November 2023 prescribed 2nd generation Xtandi as Zoladex injections became castrate resistent, he has no mets. The full dose became intolerable so Onc lowered it to 2 x 80mg, things were going ok psa was dropping good, then started to slow down.
He decided to have an Orchiectomy in March 2024 that went well.
After lots of research we decided to obtain TDEestrogen patches, low dose to replace the aromatized estrogen lost with lowered testosterone (now at 00.03) to help side effects of hot flashes and bone health, etc.,
His well being improved a lot.
We decided to get estrogen and psa tests done before starting the patch and things looked good psa still moving slowly down and estrogen in good range
After 2 months being on the patch we had psa and estrogen tests done again, Psa gone up 1.00 point, testosterone 00.04?, and estrogen to (564 !!!, an Abnormal Canadian Lab range level), that is an alarming increase. He has stopped the Patch thinking this maybe the reason for psa increase ( odd as all we have researched finds estrogen does not feed cancer). Increased Xtandi to 3 pills.
Could this be the estrogen? or is it the Xtandi losing it's efficacy? which is a known fact, but different for everyone.
Is there anyone out there doing Xtandi and TDE low dose and had this happen, big concern psa rise!!!!
Thanks for anyone's insight.
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Knittingque
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I'm not on Xtandi, but I am using TDE patches. What I discovered in the past year is that some meds can cause Labcorp's conventional ECLIA test (004515) for serum estradiol to yield extremely high and erroneous results. In my case this happened when I began using a version of transdermal testosterone (for TRT). My estradial result jumped to 285 pg/mL. But when I changed to a more precise lab test (Labcorp 140244 estradiol sensitive, an LC/MS assay) my result immediately dropped to 30 pg/mL (which I believe is the correct number).
Of course, I'm not implying that this is what's going on with your husband, but you might see if you get a different result using an LC/MS assay.
Having a mutation of the BRCA1 or BRCA2 gene is a contraindication for using high-dose estradiol to suppress prostate cancer. There is another marker, too but I cannot recall what it is. I also am not sure if low-dose estradiol is contraindicated, either.
I enrolled in the "PROMISE" study (no cost, they are gathering information). Find out more at
I cannot find the specific article I remember which mentioned the BRCA mutations that contraindicate use of estrogens to suppress prostate cancer, but if you search the internet for "BRCA gene and prostate cancer", you may find it or more information on the subject.
Yes, you are at an increased risk for breast cancer with that mutation when taking estradiol supplement. The increased risk likely depends on the estradiol dose. What's your serum estradiol level?
That is at the low end of the typical E2 range that was achieved in the PATCH study [range = 350-450 pg/ml]. I haven't seen any discussion from the PATCH researchers about increased rates of breast cancers. We'll have to see what the final Phase-III report says about this. But, I do remember reading somewhere that for BRCA-1/2 positive men taking estradiol (I don't remember the dose, though), that the breast cancer rates were increased and similar to those of women. But, I don't have that reference handy. You may want to Google the topic. Let me know if you find anything that is relevant.
My own E2 goal is 350-400 pg/ml, but I am BRCA-1/2 negative.
You may remember Brian in Vancouver Canada writing to you some time ago
l am his wife Knittingque, just wondering whether you managed to obtain the patch and if it is working for you,
We had started the low dose patch for side effects, all was improving a lot, but after 2 months had estrogen psa and testosterone blood tests and all rose
Estrogen 567 from 66
Psa 10.2 to 10.8
Testosterone 00.02 to 00.04
Stopped patch for now until new blood test in August.
Have you heard of any rise like this adding low dose estrogen 3x00.25mg changed twice per week.
It could be Xtandi is losing its efficacy after being on it for 1 year?
Therapy for Crpc no mets Xtandi and medical castration and here come the side effects in bucket fulls again
Would be good to hear you thoughts
We both hope you are having success and coping with the therapies.
I just replied to your other posts, and asked some questions for more details about Brian's treatment. Brian certainly has some unusual numbers...
I am now fully on Orgovyx and high-dose estradiol, and will get some new blood labs in a couple of weeks. I'll let you know what they are.
One of the other posters said that his serum E2 dropped considerably when doing a high sensitivity LC/MS blood test. That's the first I've heard of problems with measuring serum E2. I'm going to ask him some questions about this.
You know, Prof. Richard Wassersug lives in Vancouver, also. He's been using transdermal estradiol for over 20 years and he has very low PSA and T. You should try to contact him and have lunch or coffee. He also runs a website called LifeonADT.com.
B vitamins affect LabCorp’s test as well. I’ve read Biotin interferes. Mine went up to 200-300. Also suspect some supplements may impact. I now stop all non prescription meds 3 days before blood draw. No issue since I began doing that.
good suggestion above to retest with ultra sensitive E2 test. Don’t speculate or panic till you retest. Also great idea about cutting all non prescription sups 3 days before testing.
I have been very enthusiastic to explore low-dose transdermal Estradiol add back for estrogen recovery in circumstances of ADT and metastatic prostate cancer.
However I'm very concerned and have stopped pursuing it. Not only did my doctors refuse to prescribe it, but from what I'm reading there are risks.
In a nutshell, estradiol has equal affinity for both the ERβ and ERα versions of the estrogen receptors on prostate cancer cells. Estradiol can activate estrogen receptors and thus we recover estrogen. And then of course monitor carefully to make sure we have the right amount in our blood.
Of the two receptors, ERβ is the receptor we like, because it acts against metastatic prostate cancer. However the ERα receptor has the opposite effect - it promotes cancer. Apparently there are a lot more of ERβ than ERα. But over time this ratio might change.
There are some experimental drugs and supplements that target only ERβ. But now we're into really complex territory with a lot of uncertainty.
We are really wrestling with two issues here:
(1) a very logical and important desire to diminish the serious consequences of ADT - osteoporosis, CVD, and possibly brain fog - all because we lose estrogen along with testosterone.
(2) But it turns out that there's another issue on the table here - which is the anti and pro cancer effects of estradiol. Like most hormones estradiol is very active. This anti cancer benefits here shows up in the use of high-dose estradiol as a replacement for ADT. And apparently from a few pioneers in the space (see Richard Wassersug) this can work very well!
The point here is that when we use estradiol we are not only triggering estrogen add-back, but we are also triggering powerful processes which alter the bigger picture. We can't be naive about this.
The feedback loops and hormone interrelationships are astonishingly complex. For my part I have concluded that we don't understand what we're doing. And I have friends who use estradiol gel. I don't want to find out months or years from now that my cowboy use of low-dose transdermal Estradiol has promoted progression and resistance!
The context here of course is that the side effects of estrogen suppression are very serious. And it's not completely clear that our doctors are sufficiently pursuing the add-back angle.
Currently I'm looking at some of the supplements or experimental products that target only the ERβ receptor. I'm not that optimistic.
The UK PATCH study has been going on for 17 years, using high-dose estradiol and over 1000 men at 52 different centers. If there had been an increase in PCa rates or severity, they would have shut down those studies. But, they didn't find such an effect.
I'm currently taking high-dose estradiol gel, and I'm not worried about it.
That's correct. The PATCH study has only looked at high dose estradiol.
I would expect that low-dose estradiol would have fewer bad side effects compared to high-dose (i.e., less gynecomastia, lower risk of breast cancer when BRCA-1/2 positive, and less loss of muscle mass with low-dose E2).
This is the big question for me. But I can't say that I am confident in expecting anything. The argument for estrogen add-back is very powerful.
From what I'm reading so far it seems that high-dose estradiol which totally replaces ADT, is an overwhelming modification to the body hormone system.
Low-dose however, is not overwhelming to the system in the same way and has many processes still in place.
And then there's the question of ERβ versus ERα receptors - for which estradiol has approximately equal affinity. And as I mentioned earlier, one receptor is good and the other bad.
If one looks hard enough, one can find people and articles that say low-dose transdermal Estradiol has great for elimination of most of the side effects of testosterone suppression.
But there are no clinical safety studies over say a few years. And I haven't found any unequivocal analysis that it's safe.
More recently I'm looking at materials that preferentially target ERβ.
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