I’m writing this post with a preamble that these are my opinions, and I cannot prove any of them, nor am I trying to prove them. So, please read these conclusions with this information in mind.
I believe that information about tE2 is difficult to uncover because in the US, the medical industrial complex (MIC) wants the information about tE2 to be difficult to find and sourcing of tE2 to be equally restricted.
Following its initial discovery by American scientists in 1923, a partial synthesis of estradiol from cholesterol was developed by Inhoffen and Hohlweg in 1940, and a total synthesis was developed by Anner and Miescher in 1948. Transdermal estradiol gel was developed and marketed beginning in the early 1980s. For a complete discussion of this development history, read the Wikipedia entries.
In 1941, Charles Huggins and Clarence Hodges at the University of Chicago found estradiol benzoate and DES to be the first effective drugs for the treatment of metastic prostate cancer. DES was the first cancer drug. These were the standard drugs for treatment of advanced prostate cancer for over forty years until the GnRH agonist leuprorelin (Lupron) replaced them in 1985.
In 1980, Sindell v. Abbott Laboratories, 26 Cal. 3d 588 was a landmark products liability decision of the Supreme Court of California which pioneered the doctrine of market share liability. A lawsuit was filed in Boston Federal Court by 53 DES daughters who claimed their breast cancers were the result of DES being prescribed to their mothers while pregnant with them.
Their cases survived a Daubert hearing. In 2013, the Fecho sisters who initiated the breast cancer/DES link litigation agreed to an undisclosed settlement amount on the second day of trail. The remaining litigants have received various settlements. The advocacy group DES Action USA helped provide information and support for DES-exposed persons engaged in lawsuits.
In the US, The Centers of Excellence (COE) hospitals employ the physicians and their support staff. These COE are corporations, and these corporations are commercial for-profit businesses. The administrators of the COE are businesspeople, and they are trained to minimize risk and avoid litigation. Litigation is unpredictable and costly for businesses. The malpractice insurers of physicians and of the COE where those physicians are employed seek to avoid litigation whenever possible. Lawsuits are normally settled and seldom reach a jury verdict. Jury verdicts are unpredictable while monetary settlements can be contained and negotiated.
Following the outcome of the 53 DES daughters lawsuit in Boston, the use of E2 drugs for ADT treatment of prostate cancer in the US virtually disappeared. Now, forty years later, it should be easy to understand why the majority of the medical oncologists treating PCa today know nothing about tE2. Their employers in the COE have eliminated tE2 from the basket of ADT drugs that their employees can prescribe for their PCa patients ADT.
It may be possible to obtain a prescription for tE2 from an independent urologist or primary care physician who is not affiliated with a large MIC organization. But those independent physicians’ medical malpractice insurers may not offer them coverage if they provide a tE2 prescription to their patient. It is a risk for the physicians to do so because there are medical malpractice attorneys lurking everywhere seeking lawsuit clients who are the dissatisfied heirs whose loved ones died with prostate cancer.
Additionally, I believe that Big Pharma does not want tE2 reinstated as an ADT drug for use in the US. tE2 is inexpensive to manufacture and in other countries around the world, tE2 is available for sale inexpensively over-the-counter. I’ve seen tE2 in Mexico, the EU countries and in Canada.
For those enterprising members of the PCa brotherhood who wish to explore the use of tE2 for their ADT treatment, it has become a do-it-yourself (DIY) endeavor. Probably the best information about sourcing tE2, its practical usage and dosage and its continued monitoring using blood testing can be found on this forum or on other online prostate cancer websites.
My conclusions about tE2 and its history may be completely wrong. I’m not using tE2 yet because fortunately, my uPSA remains undetectable a year and a half after having had a RARP. So, in my case, BCR has not yet occurred. Eventually, I expect that BCR will occur. When BCR does occurs, I plan to get a PSMA-PET scan someplace and then seek SRT using PBT to try and eliminate any micro tumors that may be causing the uPSA to rise. Then, I expect to use tE2 for ADT thereafter. I expect that my ongoing tE2 ADT treatment will be a DIY adventure.
I hope you find this little essay helpful. Good luck.
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You don't need conspiracy theories. Oral estrogen had huge clotting problems, leading to deaths. Transdermal preparations avoid the hills and valleys in absorbed dose one gets with pills. But does it works as well as GnRH agonists/antagonists? That's why God invented randomized clinical trials. STAMPEDE/PATCH will provide the answer. So far, so good.
Thank you J--- for posting this. I am totally in agreement with everything that you stated. After using tE2 for three years I am delighted with the results...my last two PSAs were 0.003. If I knew Richard Wassersug four years ago I would have forgone my 68Ga-PSMA-11 PET scan that I had performed in Australia and the subsequent $75K lymph node excision that only bought me a little time.
Tall_Allen wasn't convinced that having eight 'identified' sacral lymph nodes removed was going to accomplish much since I most likely had many more that were too small to show up on the scan. He was absolutely correct since my PSA had decreased from 1.3 to 0.54 shortly after the surgery; however, within a few months it began rising again.
At that point I was a perfect candidate for ADT which I was extremely reluctant to submit to due to the typical nasty side effects. I tried to find DES as an alternative, but 'no joy'. My grandfather, father, and his two brothers all did extremely well on DES for years until it was replaced with Lupron in 1985.
About that time while having lunch with a ladyboy friend of ours, 'she' happened to be going through her purse and accidentally pulled out a tube of Oestrogel. Being the nosey guy that I am, I immediately asked what it was? She told me that many ladyboys here use it to help with the feminization. Consequently, I began doing some research and found that it was similar to DES without the CV risks.
I asked if anyone on the forum knew anything about this gel and low and behold Richard W. came to my rescue!
A number of our comrades have asked if I could send them some since they can't get it in the US. Richard W. buys it in Canada for $55/tube...here it is less than $15 and a tube lasts me about three weeks. Compare that one to Lupron injections! I also haven't seen a doctor since my LN surgery.
One of our members just sent this message to me: "There is no indication, however, that I will be able to find another oncologist nearby who dares stray from the norm of SOC. I just got a note yesterday from my urologist that he is 'unwilling' to assist with tE2 therapy."
I hoped that you’d see my post and respond. Gents seeking guidance should read your earlier postings. They should also download and read the clinical trials going on elsewhere in the world. We know that oral DES caused clotting and cardiovascular side effects, but I believe that no matter what the results of the current clinical trials turns out to be, sourcing tE2 in the US will not happen in my lifetime - however long that lifetime might be. Guidance from the COE MOs will not be forthcoming. We’re on our own whether we like it or not. This is not a conspiracy theory, It is just reality.
In case some of you missed the results of the PATCH study, here is the conclusion:
"Cardiovascular results from the PATCH study are now published comparing transdermal estradiol vs LHRH agonists for ADT. No difference in mortality or morbidity. Authors conclude that transdermal estradiol can be considered for ADT to control prostate cancer."
Yep, I saw the results, and they are positive. Noahware highlighted a few other reports with similar favorable conclusions. What I wanted to present was why I believe that information and medical assistance using tE2 will not occur in the US. The history of the litigation settlements that is wrapped up with the use of oral DES, is the life blood of medical malpractice attorneys, and lawsuits are what scares the COE administrations. The easiest way to avoid potential lawsuits involving tE2 is not to allow your employees to prescribe the drug to their patients. Besides, why prescribe a drug that should be able to be purchased at CVS and administered yourself? Where is the profit motive in that transaction for the COE? Yeah, I know, just another conspiracy theory about Big Pharma. Oh well, it’s just my humble opinion, and you can disregard it easily.
therefore, should avoid the cardiovascular toxicity seen with oral oestrogen and the oestrogen-depletion effects seen
with luteinising hormone releasing hormone agonists (LHRHa). We present long-term cardiovascular follow-up
data from the Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme.
Methods PATCH is a seamless phase 2/3, randomised, multicentre trial programme at 52 study sites in the UK.
Men with locally advanced or metastatic prostate cancer were randomly allocated (1:2 from August, 2007 then 1:1
from February, 2011) to either LHRHa according to local practice or tE2 patches (four 100 µg patches per 24 h,
changed twice weekly, reducing to three patches twice weekly if castrate at 4 weeks [defined as testosterone
≤1·7 nmol/L]). Randomisation was done using a computer-based minimisation algorithm and was stratified by
several factors, including disease stage, age, smoking status, and family history of cardiac disease. The primary
outcome of this analysis was cardiovascular morbidity and mortality. Cardiovascular events, including heart
failure, acute coronary syndrome, thromboembolic stroke, and other thromboembolic events, were confirmed
using predefined criteria and source data. Sudden or unexpected deaths were attributed to a cardiovascular
category if a confirmatory post-mortem report was available and as other relevant events if no post-mortem report
was available. PATCH is registered with the ISRCTN registry, ISRCTN70406718; the study is ongoing and adaptive.
Findings Between Aug 14, 2007, and July 30, 2019, 1694 men were randomly allocated either LHRHa (n=790) or
tE2 patches (n=904). Overall, median follow-up was 3·9 (IQR 2·4–7·0) years. Respective castration rates at 1 month
and 3 months were 65% and 93% among patients assigned LHRHa and 83% and 93% among those allocated tE2.
157 events from 145 men met predefined cardiovascular criteria, with a further ten sudden deaths with no postmortem report (total 167 events in 153 men). 26 (2%) of 1694 patients had fatal cardiovascular events, 15 (2%) of
790 assigned LHRHa and 11 (1%) of 904 allocated tE2. The time to first cardiovascular event did not differ between
treatments (hazard ratio 1·11, 95% CI 0·80–1·53; p=0·54 [including sudden deaths without post-mortem report];
1·20, 0·86–1·68; p=0·29 [confirmed group only]). 30 (34%) of 89 cardiovascular events in patients assigned
tE2 occurred more than 3 months after tE2 was stopped or changed to LHRHa. The most frequent adverse events
were gynaecomastia (all grades), with 279 (38%) events in 730 patients who received LHRHa versus 690 (86%) in
807 patients who received tE2 (p<0·0001) and hot flushes (all grades) in 628 (86%) of those who received LHRHa
versus 280 (35%) who received tE2 (p<0·0001).
Interpretation Long-term data comparing tE2 patches with LHRHa show no evidence of a difference between
treatments in cardiovascular mortality or morbidity. Oestrogens administered transdermally should be reconsidered
for androgen suppression in the management of prostate cancer.
Funding Cancer Research UK, and Medical Research Council Clinical Trials Unit at University College London.
Thanks for posting this, Jeff. Others may have noticed that after the latest PATCH update was reported in the Lancet (in Feb.) and re-posted on this site, I posted this item that I saw in Physician's Weekly, regarding that Lancet report:
' In an accompanying editorial, Charlene Mantia, MD, and Atish D. Choudhury, MD, PhD, both of the Dana-Farber Cancer Institute, Boston, MA, commented...
“The PATCH trial suggests that tE2 is an appropriate treatment strategy in men with prostate cancer, with a decreased risk of several androgen-deprivation therapy-related side-effects and similar cardiovascular risk as LHRHa. At present, no differences in efficacy have been shown between androgen-deprivation treatments; therefore, therapeutic decisions are based on availability, costs, side-effect profiles, pharmacodynamics of testosterone suppression and recovery, convenience, and likelihood of adherence. The choice of agent should be individualized based on the patient’s disease state, comorbidities, and preferences,” concluded Mantia and Choudhury. '
Coincidentally, I had just asked my Dana Farber oncologist about tE2 days before I came across this. He replied that it sounded "reasonable" and that he would discuss it with his fellow DF oncologists. A few weeks later he said we could proceed once a protocol was worked out. A few weeks MORE and... I'm still waiting.
If your theory is correct, Jeff, it is the lawyers that are keeping me waiting. The protocol could and should be pretty straightforward. Naturally I will keep everyone posted on what does (or does not) happen.
Two DF docs have written an editorial saying tE2 appears to be a safe, effective and appropriate treatment strategy in men with prostate cancer, that importantly AVOIDS some of the more severe SEs of standard ADT. So will DF (and other Center of Excellence) docs actually be suggesting it to patients, or actually have a protocol in place if patients request it? Don't hold your breath.
Oh yeah... it is VERY inexpensive. We can all conclude for ourselves what role that might play in how it is promoted or not, but it certainly is among the reasons this trial happened in the UK. Under their socialized medicine there is strong incentive to cut costs while improving outcomes. No such incentive exists in the USA. Quite the contrary.
I hope Dana Farber proves me wrong about the influence of the lawyer’s and insurer’s oversight.
DF is independent from Partners in Health, the non-profit holding company of MGH, B&W and about a dozen other hospitals in Massachusetts. Partners is the largest employer in Massachusetts, and its board of directors is populated with a who’s who in the legal community of New England. While DF and Massachusetts General Brigham (MGB) share many of the same physicians and they all hold teaching positions at Harvard Medical School, DF is not yet owned by Partners. They may still have some autonomy from the legal and insurance influences.
Yes, if used correctly... and apparently many men can reach a castrate state more quickly with tE2 than with Lupron, according to the reported results (as seen in the text Ron copied above). Consider also that with Lupron, it is possible for T to rise higher than desired levels at the very end of a 3-month cycle, right before the next injection. That would not happen with constant tE2.
I guess my best response to your question would be, it is ADT, just by a different name! The HIGH-DOSE tE2 approach should not be thought of as something you do "instead of" ADT but simply as a form of ADT that is different from either chemical castration or surgical castration. (But keep in mind that LOW-DOSE tE2 is something you do ALONG WITH those other two therapies, to add back some missing estrogen.)
Here's a link to another commentary by a well-respected doc:
My husband's experience towards the end of the first injection (Trelstar) was that T rose way higher than ever before and was still rising beyond the normal range after the second injection for a few days. When we realised this, we started him on Casodex but urologist had not warned beforehand.
Thanks for posting this 'significant' report - I have asked about this myself nd had the door slammed in my face - NOT SOC, therefore, off the table - I'm wondering if there is a work around ?
Yes, there are work arounds so you can use tE2 for ADT, and the guys on this forum who are using tE2 for their own ADT can help you and others devise a protocol. Private message ronronHU and wassersug and they’ll help you. Guys who live in other parts of the world where tE2 is easily available will also help. Unfortunately you’ll probably need to be circumspect with your USA MO about what method of ADT you’re using if you move away from what the MO is prescribing. One man with whom I’ve communicated had no problem getting his PCP to prescribe monthly LabCorp blood tests so he could monitor his T, E and uPSA. His urologist wouldn’t help him.
Thé SOC is used as a list of accepted procedures that have been vetted by the physicians professional organizations and .........their malpractice insurers and their association’s attorneys. If physicians are sued, their attorney can point to the SOC as the guideline for the treatment that they prescribed. If the physicians deviate from the SOC, they are at risk. Our medical industrial complex is a mess. But, that is just this old liberal’s opinion.
I'm a Canadian - but I have still been refused because my RO won't go there.
In fact, I became suicidal on ADT - Lupron devastated me and I arbitrarily quit it without consulting my 'care team'.
They thought I was nutz, but I have managed to get a bicalutamide mono-therapy which is NOT the SOC in Canada due to my insistence that Lupron was off the table for me.
I've been on "Caso' for about 1 month and will be testing my PSA in about2 weeks to hopefully see some positive results.
I know Richard W and would contact him at some point in time to see what he suggests as a workaround IF the conclusion is that 'Caso' isn't working.
I met a new MO and the answer I got is they are waiting to see IF / WHEN I progress to, and graduate to 'chemo'.
That 'concept' is something that is tricky to digest - MAYBE I'm one of those that could get a lot of mileage from the mono-therapy - or wait for the 'inevitable' ?
Time will tell - I'd like to get my GP to prescribe tE2 for me down the road IF it might be a better alternative - but now that would establish a clash of medical cultures - a battle I would surely lose.
I'd go 'rogue' but I'd need to see results and if they weren't there, I'd need to crawl back to the oncologists - far from ideal, but what if tE2 is the best option - how do I force the issue ?
I’d get some guidance from Richard W. He uses tE2 for his ADT, and he can buy it in Canada, so you should be able to obtain it too. You may need to have a serious discussion with your MO, RO and whomever else is a member of your caregiver team about who is directing your health care and who wants to remain on your team or not. I know this is a scary thing to contemplate, but it is your life and you need to be in charge of its care.
When I was in the barrel of preliminary options about how to treat my coronary artery disease and getting recommendations from everywhere about doing this treatment or dying suddenly tomorrow if I didn’t, it was a frightening time. Eventually, I fired several caregivers, got second and third opinions and eventually found and assembled my present cardiac team.
This was a long research slog. I did not have the recommended and aggressively advocated quintuple by-pass surgery. That was six years ago, and now I question everybody carefully about why they want me to pursue any treatment. If I do not get a clear transparent answer, I move onto more research.
But, in the 60’s my VW bug had a "QUESTION AUTHORITY" bumper sticker on it, so listen to my advice with caution.
I don't believe I have the option to FIRE anybody. In Canada, you can shop for a GP, but you won't find one because there is a shortage of GPs and about 40% of the population are underserved.
That is the definition of 'universal' health are in Canada - rationed and rigid with few options - you aren't allowed to BUY private care in virtually every situation - it is illegal !
I'll have to be 'contrarian' and go rogue AND find a willing GP / accomplice to get my way - and if I'm wrong, then what ?
Between a rock and a hard place - unless I can dictate the treatment, against their advise - something that I'm not sure I can do ....
Obviously I’m out of my depth beyond the borders of the US medical system, and I’m probably over my head here too. But, I’d definitely consult with Richard W. He is using tE2 for his ADT, so he has navigated the system somehow to get the ADT that suits him.
It is available by prescription in Canada - you need to find an oncologist who is willing to do it - instead of insisting that THEY don't like your choice of treatment.
Is there a lot,of télé-med consultations occurring in Canada? If so, maybe there’s guys on this forum in Canada using tE2 for their ADT who will share the name of their MO with you. You may be able to connect via a tele-med conference with that MO. Once you make the connection, if you can get a relationship established, it may be worth jumping on an airplane and having an in person consultation. When my time comes, I’ll go where that MO resides if the MO is a reasonable and flexible medical care provider. Good luck. PCa is tough enough without having to navigate the goddamn medical establishment mine fields.
I appreciate the 'positioning' you are taking - but there's an elephant in the room.
We can't select our healthcare providers - we can't BUY medical services - it is illegal.
IF I go 'rogue', I'll need a GP to NOT be afraid of a malpractice lawsuit.
I would need to present an 'action plan', based on solid evidence.
That is the only route I could take, unless someone could refer me to an Oncologist that would see the TRIAL results and/or refer to the UK protocol and say 'this is an acceptable' treatment option.
In terms of dosing and advise, I know where to get it.
Please forgiven my repeated ignorance regarding the regulations in Canada. I fall into the US capitalistic malstrom too easily. Maybe your Canadian colleagues will suggest the right GP. I hope you can resolve this. Hopefully, Richard W can offer some guidance.
Forcing the issue might be accomplished by means of declaring yourself”allergic” to leuprolide (Lupron, Eligard and similar). Report that you have had a reaction such as redness swelling rash and itching. They have to take your word for it and cannot continue to prescribe it. Then request estradiol patches as a safer alternative. It is manipulative, using the system to your own advantage. It is a personal decision and must be carefully considered before going there.
Hi We are in Ontario and one MO that we got to see after our disappointing urologist agreed to prescribe transdermal E2 patch on the condition that it would not be instead of but in addition to the ADT injection. He was to give the prescription a month ago and has gone very quiet.
I don't want any injections (been there, done that) and it sounds like the 'compromise' is a tall order for the MO - because he knows it's not the SOC - some of these 'pros' act more like dictators - they'll play it by the book - very Canadian ....
It might be time to post a question to the forum and ask for guidance from the brotherhood about how others are obtaining their tE2 and how they are self-administer their dosages. That is part one and twofold DIY tE2 ADT. Part three is how to monitor your T, E and uPSA without oversight from your MO. I know, it might seem daunting, but I know that other guys are doing exactly this as their DIY ADT to minimize their SEs from SOC ADT drugs.
Demand for DES (for ADT) faded because of the risk of blood clots. I suspect that when Lupron came in, DES & orchiectomy remained as good options for the uninsured poor. Eventually, DES production ceased in the U.S.
It is still possible to get DES from compounding pharmacies. When I was looking for a source 4 years ago, the local pharmacist said that there was a demand (for dogs not men), but his supplier couldn't get the powder (Chinese source.)
Eventually, I located a pharmacy that still had some, so I got a year's supply. The next year, I was told that their remaining powder had expired.
I located a source in NJ & have been using them since. A 3 month supply of 2 mg cost ~$50.
The risk of blood clots is low at 1mg, but does exist. in the pre-Lupron days, 5mg was common & higher doses were also used. Blood clots were not uncommon.
I take a fairly high dose of nattokinase to eliminate micro-clots, and use D-dimer tests to verify that I am taking an effective dose. D-dimer was discovered in the 1970's but wasn't in use until the 1990's.
If D-dimer had been available in the DES era, it could have been used to identify patients who probably had clots. They would have then been put on Warfarin. Even today, knowing that cancer patients have an increased risk of clots, D-dimer is not used.
There is no FDA-approved equivalent of nattokinase that can safely be used prophylactically.
DES is a synthetic estrogen. Unlike estradiol, it is not an estrogen receptor alpha (ERα} agonist. It is also not associated with bone loss.
Thanks for this careful historical review. Many here are using estradiol patches as their ADT ( per PATCH Trial protocols) or are supplementing other ADT drugs with lower dose estradiol patches. I have done both of these. My MO prescribed the patches for me when I presented the pertinent published research on efficacy and safety. He only asked that , if it should be shown in the future to increase cardiovascular risk, do I under and accept those risks? So I got the patches under his supervision. (It’s almost funny since it is actually LHRH drugs That increase cardiovascular risks. ) As for efficacy estradiol acts in the same way to reduce testosterone to castrate Levels as does Lupron etc: by feedback inhibition of the hypothalamic-pituitary-gonadal axis. The castrate T resulting is identical. Only the SEs and other Metabolic effects are different and seem to be mostly better.
FWIW, I agree that's it's very likely the conspiracy theory is true, but as Tall_Allen comments, "you don't need one." He also says, and I'm sure he's right, that we don't have enough long-term data to prove that tE2 is not inferior in some way to the LHRH agonists/antagonists.
To me, this means exactly nothing. If my PSA rises to the point that I need treatment, I'm going with tE2 without question. 18 months on Eligard, wishing I were dead, was an experience so profoundly terrible that I'll try anything but voodoo to avoid repeating it.
QoL issues, if they're taken into account at all, are generally minimized in medical literature, perhaps only because they're harder to quantify that death/survival rates. However, from the patient's point of view, at least THIS patient, they weigh heavily in the decision-making process.
While it is true that we don't have the long-term data to prove that tE2 is not inferior in some way to the LHRH agonists/antagonists, it is also true that we DO have enough data to prove that the LHRH agonists/antagonists ARE inferior in some ways to tE2.
So we don't know for sure that tE2 is going to prove as effective as standard chemical or surgical castration in terms of PC progression or overall survival, but we also don't have good theoretical reasons to suppose it won't be as effective.
In the meantime, we know for sure that the loss of estrogen (with chemical or surgical castration) can have serious health consequences not relating to PC progression itself. First, do no harm?
Excellent point. I'm SO glad I came across this. I was living in terror that there would be escaping a life sentence of Eligard (without being totally irresponsible).
Good question, and I haven’t seen this question asked or answered yet. Unfortunately, I do not believe that there have been a lot of documented MOs worldwide using tE2 for ADT. But, I may be wrong, and if the info is out there, someone on this forum should know. Sorry not to be more helpful.
I might be able to answer that question, Does Transdermal Estradiol cream/gel application eventually cause PCa to become resistant as it does with other ADTs? Yes, it does happen, it happened to me. Of course, that timeline varies for each person. Just my observation, it would appear that those with RP have a easier time maintaining lower PSA and less than 20 castration level T on the tE2 route. Just my opinion from my conversations with several PCa alternative comrades.
Still have my prostate. I was on Lupron shots for one year, took a ADT holiday from SOC and went on approx. 18-months on ADT2 via tE2. This past January 2021 my PSA started to rise fast and the doubling time was decreasing. I had to switch gears and start up ADT3 plus Abiraterone 100mg + Prednisone 5mg. which is dropping my PSA & T again.
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