Estrogens and Castrate/Treatment Resistance?

[Lost_Sheep]

Has anyone using estrogens (estradiol) as the primary agent of ADT (androgen deprivation therapy) had their prostate cancer become resistant (androgen independent) to the treatment?

I also do not know of a single instance of any man using TDE as the primary agent of ADT (which I have been lobbying my oncologist for since the constellation of side effects with TDE is far superior to FDA-approved agents.

I know of three men using high-dose trans-dermal estradiol (TDE) to suppress their testosterone (and thus their cancer) for 4, 6 and 20 years without progression, but these are mere anecdotal evidence. I seek more anecdotal evidence or, better yet, some authoritative data.

I would like to know if there are any contra-indications to using TDE long-term.

Thanks for reading.

[GP24]

The estrogens suppress testosterone just like lupron. So if Lupron does not work anymore, estrogrens will probably not work as well. But you can try. The advantage of estrogens is, apart from their low cost, that the estrogen level is not suppressed as it is the case with Lupron. Therefore you avoid many side effects like bone loss etc. which are caused by a low estrogen level.

[Lost_Sheep in reply to GP24]

GP24, thanks for your thoughts.

As I understand it, Lupron and other receptor antagonists work in one way. Antagonists work on the same biological feedback (hormone-regulating) loop in another way - but the same feedback loop (my redundant mention is intentional, for emphasis).

I am not sure estrogens (estradiol or E2 specifically) works in the same way as the others, or even on the same feedback loop(s). I am not convinced the scientists do, either.

I know one researcher started a study looking to see if E2 upregulated a man's immune response to prostate cancer, but in 28 days allotted for the study did not find evidence. I can imagine something involving the hormone receptors inside prostate cancer cells responding to ultra-high E2 levels in a negative way. If I was a medical researcher, I would be looking inside the cancer cells, particularly at steriodogenesis (intra-cellular production of T and DHT to feed cancer) or cellular uptake and usage of the sex hormones. Alas, I am not, so conducting a clinical trial of one with high-dose trans-dermal estradiol😁.

Awaiting publication of the finalized PATCH trial. (Prostate Adenocarcinoma Trans-Cutaneous Hormone trial).

[Scout4answers]

Ron in Thailand, Richard in Canada and who is third? My intention is to try TDE if PSA returns. Hopefully the large study of TDE will be finished this year.

[FourString in reply to Scout4answers]

I was using transdermal E2, but I switched to weekly injections (estradiol valerate). Cheaper and less hassle. Using it for two years now. My MO thinks E2 may have stopped my bone mets in their tracks. In any case, my body works a lot better with E2 in it…better bones, muscles, less fog.

[lancer82801 in reply to FourString]

four String

I am interested where you found the recomendation for Estradiol Valerate injection I have been using the Estradiol patches (TDE) for 5 years and no problems and no profound side effects. A weekly injection may well be an improvement but really the patches are not a huge problem either

[Lost_Sheep]

Scout4answers wrote, "Ron in Thailand, Richard in Canada and who is third? "

Known on this forum as "petercraig2". I also know of a guy (Bob) in South Carolina using it for 4 years, but he does not communicate much. Another in California, but I do not know his name.

Another Bob in New Mexico is actively seeking TDE and is quite the researcher and compiler of data. "janebob99" and he would LOVE to hear from you. Remember me to him, please.

Larry (Lost_Sheep) in Alaska, still looking for an oncologist near Anchorage.

[Lunadog7 in reply to Lost_Sheep]

Husband is recurrant oliometastatic hormone sensitive pc, but NOT in bones( per PSMA PET) Been on Relugolix intermittent for about 2yrs. Previously abiraterone+ He has serious cardiomyopathy, muscle loss, cognitive issues, etc. Quality of life is significantly impaired from ADT. Not a candidate for radiation. I have read the results of PATCH so far and other research on using Transdermal estradiol patches and E4, but I do not know how to access this in my area. It appears that it could help with cardio, fatique, cognition, etc. in addition to his cancer. We live near Rochester NY, He is a 100% disable vietnam vet so has access to VA. Can anyone tell me how to obtain this treatment and are there any facilities in this area that can help with. Does he need to get baseline estrogen levels or any other testing first? Thank you,

[Lost_Sheep in reply to Lunadog7]

The E2 (estradiol) may or may not help very much with the fatigue (but it did reduce mine) but muscle weakness and libido loss is to be expected with any ADT, whether by E2, Orgovyx or Lupron.

My local VA would give me the E2 if I could convince my oncologist to prescribe it. The Washington State VA... no way, no how, I am told.

I was able to get a prescription for E2 from a gender care specialist by convincing her I was serious in my research and that it is valid. I think my sincerity carried the day. With the current political climate, gender care doctors are understandably cautious dealing with cisgender men coming to them.

Also, she talked to my oncologist directly and she is confident I am being assiduously followed not only for the cancer but for other organ functions as well.

I do recommend getting baseline blood testing for PSA, Testosterone, FSH, LH, Estradiol and Estrone (E2 and E3). Knowing your husband's E2 level would be informative about the danger of bone density/strength and might suggest getting a DEXA scan.

It is my understanding, per an article I just read that E4 (Estetrol) is produced in the fetal liver, so unlikely to be found in abundance for clinical use any time soon unless it can be synthesized. Besides scarcity, it has not been tested (Phase 1) for safety in adult men.

[Lost_Sheep in reply to Lunadog7]

Does your husband participate in support groups in-person or the ANCAN.org groups? GREAT advice for veterans there, some of the guys can quote chapter and verse about getting the VA's treatments and benefits.

Also, get a copy of this book, (Third edition) "Androgen Deprivation Therapy: An Essential Guide for Prostate Cancer Patients and Their Loved Ones"

[Lizzo30]

Estrogen was originally used to castrate men and treat prostate cancer it was the scientist Huggins that discovered this

pubmed.ncbi.nlm.nih.gov/381...

However estrogen was stopped citing heart problems and companies such as Astrazenica brought out Zoladex ADT treatment - Zoladex by blocking testosterone also blocks estrogen bc a mans testosterone also makes his estrogen supply which is important

Transdermal estrogen patches should be made available bc they bypass liver and are safe for men without debilitating side affects of ADT

Ive seen data that says estrogen is good for castrate resistant pc both online and on this site

By the same token testosterone seems to be good for treating breast cancer

PATCH trial is dragging its heals imo

Big Pharma doesnt like hormones they just want to block them off - not use them in a helpful way - hormones are key

My husband has a potent phytoestrogen ( plant estrogen) called Aguaje bc he wouldnt do well on ADT

[Scout4answers in reply to Lizzo30]

Thanks Lizzo I would like to learn more about Aguaje, how did you find it and what dose does he take.

[swwags in reply to Scout4answers]

What are the nutritional properties of aguaje?

100 g of fruit contains 526 calories, 46% as carbohydrate, 38.6% from fat and 11% in the form of proteins.

Also 100 g of aguaje contain:

fibers (41.9%)

vitamin A

C vitamin

Vitamin E

0.85 mg of riboflavin

2.57 mg of niacin

0.11 mg of thiamine

91 micrograms of carotene

415.4 mg of calcium

69.9 mg of phosphorus

12.9 mg of iron

The amount of vitamin A – present in the form of carotenoids – can be five times higher than those found in carrots. Moreover aguaje is a good source of phytoestrogens and oleic acid.

Not are how this relates to cancer in any way.

[Scout4answers in reply to swwags]

Thanks for the breakdown swwags. Agree, do not see the estrogen connection.

[Lizzo30 in reply to Scout4answers]

My nephew married a Peruvian and was importing and selling Aguaje which is grown in Peru also Brazil I started using it as I was approaching menopause it stopped menopause symptoms and I have realised it also keeps arthrihis at bay

It isnt easy to get genuine Aguaje in UK

My nephew is getting a divorce so I had to find an alternative source after buying dud aguaje from India I got lucky with a seller on ebay uk I bought a load and put it in the freezer

US is near to Peru so you should be able to buy some genuine aguaje - maybe contact Peruvian gov for genuine suppliers

You don't need much it is super potent

[Scout4answers in reply to Lizzo30]

How do you determine if it is genuine?

[Lizzo30 in reply to Scout4answers]

If you don't know Aguaje ( as I do ) it's difficult I suppose But it is well worth finding genuine aguaje

[Lizzo30 in reply to Scout4answers]

There is a shortage of Aguaje globalpeatlands.org/node/13

[Lost_Sheep in reply to Lizzo30]

Relief from menopause symptoms is one thing but suppressing testosterone ( to suppress prostate cancer growth) quite another. I do not diminish your experience, but the mechanism of the one in women does not guarantee the result of the mechanism of the other in men

Just a caution. If a man chooses to use Aguaje to treat prostate cancer, checking his estradiol levels would be prudent. Checking his testosterone levels even more necessary and checking his PSA levels the defining parameter of efficacy.

[Lizzo30 in reply to Lost_Sheep]

You can doubt my experience but there's no doubt about the pioneering work of Huggins

acsjournals.onlinelibrary.w...

[Lost_Sheep in reply to Lizzo30]

I did not doubt your experience. And I do give credence to Dr Huggins and Dr Hodges. Note the Nobel Prize in 1966.

I am adamantly seeking estradiol (transdermal) as the agent of ADT (Andrew deprivation therapy). I do believe estrogens are superior to the ADTs so far approved by the FDA.

What I question is the mechanisms by which menopause symptoms are suppressed versus the mechanism that testosterone is suppressed (if it actually is ) with Aguaje. The possibility that they may be two separate mechanisms looms large in my mind and that success with the one does not guarantee success with the other.

I meant no more than that and did not mean to give any offense or doubt to your lived experience.

[Lizzo30 in reply to Lost_Sheep]

No offence taken Time will tell when my husband gets his next psa and psma scan

As I said my husband wouldn't do well on Zoladex

I think phytoestrogens and prostate cancer is such an exciting area yet no one is looking into it

[janebob99]

The best source of papers are those reports from the Phase-I and Phase-II UK PATCH trials covering the past 15 years. They have studied approximately 1000 men doing high-dose transdermal estradiol ADT in place of Lupron ADT. The main reported bad side effects are gynecomastia (from the high estradiol) and muscle weakness/loss (due to the low testosterone ). There has been no increase in blood clots or CVE's reported.

Bob in New Mexico

[Lost_Sheep in reply to janebob99]

And remember, the muscle weakness is a side effect of the Lupron anyway, so no difference there, Lupron vs estradiol.