Men's brains have a lot of androgen receptors, and androgens (mainly testosterone (T) and DHT) affect such brain functions as mood, aggression, competitiveness, libido, motivation, spatial ability, and other attitudes and behaviors. Many psychoactive substances (except hallucinogens) are addictive. The only way we know if a substance is addictive is if stopping it suddenly causes withdrawal symptoms.
Stopping T cold turkey can cause withdrawal symptoms (eg. depression, mood swings, night sweats, heart arrhythmias). Those symptoms are worse at the start of ADT but diminish over time. I suspect that over time, men adjust to the new normal, but in early days there is tremendous desire for a "fix."
Maybe some withdrawal symptoms can be ameliorated by withdrawing T slowly, say over 2-3 months? Maybe that can be done with Orgovyx (e.g., starting with 1 pill/week and gradually increasing to 7 pills/week)? Maybe someone can do a randomized clinical trial?
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Tall_Allen
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Testosterone is the fuel for men? With 3 T for over seven years ,For me first came sarcopenia then osteopenia , djd ,and my veins barely exist now ! Everything is depleted except my bad attitude!
I can truly tell you that I really don't know if there is a difference? Is it a fuel or not? I had over 700 T level when I had my radical prosectomy. With treatment, zytega and prednisone I got hit like I never have been punched before. So even with a t-level almost zero I still felt bad. That was for almost 3 years. Now was it the treatment, or the loss of my testosterone? Now I am back at over 600 (at 68) for the last year. ADT vacation. I can tell you with no treatments I've lost 30 lb. I actually have some "structure" down there again. It's not tucked away and it "looks" like a man. But still I have incredible aches and pains that are undescribable. Neuropathy terrible. I really don't know how to answer this question and I'm living through it now.
Is a man that is suddenly paralyzed or loses a limb addicted to having them? Is a blind or deaf man addicted to hearing and seeing? Do they not go through grief, anxiety and depression when it's lost? Does a man long for the days when he was actually normal in any situation where his body was drastically changed from what he once knew?
I don't think it's about addiction I think it's more about having a huge part of you stripped away and the normal function of everything you knew gone forever. I think it's about men on HT struggling with diminished muscles, incontinence, ED and loss of libido wishing they could just be normal again. It's not a temporary fix that just happens in the beginning, it doesn't go away. The treatments more often than not leave a man with issues and it's then compounded by HT. It's difficult to go through, especially for a younger man losing his testosterone and sexual function.
Yes we can adjust to what was lost but it's nothing to do with being addicted to it. The loss of testosterone and everything it effects is a pretty heavy hit. It can change current relationships and makes it difficult to find new ones. It's not something that a man can be weaned from and all is okay. It's something a man has to learn to live with. Not having testosterone is a disease by itself and can cause many health issues. A man was genetically made to function with it and not without it. It has nothing to do with addiction.
An interesting idea. I wonder if a gradual reduction in testosterone might affect the body’s tendency to reallocate the task of making testosterone. It could be like ‘the boiling frog’ and the body might not notice the loss of testosterone.
And what about the patients with chronic low T, who are more susceptible to PCa? How does their low T factor in? Is it high T fellows who suffer side effects more? Has this been investigated? If I recall, it was exposed that some 30% of low T patients develop PCa.
I've experienced very little side effects from ADT, but I've had Low T before the use of drugs to wipe it out... But I've suffered very little side effects from all my therapies so far as well. Unfortunately, my PCa has been robust as well (see profile)... Could it be that the level of drugs given in my case aren't enough? Enough needed (+) to affect the PCa and cause side effects... Are they linked?
Interesting to propose or suppose causation or effect!
Anyways...
I don't think the term "addicted" is appropriate, as it insinuates the choice of having T. Not in a cancer setting for PCa patients. For the most part, because we are seeing lately that T is not
We are born with it, it's not a choice, but a part of our being. I don't think removing it is any different than removing our thyroids... Or other organs that are necessary. Side effects subsequent to the changes would be natural and expected. Addicted? Are we addicted to eyesight? I'm sure there's serious side effects if they were removed too!
We are addicted to dopamine, GABA, and all other neurotransmitters. Runners are addicted to endorphins. Just because a psychoactive substance is naturally occurring, doesn't mean we can't be addicted to it. Try to block them, and you'll go through withdrawal. Addiction is defined by withdrawal symptoms. Try to imagine the word without the negative connotations you have culturally associated with it.
What? That's just silly... I may HAVE dopamine, gaba, endorphins and the like, but I'm not addicted! They're naturally occurring. Removing them is artificial and the body looking for what WAS there is not addicted or addiction. It is simply seeking normality.
Those examples are trying to associate a body that has been exposed to an artificial INCREASE in one substance and the subsequent removal of such and the side effects associated with the wide range or swing of that substance being there then not. A HUGE difference in scenarios!
I need water... Does that mean I'm addicted to it? If I remove my addiction, I remove my life! We all need air to breathe, does that make us addicted to it? Hmmmm... And these side effects are acute, some immediate within minutes the side effects occur! Lmao?
As I said, addiction is defined by withdrawal. Try to re-think what you think you know. You do not undergo withdrawal symptoms when you are thirsty. Typical withdrawal symptoms include depression, mood swings, night sweats, and cardiac arrhythmias. Other symptoms depend on the substance suddenly stopped. Withdrawal symptoms fade with time. You absolutely do undergo withdrawal symptoms if you suddenly block nicotinic receptors, acetylcholine receptors, dopamine receptors, etc. Why do you think it's any different if you block testosterone in the brain?
Additionally, drugs use the same receptors we already have (just likely overstimulate them, the body adjusts & a "new normal" is born) & a drug removed can cause withdrawal symptoms ..... also, if one overstimulated with say dopamine for an extended period of time & this overstimulation was removed, the body might start looking for more dopamine in order to get back to the "new normal" of more dopamine. Is this how "Drama Kings/Queens" are born???
Addiction is NOT defined by withdrawal... Sorry! Withdrawal symptoms are more an effect but not all experience it.
We could revert to the simpleton Wiki definition of "addiction" and leave it there, because what is being descibed above is NOT an addiction at all.
We don't experience withdrawal symptoms absent consumption of water? Really? I guess then dehydration doesn't exist... Or it's effects! Tell me how a person will not change their behavior, even at risk to themselves in order to obtain a drink of water when completely denied of it! Or do we exclude this to validate a particular view on the subject?
Addiction is much more complex than being presented here, and is being misrepresented totally with the use of the word addiction in the manner used above. The examples completely exclude the "reward" neurological and behavioral aspect of the condition in being addicted! Cultural negative connotations are not being used or introduced at all.
So every single patient who's had their T lowered to zilch would exhibit those telltale "addiction" withdrawal symptoms if the above statements using the word addiction were true. Do we see all patients running to doctors for a fix? Or just some...?
In a personal sense, could you please explain why I haven't experienced the effects of addiction, or the subsequent withdrawal upon removal of noted hormones? Again, not everyone does. But almost every single "addict" will experience withdrawal when removing the artificial substance the body & mind have repeatedly used or become accustomed to. My T is at 6 with the use of hormonal therapy, wouldn't I display "withdrawals" then?
For the matter: The American Society of Addiction Medicine (ASAM) defines addiction as “a treatable, chronic medical disease involving complex interactions among brain circuits, genetics, the environment, and an individual’s life experiences. People with addiction use substances or engage in behaviors that become compulsive and often continue despite harmful consequences.”
So using the opinion "the only way we know if a substance is addictive is if stopping it suddenly causes withdrawal symptoms" is subjective. Behavior without removing the substance can also be exhibited that would define an addiction, ie, needing a fix, etc. There are many addictive behaviors that are not substance dependent, or exhibit withdrawals upon removal. It is a complex development of more than just a simple biological description of cause/effect.
And for the matter, in psychology, there's this thing that's called "cognitive barrier" the illusion of explanatory depth. It means you think you fully understand something that you actually don’t. With "addiction" medical (bio) action/reaction is NOT the only thing at play, and you dismiss much of it, simplify it to achieve a personal objective, here support your use of a word, or semantics. Then argue with others to support your "opinion", etc.
More appropriate would be using the word "dependency"... Again, an opinion! Because a biological dependency can exclude the other factors that weigh in on an addiction. But hey, that's just me and my opinion on the matter. Just figured to share it
Seeking normality--the technical medical term is "homeostasis".
During childbirth a mother's pituitary gland releases oxytocin until the baby exits the birth canal. The release of oxytocin isn't regulated by other body systems. That is one of only two responses that the body doesn't regulate or attempt to regulate with other systems. If one's body fails to regulate exposure to heat or regulate it fast enough--well that is why some that play football in the heat have difficulties.
Response to nicotine withdrawal isn't a normal function of the body an example of which would be temperature regulation.
Copy all between the lines to access this article.
Apr 15, 2018 · Homeostasis refers to the steady state of internal conditions maintained by living organisms. Humans have control centers in the brain and other parts of the body that constantly
I fail to see any good reason for an extended debate about what is and what isn't an addictive substance....seems like a more of a semantics debate, with little purpose? Re " Maybe some withdrawal symptoms can be ameliorated by withdrawing T slowly"...that does seem like a VERY worthwhile hypothesis to test......and were the hypothesis to prove true, a Godsend for ....... hundreds of thousands of men worldwide ?
I continue to have a keen interest in the use of estrogen patch and/or gel to ameliorate the negatives of ADT......another responder here mentioned his success with estrogen. Are we nearing the conclusion of any meaningful trials on that? The PATCH trial???
Yes , progression of PCa results in more than just early demise....also many months of misery preceding the end. Yet, in my understanding, ADT is not curative, and almost guarantees an almost immediate rapid deterioration in QOL for the majority of men...could a stepwise decrease in T be equally, or very nearly equally, effective in giving men the extra months of life that apparently it does, while less destructive of QOL???
As some claim, are trials undertaken only where a profit-motive is involved?? Surely that was not the driving force for ADT duration studies?
Testosterone is needed for a male to develop and has nothing to do with addiction. It would be impossible to develop into a man without it. It is vital for health and well being after development and vital into our old age. Your body does not just adjust and we just go on living without it. Your body needs it for the role it plays in staying healthy. You are losing out on the hormone that is vital in body and mental function. Can you live with Parkinson's disease? Yes and I'm pretty sure the side effects (shaking, hallucinations, delusions and confusion) are not caused by withdrawals but caused from the dying nerve cells in the brain. The effects of HT are caused by the testosterone that was depleted from your body. All of the functions that use it are stripped of it. You don't get over it and it can be detrimental to the mind and body without it. Low testosterone levels in men during aging is associated with cognitive decline and dementia. It's not only mental but is needed physically as well for bone strength and muscle. The side effects have nothing to do with addiction. It is a needed hormone and not addiction. An addict only suffers from withdrawal symptoms for days, weeks or months. Taking away testosterone will make a man suffer for years if not his whole life. There is a big difference.
Addiction is the physical and psychological dependence on extrinsic factors.Testosterone or any naturally occurring chemical in a healthy body is intrinsic to its state of equilibrium and not an addiction. Therefore if your testosterone level is castrate the equilibrium is lost. Whether you achieve that level immediately or over time is irrelevant the body will react and side effects will exist.
Although the combination of Lupron and abiraterone lowered my T to <10ng/dl in a week, I didn’t feel significantly different for several months. Similarly, when I stopped, return to baseline took about 6 months.
So the testosterone loss/gain was quite gradual on both ends, and I don’t think that’s unusual. I definitely felt the fatigue, noticed the impaired athleticism, the sarcopenia and hot flashes, cognitive decline etc., but not for many months.
Also, I knew that continuing intense and regular cardiovascular exercise and weight lifting would make me miss the T a lot less and it did.
Having once been addicted to more typical substances of abuse, I can report the obvious: if I’d had a healthy solution (other than stopping, the ultimate non starter for an addict) I would have taken it. I don’t mean drugs such as Suboxone.
Tapering never worked for me all those years ago. I tried many other things instead, which didn’t work either. Trying to exercise the sickness away was to no avail for drug addiction, but it worked very well this time, even if not perfectly.
The only side effect I couldn’t beat was no libido, but I didn’t actually miss sex; I just missed missing it-a much milder affliction for me.
I think there’s a strong placebo element to it (and with all addictions) for some also. Like when I read about a guy saying how much better he feels now that his T has come back-48 hours after taking his last Lupron shot, which I presume to be impossible.
The mind is so powerful in this way. I still remember how even a most severe withdrawal episode would magically disappear not necessarily with the taking of that much needed hit, but when the path to it revealed itself. As via some unexpected check arriving, a loan coming through, dealer back in town etc. The actual drug might be many hours away, but profound relief began immediately- simply because it was on the way.
It's ridiculous to think that we need to permanently give up on testosterone to save ourselves from cancer anyway. Who says going off ADT is a death sentence. Everyone? Well, prove it.... I'm taking a break and we shall see
ok fair enough but that’s def not what I want if I have a choice and I think most men think the same as that’s what we were born with n distinguishes us from women for the most part…
An interesting thought. However, I question one of the propositions, namely that side effects are strongest on initial withdrawal of testosterone and gradually subside. In my personal experience (sample size of 1, random though I may be) my most significant SE (loss of libido, ED) took several months to develop and several months to subside, while my T levels changed abruptly (I was on Orgovyx and T dropped from 734 to 7 in a 4 weeks and recovered back to 600+ in 6 weeks).
Other men I have spoken with also comment that their SE increase with time on ADT.
Otoh, perhaps there are two types of SE, one set are addiction-like (depression, mood, etc) and would respond to gradual T reduction, but the other SE are not (ED, muscle loss, bone loss, etc)
Homeostasis! I just scanned some of the other replies and the medical term, "homeostasis" jumped out when scanning your reply.
I asked for a certain PhD for my college science classes. I even rearranged my schedule to have my classes with her. She considered teaching to be one of the most important things she did in life. She had her PhD at the age of 23 and when not teaching part time she worked in research in the Cambridge and Boston areas. Usually if a student had her for a class, it was one and done. The way she taught couldn't be done today. If someone got an A in her classes that was unusual. I always got my A. She is one of the most brilliant people I have ever met.
You must have some background too. Good for you! An excellent reply!
Read Sapolsky's book "BEHAVE" (see Amazon) to have a clearer understanding of testosterones' role in aggression. It is an amplifier but not a genesis of aggression. Fight or flight is the domain of the Amygdala not testosterone.
That is indeed a great book. Glad to find another avid science explorer here and going beyond the usual scope of PC (as important as that is to us). PM me if you have other favorites to recommend. Paul/MB
anonymoose2 wrote --- " Testosterone is man’s curse in many respects................................God have mercy on our souls ... "
Don't believe in curses AND gave up believing in God and MY religious upbringing decades ago well BC - Before Cancer along with having a SOUL.
On a MONDAY in APRIL 2015 I was informed I have PCa at which time the Urologist tells me that I have 2 choices -- Behind Door 1 is ADT - A or Behind Door 2 is ADT - B * that's needed to begin Treatment Protocol.
I told him my choice was DOOR C for CASTRATION, so 24 hours later I was a Eunuch and things have been OK.
Had no major issues or withdrawal symptoms being without *T* and eventual treating doctor got me back on *T* injections where T reaches 1,600ng/dL following injection. March this year I had the need to go COLD TURKEY so I stopped the injections and in a few weeks T < 2.5 and remained that way for a couple of months WITHOUT an addictive desire to restart. I did restart and don't really feel any RUSH or HIGH but that "empty whole body feeling along with some sweats/flashes" is gone.
I was on ADT for 12 months, and my SEs certain didn't abate over that time. In fact, I was OK until about 8 - 9 months in, at which point I became so overwhelmed with depression that I wanted to die. I quit because I couldn't stand it any longer.
Now, when you so "over time," you may mean over a period of many years, and that's certainly possible.
Here is a phase 2 clinical trial by Dana Faber for prostate cancer with SARM LY2452473 which finished Sep 2021 and results posted but I can’t find results.
Selective androgen receptor modulators: the future of androgen therapy?
Here is a part that relates to brain
Alzheimer’s disease
Androgen depletion is implicated in the development of Alzheimer’s disease, as circulating testosterone levels in older men are inversely correlated with levels of amyloid β (Aβ) protein in the brain (15). Hypogonadal men also experience a decrease in cognitive processes including episodic memory, working memory, processing speed, visual-spatial processing, and executive function (49,50), while a higher free testosterone index is associated with improved visual and verbal memory, visuospatial functioning, visual-motor scanning, and a lower rate of decline in visual memory (51). Given that these functions are regulated by AR-modulated regions of the brain (52), the potential impact of SARMs as a treatment for cognitive disorders associated with hypogonadism is significant. In 2013, the NEP28 SARM was found to increase the activity of an Aβ-degrading enzyme, neprilysin, without severe effects on the prostate (15). However, no further studies have investigated this compound.
OK and if I started ADT the usual way and experienced none of those symptoms, does that mean I wasn't a man to begin with? My testosterone was 400 before the start of ADT, now it's about 15. I don't recall how fast it fell.
I am an addict for sure. Now on ADT for two ears I sometimes get a taste in my mouth that I am craving something when I read about Supra Physiological T, even though of course I have no idea idea what T tastes like. lol
Interesting hypothesis. Like others I'm not on board with your definition of addiction in this case. However, I think there might be a strong case for gradually decreasing any substance that one's body is used to having.
As I think back, my original urologist put me on Bicalutamide for a couple of weeks before he started me on Lupron. IIRC, he said he didn't want to hit me with both right away, but wanted to ease into ADT.
That is how addiction was defined when I took a seminar in it in college. Withdrawal symptoms distinguish true addiction from psychological dependency.
Lupron causes an initial surge in T. The surge causes a negative feedback which then shuts down T production in the testes. In the interim, the bicalutamide prevents the T from activating the cancer's androgen receptor.
I read what everyone above has said, and I have most of those same symptoms.
Guys, if you talk with the guys on BAT/mBAT, and I have, they will tell you that transition from High T, back on to ADT gets harder and harder, because they feel so good on the High T phase. Some are up on High T for 1 month, 2 mos., 3 mos., but then can usually get back to undetectable PSA levels in 20-45 days. This is a great answer to the question that TA poses. They tell themselves things like…I can do this, I can do this, its only for 30 days. Almost like Heroin, and coming down off it, and the great feeling of Going back into Euphoria while back up on it ( I have never done it, because I know it would feel good, and I would probably be instantly addicted like many before me). You can draw that analogy wit T, only it truly is just a return to Manhood, our more natural state. Mike
Hello Tall_Allen, do you have any opinion on the cardiovascular risk of supraphysiological testosterone which is used in bipolar androgen therapy after long term ADT? From what I can gather most men who have participated in BAT trials were selected such that they did not have CVD issues. Should a man (I am not talking about myself) in his 70's with CVD and not tolerating enzalutamide very well, and which is also worsening his CVD, take the chance, if this was the only remaining option available? Cheers, Philip Zacarias
Really good thing to consider. I think RBC, hematocrit, etc. has to be watched carefully. It's another good reason to only do it as part of a clinical trial.
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