Estradiol for the mitigation of adverse effects of ADT.

[pjoshea13]

New Australian paper below.

It's not clear to me why this paper wasn't written ten years ago.

"Recently it has become apparent that many of the biological actions attributed to androgens in men are in fact not direct, but mediated by estradiol. Available evidence supports a primary role for estradiol in vasomotor stability, skeletal maturation ..."

"Potential role for estradiol could be ... as low dose add-back treatment while continuing androgen deprivation therapy."

-Patrick

ncbi.nlm.nih.gov/pubmed/286...

Endocr Relat Cancer. 2017 Jun 30. pii: ERC-17-0153. doi: 10.1530/ERC-17-0153. [Epub ahead of print]

Estradiol for the mitigation of adverse effects of androgen deprivation therapy.

Russell N1, Cheung AS2, Grossmann M3.

Author information

1

N Russell, Endocrine Department, Austin Health, Heidelberg, 3084, Australia [e-mail].

2

A Cheung, Medicine, The University of Melbourne, Heidelberg West, 3081, Australia.

3

M Grossmann, Medicine, University of Melbourne, Heidelberg, 3084, Australia.

Abstract

Prostate cancer is the second most commonly diagnosed cancer in men. Conventional endocrine treatment for prostate cancer leads to global sex steroid deprivation. The ensuing severe hypogonadism is associated with well-documented adverse effects. Recently it has become apparent that many of the biological actions attributed to androgens in men are in fact not direct, but mediated by estradiol. Available evidence supports a primary role for estradiol in vasomotor stability, skeletal maturation and maintenance, and prevention of fat accumulation. Hence there has been interest in revisiting estradiol as a treatment for prostate cancer. Potential roles for estradiol could be in lieu of conventional androgen deprivation therapy or as low dose add-back treatment while continuing androgen deprivation therapy. These strategies may limit some of the side effects associated with conventional androgen deprivation therapy. However, although available data are reassuring, the potential for cardiovascular risk and pro-carcinogenic effects on prostate cancer via estrogen receptor signalling must be considered.

PMID: 28667081 DOI: 10.1530/ERC-17-0153

[Dan59]

Thanks Patrick, I know Myers was using estradiol patches for relief from hot flashes ,and to support bone health in castrate males more than a decade ago, and also in combination therapy with ketoconazole way back as a mainstay treatment before zytiga and xtandi. I myself felt that I had multiple responses to high dose estradiol as I re challenged with it multiple times after getting a good and immediate response early on, although in the end I felt I had a withdrawl response. When a person is hormone deprived as many of us are even the presence of a female hormone is better than none at all. As Ludwick used to say " I really enjoyed estradiol patches, for me it was the only time in my life I could win an argument with my wife."

[rococo in reply to Dan59]

Sometimes these med have positive side effects for SOME. At age 78 went back on lupron with extandi and avodart. Feel calmer, stronger work outs. Too early, maybe T flare. Will see. Rocco

[Blair77]

Very interesting. Hope they start looking into this!

[Neal-Snyder]

I've been interested in this since I first saw Patrick & others discuss it here. But my med onc is only interested in new treatments after they're proved to be worthwhile in Phase III clinical trials. This new study only seems to be discussing potential benefits, & risks, as well. So I'm still waiting for the kind of evidence that my med onc, & others in the genitourinary cancer team at my hospital, need before they'll act.

Neal

[pjoshea13 in reply to Neal-Snyder]

Neal,

For many men on ADT, estradiol [E2] falls below 12 pg/mL. This is dangerous for bones. There are epidemiological studies that demonstrate that.

I don't thing that there are reasons to supplement above 12 pg/mL, although LEF recommends 20 pg/mL as the lowest one should go.

-Patrick

[leswell in reply to Neal-Snyder]

Phase 3 trial positive results there must be or no prescriptions will be granted. I agree with you, Neal, that this is so, except that our oncologist did permit both a trial of estradiol (stopped due to painful breasts and gynecomastia) and also Metformin (a one-time prescription for PCa, not diabetes). I can’t accuse him of not having an open mind.

This morning I had to repeat my request for Avodart and Proscar prescriptions. The nurse said finasteride and dutasteride were basically the same thing. (Good, if they work together to stop the conversion to DHT and E2.) She did get permission from our urologist/surgeon, and we are buying those plus Casodex (all generic) tomorrow at a price of $162 which was a shock until the pharmacist said it was for three months which I very much appreciate. (It also, I think, includes our second third of this year’s deductible. In 2018 the deductible goes up to $250 should anyone be interested in the finances of this “ordeal”. )

A student of mine when I was twenty is now on dialysis and has been for eight years. I talk to her on Tuesdays, and she uses “ordeal” to describe good and bad events. She was once a sweet, coppery-haired seventh grader with two alcoholic parents. Dying kidneys do not help a person’s disposition, but we still care about each other. I was a student teacher in a tough district in which kids carrying knives were common, but I had a dignified, dressed-in-suits, female supervising teacher who had sixty or so mostly disadvantaged kids following her rules and singing lustily. I played the piano for her and tried to pass the Ford Foundation judges’ inspection who were observing me from the last row. They told me to raise my voice; now Les tells me to lower it. He’s getting new hearing aids from Costco in November. Sorry. I’m way off topic again.

We still don’t have the appointment to install the Vantas, and Les is running out of Lupron tomorrow. The clinic does not want the injections and insertion to overlap. I wonder if there’s anything we can ascertain from switching to Casodex (for the first time) BEFORE the Vantas and seeing what the bicalutamide can do to his immovable 21.46, .98, and .97 PSA three months in a row. The cessation of decline is scary.

Btw, I don’t think I’ve said that we were members of LEF for many years. The most we learned about supplements prior to joining this site was from writers on that one. Ultimately, it was just too much money, we had organic garden food, etc. Les’s D3 and K2 now come from LEF via Amazon. What goes around...

This discussion was a find. Thanks, as always.

Mrs. S - he’s asleep

P.S. We moved the remaining squash to a new spot on the lawn so that the former area wouldn’t die. Les hauled heavy sacks of leaves which were brought over the back yard fence by a kind neighbor (who has a 20 PSA himself and is treated at the same clinic but doesn’t think he has cancer). Les then distributed the rest of our compost “gold” in the raised beds for next year.

Sorry you were the one to dump on today, Neal. Patrick has had surfeit of my mental wanderings. Also, you struck a nerve about an issue. Why not try some new combination if Lupron alone isn’t working? Rules are rules, I guess.

And that leads me to politics. No way am I going there.

[Hidden]

I think that this is pretty well known. I cannot understand the reluctance to use an estrogen patch on the skin. Maybe I am missing something. It's not PE.

The role of the estrogen receptor (α AND β) is mentioned in another thread:

healthunlocked.com/advanced...

[pjoshea13]

Nalakrats,

True - but adding back enough E2 to get above 12 pg/mL would not accelerate growth IMO.

The threat in PCa is not so much circulating E2, as elevated levels of aromatase (which converts T to E2).

-Patrick

[leswell]

Hello on October 17th, 2017.

Three bottles of BioResponse DIM arrived from Amazon today. I will do my best to get Les to take two at least. We are waiting for notification of a date for the Vantas insertion. Even though you aren’t a doctor (as you protest too much) you are one of our best teachers. Thinking of you and wishing you well. Mrs. S

[leswell]

Hi Martin, Even though this discussion was 3 months ago, I enjoyed reading you men tonight. Les felt better on the patch but his breasts enlarged and hurt. I wish he could have some estrogen and testosterone, but then he will die. Truth is, he will die either way, low or high. With stage four, he can’t have high E or T, and those are both life extension agents for someone aging without cancer. If you disagree, just say so somewhere if you haven’t already. I bump into these responses at odd times. Btw, if I could find a photo as perfect as your profile’s, I’d post it! Mrs. S

[Break60]

I’ve been using estradiol patches since 2015. They’ve done a great job stopping hot flashes.

Bob

[Dan59]

Nalakrats, being I had an withdrawl rsponse, on the 4th time I rechallenged with estradiol patches and my psa dropped 35% when I stopped ,I suspect I should lower my e2 level as well That was just one year ago and I got 4 months out of that withdrawl , Is it the bioresponse DIm that you do to reduce estradiol?,Thank You. I too am sure glad we have some smart people on here, it helps a lot

Dan

[pjoshea13 in reply to Dan59]

Dan,

Low-dose estradiol [E2] patches are good for getting E2 into the 12-18 pg/mL range for bone health, while on ADT. More natural than a bisphosphonate!

When not on ADT & is E2 >30, Arimidex is the preferred way to control E2. 20 pg/mL is a reasonable target, but it can go lower - but it must not go below 12 pg/mL.

An alternative to Arimidex is chrysin (no prescription required). It must be taken with bioperine. Chrysin is an aromatase inhibitor too.

Regarding E2 metabolism, the 16α pathway metabolites are pro-growth, whereas the 2 pathway metabolites are not - & may even be anti-growth. DIM should lead to a better 2:16α ratio.

The instructions on the BR-DIM bottle say 2 caps for women, 2 caps twice for men. & for more intesive use, double the dose. Nala is more cautious. I took 8 caps for years. I take 4 now, since I know that my E2 is low.

-Patrick

[Dan59 in reply to pjoshea13]

Thank You very much for this Patrick, I think the first step is to get an e2 test from the DR and see where it is.

Dan

[Dan59]

Thanks I will check that out. I think Arimimedex requires a prescription.

Dan