Mental health and ADT: an objective review

As regular readers will be aware, there has been some intense debate over the past year or so about whether there is an association between treatment with androgen deprivation therapy (ADT) and risk for dementia.

A new review article, written by a team from the Memorial Sloan-Kettering Cancer Center (McHugh et al.), has attempted to place this question into a more objective clinical context. Unfortunately, only the abstract of this article is freely available on line. Your sitemaster, however, has had the opportunity to review the entire text of this article.

McHugh et al. have offered a thorough analysis of the available, published data related to both cognitive dysfunction (as a side effect of treatment with ADT) and the risk for development of dementia (inclusive of Alzheimer’s disease) as a consequence of treatment with ADT. They make numerous important points in this article that are worth summarizing briefly:

  • Cognitive dysfunction and dementia aren’t really the same thing at all (although dementia almost invariably includes a significant degree of cognitive dysfunction.
  • In the context of prostate cancer and its treatment with ADT,
    • McHugh et al. define cognitive dysfunction as implying changes in cognition and mental function potentially related to ADT and its effect on brain function.
    • They define dementia as a spectrum of clinical syndromes (including multiple subtypes) involving the progressive deterioration of intellectual function.
    • They note that, depending on the etiology or causes of the problem, cognitive dysfunction associated with dementia can span various cognitive domains, including such skills and capabilities as memory, language, reasoning, decision making, visuospatial function, attention, and orientation.
    • Your sitemaster concurs with these key points.
  • There is no doubt whatsoever that
    • Treatment with ADT has been reported to induce cognitive dysfunction of differing types and varied levels of severity.
    • Length of time on treatment with ADT can be correlated to risk for more serious levels of such cognitive dysfunction.
    • There are plenty of men for whom such levels of cognitive dysfunction are relatively minor.
    • There are also men for whom such forms of cognitive dysfunction are serious and debilitating.
    • But … One of the largest and best controlled studies to date showed no correlation between treatment with ADT and loss of specific forms of cognitive function.
  • There is also no doubt that
    • Differing studies have shown either an association or no association whatsoever between treatment with ADT and onset of either dementia in general or, more specifically, Alzheimer’s disease.
    • The structures of the various studies, to date, vary considerably.
    • None of these studies have been randomized, well controlled clinical trials.

The bottom line at present is that — some 70 years after we first started to use ADT as a treatment for progressive and metastatic forms of prostate cancer — we really don’t know to what extent it impacts either cognitive function or risk for specific types of dementia.

McHugh et al. conclude that, at this time:

A discussion of the correlation between ADT and cognitive decline and dementia should be part of the conversation about the merits and drawbacks of initiating ADT in a given clinical context, with consideration of the patient’s disease risk, comorbidities, and expected longevity. At this point, the specific risk factors for cognitive decline and dementia, physiologic correlates, effects of ADT scheduling (continuous vs intermittent), or the global impact of mood or fatigue on cognition have not been fully elucidated. For many viable patients who face high risks of death or disability from disease, the possibility of neurocognitive risks is acceptable.

The problem is that some men may be at significantly higher risk for one or both of these problems that others. Like a lot of things we now know about the risks for and the management of prostate cancer, this is one more example of why prostate cancer is not a “one size fits all” disorder. A treatment that can be relatively easy to deal with for some men can be utterly debilitating for others.

We still have a lot to learn about the ways to optimize quality of life for many men with progressive forms of this disease.

In the meantime, this review is one that many support group leaders might want to try to get a copy of for their files and for their own careful scrutiny. If you have access to a good medical library, this shouldn’t be a problem.

7 Responses

  1. I cannot speak to ADT confusion but I can all too well to medication confusion.

    Take a memory off the shelf while you are confused and that confusion sticks with it when you put it back on the shelf. An eraser of the life lived.

  2. I have access to Tanya Dorff, MD, now over at City of Hope, whom I have worked with on trial design for this very topic. We’ve been discussing it for over a year and I think it’s a well-needed trial.

    There is belief among researchers that there is a correlation between mental illness and ADT but how to set up such a trial is not easy. Setting baseline analysis before starting treatment is a very rigorous process to declare a man at the start of ADT is not already expressing symptoms of these ailments.

    As far as McHugh et al.’s recommendation to discuss these issues during the shared decision making (SDM) process, it could only be stated that ADT may have these side effects but that it’s not known through scientific studies done to date there is no hard evidence.

    We do know obvious mental issues such as depression, mood swings, etc., are common side effects. Are they caused by the medications or are they caused because of other side effects like fatigue, weight gain, or simply by the diagnosis of an progressing or advanced cancer? It will be difficult to trial.

  3. I beg to differ with this study. My husband had his wits about him the first year after receiving ADT and before chemotherapy. Here we are 5+ years later and nothing more the doctors can do, except continue the ADT; Flomax; Lasix; potassium — add in the Namenda and donepezil for the “dementia” and also Xarelto due to a blood clot he’d had.

  4. I am of the opinion that the result of any deep research/study will depend on the individual patient in the study. Unless there are issues that indicate early confusion or dementia at the time of initiating ADT, it will be difficult to absolutely pin the blame on ADT.

    I have been on, and continue on, pretty much the gamut of ADT medications for the past 21 plus years and have never experienced any confusion whatsoever that could be pinned on my ADT. Yet, that being said, I have been aware of many prostate cancer patients claiming they were experiencing confusion/memory loss once on ADT. Did they just jump on the bandwagon of blaming ADT because there have been many reports indicating ADT could be the cause, or did they permit their mindset to actually believe it was the ADT and not because of some other mitigating factors? Possibly metastases to parts unknown could generate confusion of the mind. Possibly just the patient’s treatment has drummed up a myriad of thoughts/feelings that the patient lays blame on ADT when that is not the actual case.

    Coming to a conclusion that ADT is to blame is going to be very difficult to determine. For some, maybe it is, for others maybe it is not.

    For me, after this 21 years plus and continuing on ADT medications and now at 85 years of age, though I have periods of not immediate recollection of a name or reference, it either comes to me shortly or I know where to look in my folders to jar my memory. My opinion is that mine is an aging factor rather than ADT that has served me well these many years with no issues of cognitive function/confusion.

  5. I can read the whole thing and will try to comment. Two points for starters. First, it is highly desirable to include psychosocial help in all treatment plans. Although little detail is known, mental issues are common with ADT. They should be treated, just as any other side effects might be. Forget stigma.

    Second, open access to academic publications should extend to every single article and many books. Academics often make enough and they should not gripe about which classes of society should be able to access the results of their work. This will save lives in future, it helped save mine (for now) and definitely kept me in an upbeat mood. For information to the public was nonexistent in Uppsala’s hospital, as was psychosocial help. I hear that has improved now. I had cancer fatigue, had at first no idea what was going on, and received no help except from one fine doctor. One guy just said “exercise” and made some gung ho hand motion. Whether that advice was medically warranted or not depended on the type of fatigue. I got no exclusion diagnosis. If it had been ME/CFS exercise would have been contraindicated (a very long story involving a 30 year medical fraud designed to let insurer UNUM avoid payouts for it and destroy the British welfare state. It worked. Last August a competent UN Disabilities Commission declared the British effects “a human catastrophe” — at least 120,000 extra deaths traceable to austerity since 2010, thousands of those probably due to a test associated with Welfare Reform from 2008 on. My group, Disabled People Against Cuts, requested the UN investigation.)

  6. The Discussion with the Patient about ADT and Risk of Cognitive Dysfunction

    Thanks for spotlighting this important research. (And thanks for your comment, Tony.)

    Having been on ADT intermittently for just over 14 years until 2014, and having known many friends in my Us Too chapter through the present who have been on ADT for years, I doubt the causal connection to dementia and Alzheimer’s, but suspect that some of the side effects Tony notes, especially uncountered fatigue and related disturbed sleep, do lead to some cognitive dysfunction that can be transient or not, mild or not, and short term or not, partly depending on countermeasures.

    However, I’m betting it will be hard to communicate this to many patients at the time they need to decide whether to go on ADT. I studied experimental psychology in undergraduate school, so the phrase “cognitive dysfunction” trips right off the tongue without a second thought. (Yes, a pun.) But many men and their loved ones are going to have trouble understanding what either of those words mean, let alone the combination.

    It is important that men facing ADT be well informed on how to counter the various risks that come with ADT, including cognitive issues, so that side effects can be minimized. I am fully convinced that most of the main side effects can be countered, though some just a bit while others completely. There are a number of important tactics, but exercise is key. Health teams need to focus on that proactive approach with their patients rather than knocking them psychologically back on their heels by raising likely risks with no discussion of mitigation. Unfortunately, as I sense from my Us Too group interactions, that happens too frequently.

    My main impression is that I and others generally do very well cognitively on ADT over the long term, with relatively mild impacts, disturbed sleep as a primary suspect, especially if we use countermeasures, and with full recovery if and when ADT is no longer needed. That said, I have had a good friend, a survivor of well over 20 years — many of which were on intermittent ADT, who clearly slipped into dementia over a number of years when he was in his upper 70s. He is often in the thoughts of our group leadership, and we miss him. I am pretty sure he is suffering from dementia unrelated to ADT. In general, I suspect it is hard for many loved ones to assess the degree to which ADT is responsible for these problems, and not aging or other health, lifestyle, or medical causes.

  7. @Jimwaddenfels

    I might be able to fill in what you wrote. As I understand it, the ADT reduces serum testosterone to nearly zero. Prostate cancer cells cannot thrive without it, so the disease does not progress, or slows down. But every cell in your body uses testosterone for energy production. Without it you get fatigued, having too little energy to function normally. All systems are dysfunctional, including whatever regulates sleep. Finally, if your testosterone level does not return to baseline after you stop ADT, you are called “hypogonadic.”

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