CRPC and low dose Estradiol patch

[Knittingque]

Can anyone tell me if being Crpc and doing low dose estradiol have a negative effect on psa

[JohnInTheMiddle]

It's a very complicated question and very interesting to me. And the low dose regime is completely different than the high dose regime. My understanding is that the transdermal low dose estradiol is mostly to combat the effects of ADT and estrogen suppression. So you get good results on bone density and probably on other side effects of estrogen suppression too.

But the advocacy for estradiol on low dose is not because it might be effective against mPCa itself.

Which is not to say it may have an effect. After all my reading I am not pursuing this anymore because there are also risks. (See the "two different main types of estrogen receptors" that are activated by estradiol. One is our friend and one isn't.)

[Knittingque in reply to JohnInTheMiddle]

Thanks JohnIt is a difficult question yes and one l cannot seem to get any answers on.

My husband is CRPC with no mets thankfully.

Treatment since 2013 ADT, 36 round of Radiation which then brought psa down from 63 to 0.064, a fantastic drop.

He stopped Adt after 2 years due to side effects and then did a watch and wait, things were good but psa was rising but very slowly.

After 6 years and a psa of now 34( what a holiday), we insisted the Urologist have him take Zoladex again but this only lasted 6 months, psa dropped but then increased, testosterone was now good at 00.04. However now he was CRPC not mets.

In the meantime whilst waiting for the Cancer Agency to get in touch the psa had risen to 82, we had 2 conversations with Urologist who again wrote to the Oncologist.

Finally after pushing, it turned out that the Agency had renovations done and my husband had been lost in the system,

that was alarming.

After many apologies finally we saw the Oncologist and was administered Xtandi 160mg and still taking Zoladex. Then the fun began as if there wasn't enough with Zoladex, massive blood pressure increase, cardio fib, fatigue brain fog. Hot flashes worsened.

The psa was dropping with the Xtandi but because of side effects the dosage was dropped to 80mg, in the meantime we made the decision to have Orchiectomy to avoid having Zoladex and all went well. Now we were basically on 2 therapies Xtandi and medical castration.

We had researched loads on the low dose estradiol patch to eliminate the side effects and were willing to try it to add back the aromatized estrogen now taken with having extremely low testosterone. He did 3x 0.25mg patches and changed twice weekly. He felt so much better.

Blood tests were ordered for estrogen 66 psa 10.2 testosterone 00.03 before using patch and then again 2 months later this is the part that gets interesting

Estrogen 568!!!!!

Psa 10.8

Testosterone 00.04

Arrrrgh whats going on,

We stopped the patch and increased Xtandi by 1 x40mg total

3 instead of 2 pills and now we wait until August 15th to get new bloodwork done and see Oncologist.

Our thinking logically was it was due to the estradiol patch but then was it the Xtandi being dropped and/or losing its effect.

So thats what my question was, does being NMCRPC and using low dose Estradiol as an add back cause the psa to rise.

We are aware that estrogen does nothing for treating pc cancer only side effects of drugs and supressing testosterone.

I guess we will have to wait until next blood tests to see where we are with the numbers, but it's the wait again that is agony and in the meantime here come back all the side effects oh yea a new one edema from the blood pressure drugs, so now switching to another drug with side effects,.

I know there are many men on this site who are in a much much worse situation than we are here and we have empathy for each and everyone and there carers. So we are wishing everyone all the best on there journey.

Thanks from Canada

[JohnInTheMiddle in reply to Knittingque]

Amazing story Knitting! By the way and I can't remember if I mentioned this before I'm also from Canada. And you are in a very complex world that I can't comment on.

I will say one thing in that from my reading it is not true to say that low-dose estrogen add-back does not do anything directly related to prostate cancer, and only addresses side effects.

There are two estrogen receptors - ERα and ERβ. And estradiol has apparently approximately equal affinity to both. Apparently the ERβ actively helps suppress PCa. The other receptor however does the opposite.

It was at this point that I realized I was out of my depth and not being able to find any physician or doctor that wanted to explore this, I decided to back off. This despite my concern about ADT and PCAms therapy side effects.

I cannot say it all whether this is in the slightest way relevant to you.

[janebob99 in reply to Knittingque]

Your PSA seems to be unusually high, given your that your testosterone level is very low. I wish I had a good recommendation for treating your high PSA. Perhaps Tall_Allen has some ideas

You said that you are using "0.25 mg E2 patches". I wasn't aware that anyone made such large patches! The largest of the dozen or so manufacturers that I have researched only go up to 0.1 mg E2/24 hrs in a single patch. Who makes your 0.25 mg E2 patches?

Bob in New Mexico

[Knittingque]

Yes the 2 receptors are interesting but why are we not seeing at least some info on this namely from the Patch trial, then again all results will not be out until the late fall. Maybe there will be some explanation.I know how you feel "out of your depth", I feel the same but l am like a dog with a bone and will keep researching.

The Onco will not be willing to go there, even if he could he wouldn't green light the patch for some obscure reason, but we needed to go ahead with it anyway, our own GP who is very open minded agreed to trying it low dose and yes it worked very well for the side effects.

We carry on investigating regardless.

Have a great day, hope you are not in Toronto with the flooding its mental right now. The worlds gone mad!

G😊

[JohnInTheMiddle in reply to Knittingque]

Flooding in Toronto! As for the marvelous PATCH trial, my understanding is that this trial is primarily focused on transdermal high-dose estrogen as ADT replacement for the purposes of suppressing testosterone.

With the idea of low dose estradiol in support of estrogen add-back, one continues ADT and other therapies as usual. And to your earlier point our focus is on the low-dose regime is not on metastatic prostate cancer directly - rather on the debilitating side effects of the primary therapies.

So it's very important to distinguish between low dose and high dose estrogen therapy regimes for the suppression of testosterone in circumstances of metastatic prostate cancer. The to regimes have a completely different purpose, and work in very different ways. Where they do share is that everything is so dang complicated!

The PATCH trial is a huge endeavor and it may be that there are analyses separately that may be relevant for low dose, I don't know.

[FourString]

Been on E2 for a couple years. High dose for a year. No PSA effect. Other very good effects. I found it’s easier to get my primary care physician to prescribe than my oncologist.

[janebob99 in reply to FourString]

Just a clarification...When you say "No PSA effect", do you mean "No increase in PSA while on E2"? Did your PSA go down while on E2?

Like you, my PCP prescribed my E2. I currently use estradiol gel, compounded by my local compounding pharmacy. It's the cheapest source, and doesn't have skin irritation problems with the patches.

Thanks,

Bob in New Mexico

[FourString in reply to janebob99]

No effect either way. I have been surgically castrated, but after awhile became castration resistant whereupon I started Prednisone/Zytiga. A year after that I started E2 to manage side effects. For me, that’s all it seems to do. No effect on PSA which after a couple years went back up as I became Zytiga resistant. No I’m on chemo (docetaxil) and PSA going down again. I continue the E2 because it counteracts the effects of chemo and gives me a hormone. Not fun living without any hormones at all. E2 makes me feel like a man rather than a nothing.

[janebob99 in reply to FourString]

Thank you for the explanation. Sorry you're on chemo.

You're a great example of the benefits of tE2.

I'm sure you're up to speed on the benefits of tE2 ADT compared to Lupron ADT, but maybe other readers will benefit from viewing this slide.

What form and dosage of E2 do you take? Do you measure your serum E2 levels?

Have you had a recent DEXA scan?

I'm currently taking Orgovyx and high-dose estradiol gel, applied 50/50 to the hip and scrotum. I will slowly transition to 100% scrotal application over a period of about 1 month. My plan is to wean off of Orgovyx after 2 months, when I can demonstrate to my MO that high-dose estradiol is sufficient to keep the PSA and T very low. The Orgovyx is too expensive, more than 200X more expensive than estradiol gel.

Bob in New Mexico

Benefits of Estradiol vs Lupron

[VHRguy]

I had a 2013 diagnosis with G9 (5+4) stage cT3a (by MRI), biochemically recurring 6 years after primary therapy. So, I had an orchiectomy over 5 years ago because I didn't want a lifetime of Lupron shots.

To mitigate the miserable side effects of no T, I was on low dose estradiol briefly, then increased it so that I would feel good as a backfill strategy. The risk for aggravating PCa was acceptable, since Dr. "Snuffy" Myers used it with his patients on long term ADT, and Dr. Richard Wassersug has been using it himself for a very long time.

I'm now at nearly five years on estradiol, and still have an undetectable PSA. I feel great, plenty of energy, active with kayaking, hiking, archery, and chasing my 8 year old grandson around waterparks.

In no way am I recommending anything, everyone must make their own risk assessments. But for my sample of one, the medical status is fine today, and I feel great 11 years out from a fairly dire diagnosis.

[Knittingque in reply to VHRguy]

Thanks for all your informative replies, they are very helpful to my husband and l. The only difference to everyone here, l believe, correct me if l am wrong, is that he was pronounced Castrate Resistant on Adt and then started Xtandi so we don't know whether being CR has any effect on the estradiol to raise the psa (only slightly) but going the wrong way.

As l said above the timing of taking the patch and maybe the Xtandi losing it's effect maybe the problem we do know that the psa took a big drop firstly after starting Xtandi then started to dwindle down slowly for the last few psa tests so it could be the Xtandi, hard to tell until next psa.

However, so far l haven't found an answer to being on the patch and being CR causes a psa rise. So we wait until August for new blood tests.

In the meantime l hope to find an answer somewhere out there.

Thank you and wish you all good days G😚

Ps to VHRguy and Four Strings, as you both had an Orchiectomy like my husband, did you have any fluctuations in psa after the surgery. Cheers

[janebob99]

I am currently taking high-dose estradiol gel from my local compounding pharmacy (prescribed by my PCP, not my MO), and I am doing great on it. My serum estradiol is about 200 pg/ml, and my goal is to reach 400 pg/ml. I'm currently taking Orgovyz and Dutasteride. I've had some increase in gynecomastia, though, but my PSA has dropped considerably.

I've been working with Prof. Wassersug and another patient in Canada (Patient #1), collecting all available published data about transdermal estradiol therapy (TDE or tE2). We have reviewed over 50 different papers, and more every day.

Here is a plot showing the association between PSA levels (normalized to a maximum value) versus Serum Estradiol levels. Clearly, the higher the serum estradiol is, the lower the PSA is.

This happens because estradiol does the same thing as Lupron ADT. Both cause a significant drop in LH and FSH hormones, which, in turn, causes a significant drop in testosterone, which, in turn, causes a significant drop in PSA for hormone sensitive men. The more estradiol you have in your blood, the greater the effect is.

The UK PATCH study has been going on now for 17 years, starting out at low doses (1-2 patches per week), and gradually increasing to high doses (3-4 patches per week). This study involves over 1000 men at 52 different centers of excellence in the UK. If they had seen an increase in PCa AT ANY TIME during the 17 years, they would have stopped the study. But, they didn't!

The 10-yr survival results of the Phase-III trial will be published later this Fall. We are all anxiously awaiting those results.

I would suggest that you stay on the estradiol patches, while continuing to do some form of ADT...Lupron, Orgovyx, etc.. The supplemental estradiol will to treat the bad side effects of ADT, especially hot flashes, fatigue, and osteoporosis. I believe it's safe (or I wouldn't be using it myself).

Bob in New Mexico

PSA vs Serum Estradiol