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.
The 99% 10 year survival would be disease specific. This is pretty normal for a cohort first diagnosed with PCa. Most are low risk low grade cases and survival is good. Other causes of death are usually orders of magnitude higher e.g 10-20% over 10 years at age 60-70+.
Hormone ablation is mostly to buy you maybe a couple years of 'life'. I put 'life' in quotes because having experienced it I found it more like a living death - but your mileage may vary.
People differ in how they prioritize length versus quality of life. Most people cling to life at almost any price, perhaps until the last few weeks they stop treatment. People even cling to the hope of life at almost any price. I have friends enrolling in "cancer trials" of some slight variation of a chemo drug that has very little if any chance of curing them.
A recent study found that most men who died of PCa had some major, invasive, 'unpleasant', difficult, futile treatment in the last six months of life. The price of 'hope' can be high.
People dying with cancer or other diseases often come under enormous pressure from the people around them to survive as long as possible. I have experienced this myself.
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.
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.
I'd rather die a bit earlier than lose my mind. I reject this fetishization of prolonging life at all costs, including dignity and autonomy. A good death is far preferable to a shitty life in my view; an ideology of survival at all costs is only suitable for slaves. Frankly I don't care for the notion of an autopsy either since my body is not anyone else's property, and if that seems a likely outcome I plan to take steps to prevent my own body being recovered.
My first interesting job was in a nursing home so I've had ample exposure to end-of-life situations and living conditions. I've also had a disproportionate number of near-death experiences so this is a considered position rather than a mere posture.
That's a bit ambiguous. I assume you reject extra years that entirely consist of dementia. But what if you can have extra years, and only some of them will have dementia?
> Frankly I don't care for the notion of an autopsy either since my body is not anyone else's property
I don't understand what you mean by this at all. Doctors have looked and poked inside my body many times, and that never made me feel like property.
>Draw the entire tree. You need to survive first. //
Depends how soon the dementia follows. I'm not sure if living is so good with severe dementia. Actually, if it's very severe then you're probably OK - my mother has a complex dementia and her medical team have now found a drug regime that "works", unfortunately that makes her more lucid and aware, enough that she has become severely depressed. Looking in on her condition I think I'd find death a welcome end if it were me; there's a strong sense of being locked in.
Whilst our instinct is to live on I'm not convinced that is always right.
A family member died from Alzheimers last year. She was both physically and mentally gone. If I had to choose, I'd go out swiftly like my dog, whose spleen fissured from cancerous growth and was put to sleep in the hour. Slow, agonizing death is horrible.
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..."
I have been through this study and the supplements carefully.
The major problem is that they mixed patients with low risk (Gleason score of 6) and those with moderate risk (Gleason 7) and even some with high risk (8+).
When you look at the supplement the death rate for the Gleason 7's on active surveillance was 10X higher than for Gleason 6. Why on earth they combined the 7s and 6s together in the statistics would be a complete mystery to me if I had not been reading medical papers for 40 years and come to expect this sort of statistical idiocy as par for the course.
I don't get it. How can they draw such a conclusion based on a very small sample? The difference between 4 and 8 deaths could easily be due to random luck. I wouldn't make healthcare decisions based on that study until it's replicated with ~10× as many patients.
I got a p value of 0.19 for getting at least as extreme results in this direction under the nul hypothesis that there was no difference by the treatments. So I agree this is pretty weak evidence.
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.
They are just saying that metastasis occurs more frequently with monitoring as compared to active treatment, not that PSA testing itself causes metastasis.
The difference is not that monitoring causes disease, but you are not doing surgery or radiotherapy, and it is not doing that which results in higher risks, in some patients.
Unfortunately they mixed up Gleason 6 (low risk) and 7+ (intermediate and high risk) patients in the statistics.
In the supplement they give information which allows you to see that the risk of dying is far higher (~10X higher) for the 7+ patients. But they do not provide this breakup for the risk of progression and metastases. So we cannot know what the risk is for low risk patients. And it is low risk patients who are usually recommended for active surveillance.
People have a hard time believing this, but this kind of statistical fail is common, even normal in medical research. The average doctor, including medical researchers, has zero formal training in statistics. So they basically use cookbooks without really knowing what they are doing. So you get researchers saying that because they has a statistically insignificant result, they showed there is no effect.
We had a study which had a slightly below significant result for fish oil reducing post natal depression in women with a 30% reduction(P=.11m where < .05 is arbitrarily counted as 'significant'). The lead researcher then gets on the media and tells the country <we showed fish oil is useless>.
The Bayesian revolution in statistics has largely bypassed medicine even though it is well accepted in many other fields.
> 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.
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.
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"
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.
That's not necessarily a relevant comparison since the goal of HRT in trans women is not simply to lower testosterone, but also to raise estrogen (and sometimes progesterone) to female levels.
Trans women on HRT are not hormonally like cis men (including men on ADT), so extrapolating any effect of sex hormone from cis men to trans women is going to lead you astray.
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.
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':
The number of medications in this list (29) is rather striking. Assuming the FDA approved all of these drugs to treat a single condition, this treatment must be VERY profitable!
It's annoying how the press release manages to have links for the institutions involved, the authors, various initiatives and departments, but not for the paper itself. Surely encouraging folks to read the work should be as important as trumpeting the fact that the work was done.
ADT is Androgen deprivation therapy, a superset of using anti-androgens.
And Finasteride is only kinda an anti-androgen itself. It blocks conversion of some Testosterone to DHT, which is another androgen which is more potent WRT hair loss, body hair growth, and prostate problems, but I believe less potent WRT other effects of androgens.
5 alpha reductase inhibiters like Finasterade slow the conversion of Testosterone to DHT, which is a more potent androgen. This conversion occurs in the skin, liver, prostate and retina.
Using a 5aR inhibiter mostly affects those organs alone. There would be a slight decrease in effective Testosterone levels and these drugs can sometimes affect libido and erectile function. But the reduction will be minor compared to hormone ablation (HAT), which takes you close to zero.
HAT affects you in many ways: mood, bone loss, muscle loss are the main ones. To which we can now add dementia.
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?
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.
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.
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.
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.
That's absolutely true, but we often forget that all medical interventions have to be balanced in terms of risk and benefit. Most patients expect treatment when they go to their doctor, even when the only available treatment options are marginally effective and carry significant risk.
For a variety of reasons, healthcare professionals find it very difficult to refuse treatment. We tolerate the risks of treatment far more readily than we tolerate the risks of watchful waiting, which leads to a lot of bad clinical decisions.
From the opiate epidemic to antibiotic resistance to rampant increases in insurance rates, overtreatment is a slow-burning crisis in healthcare.
I agree with both of you, but let me combine the thoughts.
An unknown number of medical advances do more good than harm. Maybe it's over 50%, maybe not.
Regardless, from the US citizens I've spoken with in several states, people often are not educated about know side effects when being put on a new drug. Many drugs have serious side effects and since most people are put on several over the course of a treatment, people need to be aware of the potential danger to a different area of their live / lively hood.
Medical error is still arguably the 3rd largest killer of US citizens, so misinformation (or a lack of communication) about side effects is very present as well.
> people often are not educated about know side effects when being put on a new drug
Since you're talking about the US, that's a defect with the people, not system. When you pick up a medicine from the pharmacy, the cashier asks if you want a consult with the pharmacist to talk about the medicine (including side effect). You can decline.
The medicine itself comes with an insert outlining usage and side effects in great detail.
If you don't know possible side effects of a medicine you're taking, you've got nobody to blame but yourself.
> The medicine itself comes with an insert outlining usage and side effects in great detail.
Senator Nelson called hearings (1970) when women started dropping dead from their birth control prescriptions [1]. The outcome of the hearings was that the drug companies had to warn their customers that their prescriptions might have side effects.
Eventually the drug companies realized women didn't need so much estrogen to shut down their menstrual cycles. All the old high-estrogen pills have now been withdrawn, but a few women still react very poorly to their birth control prescriptions. Doctors commonly don't consider the role that birth control plays in their patients' problems.
I agree people should read, but it starts with the doctors.
By the time they arrive to pickup a prescription they have already discussed everything with their doctor. It's kind of late to start questioning if this is the best choice or if there are other alternatives.
Wow. Such a bold indefensible statement. By any chance, are you running for President?
Children with infections might beg to differ with you. Or people with hypertension. Or coronary disease. Or HIV. Or diabetes. Or organ transplants. The lives of many millions like these added decades due to drugs.
The impact of vaccines on increasing life expectancy is simply staggering, and vaccines are virtually indistinguishable from biologic drugs.
Literally BILLIONS of people live for decades longer and better because of drugs.
> Wow. Such a bold indefensible statement. By any chance, are you running for President? [...] Literally BILLIONS of people live for decades longer and better because of drugs.
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.
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.
Well the question is whether drugs overall improve people's life expectancy, not whether some specific class of drug can lengthen people's lives. Some drugs make people live longer, but other drugs decrease life expectancy.
And even with antibiotics in specific, they save lives, but they also kill among the most people of any class of drug. They're a clear win if you're a burn victim or something, but most situations that are less acute either go away on their own or else were treated successfully with plant-based antibiotics. Despite what the pharma industry would have you believe, there's no law of the universe that decrees that fungi-based antiobiotics should be inherently more effective that plant-based antibiotics, the main reason the former are used today is just that they're less expensive to mass produce.
Although, why is my above post getting downvoted? Too cynical? I'm sorry. Next time I'll lie and say pharmaceutical industry is doing a splendid job and mother nature has taken second place and nobody is getting dementia from prostate medication.
Clearly, life is just roses and daisies here on HN.
Antibiotic resistance is a problem because antibiotics may not save as many lives in the future as they have in the past. That's not what "tit for tat" means. But it seems you've made up your mind already.
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.