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ADT paradox study.

Posted by hanscasteels @hanscasteels, Jan 10 9:27am

I found a recent study that challenges the established ADT dogma. I found that the study suggests that androgen levels might have a more nuanced impact on AR signaling than we typically consider. Specifically, it found that low-dose androgens stimulate tumor growth by activating the mTOR pathway through AR monomers, while high-dose androgens suppress growth by forming AR dimers/oligomers, which inhibit c-MYC and promote differentiation.

It seems like this challenges the longstanding dogma that all androgen signalling drives cancer progression, particularly in advanced or resistant cases. In my case, this tumor grew in a naturally low testosterone environment, and my uninformed mind thought that perhaps eliminating testosterone in a naturally low testosterone environment would make the tumor even more aggressive than it already is, therefore accelerating tumor development rather than slowing it.

I was curious about the audience’s perspective on this. How do findings like these fit into our current understanding of androgen deprivation therapy? Do you see any potential for insights like this to guide more personalized approaches in the future?"

Shared files

s41467-024-52032-y (s41467-024-52032-y.pdf)

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hanscasteels | @hanscasteels | Jan 12 8:16am
In reply to @heavyphil "I would agree that the article is NOT saying that. And “dogma” can sometimes be a..." + (show)
@heavyphil

I would agree that the article is NOT saying that. And “dogma” can sometimes be a good thing since in the medical field it is based on countless outcomes supported by facts.
It is KNOWN that testosterone can fuel prostate cancer; it is KNOWN that Prostate cancer can become castrate resistant.
But if you don’t follow the dogma - the facts - what would be your alternate course of action? No ADT? T supplements for a highly speculative already castrate resistant strain of PCa? No doctor would ever agree to that.
May I make a suggestion? Why not go with the dogma for now and see what happens. If your PSA drops and stays very low during the course of treatment, you’ll absolutely know that you are on the right path. If, however, your PSA starts to noticeably rise you can then make the course correction - if your doctors agree - to take an ADT holiday and see if the PSA comes down….or goes even higher. That can happen as well.
You are not going to cause yourself to have a fatal outcome by going on ADT for a short period of time, if that is your main worry.

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Thanks for the info. The original question really was that, if a tumor manages to grow in a very low natural T environment, wouldn’t cutting off what’s left of T not making that tumor more aggressive by accelerating its desire to survive through alternative sources ? I get that dogma is what it is. Just asking for a friend…

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1 reply
heavyphil | @heavyphil | Jan 12 9:48am
In reply to @hanscasteels "Thanks for the info. The original question really was that, if a tumor manages to grow..." + (show)
@hanscasteels

Thanks for the info. The original question really was that, if a tumor manages to grow in a very low natural T environment, wouldn’t cutting off what’s left of T not making that tumor more aggressive by accelerating its desire to survive through alternative sources ? I get that dogma is what it is. Just asking for a friend…

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Tell your friend that if he has a tumor that is so aggressive and so quickly adaptable to anything modern medicine has to offer, he has no chance whatsoever of surviving; and perhaps he should seek no treatment at all and let nature take its course.
Just my opinion as a layman; I offer no medical advice or treatment.

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1 reply
heavyphil | @heavyphil | Jan 13 6:46am
In reply to @heavyphil "Tell your friend that if he has a tumor that is so aggressive and so quickly..." + (show)
@heavyphil

Tell your friend that if he has a tumor that is so aggressive and so quickly adaptable to anything modern medicine has to offer, he has no chance whatsoever of surviving; and perhaps he should seek no treatment at all and let nature take its course.
Just my opinion as a layman; I offer no medical advice or treatment.

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Hans, I hope you realize that my suggestion about your imaginary friend’s treatment was a snarky reply to your statement!😉
I truly appreciate your wry Euro sense of humor and most of your posts are tinged with a wink and a nod.
Because I like you so much I would like to grab you by your figurative lapels and scream: “RELAX!!!!”
You do not have some one in a billion case of PCa; you have what ALL of us have and you should just have it treated….period!
If you think your proposed treatment is less than what you desire, get on a plane and go somewhere you will get the answers you desire. Your LIFE SAVINGS may truly turn out to be an appropriate phrase!

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weakbutstrong | @weakbutstrong | Jan 13 3:29pm

Hello Hans, Fellow Men and those who feel less than Men,
I had 25 EBRT, HIR and Lupron for 2-1/4 years. I’ve been off the Lupron for 1-1/2 years. Yes, low RBC and WBC, testosterone is slowly rising now at 134, PSA at0.03 (originally at 19.4). And yes George of Sienfield Fame- I have MAJOR Shrinkish! I’m 70, have been blessed with children and grandchildren, one wife for nearly 50 years of whom I was fortunate enough to keep myself “pure” for her and feel immensely blessed to have waited for her thru the temptations of my younger years. Yes the passionate, and extremely rewarding physical marriage embrace has ended and most likely may never return; but love, connectedness and sharing life, laughs, and a less frequent tear is still a rewarding and Great Life. So for those who are losing hope through the loss of our great strength, endurance, aerobic capacity, and sexual ability; Life is a marvelously wonderful gift from Our Creator! May you all have hope and joy in this New Year and in our changed lives.
Peace to you all,
Weak but strong ( a former All-American Collegiate Wrestler and marathon jogger)

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1 reply
hanscasteels | @hanscasteels | Jan 13 3:34pm
In reply to @weakbutstrong "Hello Hans, Fellow Men and those who feel less than Men, I had 25 EBRT, HIR..." + (show)
@weakbutstrong

Hello Hans, Fellow Men and those who feel less than Men,
I had 25 EBRT, HIR and Lupron for 2-1/4 years. I’ve been off the Lupron for 1-1/2 years. Yes, low RBC and WBC, testosterone is slowly rising now at 134, PSA at0.03 (originally at 19.4). And yes George of Sienfield Fame- I have MAJOR Shrinkish! I’m 70, have been blessed with children and grandchildren, one wife for nearly 50 years of whom I was fortunate enough to keep myself “pure” for her and feel immensely blessed to have waited for her thru the temptations of my younger years. Yes the passionate, and extremely rewarding physical marriage embrace has ended and most likely may never return; but love, connectedness and sharing life, laughs, and a less frequent tear is still a rewarding and Great Life. So for those who are losing hope through the loss of our great strength, endurance, aerobic capacity, and sexual ability; Life is a marvelously wonderful gift from Our Creator! May you all have hope and joy in this New Year and in our changed lives.
Peace to you all,
Weak but strong ( a former All-American Collegiate Wrestler and marathon jogger)

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I get it. What I don’t get (don’t get it wrong, I love sex as anyone else) - but why is there such a focus on erections etc? It’s almost as if life dice when twinkie does as well.

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2 replies
northoftheborder | @northoftheborder | Jan 13 5:54pm
In reply to @hanscasteels "I get it. What I don’t get (don’t get it wrong, I love sex as anyone..." + (show)
@hanscasteels

I get it. What I don’t get (don’t get it wrong, I love sex as anyone else) - but why is there such a focus on erections etc? It’s almost as if life dice when twinkie does as well.

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I hear you. In my case, I didn't expect to live all that long at first, so erections were the least of my concerns. Over 3 years later, they're still only on my "nice to have" list.

Seeing the sun rise for more mornings is on my "need to have" list. For giving me that, ADT and Apalutamide feel like miracles.

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weakbutstrong | @weakbutstrong | Jan 14 7:20am

It’s the loss of that spiritual and physical and gestalt oneness of the human trinity of life and mature marriage: oneness and immense gratitude for God and this great gift of one wife and openness to creating a new life of a child added to our family, with the joy and reward of looking into my wife’s face and eyes and seeing her happiness as well as feeling my happiness of being one body and giving her all I have in my total love and oneness! Many of our wives are strong, healthy, vibrant, intelligent, sassy, funny, generous, pretty, mostly beautiful women and our loss of the old gift of “steel “ from our rectum to what use to feel beyond our glans (tip of the penis) how large we felt and how immense that desire and power from our abdomen and shoulders thru our forearms, fingers, buttocks, legs and toes that entire and complete giving of our power and love…! That has all disappeared, disappeared in an instant! My penis is so small now that there are times I urinate on my fingertips because I am too small, there is NO feeling, from my abdomen, from my legs, from my loins, from my back, No physical stimuli and no desire, I remember, I hug and kiss, but the desire has left me, the ability has left me. And sorrowfully, that has also impacted my beautiful, faithful, totally healthy wife. So, my and her, our life has changed. We, knowingly, or we thought we knew what would happen…
But, our life has changed. So younger men, may you be happy with your wife and live in the present for that beautiful gift of your wife and both of your beautiful gifts of giving yourselves totally to one another for, unfortunately, this too shall pass. (For those men who find it difficult to remain or be faithful, I pray for your strength, fidelity, prudence and temperance and I hope your mind doesn’t turn my story into your excuse to “jump onto anything that walks” because of a fear of losing sexual function.) And for those of us who may be like me; Every Day IS A GIFT!!!! The Creator has granted you and me and our wives and families, neighbors, communities, life and no matter what functions we have or will lose we can still pray for others needs and benefits and hopefully serve others in their needs. Good Luck in your choices for care, your mental, emotional and spiritual outlook; and you and those of you married or with a friend and partner hopefulness and joy in This Magnificent Gift of Life so Generously Given to us by The Creator!
God Bless You All,
Agape Love and Peace my brothers and sisters.
Weak but strong

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hanscasteels | @hanscasteels | Jan 14 7:58am

Thank you for your deeply personal and heartfelt reflection on the profound impact of changes in physical, emotional, and spiritual intimacy within marriage, particularly in the context of health challenges such as androgen deprivation therapy. I really appreciate how you express grief over physical losses while also finding gratitude and purpose in spiritual connection, love, and service to others. A good model to follow.. thank you

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heavyphil | @heavyphil | Jan 14 9:03am
In reply to @hanscasteels "I get it. What I don’t get (don’t get it wrong, I love sex as anyone..." + (show)
@hanscasteels

I get it. What I don’t get (don’t get it wrong, I love sex as anyone else) - but why is there such a focus on erections etc? It’s almost as if life dice when twinkie does as well.

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Yup, some men just don’t understand that this could be serious life and death stuff. Live first, worry about the rest later!

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proftom2 | @proftom2 | Jan 15 9:09am

Kind of like a Step-up-Batch trial? Maybe?

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