get me wrong: I’m not hating on ADT. If you need it, you need it. But it’s not just like taking a vitamin supplement or getting a flu shot. There are serious side effects with long-term ADT – things that testosterone normally helps protect you from – including thinning of bones, loss of muscle mass, weight gain, loss of libido, hot flashes, mood changes, depression and the risk of cognitive impairment.

Coming up next:  ADT and metabolic syndrome, and how to fight it.

More of this story and much more about prostate cancer are on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.” The PCF is funding the research that is going to cure this disease, and they have a new movement called MANy Versus Cancer that aims to crowd-fund the cure, and also empower men to find out their risks and determine the best treatment. As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

Regular disclaimer: This is a blog. It is not an encyclopedia article or a research paper published in a peer-reviewed journal. If a relevant publication is involved in the story, I mention it. Otherwise, don’t look for a lot of citations, especially if I’m quoting from a medical professional.