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
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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.
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."
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.
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.
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.
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.
"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). "
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.
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.
I hear ya, but it doesn't do what once it did. But I understand we must not say that Lupron has failed. I suppose it has simply lost its full effectiveness, and we then have to add or change to something else more painful and costly.
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:
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.
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.
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 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
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.
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.
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.
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.
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.
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