
Common prostate cancer treatment linked to later dementia, researcher says - CapitalistCartr
http://med.stanford.edu/news/all-news/2016/10/common-prostate-cancer-treatment-linked-to-later-dementia.html
======
wjnc
Good read. Been through exactly this with my father. Obviously no causality,
he could have started dementia without the treatment, but gives some backstory
to what my family went through.

One important point is that the hormones probably add more life than they
take. You don't start on hormones AFAIK before they figure they can't cure you
anymore. It's then about prolonging life. First to admit that dementia is
horrible as well, but for most patients a risk worth taking.

Further reading:

-99% survival in 10 yrs regardless of initial treatment in the dataset (in article)?

-It seems there is a subset where ADT is first treatment. That is at odds with what our oncologist told us iirc. ADT prolonges, but does not cure. Makes some sense to prescribe ADT if alternatives are too heavy, but that is at odds with the 99% 10 yr survival.

As an actuary: only children have 99% 10 yr survival (guesstimate).

Went to the article. Not paywalled (nice). They include common logic
comparisons and stuff. Love the approach to text processing. But no basic data
tables?

Death should be really common when studying 60-70-80 yr olds. Gleason score
mostly 6 or higher. That gives you a 30%+ baseline of dying (ballpark,
Google).

Next thought: data gathering conditional on survival. Only if there is a
follow-up, you can be included. That still makes sense re the study (relative
chance of dementia), but makes interpretation harder. It's an analysis in one
branche of the probability tree. ADT might make your dementia chance 100% if
nothing else kills you first.

Still a nice study. Just don't think of this if you've just been diagnosed.
Draw the entire tree. You need to survive first.

~~~
pfarnsworth
My mother is suffering from dementia right now and my family is trying to deal
with it. One of my closest friends is also dealing with this with his mother,
who was just put into an institution where she can't leave the floor because
she wanders. It's the cruelest disease, cancer is more merciful at this age.

~~~
anigbrowl
I could not agree more. Not only is dementia horribly corrosive for the
family, it's frightening and confusing for the patient in most circumstances.
By far the most depressing cases I dealt with as a nurse's aide were those
patients who were still physically healthy and strong but suffering from
dementia, because they were the most likely to need to be manhandled if they
wandered away or got into an altercation with the nurses. I still remember the
fear and confusion in some patients' eyes 30 years later and have no desire to
experience that.

------
said
Dementia is associated with low levels of testosterone in men. [1]

Unfortunately, (over-the-counter) DHEA seems to have no effect on Alzheimer's,
[2] though I'm not sure about other forms of dementia.

[1]:
[https://www.ncbi.nlm.nih.gov/pubmed/24035146](https://www.ncbi.nlm.nih.gov/pubmed/24035146)

[2]:
[https://www.aan.com/PressRoom/Home/PressRelease/39](https://www.aan.com/PressRoom/Home/PressRelease/39)
and
[https://www.ncbi.nlm.nih.gov/pubmed/16977674](https://www.ncbi.nlm.nih.gov/pubmed/16977674)

~~~
orthoganol
If [1] is established, it's disturbing it's never mentioned regarding
Propecia, a hair loss treatment a significant percentage of men I know take.

~~~
ClassyJacket
I take it. Does this mean I should stop?

~~~
orthoganol
I should have searched for Finasteride before commenting, there is some
discussion further down.

------
v0x
Part of the Stanford article is highly misleading. They say:

"That study, published in September in The New England Journal of Medicine,
revealed that prostate cancer patients randomized to either active monitoring,
surgery or radiation therapy all had the same risk of death from the cancer
after 10 years. Ninety-nine percent of men in the study survived regardless of
initial treatment. These startling results suggest that active monitoring of
prostate cancer patients may be as good as early radical treatment and may
cause fewer side effects."

In the actual NEJM study they reference, though, the conclusions are the exact
opposite:

"...death from prostate cancer occurred in 8 of the 545 men assigned to active
monitoring, 5 of the 553 men assigned to surgery, and 4 of the 545 men
assigned to radiotherapy"

"For today, we can conclude on the basis of level 1 evidence that PSA
monitoring, as compared with treatment of early prostate cancer, leads to
increased metastasis. Therefore, if a man wishes to avoid metastatic prostate
cancer and the side effects of its treatment, monitoring should be considered
only if he has life-shortening coexisting disease such that his life
expectancy is less than the 10-year median follow-up of the current study..."

[http://www.nejm.org/doi/full/10.1056/NEJMe1610395#t=article](http://www.nejm.org/doi/full/10.1056/NEJMe1610395#t=article)

~~~
pcrh
From the article: "causality between an increase in metastatic disease and the
use of active monitoring versus treatment was established."

The notion that monitoring PSA levels can per se increase the risk of
metastasis is ridiculous. It's far more likely that some other factor caused
the increased incidence of metastases.

~~~
v0x
They are just saying that metastasis occurs more frequently with monitoring
_as compared to active treatment_ , not that PSA testing itself causes
metastasis.

~~~
pcrh
Ah yes, you're correct...

------
nylonstrung
It is becoming increasingly obvious that androgen deprivation has massive
neurological effects.

I seriously think there should be some inquiry into whether it is a driver for
the epidemic of post-transition MTF trans suicides

~~~
teslabox
> It is becoming increasingly obvious that androgen deprivation has massive
> neurological effects.

Progesterone USP is both a pro-hormone and a neurosteroid [1]. The science
literature commonly confuses Progesterone USP with various "progestins" (xeno-
hormones), so there is much confusion on the effects of this substance vs the
fakes.

> I seriously think there should be some inquiry into whether it is a driver
> for the epidemic of post-transition MTF trans suicides

At one point I made a progesterone supplement, which I sold on Amazon -
topical progesterone formulas are grandfathered as non-prescription because
they are safe, and because the substance was available before the food & drug
act was passed. My best customer was "Billie", whom I never met, but who I'm
certain was MTF. SHe emailed me recently when she ran out of her last purchase
- I told her what to buy instead.

MTF probably usually do poorly post-transition because they only supplement
with "the heart attack hormone"/"The Cancer Hormone" \- Estrogen. Progesterone
USP is essential for balancing the toxic effects of any kind of estrogen/xeno-
estrogen. Fertile women are protected from their estrogen load because their
bodies produce large amounts of Progesterone during the second half of the
cycle.

[1]
[https://www.ncbi.nlm.nih.gov/pubmed/11108866](https://www.ncbi.nlm.nih.gov/pubmed/11108866)

edit: gender pronouns

~~~
jauer
I've noticed a patient-driven push to add Progesterone to transwomen HRT based
on anecdotes about mood, sex drive, and breast development. Alas there isn't
much research into trans health.

------
alejohausner
I find this depressing. As far as I know chemical castration (another name for
this treatment) tends to _increase_ deaths from cancer and other causes!
That's what table 2 tells me in this[1] retrospective study. It all seems
backwards and wrongheaded.

1.10.1200/JCO.2013.54.2043, or Google "Effectiveness of primary androgen
deprivation therapy"

------
jmcgough
Wonder if this translates over to hormone replacement therapy in transgender
people :\

~~~
auganov
Well women are generally much likelier to get dementias. Close to 2x the risk
(as compared to males) too I think. A quick google search shows there's
studies suggesting giving women testosterone could help with dementia.

~~~
pervycreeper
That's a consequence of their increased empirical longevity.

------
bawana
Steroid deprivation in general leads to depression- post partum depression,
etc. Steroid administration leads to a type of 'euphoria' or well being -
'steroid high'. The link between steroid levels and mental status is an old
story. The question becomes what was the patient's testosterone before
ablation was initiated and how far did it fall. This value may be the more
relevant predictor. So, patients who already have a low T(<150) might not be
at risk for altered cognitive function though no one has really looked at
this.

------
go_prodev
Is ADT in any way similar to finasteride (anti-androgen for hair loss and
prostate enlargement)?

~~~
msamwald
That was also my first question. I looked at the original paper [1], the
medication names they used to identify individuals on androgen deprivation
therapy are listed in the 'eAppendix':

Leuprolide, goserelin, triptorelin, histrelin, Degarelix, flutamide,
bicalutamide, nilutamide, Enzalutamide, Cyproterone acetate, Lupron, Zoladex,
Trelstar, Vantas, Firmagon, Eulexin, Casodex, Nilandron, Xtandi, Nizoral,
Androcur, Eligard, Cyprostat, Anandron, Flutamin, Cytomid, Cosudex, Calutide,
Kalumid

So relax, finasteride does not seem to be on the list.

[1]
[http://jamanetwork.com/journals/jamaoncology/fullarticle/256...](http://jamanetwork.com/journals/jamaoncology/fullarticle/2569059)
(probably paywalled)

~~~
spatulan
I'm on Cyproterone Acetate. Does it say anywhere in the paper if certain anti-
androgens are worse than others?

~~~
msamwald
No, all of the medications seem to be lumped together.

------
petronic
My father's currently 9 months into an 18 month course of Lupron (paired with
an earlier course of radiation) for advanced, inoperable prostate cancer. He
won't get his next 3-month shot until December.

I've already shared this study with him and asked him to talk about it with
his oncologist. At this point, is there anything else that he can do with this
information?

------
randcraw
No doubt there are confounding factors to the influence of ADT, such as
surgery, radiation, or other support meds. But the impact of long term
exposure to cancer cells can't be discounted either. Because slow growing
cancer is a fairly recent phenomenon, I suspect living with active cancer for
5-10 years is probably not well documented or fully quantified yet. The
effects of such stress on the immune system alone must lead to uncharted
waters.

There's other evidence that persistent inflammation (or protein
glycosylation?) may accelerate dementia, as suggested by the ~45% protective
effect of Actos (pioglitazone) against dementia, for both those with and
without diabetes.

[http://www.nytimes.com/2006/07/17/health/17alzheimer.html?_r...](http://www.nytimes.com/2006/07/17/health/17alzheimer.html?_r=0)

------
adrianN
What factors decide whether ADT is done? I doubt it's random. Maybe those
differences explain the dementia differences?

~~~
dumbmatter
This article actually does a decent job of explaining the limitations of
retrospective analysis, unlike most articles about retrospective studies. See
the "Retrospective complements prospective" section at the end.

------
alabamamike
Ugh, leaving us guys with a tough choice: Do we want to pee or think?

------
zizzles
Not surprising.

Trying to overcome faulty genetics with medication is a double edged sword.
You are almost always trading one issue for another, tit for tat. Prostate
cancer medication? Enjoy dementia. Chemotherapy treatment for cancer? Enjoy
having healthy cells destroyed. SSRI for depression? Linked with autism in
pregnancy, heart disease, numerous other issues. Steroids for improved
performance? Gynecomastia. Ball shrinkage. Acne because of raised hormones.
Accutane to fix acne? Liver problems. Crohns. Finasteride to retain your hair?
Lowered DHT levels, diminished sexual drive.

That's just the tip of the iceberg. Mother nature seems to be an unstoppable
force.

~~~
mjb
No, that's not true.

A huge number of medical treatments and interventions have been developed -
mostly over the last 100 years - that are way more beneficial than they are
risky. Some treatments have side-effects. Some have unexpected, or long-term
side effects. Some have awful life-altering side-effects. That's all true.

But to say "mother nature is an unstoppable force" to support the idea that
all medical treatment does equal harm and good is crazy. Health interventions
- from clean food and water to drugs and surgery - have improved and
lengthened the lives of billions over the last century.

~~~
Alex3917
> Health interventions - from clean food and water to drugs and surgery - have
> improved and lengthened the lives of billions over the last century.

Public health interventions, such as clean water and vaccines, have lengthened
life expectancy. Drugs haven't made much of an impact though.

~~~
NoPiece
Antibiotics?

~~~
ajross
And vaccines. Those two alone account for some huge chunk of our wins against
death. The upthread posters are making a sorta valid point: the low hanging
fruit has been picked, and recent innovations are more incremental. And that's
true enough, though I agree that cynicism isn't the right response.

~~~
randcraw
Statins are only about 20 years old. As are hypertensive drugs. Both have had
clear impacts on longevity.

Can we be so sure that the next generation of superdrug won't give rise to a
comparable revolution in reducing risk? I'm not, and I work in the pharma
industry.

True, I'm not especially upbeat about the prospects of jobs here or the
survival of individual pharma companies (oft mismanaged, IMO). But I do
believe major innovations are on the horizon and may have major impacts,
bigger than the aforementioned statins.

Gene therapy, pluripotent cell line therapy, immune system driven therapy --
these all have stunning potential on a wide range of targets. Yes, the future
of traditional small molecule drugs is cloudy. But the next generation of
genomics and biologics may blow your socks off.

