From 2018, when diagnosed, I have been told by doctors, urologists and oncologists that; "Testosterone, in prostate cancer, is like gasoline on a fire!"
When I first heard this it seemed dubious since what I "knew" about PCa was that young men with high T did not get it and that older men with declining T did get it. So it seemed that testosterone might actually be protective rather than something to be feared and eradicated.
Later on I learned ---
* That young men in their late 20s, who had lost their lives in gang violence, on autopsy showed lots of cancer but not active cancer.
* that a researcher at John-Hopkins found that men with the highest DHT at diagnosis survived longer. (Higher DHT - higher T)
* that Dr. A. Morganthaler had given hundreds of men with cancer testosterone without any serious blow-ups in their disease.
We all know that depriving PCa of T kills cancer cells and reduces symptoms-- the basis of ADT -- but despite doing a lot of reading about PCa and its treatments I have never come across any definitive study or evidence showing that PCa was aggravated by T except for the paper by Fowler and Whitmore.
The "gasoline" theory leads to a "castration" treatment bias whether by orchiectomy, Lupron or estrogen. May patients are led to extreme measures and try to suppress every molecule of T throughout their body -- ala the "Triple Androgen Blockade".
So, where did this "gasoline" theory come from?
Is there any hard evidence that testosterone by itself drives or exacerbates the disease?
As far as I can tell...
* It was Huggins who (suggested) that testosterone might act as "fuel" for PCa.
* It seemed "reasonable" that if denying PCa testosterone improved symptoms, that the converse - providing T - would aggravate them.
* And also, the idea that since estrogen -- the "female" hormone -- was the important factor in uterine and breast cancer; testosterone-- the "male" hormone-- must be the important fact in prostate cancer.
But a paper by Prout and Brewer in 1967 who gave testosterone to 34? patients found "the effect of exogenous testosterone on patients with advanced prostatic carcinoma is neither clear-cut nor predictable in many instances." ------ There was no mention of gasoline-like responses.
For "evidence", I was left with the 1981 paper by Fowler and Whitmore who had given testosterone to some? of their patients from 1949 to 1967 and found that many of them had an immediate worsening of their symptoms and that eventually all of the previously treated patients did so. The only "holdouts" were four patients without prior treatment (two of whom actually improved with testosterone.)
So ... is that it? A few "reasonable", "rational" assumptions and then the results of Fowler and Whitmore provide the main supporting evidence for the testosterone "gasoline" theory?
Written by
VoxHope
To view profiles and participate in discussions please or .
1. TRT for healthy men. Normal levels keep healthy prostates healthy.
2. TRT for men with advanced PCa - this is throwing gasoline on a fire. The AR amplifies with progression, so giving more T is certainly giving the cancer more fuel.
To confirm #2? Huggins and Hodges discovered it in 1947. No one other than Mengele would give advanced PCa patients T since then, except in carefully watched clinical trials.
"Why can't we just give continuous high doses of testosterone?
It's been known for a while that testosterone plays a role in keeping healthy prostate cells healthy. We have observed that hypogonadal men (men who have low natural levels of testosterone) are more likely to have prostate cancer, and more virulent types. For a thorough recent review of this subject, see this link. In fact, one pilot study showed that men with mCRPC who had higher plasma testosterone levels (but still at castration levels) survived twice as long. They responded better to chemotherapy as well (see this link).
In 2009, Robert Liebowitz et al. reported on 96 patients who received very high dose testosterone replacement therapy (TRT) after some kind of prostate cancer treatment. For 59 of those men, the only treatment had been androgen deprivation. 12% were detectably metastatic. 60% had PSA progression while on TRT, but few had metastatic progression in that time period. For most of those, discontinuing TRT reversed the PSA progression.
There was a small (12 man) safety trial at Memorial Sloan Kettering. None of the men achieved supraphysiological serum testosterone levels from the transdermal gel they used. One man had to discontinue when he experienced spinal pain, but there weren't any other major side effects. Of the 12 men, 7 had decreased PSA (one had a 50% decrease). The other 5 had increased PSA, 2 by more than 50%. There was no regression of metastases in any of the men.
Other small trials of TRT alone had mixed results (see this link and this one).
I am intrigued by these threads. One point is that it seems that all these studies have been very small. I would like to review them so if any of you are willing could you post the references to speed my research. I’m sure I can find them without but it would speed me up!
Didn't Huggins just discover that blocking T to the prostate had beneficial results. Since he never administered T he didn't "know" that T was gasoline on a fire but he thought it might be.
That's why I was asking about Fowler & Whitmore who may have been the first? to actually administer T to metastatic PCa patients. Although there are alot of unusual aspects to their work-- why they continued so long given the bad results and why the long delay from the last patient 1967 until publication 1981, I wouldn't call them Mengeles by any stretch.
Liebowitz ... "after some kind of cancer treatment". This is rather dismissive of Dr. Bob's Trademarked! "Triple Androgen Blockade" which he did for 11? months and after which he was reluctant to repeat due to fear of pushing the patient into resistance. I have respect for Dr. Bob's dedication and his "inside the box" thinking that helped many patients.
They determined that castrate levels of testosterone are necessary to prevent activating the androgen receptor.
There are whack jobs who add fuel to the fire. Dr. Bob, for example, had all his patients sign a waiver stating, "I have been informed that this may kill me and agree not to sue if it does."
You may respect doctors that I consider to be "whack jobs." I base my assessment on what they've published.
(1) androgen deprivation therapy (ADT) which is chemical or physical castration. Castration is defined as serum testosterone of at most 50 ng/dl, but preferably 20 ng/dl (progression is significantly better reduced). ADT includes GnRH agonists like Lupron; GnRH antagonists like Firmagon or Orgovyx; and orchiectomy.
(2) anti-androgen therapy (AA), which blocks the androgen receptor (AR). It doesn't directly prevent production of testosterone (T). But because T can't be used, it often accumulates in the bloodstream. Then when T levels get very high, the pituitary may shut down further production
(2a) Early AAs included bicalutamide and nilutamide. But they were found to be inferior to ADT and the AR adapts by feeding on them. Bicalutamide (Casodex) is now principally used for short term use to prevent activation of the AR by GnRH agonists (like Lupron), which would otherwise be like gasoline.
(2b) Second generation AA comprise enzalutamide (Xtandi), apalutamide (Erleada), and darolutamide (Nubeqa). They block the ARs more completely, and though there have been cases of the AR feeding on them, it is rare before resistance kicks in.
(3) Abiraterone (Zytiga). This prevents the adrenals and tumors from producing secondary sources of testosterone and other androgens.
(2b) & (3) have been tested combined with ADT and increase survival and delay progression compared to ADT alone. They have also been tested experimentally as monotherapies (without ADT). The recent EMBARK trial proved that adding ADT to Xtandi significantly delayed castration resistance, metastases, use of chemo and increased survival compared to Xtandi monotherapy.
>>>> I base my assessment on what they've published.
What Dr. Bob has published looks pretty solid to me... I am looking at this--
--------------------
"Primary triple androgen blockade (TAB) followed by finasteride maintenance (FM) for clinically localized prostate cancer (CL-PC): Ten-year follow-up."
Results:
* After median 126 months followup, disease specific survival is 98.5%
* Overall survival is 86.4%
* No low or intermediate risk men died of PC
----------------------
Now, everyone on this board respects your knowledge TA, so why hide behind your "ad hominem" mode when you can tell us just what you think Dr. Bob did wrong and what made him a "whack job"
>>>had all his patients sign a waiver
Again, no specific from you on the background of this, but with anyone departing, how ever so slightly, from the straight-jacket of SOC, I can see why Dr. Bob would want to head off "bad outcome" lawsuits. Similar to "Snuffy" Myers he seemed to be able to "think" about the treatment and how to bend it to get better results unlike so many who just follow the script.
You are citing the wrong study. What you are citing is a trial of triple androgen blockade (GnRH agonist+antiandrogen+finasteride) not his use of TRT.
In 2009, Robert Liebowitz et al. retrospectively reported on 96 patients who received very high dose testosterone replacement therapy (TRT) after some kind of prostate cancer treatment. For 59 of those men, the only treatment had been androgen deprivation. 12% were detectably metastatic. 60% had PSA progression while on TRT, but few had metastatic progression detected via bone scan/CT in that 3 year time period. For most of those, discontinuing TRT reversed the PSA progression.
The goal was to provide relief of hypogonadal symptoms. He lumped together all kinds of patients. All of the patients had been previously treated: 39% curatively, 61% with ADT-only. It was no coincidence that after 3 years, 60% had PSA progression with TRT. There has been no f/u since then.
It is important to understand what has come before instead of pursuing whacky hypotheses based on ignorance.
Exactly this. There is a big difference in how something can affect a healthy person vs. what It can do to someone who is already sick.
Just think of how salt doesn't cause high blood pressure, yet it's clearly harmful to people who already have high blood pressure.
Same with sugar, it doesn't cause diabetes, but is clearly harmful to people who have diabetes.
Similarly Testosterone doesn't cause prostate cancer, but is clearly harmful to people who already have it, otherwise ADT (as well as literal castration) would not work, which the evidence for is clearly proven.
That's not a clinical trial. Show one (in humans) that actually shows that giving testosterone to people who already have prostate cancer helps them.
Observational studies and laboratory studies are interesting and can be suggestive, but they are not clinical evidence.
There is literally abundant clinical evidence that suppressing testosterone is beneficial in people that have prostate cancer. It is "reasonable" to expect that anyone theorizing the opposite have clinical evidence to back up their theory. As of now, there is none.
It is a trial now at Johns Hopkins, STEP-UP. I have been doing this for a year, a local trial in Oslo. I am alternating between high T and very low, Darolutamide after T injections. A year ago my PSA was 3.4, now 2.9, expected to go down to 0,x.
Conflict of interest: ESA is a paid consultant/advisor to Janssen, Astellas, Sanofi, Dendreon, Pfizer, Amgen, Lilly, Bayer, AstraZeneca, Bristol-Myers Squibb, Clovis, and Merck; he has received research funding to his institution from Janssen, Johnson & Johnson, Sanofi, Dendreon, Genentech, Novartis, Tokai, Bristol Myers-Squibb, AstraZeneca, Clovis, and Merck; and he is the coinventor of an AR-V7 biomarker technology that has been licensed to Qiagen. SRD has received research funding to his institution from Astellas. AMD is a paid consultant/advisor to Merck and Cepheid and has received research funding from Janssen and Myriad for unrelated work. SY receives research funding to his institution from Bristol-Myers Squibb and Celgene, Janssen, and Cepheid for unrelated work and has served as a consultant for Cepheid. He owns founder’s equity in Brahm Astra Therapeutics and Digital Harmonic. MCM is a paid consultant to Clovis and Exelixis.
You misunderstood the article you posted. It does NOT show testosterone resensitizes CRPC back to HSPC. It suggests that in about ⅓ of men with asymptomatic mCRPC, they have high AR activity that might respond to bipolar androgen therapy (BAT) with ADT+enzalutamide. (There is no such effect using ADT+abiraterone).
Most (⅔) men with asymptomatic mCRPC have either no response to BAT or a disastrous response. Johns Hopkins is trying to identify the ⅓ who have a good response, so they developed a biochemical test for high AR activity. To my knowledge, one can only get the test at Johns Hopkins.
very thought provoking. Worth considering that prostate cancer is not a single clone of cells (monoclonal) but many clones (polyclonal) and the clones that ultimately kill tou are the ones that are not testosterone dependent and unresponsive to ADT. Just like bacteria and antibiotics, use of ADT ultimately results in selection of ADT resistant clones.
True, but it has been learned that reducing the volume of clones has a greater effect on patient survival compared to resistant clone selection increasing mortality.
I used to wonder why young men didnt get prostate cancer when they have so much testosterone but learnt it is to do with dihydrotestosterone (DHT) approx 10% of testosterone is converted into DHT by the enzyme 5alpha reductase DHT is the driver of prostate cancerAs men get older testosterone declines but DHT increases
5 alpha reductase inhibitors work to prevent the conversion of testosterone to DHT an example is Finesteride but there are food sources and suppliments that also act as 5 alpha reductase inhibitors
This is highly interesting, this has been studied in detail. When you are using ADT and ARSi over time the cells adopt the low level of T (<0.4ng/dl) by AR amplifying, AR copy gain can be increased up to 90! This is logical, when the AR receptor receives too little for the AR transcription and licensing in the DNA replication phase it just copies itself in order to get enough. So, remove T and AR amplifies. Vice versa, add lots of T and AR is REDUCED to the previous untreated level. This is proven, just read the attached study. Add gasoline (T) and AR goes down. I have tried this, using the logic behind. Three months of high T cycles, PSA rose from 2 to 7. Introduced Enza a month, PSA down to 0.1. AR will start amplifying again because AR is removed, then T again like in the STEP-UP trial.
T or «Gasoline» reduces AR fast, two months with T injections. This is the only way to make pCA a chronic disease. It’s cheap and Big P is not interested, FDA will never accept. T is doping, my H went from 12 to 15!
Yes, by reducing T with ADT/ARSi AR is gradually increasing by amplifying/ copying itself in order to scoop up - perfectly understood. This is the resistance process.
And vice versa, increasing T to supraphysilogical levels the AR reverse the process, gradually lowering the expression of AR back to the previous untreated levels. Denmeade and co looked at the biopsy after three periods of high T (BAT) - monthly injections of T Cypionat, AR back to normal. Then you can use ARSi again, the cells are resensitized.
This is what they are doing in the STEP-UP trial.
I convinced my MD to try this, there was heavy opposition from the hospitals leaders, claiming this is insane - actually used the words : Gasoline on the fire……. After signing papers that I took the full responsibilitis, they gave in.
PSA was at 2 in 03/23, rose to 3 04/23, then 3.4. I did not have more T due to import restrictions, PSA rose to 7 during 06/23 with no treatment. My MD had contact with Denmeade in this period.
Then came the exam, what happened to the T treated cells? (Iwas CRPC in 05/21)
I started to take Enza in July 23 again, and what happened was just like the theory.
PSA dropped to 0.5, after 6 weeks 0.14 before slowly started to increase again.
My MD was very excited, your cells are reprogrammed. The skeptics are silenced, no comments
Now it is enough with two cycles to bring PSA all the way back again. I tried with one month, but that was not enough, PSA dropped 50%, not 98%.
I will start with Daro 8th of May, wil know the result one month later - fully resensitized?
(Side effects of T are only positive, hemo from 12 to 15)
The huge problem is that no one believes the results acc to the Gasoline understanding. It is counter intuitive! Prostate cancer? Remove T by all means!
I was 100% sure that advanced prostate cancer was lethal, after CRPC no more options.
I am now 54 months on this journey, diagnosed with G9, intraductal, PNI, PTEN loss and BRCA2/ATM - SBS3 profile, average lifespan 3 years.
I am the only patient in Norway receiving this theraphy, MDs are refusing to give «Gasoline» to their patients.
I have posted about my history with this, not TRT, but testosterone recovery while off treatment. Attached is my clinical history. I did on triplet therapy from January 17 to May 18. Last Lupron shot was early May 18, 90 day one, so sometime in July-Aug it would start to clear my system.
Urologist checked T in October, 135.
We checked again in February 18, it was 481.
My PSA began a steady rise in March 2022 from .06 to .12, then continued upwards to .77 in March 2023. We did the Plarify scan, identified a single PLN, decided on SBRT and 12 months Orgovyx. Oncologist checked T before I did the loading dose, 608.
So, why did I "enjoy" a progression free survival from say October 2018 until March 2022 with T somewhere between 481 and 608 (higher than when I started triplet therapy!), I don't know, study of one as I say.
My radiologist, oncologist and I agreed on 4 April to come off Orgovyxx after 12 months. We will actively monitor with labs and consults every three months, decision criteria to image - three or more consecutive PSA increases, PSA >.4, then informed by clinical data decide when, with what and how long to go back on treatment.
Just shy of four weeks off Orgovyx, muscle and joint stiffness along with fatigue pretty much gone, genitalia shrinkage still evident and alas, damn hot flashes,I swear are worse than when I was on Orgovyx.
I did get in a 50 mile bike ride earlier this week, felt pretty good.
So, has my T began its recovery, probably, we'll see in July when we do labs. With that, has my PSA increased, we'll see in July....
If you search PubMed for "Morgentaler Testosterone" you will find that he wrote or co-authored 142 articles about this. A detailed review of this literature would be an excellent way to learn about the benefits of supplementing testosterone in castrate-resistent men with CRPC.
As an example, consider this chart that shows Prostate Cancer Specific Mortality (PCSM) versus time for low and normal testosterone levels. Men with normal T had lower rates of PCSM compared to men with low testosterone who had higher rates of PCSM.
Many thanks for giving us these plots which summarize the data for easy understanding.
In this plot however, the decline in the number at risk for the Normal T declines to the same low level as the Low T but your plot flatlines. It would seem that the Normal T plot should rise in a similar but different fashion. What am I missing here?
Sorry, I don't know the answer. It's just plotting the data points. I, too,would have expected the Normal T curve to have turned up at some point. Perhaps that rise would have shown up if they would had followed these men for 20 years?
It's an impressive comparison, though, and contradicts the common belief that high testosterone is bad for men with PCa. The key point is separating the groups into hormone-sensitive and castrate-resistant men. In the first group, you want have very low T levels by doing ADT, but in the fully castrate-resistant men the opposite appears to be true.
It is important to look at the results of a 12 year study in which 412 hypogonadal men received testosterone, with a control group of 380 hypogonadal men did not. Prostate cancer was detected in only 2.7% of the treated men, as opposed to 8.9% of the untreated men. All of the cancers in the treated men were detected within the first 18 months and all but one of those men had a Gleason score of 6 or less. None of the untreated men had a Gleason score under 7. There can be no question that both groups of men should have had appoximately the same percentage of occult tumors at the start of the study. This means that logically, the increased level of testosterone either was killing prostate cancer cells or was slowing down their growth rate to such an extent as to prevent detection.
Also, a retrospective study of 189,461 non-diabetic men aged 40-60 showed that testosterone therapy reduced the risk of prostate cancer. They concluded: "increased use of testosterone therapy is inversely associated with prostate cancer".
Finally, researchers have shown that low-risk prostate cancer patients who have undergone robotic radical prostatectomy lower their risk of recurrence if given testosterone.
This chart shows the beneficial effects of having higher testosterone in CRPC men. Higher testosterone was associated with three effects: (1) longer median survival times (8 years vs 4 years), (2) longer PSA doubling times (11 months vs 3 months) , and (3) longer Time to PSA Failure (40 months vs 25 months) for higher levels of testosterone. Cohort is men having done RT and 6 months of ADT.
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.
New Data: Finasteride Safely Prevents Prostate Cancer'These Results Are Transformational,' Says Researcher May 20, 2018
