I seek the experience (and even the opinion!) of the hive mind on this:
I hear and read occasionally about oestradiol as being equivalent to LHRH agonists for testosterone suppression minus some of the famous nasty side effects.
My instinct is that it’s too good to be true but I’m keeping an open mind. 14 months of Lupron to go and quite naturally such an alternative is pretty sexy. Thanks!
I’m waiting for others to answer you also?
Hi, London... are you IN London? Because the UK seems to be the place where they are most keen on trying transdermal estrogen (see PATCH trial studies). I would like to try it myself, but am still having trouble finding an MO (in New England, not old England) who wants to do anything other than the mainstream SOC.
Many of the bad side effects of ADT are not from the loss of testosterone directly, but from the loss of estrogen that is an indirect result of losing T. The resident expert on this forum is Richard Wassersug, who has co-authored a book on ADT and has been on transdermal estrogen himself for many years.
While on Lupron, you might consider asking your MO about adding some estrogen back. I think Snuffy Myers had some of his ADT patients on very low-dose E-patches or gel to help with osteoporosis, etc.
But as to the question, can estrogen therapy alone directly cause a reduction in T (and consequent lowering of PSA)? Yes, absolutely. Aside from castration, it's the oldest systemic therapy for PC (although the original form, oral DES, had harmful effects that transdermal estradiol avoids.)
My husband has been on loupron since nov. 2017 and the Dr added a low dose estradol patch over a year ago his PSA has remained at .01 The patch has helped with the hot flashes.
Thanks for the note. I’m luckily not in the hot flash club...yet anyway. I did develop a mild case of gynecomastia and was pleased that my MO had no problem with a prescription of Tamoxifen for it. Good to know about the patch as hot flash remedy, I had heard of it only in that context. Appreciate it...Great luck to your husband!
Hi Noah I am not in London I’m in Washington DC. I’m keeping the prez off my trail...My wife is from New England. I’ve read a little on those studies, I’ll do some more.
SOC SOC all I hear is SOC. Are we not slightly weary of that term? I’m in a clinical trial at Johns Hopkins. My Lupron sentence SOC is 2 years and my MO has told me it might be shortened to 18 months. Might.
I think they like keeping guys on it who tolerate it well. In that class I’m afraid. I don’t have any hot flashes and really no sides at all except for a little weight gain, which would likely subside if I’d stop baking my way through the pandemic, sampling often.
Plenty of exercise obviously helps. Sure would like to sub out the Lupron anyway duh.
I’m going to PM Wasserburg I know he is the man on this. Thanks and keep safe up there!
There is evidence that the some of the most noticeable side effects of drugs like Lupron are age dependent. This has been shown, for example, for hot flashes, which armoire bothersome for younger men.
[Minor note: It is Wassersug, not Wasserburg.]
I suggest you send a private message to Richard Wassersug - he is our resident expert in estrogen therapy.
Will do Allen, I know only a little bit about him. Thanks very much!
How do I send a private message?
On the upper right, click on the "Chat" icon
Then on the right, click on "Compose"
Then next to "To:" type Wassersug
I’m sorry.. how do I do that?
High-dose estradiol seemed too good to be true at me at first as well. And I'm sure there are **some** SEs, but they're are far milder. This is definitely the tack I'm taking when my PSA hits an unacceptable number.
It has been 2 years since anything was published on the PATCH trial:
bjui-journals.onlinelibrary...
-Patrick
I see my name being mentioned here.
I am happy to discuss the pros and cons of using transdermal estradiol (E2) for ADT. Several pages are devoted to that topic in the ADT book.
To discuss this option with me individually, just send me an email. My email address is in my first and last names with a dot between them and then "ubc.ca" after the "at" sign.
As for using transdermal E2 for ADT... to be clear, it is an off-label use and I am cautious about promoting off-label drugs. However it is an option that patients can certainly discuss with their physicians. Be aware that many MDs are reluctant to go off label when there are LHRH agonists and antagonists that are well established options for ADT.
The major side effect of E2 is gynecomastia. Also, if one has a family history of estrogen sensitive breast cancer, it is probably not a good idea to be taking E2.
Among the advantages of transdermal E2 over the LHRH drugs are no hot flashed and no night sweats. That can mean better sleep and less daytime fatigue. That hasn't been strictly documented for humans, but my colleague, Eric Wibowo, showed that estradiol administered to castrated male rats improved their REM sleep. And the rats indeed had better (i.e., more) activity during the active phase of their daily sleep-activity cycle.
Furthermore E2 protects against osteoporosis. It can also help raise sexual interest above the castrate levels seen with drugs like Lupron, although not to the level one sees in males with normal testosterone levels.
Patrick (et al.) , I believe the next set of results for the PATCH study should be out in a year or so, assuming that recruitment has been holding well since I was last updated on that. But that was more than a year and a half ago.
I am happy to take E2 questions from anyone here. If a proper answer requires extended discussion, I'll suggest we make voice.
Richard W.
What would be expected result with Estradiol patches in someone with LOH (hypogonadal) with high levels of LH (26) and FSH (35)?
Very low free T with recent increase level by 50% (3.3 to 5.1) after discontinuing of Pravastatin. This also resulted in increase Cholesterol from 126 to 211 and TT increased ~ 20% (374 to 457). On TRT in past for TT levels in 280s and markedly symptomatic.
RRP in October 2016 with trial of Tgel for 15 mo. period but stopped when PSA first became measurable at 0.015.
Could the increase in Cholesterol contribute to the rise in T and fT?
Episode last fall of extreme elevation of Estradiol over a two month period when Aven Sativa and DIM were being used to possibly free some T from proteins and help with Osteopenia.
During that period E2 shot up from 20 to 210 and 170 subsequently falling to 20 after discontinuation of the Avena Sativa and DIM???? Endo thinks these may have contained Estradiol.
Appreciate any thoughts on this complicated case.
Dear Humptedumpte,
I am just now getting to all the messages and emails that I got over the past week.
Sorry for the long delay.
In terms of the simple question you start off with, high dose estradiol (E2) should be able to suppress LH and FSH. But you don't say what dose you are taking and at what intervals. Serum E2 levels can vary widely , even with a stable constant amount applied to the skin. This is because estradiol can regulate its own receptor density. You don't say though what amount of transdermal E2 you are taking.
I do not have an answer for you about what is going on with the other compounds you mention. Given your medical history—plus all the drugs and supplements you are taking—is beyond the limited knowledge I have and that yu have relayed in your message. For example, why were you taken a statin and why did you stop taking it?
Why does your endocrinologist think that the oat supplement you were taking was laced with estradiol?
I personally tend to stay away from supplements, which I have not been shown to be efficacy in controlling PCa. I know of no data on how the ones you are taken interact with each other and the other things you are taking. When they are herbal products, they are not single compounds but a multitude of compounds. Thus I can 't begin to make an informed guess as to what is going on in your situation.
For those, though, that I wondering about some of the supplements you are taking, DIM is diindolymethane, which can affect estrogen-related compound. Here is a publicly available reference on that:
Effect of Diindolylmethane on Estrogen-related Hormones, Metabolites and Tamoxifen Metabolism: Results of a Randomized, Placebo-controlled Trial
CA Thomson, SHH Chow, D Roe, B Wertheim, P Chalasani, M Altbach, P Thompson, A Stopek and G Maskaranic
Cancer Epidemiol Biomarkers Prev March 1 2017 (26) (3) 435; DOI: 10.1158/1055-9965.EPI-17-0027
Avena sativa is the correct scientific name for the common oat plant.
Sorry, that I can't be more helpful.
Richard W.
I notice the word estradiol ends like cannabidiol, or CBD. Are these possibly in some way similar? I ask since I am on pembrolizumab, and know the mabs are checkpoint inhibitors.
Dear Fuzzman,
The "-diol" refers to a molecule that has two couplets of a Hydrogen (H) and Oxygen (O) combined. A single one of these is a hydroxyl group (-OH). Any molecule with two of those nearby is a "-diol" and there are MANY such molecules.
You can look up images of the the estradiol and the CBD molecule in Google images. You will see that they are very different, which means they have very different properties. Estradiol is a steroid, which means that it four adjoining rings. It is derived from cholesterol. Nothing like CBD.
Mabs are monoclonal antibodies and there are many of them beyond just check point inhibitors. Again, wikipedia is good source of inflation on that. See:
en.wikipedia.org/wiki/Monoc...
Pembrolizumab appears to be helpful for a small set of men. I hope it is working for you.
Thank you for the information. Knew this was the best place to ask!! I do believe Pembro has helped me as I felt it within a day or two of the first infusion. I actually felt so much better I tore both calf muscles because I turned into a working maniac. Two years in July. PSA started going up and is at .24 now so doctor added Zytiga. Even though for me it had quit working three years ago within two months when the APCEDEN dendritic cell vaccines were added my testosterone returned to around 10-15 so it still had some efficacy but needed a boost you could say. After five years from a PSA of 212, and Gleason 9, and being stable for two years, and a year of encouragement from three oncos and three immunologists I had it removed last September. PSA did hit <.01, but it didn’t last. Think it may be trying to in my sacrum again. The prostate itself showed contained in the path with no seminal vesicle involvement and Gleason 5 with quite a bit of the prostate showing dead cancer so don’t think it’s there. Talk with the RO Tuesday to try to get an Axumin scan to see if it can be seen to be zapped if there’s only one or two mets. No Lupron or hormones like that since January, 2016. Almost killed me from side effects, but maybe estradiol would make it tolerable? 60 full body hot flashes a day to the point of continual renal failure and the onco I had then refused to help me and refused the estradiol patches too. Would like to get a PSMA PET scan again since I have had five in India, but it isn’t SOC here like it has been there since at least March, 2017. I can fly there, see my onco, have the scan, and spend a week there for less than $2,000 for everything including the flight. That’s how U found out it was in my sacrum in the first place but because of pain and pressure there I am sure it was there at diagnosis, just wasn’t showing up on the inferior scans we have in the USA. As you can see now our healthcare system here has failed us since it it’s primary function is their profit. By the way, I know that a prostatectomy isn’t common for a guy like me, but it sure did make me feel a lot better. They are treating me as a new patient now with the exception they don’t want to give me Lupron, and I really think I’d rather die than take it again.
Fuzzman,
Supposedly access to Ga 68 PSMA scans has improved in the USA in the last few months. Unfortunately I believe, the COVID situation has screwed that up to see extent. Tall_Allen has posted recently on the improved access, but I don't know the details at least for the USA now that we are in COVID quarantine. [I'm based in Canada.] I'd be curious to know what is the actually situation for access right now in paces like Southern California.
Has anyone been in the queue for a Ga 68 PSMA PET scan in the USA , who then had it put on hold because of COVID concerns? If so, where were you scheduled to have the scan?
Thank you Wassersug. Ya, the virus doesn’t make things any easier. It’s all over in NE Pennsylvania where I live. Six relatives with it so far with two getting very sick. When it is safer to travel again the cost of the five I’ve had done have been between appx $325-550.00 USD with and without contrast for the PSMA PET scans. Plane flight is $800-1,200 depending on when you fly. Inexpensive to stay also. Anyone needing the info it’s in other messages or contact me.
"it is an option that patients can certainly discuss with their physicians." What will be the result of that discussion? The doctor will say: take your Lupron shot, everything else is very evil ! As a patient you have to decide on your own to take Estradiol patches. Very few patients will do so.
Even if you just want to take patches to mitigate the side effects of Lupron, doctors will try to convince you not to do that. Estradiol would mitigate most of the side effects of Lupron, why do doctors insist that their patients suffer from these?
GP24,
I would not assume that every MD will say that every ADT agent other than Lupron is evil. There have been a handful of papers published on the PATCH study. You could ask your MD to read them, couldn't you?
That said, the fact is that oral estrogens increase the risk of plot clots. But taking the drug via the skin seems to reduce that risk greatly. MDs, to the best of my knowledge, do not "insist that their patients suffer from [i.e., Lupron side effects]." They may simply not have been following the literature that closely. You have the freedom to ask about alternatives to Lupron. If your oncologist don't want to read a bunch of technical papers, the topic is summarized in common English in the ADT book.
I am talking from experience here as I brought a couple of the early papers from the PATCH team in the UK to my own oncologist. After she read them, she was OK with my going on the PATCH protocol.
Allmost all MDs follow the guidelines and these do not mention Estradiol to fight prostate cancer (yet). Your oncologist knows you wrote the book on ADT and therefore did not object prescribing what you were asking for.
What I meant regarding side effects is that MDs are not concerned about the side effects Lupron causes and often do not know what can be done against it. The APCCC in Basel was the first conference covering side effects in several presentations.
I think Estradiol is the most effective drug against these side effects. However, as a patient you will have a hard time to get a prescription for that.
Hi GP24,
I agree that most "MDs follow the guidelines and those do not mention estradiol to fight prostate cancer." This is understandable since transdermal estradiol is still in clinical trial. But thousands of patients have been in that trial so far and good-quality, evidence-based medicine typically starts with clinical trials.
What this suggests to me is that one might approach their physician with a request to explore either being enrolled in the PATCH study [now part of the STAMPEDE trial] or follow the protocol used in that trial.
STAMPEDE is a huge, well known and respected, multi-arm study. Information about it is available to anyone on the clinicaltrials.gov website. My feeling is that one approaches their physician not by suggesting that they prescribe some unestablished and uninvestigated herbal remedy, but rather that they ask their oncologist to read up on the tE2 arm of STAMPEDE for further discussion at their next visit.
As for ADT side effect management, there has been a lot of literature on it. But patients, who are suffering for standard ADT side effects, need to let their MDs know how badly they are suffering. Too often I have talked to patients, who somehow feel that the ADT must be working in controlling their cancer because the side effects are so bothersome. However for many ADT side effects, there is no correlation between cancer control and side effect burden.
As a minor point, I suggested to my oncologist that I try tE2 for ADT more than a decade before my colleagues and I wrote the ADT book. It was my own effort to deal with ADT side effects that led to the development of the ADT Educational Program, the research to evaluate that program and development of the book. [see LIFEonADT.com]
Richard W.
Hi Wassersug, I have used E2 patches for ADT last year and found that to be excellent in providing castrate T levels with favorable SE profile. I used the protocol from the PATCH trial of four patches (biweekly type) 0.10 mg/24hrs per patch and changing one out daily.
I am interested in how I would approach replacing this with transdermal E2 gel for when I next go back on an ADT regimen. What is the equivalent amount and approximate surface area of application needed for full effect? Any specific brand(s) that you suggest? Thanks.
I use Estrogel. In North America it comes in a metered canister and I use 3-5 squirts once a day after a shower. I rub it on my arms thighs and abdomen spreading it out over a large are of skin. It completely dried on a minute or so without any residue.
I don't worry if it is a bit more or less a day or even if I miss a day. I find this far less bother than figuring out and holding to a rotation schedule with the E2 patches used in the PATCH study, although I used the patches myself for a couple of years.
Richard Wassersug, PhD. has been my mentor in my tE2 (estradiol gel) journey for two years now and I am thrilled with the results. The only side effect is some gynecomastia which doesn't affect my QOL in the least. I just wear loose fitting shirts which do a pretty good job of shrouding my new endowment. If anyone is interested in my history, I have numerous posts on this forum.
Thanks ronronHU. I don't think of myself as a "mentor" though. I am just another patient and not an MD. I didn't much like the side effects of Lupron when I wagon that drug. So I started studying them and looking for ways to reduce those side effects or was to avoid them completely.
One needs to work with their MDs to explore options, and that includes bringing to their attention the scientific literature on those options. Telling your oncologist that you read about something in a patient chat list (lie this one) is not like to get their buy in.
What can help is pointing your prescribing physician to some of the key papers on the PATCH study, which are freely available via PubMed. You can also point them to clinical trials. gov. The URL is: clinicaltrials.gov/ct2/show...
"PATCH' is arm L in this mammoth multi-arm study.
If nothing else, point them to the ADT book. 
Dear Richard, may I ask you a question?
Do you think that, with regard to the time to become castration resistant, is there a difference whether you are on ADT or on transdermal estradiol?
Dear bwochf,
I would not expect there is be a difference in "the time to become castration resistant...between ADT [with a standard LHRH agonist, like Lupron or Zoladex] or ADT with [high dose] transdermal estradiol."
The PATCH study may yield some data on this question within the next couple of years. But it probably will not have a sample size large enough to give a truly clean answer. Ideally one would want to compare men at the same age, tumor stage, maximum PSA, PSA nadir, when starting ADT, genetic profile, etc.
Assuming the two treatment groups are similar on variable like those just mentioned, what might then matter, I suppose, is that dose of the transdermal estradiol is adequate to give comparable levels of testosterone suppression to the LHRH drugs.
Richard W.
Dear Richard, thanks a lot for your prompt feedback.
May I ask you additional questions?
By the way, I´m a proud owner of your book: Androgen Deprivation Therapy (second edition).
I started my ADT - therapy end of November 2019 and middle of February 2020 the Zytiga / Prednison treatment. If you would be in my / this situation, based on your vast experience:
1. What would you recommend to do, to stay as long as possible castration sensitive (- besides intermittent ADT treatment (on page 12 in your book))?
2. What would you, under all circumstances, avoid to do to stay as long as possible castration sensitive?
Thanks in advance for your feedback.
With the very best regards Franz
Hi Franz,
If I were in you position, I would want a fair bit more information on my cancer status, general health status, PSA history, etc. before I would make decision about changing treatments (i.e,, your question #1).
As for question #2, I would do everything possible to stay healthy overall. The would mean maintaining a heart healthy diet and an exercise program as best possible. This might be tricky during COVID19 quarantine, but it is generally possible to get a good physical fitness workout even in a one room apartment and with little or no equipment. There are thousands of home exercise routines posted on Youtube for folks who are staying indoors.. Assuming you MDs say you are fit to exercise, I encourage you do it that.
Admittedly there are not a lot of data to show that exercise significantly delays PCa from becoming castrate resistant, but most of us PCa patients are more lily to die of cardiovascular disease that PCa. So we need to be attentive to that.
My apology for not giving you more precise answers, but I hope these comments are nevertheless somewhat helpful.
Richard W.
I was also on Lupron for almost 2 years with considerable effects on my quality of life - mood swings, debilitating hot flushes multiple times a day, constant fatigue and anxiety to name a few. I've been using transdermal Estriadol gel for almost a year now after discontinuing Lupron. My Psa has continued to drop (previous bloodwork 3 months back 0.16-down from 425at dx).
My oncologist always advises me to have the Lupron injection but does not insist. I'm currently in Malaysia. He approves of the use of transdermal Estriadol gel however I don't think it is a standardized treatment as yet therefore it is an "off the record" approval.
In addition the Estradiol gel is not available in Malaysia so I have to source it in Thailand.
In my case it is doing the job. From what I gather in the literature Estriadol used to be a standard treatment at one stage however taken orally in pill form it caused blood clotting and thus was discontinued.
I have compared the transdermal estradiol get product from Thailand with what is available in Canada and the USA. It is much cheaper in Thailand and appears to be exactly the same produce but with different and cheaper packaging. The gel in North America is still much cheaper that the LHRH agonists and antagonists.
I switched to estradiol patches 14 months ago. Best move I ever made! See my profile.
I was in a clinical trial in 2017 using estradiol cream/gel daily by rubbing on shoulders. It was blind study so you did not know what dose you were getting. If you Testoster those over 50 you were eliminated from the trial. There were 4 men in the facility where I was and I was the only one to make it the full year. It worked great for me. Both PSA and Testosterone 0, and no side effects.
Unfortunately the pharmaceutical company abandoned the trial and never published their results. For various reasons I have not used it since, but there are a number of men on this site that have been using it successfully.
I might add that during the trial I had complete examinations every 2 weeks for the first 6 months then once a month for the last 6 months. I had no abnormalities in any of the tests so for what its worth it should be some indication of its safety.
I know the trial. As I understand it, it failed to accrue adequately. I wrote a grant that was funded to do a similar study at the Vancouver General Hospital, when I was working there. It was funded by Prostate Cancer Canada. But then I retired. I found out some years later that my clinical colleagues there also failed to accrue for it.
There is an interesting political reason, I believe, that tE2 studies are hard to accrue for in North America. I can't prove this, but there is little financial incentive for the companies or the medical community to push for these studies simply because estradiol is a natural hormone and no one company can get propriety rights to market it. It takes a country like the UK with socialized medicine and a great research unit—like the clinical trials program and Kings College London (and its StAMPEDE trial)—to get research done on this.
That said...I think you could write the company to find out what they learned from the data they collected. If you do the, let us know what you find out.
Thanks. We did talk about this once before. I think your theory is correct because there seem to be a fair number of men using it and doing well. I also did and felt great during the year I was on it. I will try to follow up with the company and let you know what I learn.
Joe
My MO won’t order anything other than Lupron. Isn’t estradiol a viable alternative? PSA currently heading up from 0.2 to 2.5. I hate the frequent hot flashes and other SEs from Lupron.
Rod935@gmail.com
My MO is adamantly against estradiol on the basis of CVS events (documentation of which doesn't seem to exist), ignoring the facts, of which he's fully aware, that Lupron:
- has a huge and growing list of morbidities itself
- made me desperate to kill myself the first time around.
Yes, he recommends it unequivocally.
Lupron is extremely expensive, and estradiol is dirt cheap.
You may think all this is a coincidence. I don't.
Every Lupron shit you take in the USA anyway your oncologist receives a kickback for it so yes, you are correct. My first onco was the same way and didn’t care if he killed me as long as he got his kickback. Thankfully I have an excellent onco now.
Well this is all very interesting. I’m going to keep after the info. From what I gather so far some guys would take daily hot pepper suppositories and wear a Trump wig-almost on blind faith-if they thought there was half a chance it would lower T to castrate levels.
I’m probably handling it better than most but I’m still right there with them😀
Estradiol patches relieve the symptoms of having no T. Our bodies are designed to work with sex hormones, and either T or E will do. So if your disease says no T, then E will do instead. The transdermal patches avoid issues of older methods. It's best to get blood tests to verify E2 (estradiol) level in the blood, as there are large differences in skin absorption from the patches.
Dr. Snuffy Myers recommended 25 - 50 mcg/day patches to minimize side effects for his patient on long term Lupron.
Regarding gyno, a lot of guys over 60 have some degree of that anyway. So unless you're a senior lingerie model, or picking up chicks on the beach, it's not such a big concern.
But without T, a proper E level will allow you to feel quite good, for what it's worth. Enough E will apparently suppress T also, so it's a win-win.
Actually I would suggest that you take daily hot pepper suppositories and start wearing a Trump wig.
Good Luck, Good Health and Good Humor.
j-o-h-n Tuesday 04/21/2020 10:52 PM DST
Hello London,
I had surgery in January 2017 but PSA was subsequently elevated and climbing and so changed oncology centres and found a doctor with whom I could discuss my research on estrogen patches.
He was willing to support me on that strategy and has provided the necessary scripts for 100mg Estradiol patches. PSA following surgery was 5.3 and Tst was 13.9.
PSA has been decreasing since started Estradiol in Sept '17 and from March 2019 has been steady at <.008 which is lowest the lab can measure and Tst has been <.01 pretty much from when I started on Estradiol.
No heart aryhthmia, no night sweats or other adverse effects apart from some gynecomastia but not difficult to live with.
I am very happy with this outcome, it may not be for every one but works for me.
Petercraig tells me:
No heart arrhythmia
No night sweats
No other adverse effects other than some gynecomastia
But...
“It may not be for everyone”
You’re a funny guy 😀
I know what you mean but it’s still funny. Thanks for this.
I did estrogen ADT in 2019. Worked great. I dreaded Lupron and every doctor I interviewed wanted me to do Lupron. 100% of them (4/4) said that estrogen would not work to get my testosterone to castrate levels. High school biology told me otherwise. T undetectable after 6 weeks.
Lifelong ADT vs Adjuvant ADT and other questions
Lupron vs Zoladex or another adt? 
Doc + ADT vs Zytiga + ADT
Transdermal low dose patch Estradiol for ADT S.E.
