are transdermal estrogen patches goin... - Advanced Prostate...

Advanced Prostate Cancer

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are transdermal estrogen patches going to be a thing?

Darryl profile image
DarrylPartner
113 Replies

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

113 Replies
Kaliber profile image
Kaliber

great info

❤️❤️❤️

Tall_Allen profile image
Tall_Allen

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.

CAMPSOUPS profile image
CAMPSOUPS in reply to Tall_Allen

Maybe help with cognitive issues as well.. Case in point I read or brain interpreted:

To Richard Wasserburg:

lol.

cesces profile image
cesces in reply to Tall_Allen

"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.

podsart profile image
podsart in reply to Tall_Allen

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.

Tall_Allen profile image
Tall_Allen in reply to podsart

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...

podsart profile image
podsart in reply to Tall_Allen

thanks

Gabby643 profile image
Gabby643 in reply to Tall_Allen

thanks T A

sszyszkiewicz profile image
sszyszkiewicz

Is transdermal estrogen more tolerable compared to Lupron or equivalent?

lewicki profile image
lewicki in reply to sszyszkiewicz

It is cheaper.

ronronHU profile image
ronronHU in reply to sszyszkiewicz

Far more tolerable!

CountryJoe profile image
CountryJoe in reply to ronronHU

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.

ronronHU profile image
ronronHU in reply to CountryJoe

Thank you Bro!

R U not using anything at this time?

CountryJoe profile image
CountryJoe in reply to ronronHU

Its my third month without anything, Feeling better and stronger every day, but watching PSA carefully. Still less than . 2.

Tall_Allen profile image
Tall_Allen in reply to sszyszkiewicz

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...

smurtaw profile image
smurtaw in reply to Tall_Allen

50%-90% of guys get gyno. I had gyno after 3 months of estrogen.

However, it does not appear that I had bone density decreases during estrogen patches (my DEXA scans weren't lined up perfectly with the start and stop so I can't be certain).

I did not see any libido increase (zero). My mood was very good other than when I looked at my boobs in the mirror.

Tall_Allen profile image
Tall_Allen in reply to smurtaw

Richard W. raised the question of whether tamoxifen will interfere with anti-PCa effect. It needs testing, but first things first.

smurtaw profile image
smurtaw in reply to Tall_Allen

I was looking into tamoxifen, but my MO was against it for blood clot issues. I'm looking into it. Do you happen to know of any RCTs that show CVD issues among AEs?

Tall_Allen profile image
Tall_Allen in reply to smurtaw

It's available as a transdermal patch from compounding pharmacies. Clotting issues are caused by pills.

Shorter profile image
Shorter in reply to Tall_Allen

I assume estradiol injections also safer than pills? I inject every other week.

Tall_Allen profile image
Tall_Allen in reply to Shorter

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.

Shorter profile image
Shorter in reply to Tall_Allen

Estradiol Valerate 20mg/ ml. I suppose that is what you are talking about. Injecting about .25 ml intramuscular every other week. Thanks TA.

ronronHU profile image
ronronHU in reply to Tall_Allen

As long as my my PCa continues to sleep, my little boobies are insignificant!

No_stone_unturned profile image
No_stone_unturned in reply to sszyszkiewicz

I can’t even begin to tell you… wish I found this alternative a year ago.

ARIES29 profile image
ARIES29

I hope it becomes available down here in OZ, at least before I expire.

MateoBeach profile image
MateoBeach in reply to ARIES29

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.

Ramp7 profile image
Ramp7 in reply to MateoBeach

My local MO said he would work with me after I have completed the Trial Study with LuPSMA177.

Seasid profile image
Seasid in reply to ARIES29

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.

Seasid profile image
Seasid in reply to Seasid

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). "

Darryl profile image
DarrylPartner in reply to Seasid

glad that Malecare is helpful to you

Seasid profile image
Seasid in reply to Darryl

It is like a compass. Helps me to navigate.

ARIES29 profile image
ARIES29 in reply to Seasid

Richard Wassersug PHD in Melbourne referred me to Dr Russel, a endocrinologist but I still could not obtain a script.

Tall_Allen profile image
Tall_Allen in reply to ARIES29

Compounding pharmacies can make it up.

dhccpa profile image
dhccpa

I've started working on my MO to update himself on both that and BAT. We'll see.

Ramp7 profile image
Ramp7 in reply to dhccpa

I'm with you.

smurtaw profile image
smurtaw in reply to dhccpa

That's one of the challenges, some MOs are already with it but some don't know yet. Get them up to date.

cesces profile image
cesces

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.

smurtaw profile image
smurtaw in reply to cesces

In 2019 I did it for 4 1/2 months. T undectable. PSA < 0.01.

i. PATCH trial Prostate Cancer Clinical trial

patch.mrcctu.ucl.ac.uk/

ii. Estrogen reduces testosterone faster than Lupron and has slightly fewer cardiac events: Transdermal estradiol for androgen suppression in prostate cancer: long-term cardiovascular outcomes from the randomized Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial program – PubMed

pubmed.ncbi.nlm.nih.gov/335...

iii. Estrogen is superior for hot flushes, libido, and fatigue. It is inferior for gynecomastia: Quality-of-life outcomes from the Prostate Adenocarcinoma: TransCutaneous Hormones (PATCH) trial evaluating luteinizing hormone-releasing hormone agonists versus transdermal estradiol for androgen suppression in advanced prostate cancer – PubMed

pubmed.ncbi.nlm.nih.gov/277...

iv. Estrogen superior for bone density: PCa Commentary | Volume 126 - September 2018 - Grand Rounds in Urology

grandroundsinurology.com/pc...

v. Therapy Insight: parenteral estrogen treatment for prostate cancer—a new dawn for an old therapy | Nature Reviews Clinical Oncology

nature.com/articles/ncponc0...

vi. Early hormonal data from a multicentre phase II trial using transdermal oestrogen patches as first‐line hormonal therapy in patients with locally advanced or metastatic prostate cancer - Langley - 2008 - BJU International - Wiley Online Library

bjui-journals.onlinelibrary...

vii. Emerging potential of parenteral estrogen as androgen deprivation therapy for prostate cancer – PMC

ncbi.nlm.nih.gov/pmc/articl...

viii. Estradiol for the mitigation of adverse effects of androgen deprivation therapy in: Endocrine-Related Cancer Volume 24 Issue 8 (2017

erc.bioscientifica.com/view...

ronronHU profile image
ronronHU in reply to smurtaw

Thank you!

smurtaw profile image
smurtaw in reply to ronronHU

Sure.

I used estrogen patches (0-3-0.4 mg/day Climara weekly patches). It took 5 weeks for my T to go to <10. And then I added Zytiga.

So all I can say for certain is that the estrogen patches took my T to castrate. I can't say that the Zytiga did not help hold it there.

Seasid profile image
Seasid in reply to smurtaw

Of course Abiraterone helped you to keep your testosterone levels low.

smurtaw profile image
smurtaw in reply to Seasid

I don't know. They didn't use AA in the patch trial. And I didn't add the AA until after my T had gone low. But I can't say that in my particular case it didn't help.

AA by itself does not hold my T low. I've tried and that is why I had to add Lupron to pBAT.

Seasid profile image
Seasid in reply to smurtaw

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.

smurtaw profile image
smurtaw in reply to Seasid

Dang. Could you talk to your MO about the addition of a low-dose estrogen patch? It should help decrease the bone loss.

Seasid profile image
Seasid in reply to smurtaw

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.

Seasid profile image
Seasid in reply to Seasid

I believe that I just need more exercise.

I feel fine psychologically, i am actually stabilized. i dont have depression or mood swings not even noticable hot flashes.

I just realized that I am going down the slope. Every extra year on ADT I am weaker and weaker.

Seasid profile image
Seasid in reply to smurtaw

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.

smurtaw profile image
smurtaw in reply to Seasid

If I had to guess, I'd wager that 95% of the pain is due to inactivity. If I take more than a week or two off of exercise, I start feeling it in my joints and back.

Have you had a DEXA scan? If your bone density is fine and you don't suffer much from ADT sides then estrogen probably isn't needed.

Seasid profile image
Seasid in reply to smurtaw

Summer is coming to Australia and i will walk more.

How many mets did you have? I know now they are not detectable.

smurtaw profile image
smurtaw in reply to Seasid

I had RP in 2018. I had bladder, seminal vesicles, and lymph node spread.

I had a Pylarify scan a month ago. No mets or cancer detected.

Seasid profile image
Seasid in reply to smurtaw

Are you concidered curable?

smurtaw profile image
smurtaw in reply to Seasid

I've never asked. Mayo docs apparently didn't think so. I don't know what my current MO thinks.

Seasid profile image
Seasid in reply to smurtaw

WOW

Seasid profile image
Seasid in reply to smurtaw

Can you contact Dana Farber cancer institute?

viewray.com/mridian-treatme...

smurtaw profile image
smurtaw in reply to Seasid

Thanks. I'll talk to my MO about this the next time I see her.

Seasid profile image
Seasid in reply to smurtaw

Just change institution as soon as possible.

Seasid profile image
Seasid in reply to smurtaw

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?

smurtaw profile image
smurtaw in reply to Seasid

An MO, a PCP, a urologist, and an RO for consultations. And myself. So far things have gone quite a bit better than predictions. My MO is a perfect fit for me and my personality.

Seasid profile image
Seasid in reply to smurtaw

All sounds great just find out if you are still curable.

Seasid profile image
Seasid in reply to smurtaw

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

smurtaw profile image
smurtaw in reply to Seasid

Something that helps me a lot is simply getting the blood moving. Walk around. Light stretching (if you're unstable start with hamstring and back stretches on the floor).

And it amazed me how much electrolytes can play into it. I doubt that this is your issue but I was getting some really bad hip pains and some cramps and pains in various areas of my body. My MO told me to increase my electrolytes (my PCP told me the same thing). I did and the pains went away almost immediately.

Seasid profile image
Seasid in reply to smurtaw

If you drink lot of water you could even end up with a swollen brain.

youtu.be/TI39SNPie_M

smurtaw profile image
smurtaw in reply to Seasid

Well, my wife always complains about my tiny intellect. So maybe I should drink more water!

Hydration is important but you don't want to overhydrate. I try to keep my urine straw colored.

Seasid profile image
Seasid in reply to smurtaw

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.

CAMPSOUPS profile image
CAMPSOUPS in reply to Seasid

Not quite. Forgot the trial but in patients with bone mets bone builders (Zometa, etc.) plus Celecobrex improved overall survival by 20+ %.

Seasid profile image
Seasid in reply to CAMPSOUPS

I know that

Do you have a link?

CAMPSOUPS profile image
CAMPSOUPS in reply to Seasid

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...

Seasid profile image
Seasid in reply to CAMPSOUPS

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.

Benkaymel profile image
Benkaymel

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).

smurtaw profile image
smurtaw in reply to Benkaymel

You are correct.

Estrogen is superior for hot flushes, libido, and fatigue. It is inferior for gynecomastia: Quality-of-life outcomes from the Prostate Adenocarcinoma: TransCutaneous Hormones (PATCH) trial evaluating luteinizing hormone-releasing hormone agonists versus transdermal estradiol for androgen suppression in advanced prostate cancer – PubMed

pubmed.ncbi.nlm.nih.gov/277...

pubmed.ncbi.nlm.nih.gov/335...

(86% had gyno)

I did it for 4 1/2 months. Gyno set in in the 3rd month. If it goes on long enough to establish an infrastructure, it's hard to reverse. My duration was too short for it to take root so my gyno was temporary.

Benkaymel profile image
Benkaymel in reply to smurtaw

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.

ronronHU profile image
ronronHU in reply to smurtaw

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.

in reply to ronronHU

They probably assume you're one of those Thai boys. Don't even bat an eye.

Hi There Big Fella
ronronHU profile image
ronronHU in reply to

Probably!

ronronHU profile image
ronronHU in reply to Benkaymel

Small boobs are not a big deal considering the battle that we are all fighting!

dhccpa profile image
dhccpa

Do estrogen patches have a failure rate similar to Lupron or Firmagan?

ronronHU profile image
ronronHU in reply to dhccpa

Not that I'm aware of?

CAMPSOUPS profile image
CAMPSOUPS in reply to dhccpa

Thats a good question. More specifically average time to castrate resistance on estrogen.

dhccpa profile image
dhccpa in reply to CAMPSOUPS

Another question is: does it work once Lupron (or Firmagan or similar) has failed?

Seasid profile image
Seasid in reply to dhccpa

Good question.

Maybe yes, even only as an 1 mg per day (i am making this up from memory) add on to the ADT.

CAMPSOUPS profile image
CAMPSOUPS in reply to dhccpa

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.

dhccpa profile image
dhccpa in reply to CAMPSOUPS

Lupron hasn't been that bad, but I do worry about it failing.

CAMPSOUPS profile image
CAMPSOUPS in reply to dhccpa

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.

dhccpa profile image
dhccpa in reply to CAMPSOUPS

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.

smurtaw profile image
smurtaw in reply to dhccpa

It failed to do the job of controlling PCa. It did not fail to keep testosterone low.

dhccpa profile image
dhccpa in reply to smurtaw

I understand. Can T eventually rise on Lupron, though, if only after initial castrate resistance? Or no?

smurtaw profile image
smurtaw in reply to dhccpa

If you keep doing ADT, your T shouldn't rise (sometimes it will go up a little but this is not a function of CRPC or HSPC).

What happens is that your cancer adapts to live in a lower and lower testosterone environment. That's why Zytiga or an ARSI can delay the time to CRPC. They are actually just lowering the real or effective T action so it takes cancer a longer time to adapt.

Example:

Fat, dumb, and happy cancer likes living in a normal testosterone environment. Food is plentiful.

Now we go to Lupron. Our T goes down to 15 ng/dl. Now food is fairly scarce. Fat, dumb, happy cancer has to figure out how to live without a lot of food lying around. Maybe it makes some better cookpots or utensils or grows a few more arms to collect the food. It's "resistant" to starvation in the 15 ng/dl environment.

So, we add Zytiga. Our T goes down to 10 ng/dl (inside the tumor it makes even a bigger difference but that's not really important for my silly story). So now our cancer, which was okay with the 15 ng/dl environment, has to adapt to 10 ng/dl. This takes a little more time as it figures out new methods of cooking, grows some more arms, mutates its hands so that they are bigger and can grab up more food, or adapts to eat other types of food (maybe prolactin pot pie).

We don't know how to go lower so once our cancer adapts to live in the 10 ng/dl environment it is called castrate resistant.

Suppose we develop better drugs; we could push the threshold down lower. That will delay CRPC more and if we can go low enough the cancer has to adapt to eat other foods. The yummy testosterone is scarce.

And if we go too low what happens to our bodies with no T? As far as I know we haven't ever gone to absolute zero.

Sorry for the lame story. I'm so used to making stuff up for my kids my story telling is morphing. Kind of like what I call humor. Dad humor. Bad...

dhccpa profile image
dhccpa in reply to smurtaw

No, that's very useful. Thanks.

in reply to dhccpa

Theoretically they should...castrate resistance is the term used when the cancer evolves to thrive in a low-t environment. ADT are meds that lower a man's T level(firmagon, lupron, zytiga) or blocks the T from binding to the pca AR (lutimides). How quickly the cancer evolves will determine the effectiveness of the meds.

dhccpa profile image
dhccpa in reply to

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.

smurtaw profile image
smurtaw in reply to dhccpa

Low T is low T.

I understand your point though. If Lupron only gets you to 25 ng/dl and estrogen patches get you to 5 ng/dl, then CRPC would be delayed (lower T = a higher threshold of resistance). This is likely to be person dependent. I am doing PROP-BAT so had to switch from estrogen patches to Lupron. Using estrogen patches got me to undetectable T. Lupron only gets me to 20-40 ng/dl.

Are there other mechanisms in support of estrogen? I have seen very low-quality studies that determined that there are. I'd like to see more robust data.

smurtaw profile image
smurtaw in reply to dhccpa

Thought more about it.

From the Patch trial the castrate rate via Lupron at 3 months was 93%. The castrate rate via estrogen patches at 3 months was 93%. At one month estrogen was vastly superior. But it was inferior to the studied rates of GnRH antagonists (e.g., Firmagon, Orgovyx).

I would guess that the castrate failure rate might be better for a combination of estrogen and Lupron because testosterone might be lower. But this is just a guess and a weasly one at that. I haven't seen any data to support or refute my weasle guess.

Along those lines, I wonder if Zytiga, estrogen patches, and a GnRH drug would extend the time to castrate resistance. If there is a study out there I haven't seen it.

If they can create a subcutaneous depot then I think they have a win/win solution. For me, applying patches or gel would be a deal breaker. I prefer thd 3 month eligard injection.

smurtaw profile image
smurtaw in reply to

I found application of weekly patches a lot easier than going into my doctor's office for an injection every 3 months. I couldn't make it to my appointment 2 weeks ago and now they are having a temporary supply issue so my shot will be at least 4 weeks late. That wouldn't have happened with estrogen patches.

(I am using Lupron because I am doing a BAT program)

There is a depo-estradiol injection that is similar to T-cypionate WRT half-life. But as far as I know, no clinical trials have used it.

in reply to smurtaw

My shots are scheduled separately from my MO appointment...I am not dependent on the MO being in the office for my Eligard injection. I have a unique setup in that where the majority of my treatments, diagnostic tests and procedures is 2 miles from my house. Brand new hospital with all the bells and whistles.

What do you do with the patch if you're in the ocean for several hours Jet Skiing, etc....With the injection I don't have to worry about my patch getting ripped off if I fall off the jet ski.

smurtaw profile image
smurtaw in reply to

I could swim for hours and I don't recall the patch ever coming off or being visually compromised.

If one ripped off I would have replaced it. T is going to take weeks or months to recover.

I also have my injection and MO appointments separated. Didn't matter. I would have had the same issues going to a shot appointment and they would have had the same supply issues. But if the office was 2 miles away I might have been able to get to it.

And some MOs will allow you to self-inject. Unfortunately, mine will not.

Some guys hate injections (over half the guys I know who inject substances have their wives or friends do it lest they pass out). In your case, you hate applying a weekly patch. I never considered that before.

CAMPSOUPS profile image
CAMPSOUPS in reply to

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:

bjui-journals.onlinelibrary...

in reply to CAMPSOUPS

But I have none of the SEs except mild hot feelings...so I was speaking for myself.

CAMPSOUPS profile image
CAMPSOUPS in reply to

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.

in reply to CAMPSOUPS

I doubt I'm unique but I am lucky not to have the worse of the SEs

No_stone_unturned profile image
No_stone_unturned in reply to

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.

cesces profile image
cesces

Are there any conterindications to concurrently using BOTH estrogen AND ADT together?

Why not?

smurtaw profile image
smurtaw in reply to cesces

I'm currently on low dose estrogen (0.1 mg/day) along with Lupron. I also use bicalutamide and/or Xtandi (I'm almost a month late for my Lupron injection). And I use Zytiga.

I never tried high dose estrogen patches along with ADT.

Ramp7 profile image
Ramp7 in reply to smurtaw

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.

smurtaw profile image
smurtaw in reply to Ramp7

Looks like your MO understands some hormonal actions. Hold onto him!

Ramp7 profile image
Ramp7 in reply to smurtaw

Between my regular MO and the one at Dana Faber, I am very pleased with the Team.

smurtaw profile image
smurtaw in reply to cesces

I'm not always the least risky person in the game (not always meaning never). I wouldn't hesitate even a femtosecond to try that. I would try it today if my low T cycle was longer (it's only 4-8 weeks and I'm experimenting with some short high T bursts during "ADT" that I don't want to mix with high estrogen).

SViking profile image
SViking

Is there a way to control the gynecomastia like using radiation to the breast area?

smurtaw profile image
smurtaw in reply to SViking

Yes. I was looking into my options and one was radiation to the boobs.

I chickened out of ADT after 4 1/2 months and the gyno went away.

GP24 profile image
GP24

Nick James said a few days ago, the big STAMPEDE report will be released in 2023

PhilipSZacarias profile image
PhilipSZacarias

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

smurtaw profile image
smurtaw in reply to PhilipSZacarias

100.0% correct.

The only thing we differ on is that he prefers gel to patches, and I prefer the constant estrogen release of patches over daily dosing of gel. My experience with compounded creams hasn't been a good one. Sometimes they seem to have the correct dose. Sometimes I wonder if an inactive ingredient was substituted for the active one.

Seasid profile image
Seasid in reply to smurtaw

Very risky indeed.

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