a tweet from Matt Cooperberg M D
3rd time in past 2 months I've heard updates on transdermal #estrogen as alternative to #LHRHa...seems this has been brewing since I was a resident, but with a big STAMPEDE report coming, it could be a huge game-changer re: both cost and toxicity
To Richard Wassersug, it's been a thing for over 20 years. Others on this site use it too as their only ADT. So far, the news from the UK has been good - good SE profile (no increased incidence of clotting, which was the main concern), and good suppression of testosterone. We're just waiting for confirmation that it increases survival in metastatic men as much as GnRH agonists.
Maybe help with cognitive issues as well.. Case in point I read or brain interpreted:
To Richard Wasserburg:
lol.
"and good suppression of testosterone"
That's interesting, I didn't know that estrogen suppressed testosterone.
I thought it had its own mechanism of action.
good to her about no increased incidence of clotting. My Dr inherited a number of Dr Myers patients who were on these patches and a number of them had clotting problem he had to deal with.
That's why it's so important to have randomized trials. Your doctor has no idea if the clotting problems he saw were because of the estrogen.
"Overall, cardiovascular events occurred in 89 patients (10%) in the transdermal estradiol group and 64 (8%) in the LHRHa group. A total of 30 (34%) of 89 cardiovascular events in the transdermal estradiol group occurred more than 3 months after patients stopped transdermal estradiol or switched to LHRHa. Overall, rates of cardiovascular events or sudden death without postmortem report at 12, 24, and 36 months were 2.8% vs 2.8%, 6.4% vs 5.3%, and 8.0% vs 7.2%.
No significant differences in time to first cardiovascular event between the transdermal estradiol vs LHRHa groups were observed, whether analysis included sudden deaths without postmortem report or only confirmed events."
thelancet.com/journals/lanc...
thanks
thanks T A
Is transdermal estrogen more tolerable compared to Lupron or equivalent?
It is cheaper.
Far more tolerable!
You are the pioneer of estrogen use in this group, my brother. If estrogen eventually becomes SOC, you will have much to do with it. Felicidsdes!!! I am in my third month of vacatión with PSA stable. Be well.
Thank you Bro!
R U not using anything at this time?
Its my third month without anything, Feeling better and stronger every day, but watching PSA carefully. Still less than . 2.
The major side effect is gynecomastia - it depends how much that would bother you. Hot flashes are reduced. Better bone mineral density, lean muscle mass maintenance, and libido. Fewer mood disturbances.
bjui-journals.onlinelibrary...
As long as my my PCa continues to sleep, my little boobies are insignificant!
I can’t even begin to tell you… wish I found this alternative a year ago.
I hope it becomes available down here in OZ, at least before I expire.
it is there. You may just have to go after it. If the MO won’t prescribe it based on PATCH trial results, then perhaps consult a naturopath for estradiol patches or topical gel.
My local MO said he would work with me after I have completed the Trial Study with LuPSMA177.
I read on health unlocked (our site) that somebody around Melbourne prescribed it. I can't recall 100% but it was possible to get somehow in Australia. Maybe you could search our site. I am on Firmagon and I am fine now.
I believe one of our member said that estrogen is contraindicated if you have a BRCA genetic mutation.
From purple bike profile:
"when I learned that estrogen may accelerate PC growth in the presence of BRCA+. As of September 2022 I am still on vacation, with no evidence of disease from bone-ALP, LDH, PSA.
With help from this great site am prepared if cancer strikes back, I will then probably go on BAT, PARP inhibitor and/or darolutamide+ADT as per ARASENS (not clear that docetaxel helped). "
Compounding pharmacies can make it up.
I've started working on my MO to update himself on both that and BAT. We'll see.
I had it together with ADT, though probably at lower dosages.
If it works at high estrogen doses alone.
I'd be interested in seeing data on how high estrogen doses work with strong ADT.
It does sound interesting but I read in another post on here that estrogen as an alternative ADT is more likely to cause gyno (apparently 80% of guys affected).
Thanks, I'm approaching 3 months on Prostap and so far, fortunately (touch wood!) my only obvious SE is mild hot flushes. However, things will likely change when I start the second line HT shortly.
Do estrogen patches have a failure rate similar to Lupron or Firmagan?
Thats a good question. More specifically average time to castrate resistance on estrogen.
Another question is: does it work once Lupron (or Firmagan or similar) has failed?
Good question.
Maybe yes, even only as an 1 mg per day (i am making this up from memory) add on to the ADT.
Don't know but thinking more about it its use as a testosterone suppressor with less side effects is at the heart of the interest.
Even when we become castrate resistant it is critical to continue testosterone suppression so in a sense some of my question is a mute point.
Lupron hasn't been that bad, but I do worry about it failing.
I won't beat you up for using the term failing as we all seem to use that term for Lupron, Zytiga, etc. when our PC progresses despite our use of said drugs.
But keep in mind that the Lupron doesn't normally fail so to speak. It continues to keep Testosterone at castrate levels but eventually the PC finds a mutational work around and we find we are castrate resistant.
I think you knew all that but maybe helpful for others.
Thank you!
I understand, but wondered if transdermal E2 actually worked that same way in the field. Seems the answer should be out there, but I haven't come across it.
I don't know. Less frequent, less severe hot flashes. Less loss of muscle mass. Less fatigue. Less cardio SE's. Better bone density outcomes. Fewer in trial had loss of libido compared to lupron although I assume one's package is still shrunk.
That all sounds good to me. Even sounds too good to be true but apparently the trial is proving it to be so.
If you missed the link TAllen provided here it is again to the trial:
Richard W. raised the question of whether tamoxifen will interfere with anti-PCa effect. It needs testing, but first things first.
It's available as a transdermal patch from compounding pharmacies. Clotting issues are caused by pills.
I assume estradiol injections also safer than pills? I inject every other week.
I wouldn't count on it. It depends on which ester you are using. But injectable steroids usually have a rapid peak absorption. It is the peaks that can be dangerous. Transdermals are much safer.
Estradiol Valerate 20mg/ ml. I suppose that is what you are talking about. Injecting about .25 ml intramuscular every other week. Thanks TA.
Ahhh. Deserves a smart ass reply like "Well, you lucky dog"! lol.
Anyway yea in that case a different or almost unique perspective for you.
Small boobs are a small price to pay to keep the PC at bay!
I live in a large condo complex in Thailand and often remove or unbutton my shirt in the gym and don't worry about anyone seeing my boobs. I also swim shirtless in our pools.
I am sending a bunch of E2 gel back to America for some of my friends who are using it, including R.W.
Of course Abiraterone helped you to keep your testosterone levels low.
Probably!
Is there a way to control the gynecomastia like using radiation to the breast area?
I am sticking with Degarelix for more than 4 years now. I have even problems walking. Walking is painful. It is probably related to COVID 19 restrictions and not exercising enough. Everything happened in a last year. I am getting weaker every month. First my knees than now I started to feel my hip. Unbelievable.
We will see soon, after my 68 GA-PSMA PET scan, for how long i will stay on Firmagon alone.
I already mentioned it once but looks that they don't believe I need it.
After some thinking I decided to stick to a simple ADT.
I know estrogen could be helpful for my bone mineral density.
I will ruther do more walking that will save me some money.
Do you believe that my current problem pain in my kmee and hips are actually caused by bone loss?
I believe that my problem is relatef to the COVID 19 pandemic and the lockdowns. I am trying to stay free from COVID 19 infection.
Summer is coming to Australia and i will walk more.
How many mets did you have? I know now they are not detectable.
I had a dexa scan but I am afraid to repeat it. They would push me to have a bone medication. Stamped trial didn't show any survivor benefits in a use of the bone medication. Only needed if I plan Xofigo and Abiraterone plus Prednisone
Not quite. Forgot the trial but in patients with bone mets bone builders (Zometa, etc.) plus Celecobrex improved overall survival by 20+ %.
I know that
Do you have a link?
I have one here. Possibly results have been updated since I last read them 2 or 3 years ago. The benefit doesnt look as good as I remembered. However due to possible method of action on the bone mets with the combo Celecoxib + Zometa and my full skeletal mets I will continue to take the combo.
Cox-2 inhibition is associated with inhibition of carcinogenesis,9-12 and case-control studies have shown a reduced risk of CaP.13-15 ZA has known anti-CaP effects, demonstrated both clinically in later-stage disease16 and in vitro.17 The first-generation bisphosphonate clodronate improved survival when used concurrently with long-term HT for metastatic CaP.18 The anticipated mechanisms of action of Cox-2 inhibitors such as Cel and bisphosphonates such as ZA were considered complementary, allowing targeting of both bone progression and the underlying molecular changes that lead to progression.
In the trial Cel=Celecoxib (Cox-2). Za=Zometa
ascopubs.org/doi/10.1200/JC...
Thanks, i will read it.
I don't want to add anything to Degarelix until I see my PSMA PET scan result.
They want me on bone strengthening medication but they didn't say anything about cel.
I am not going to jump into any extra medication without a very good reason.
Until then I will just risk to live 20+% shorter.
I believe in science but i am not going to pay my money for extra medication what I may don't need.
Good point ypu you can drink lot of fluid but not plain water in order to keep a balance of minerals.you don't want to run a marathon and to drnk only plain water. You need fluid but not plain water.
Are you concidered curable?
I understand. Can T eventually rise on Lupron, though, if only after initial castrate resistance? Or no?
WOW
Nick James said a few days ago, the big STAMPEDE report will be released in 2023
Just change institution as soon as possible.
Do you have a team treating you? In Dana Farber you would have a team. Do you have a RO in your team? Do you have an MO or just a urologist?
I use the gel. Once in the a.m. once before bed. Usually rub it on my thighs when sitting on the can. Couldn’t be easier. Drys fast. The brand I use now comes in packets, but the pump is just as easy.
All sounds great just find out if you are still curable.
On behalf of Dr. Richard Wassersug's I am posting his "Long Essay" on Estradiol
Three days ago, Darryl, the Moderator of this list, posted a brief comment on the use of transdermal estradiol to treat prostate cancer. In two days that comment generated 80replies. That may be a two day record.
Although I do not normally engage in discussions in online forums (preferring one-on-one discussions), I am named in the thread, so I felt I should check in. I’m positively impressed by the civility, curiosity, and commitment to helping educate others in this discussion. As such, I thought I could help with some of the questions raised here.
By way of background, I am a research scientist (PhD, not an MD) and a prostate cancer patient. I am the co-Lead on the Androgen Deprivation Therapy Educational Program in Canada (see LIFEonADT.com). And I have been on ADT almost continuously for over 20 years, with good PSA control.
I am also familiar with the PATCH study protocol and am a co-author with a bunch of MD on the PATCH teams “quality of life” paper listed in this thread.
High-dose estradiol—the dominant estrogen in both males and females—can regulate testosterone levels through the same feedback loop that normally regulates testosterone levels in the male body. This is because it works through the same endocrinological loop that goes from the testes to the hypothalamus within the brain and then to the pituitary gland at the base of the brain. The pituitary gland sends chemical signals to the gonads (be they testes or ovaries) to make their dominant hormones. So, yes, high dose estrogen can suppress testosterone production from the testes.
There’s a lot of interesting history here and we are not talking about some obscure, untested alternative therapy. The first drug used to treat advanced prostate cancer was an estrogen. However, it was an oral drug that caused blood clots. Thus, it was sidelined when LHRH agonist became available over three decades ago. The LHRH drugs did not carry the same blood clot risk as oral estrogens.
However…
All drugs have side effects. So, when the question is asked, “Is transdermal estradiol more tolerable than, say, Lupron?” that depends on what side effects one is concerned about. The dominant, conspicuous side effects of high dose estrogen is breast sensitivity and breast growth (i.e., gynecomastia). For some men, this is inconsequential and for others it is intolerable. However, data are already published and referenced in this thread that high dose transdermal estradiol does not increase cardiovascular risk, and in particular blood clot risk, compared to the common ADT drugs, like Lupron or Firmagon. However, this is not true if the estrogen is taken orally because anything we digest goes from the gut to the liver and it is in the liver where the clotting factors are made. By taking the drug through the skin rather than orally, one avoids this surge to the liver and the increased risk of blood clots.
It is to the credit of the Brits is that they are willing to do a large scale trial comparing transdermal estradiol to the LHRH drugs in a head-to-head comparison. That is the PATCH study, which is now part of huge, multi-arm trial called STAMPEDE. No drug company would back such a trial in the North America because there was no way they could profit from the findings.
Transdermal estradiol is likely to be cheaper than any of the agents currently approved for androgen suppression in North America or Europe. However, because it is a natural compound, no drug company can get proprietary ownership. There would be no incentive to study it or marketing it, as all the companies would end up competing for the same market and none could make a big profit.
Some advantages of using transdermal estradiol for ADT, which has already been published, are that it likely to be protective of the bones and it significantly reduces hot flashes. It has been suggested that one could take the selective estrogen receptor modulator tamoxifen to limit gynaecomastia, but there is an unpublished concern that tamoxifen may limit the protective role of estradiol on the skeletal system. Given that concern, patients in the PATCH study are not supposed to take tamoxifen.
Someone asked about taking estrogen as an injectable drug. It is possible, but it appears that the transdermal route is preferable. However. I haven’t dug into the literature to see if the two routes have been explored in a head-to-head comparison.
A concern about estrogen-sensitive cancers is valid and before one goes on high-dose estrogen long-term, they probably should make sure they don’t carry such a risk. If they come from a family with a strong history of breast cancer and prostate cancer, they should probably have some genetic screening done first. Such screening is increasingly common in the USA, but less so here in Canada, where I am based.
Of the various ways to take estrogen through the skin, I personally think that the gel product is better (i.e. easier to manage) than any of the compounded creams or patches. That’s a personal opinion and I have no investment in any of the companies that make any of these products.
The evidence that estradiol is cognitively protective for men on ADT is mixed. In a recent study using low-dose transdermal estradiol taken long with standard ADT, no positive benefit on cognitive function was found. That was one of the many studies led by Nick Russell, MD and his colleagues out of Melbourne, Australia [i.e., Dr. Nicholas Russell, MD
Endocrinologist & General Physician, Austin Health]. One can look up his papers in PubMed. A problem with that study, was that it was underpowered, because COVID closed it down early. I personally suspect that estradiol is cognitively protective, but we need more research.
An important set of questions in the thread relate to whether transdermal estradiol has a failure rate similar to Lupron or Firmagon. There have also been a few questions about whether it can be used effectively as a follow-on therapy should Lupron and Firmagon fail to control the cancer.
We really need the final paper(s) from the PATCH study, which is (are) due out in the next half year or so to know whether transdermal estradiol has better survival than the LHRH drugs (like Lupron and Firmagon). But based on the endocrinological regulatory pathway, I do not suspect that transdermal estradiol will have any greater benefit on prostate cancer control that the standard LHRH agonist and antagonist. Afterall, it works along the same regulatory pathway.
So… we await the final results from the PATCH study in the UK.
Given the interest of this topic perhaps, Darryl might consider Malecare offering a zoom information session to discuss those results when they are published.
I hope some of this information is helpful.
Richard Wassersug, PhD
My regular MO said he would work with me on using 3 month Lupron injections and topical Estrogen. The specifics have not been discussed. I am just completing the Trial Study with LuPSMA177 at Dana Farber.
Between my regular MO and the one at Dana Faber, I am very pleased with the Team.
No, that's very useful. Thanks.
Very risky indeed.
Early Results from Transdermal Estrogen PATCH trial
Anyone on BAT or intermittent with estrogen patches? 
