ADT & Addback Estradiol.: New... - Advanced Prostate...

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ADT & Addback Estradiol.

pjoshea13 profile image
24 Replies

New Australian study below [1].

I remember reading old writings years ago that stated that, while women needed estradio [E2] for bone health, men only needed testosterone [T]. Made no sense, of course - why would there be two mechanisms? Men who had osteoporosis & very low T, also had low estradiol. Most male E2 comes from the aromatization of T. T supplementation in otherwise healthy men fixes the bone problem, but primarily because it restores E2.

The new paper politely opens with:

"There is increasing recognition that, in men, some biological actions attributed to testosterone (T) are mediated by estradiol (E2)."

The subject of addback E2 via low-dose patches has come up here a few times. There is a vlog post by Dr. Myers that is useful, but I have often wondered why the approach is not standard practice for men on ADT. If E2 dips below 12 pg/mL, prescribe the patch.

In the Australian study:

"E2 treatment reduced hot flushes and bone resorption."

When serum calcium levels dip, osteoclasts break down bone to obtain calcium (resorption). This is a short-term response which is followed by calcium uptake from the gut &, ultimately, osteoblastic activity to rebuild bone. For this we need some calcium in the diet, vitamin D, a few other things, & ... E2.

...

But perhaps doctors prefer to treat with a bisphosphonate because T is also very important?

Here is a 2013 paper from "Current opinion in endocrinology, diabetes, and obesity" (no doubt widely read by oncologists) [2]:

"Evidence from recent studies shows that the contributing role of testosterone to osteoporosis is modest and likely trumped by other factors such as estradiol levels. A few studies have documented an association between low testosterone levels and lower bone mineral density (BMD), increased prevalence of osteoporosis of the hip and low bone mass-related fractures. Other studies, however, have found that testosterone levels are not independent predictors of bone resorption or formation markers, BMD at the hip or incident fractures."

"Although male hypogonadism is associated with osteoporosis, estradiol is likely to be the more important hormone for bone health."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/295...

Eur J Endocrinol. 2018 Mar 16. pii: EJE-17-1072. doi: 10.1530/EJE-17-1072. [Epub ahead of print]

Short-term effects of transdermal estradiol in men undergoing androgen deprivation therapy for prostate cancer: a randomized placebo-controlled trial.

Russell N1, Hoermann R2, Cheung AS3, Ching M4, Zajac J5, Handelsman DJ6, Grossmann M7.

Author information

1

N Russell, Department of Medicine (Austin Health), The University of Melbourne, Melbourne, 3084, Australia nicholas.russell@austin.org.au.

2

R Hoermann, Innere Klinik I, Klinikum Lüdenscheid, Lüdenscheid, 58509, Germany.

3

A Cheung, Department of Medicine (Austin Health), The University of Melbourne, Heidelberg, Australia.

4

M Ching, Pharmacy Department, Austin Health, Heidelberg, Australia.

5

J Zajac, Medicine, University of Melbourne, Heidelberg, 3084, Australia.

6

D Handelsman, ANZAC Research Institute and Dept of Andrology, Dept of Andrology, Sydney, 2139, Australia.

7

M Grossmann, Medicine, Austin Health/ Northern Health, University of Melbourne, Heidelberg, 3084, Australia.

Abstract

OBJECTIVE:

There is increasing recognition that, in men, some biological actions attributed to testosterone (T) are mediated by estradiol (E2). This study used two low doses of daily transdermal E2 gel to assess effects on circulating E2 concentrations in men with prostate cancer with suppressed endogenous E2 production arising from androgen deprivation therapy (ADT). Secondarily, we aimed to assess short term biological effects of E2 addback without increasing circulating T.

DESIGN:

28-day randomised, placebo-controlled trial Methods: 37 participants were randomised to either 0.9 mg or 1.8 mg of 0.1% E2 gel per day, or matched placebo gel. Fasting morning serum hormones, quality of life questionnaires, and treatment side effects were evaluated at baseline, day 14 and day 28. Hot flush diaries and other biochemical measurements were completed at baseline and study end.

RESULTS:

Transdermal E2 significantly raised serum E2 from baseline to day 28 compared to placebo in the 0.9mg dose group (median 208 pmol/L; interquartile range 157-332), and in the 1.8mg dose group (median 220 pmol/L; interquartile range 144-660). E2 treatment reduced hot flush frequency and severity as well as beta carboxyl-terminal type 1 collagen telopeptide.

CONCLUSION:

In men with castrate levels of E2 and T, daily transdermal E2 0.9-1.8mg increases median serum E2 concentrations into the reference range reported for healthy men, but with substantial variability. E2 treatment reduced hot flushes and bone resorption. Larger studies will be required to test whether low dose E2 treatment can mitigate ADT-associated adverse effects without E2-related toxicity.

PMID: 29549104 DOI: 10.1530/EJE-17-1072

...

[2] ncbi.nlm.nih.gov/pubmed/?te...

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24 Replies
gusgold profile image
gusgold

Avodart raises free T, so wouldn't that increase E2

pjoshea13 profile image
pjoshea13 in reply to gusgold

Gus,

The only way to know how much E2 one has is to test.

-Patrick

leswell profile image
leswell

To the above and below, i.e. gusgold and pjoshea13, Leswell is taking Avodart which is supposed to prevent conversion of T to DHT and E2. How can it increase AND decrease E2, Gus? (Yours is a good and confusing question.) Seems to me T and E, in general, are necessary and highly desirable for health and happiness—unless a person has Stage Four PCa! Talk about being between a rock and a hard place. Taking Estradial is not without its side effects. We, which is to say he, gave it up because he was becoming me if you know what I mean. Mrs. S

leswell profile image
leswell in reply to leswell

Edit: Estradiol

gusgold profile image
gusgold in reply to leswell

Les,

by blocking T to DHT there is more free T and some of that T will convert to E2 unless you block the conversion with arimidex

leswell profile image
leswell in reply to gusgold

Thank you. I’ve heard of it and will look it up. Mrs. S

jdm3 profile image
jdm3 in reply to gusgold

So, I'm confused. What is the general consensus - Dr. Myers and otherwise? Block the T to DHT with Avodart/Proscar and add Armidex to minimize E2 or is a little E2 okay or even beneficial? And other than the hot flash relief, is there a reason to have E2 in the PCa battle? Thanks.

pjoshea13 profile image
pjoshea13 in reply to jdm3

You want to have E2 to be no less that 12 pg/mL IMO. This is for bone health.

Life Extension uses the 20-30 pg/mL range as being a good place to be, & suggests that men use Arimidex if E2 gets much higher.

Myers, I believe, is not interested in elevated E2, but has prescribed the Vivelle-Dot E2 patch (low dose) for low E2. One should only use the dose that solves the immediate problem. No reason to aim for 30 pg/mL, or accidentally stray much higher.

While some have implicated E2 in PCa growth, E2 cannot act independently of testosterone [T]. So E2 is not a threat while on ADT.

In the off-phase of IADT, it would be interesting to track E2. T recovers very slowly & estrogen dominance might be an issue.

-Patrick

jdm3 profile image
jdm3 in reply to pjoshea13

Thank Patrick. Interesting. This site is like crack for inquiring minds. So much to know and so many variables to balance in the process.

vandy69 profile image
vandy69

Good Wednesday Morning pjoshea13,

When I first began treatment with Dr. Myers in 9/2012, he prescribed Vivelle dot patches of estrogen to moderate side effects of ADT. Wore 3 days/4days or 2 patches/week.

One year later after trip to South Africa (14 hour plane flight), a set of scans for PCa picked up multiple pulmonary emboli (had no symptoms) and I had a subsequent 8 day hospital stay to run up my clotting factor. No more Vivelle dot and warfarin became my new best friend.

Be careful with estrogen!

Best wishes. Never Give In.

Mark, Atlanta

pjoshea13 profile image
pjoshea13 in reply to vandy69

Mark,

Estradiol [E2] is not a problem for men up to at least 30 pg/mL. The low-dose Vivelle patch should not have taken you much above 20 pg/mL. I doubt that it contributed anything towards the clot.

Unfortunately, with cancer, we have screwed-up coagulation factors. When I had my double-DVT experience & ended up on Warfarin, I was using Arimidex to keep E2 at about 20 pg/mL. Estrogen wasn't my problem. I can't even blame a long plane flight. Sitting in my computer chair for hours was probably enough.

I hated Warfarin & was anxious to resume vitamin K2, so I convinced my doctor to allow me to switch to nattokinase. Much safer, IMO, & more convenient. & unlike Warfarin, it actually dissolves clots.

Best, -Patrick

EdBar profile image
EdBar

Myers prescribed estradiol patches for severe hot flashes back in 2015, worked like a charm. He later increased the dose once my scans showed my skeleton to be free of active disease, he was using estradiol to heal the sclerotic areas left behind by cancer. I remain on the patches today and Myers replacement, Dr. Sartor, agrees and also has me using estradiol patches.

The patches allow the estradiol to be absorbed through the skin not the liver like the pill form is thus avoiding the formation of blood clots.

Myers combination of ADT meds, supplements and diet continue to work for me, so on we go.

One more cast...

Ed

middlejoel profile image
middlejoel in reply to EdBar

Edbar,

What dosage are you on and how often do you change them?

jalf

EdBar profile image
EdBar in reply to middlejoel

Jalf,

I'm on 0.1mg patch, I keep 2 on and change one daily. Myers had me wearing 3 patches at one time, changing one each day for a while, Sartor thought it would be fine to go with 2.

If you google Snuffy Myers and estradiol there are several videos on you tube including one where he explains the benefits of estradiol if you are on ADT and how estradiol actually helps REDUCE the risk of blood clots caused by cancer which is one of the ways that PCa can kill you. It's a 10 minute video and he has the full white beard.

Ed

pjoshea13 profile image
pjoshea13 in reply to EdBar

The only way to know for sure is to test estradiol [E2]. IMO, E2 should never be <12 pg/mL or >30 pg/mL - 20 pg/mL is a reasonable target.

-Patrick

Break60 profile image
Break60

I use estradiol patches changed twice weekly for hot flashes. They work well. Are you saying there are other benefits?

Bob

pjoshea13 profile image
pjoshea13 in reply to Break60

The main benefit is on bone health.

Some reported benefits for libido & mood too.

There are estrogen receptors in many tissues - including the brain. Safe to assume that it would be unwise to live with castrate E2. Best to test - & perhaps aim for 20 pg/mL.

-Patrick

Break60 profile image
Break60 in reply to pjoshea13

Patrick:

My recent lab work indicated the following as being low:

Serum T 7.2; Bioavailable T 1.4.; dihydroT 1.7; Alk phosphatase bone specific 7.3; prolactin 0.2; platelets 149; alkaline phosphatase, S 38; PSA .175

My RO didn't specify testing estradiol.

I'm taking cabergoline (for prolactin), metformin, estradiol patches, calcium, vitamin D3, trelstar, bicalutamide, dutasteride, celecoxib, rosuvastatin, duloxetine.

I'm monitoring PSA since it rose from <.1 to .175 in three month while on ADT3.

Bob

pjoshea13 profile image
pjoshea13 in reply to Break60

Bob,

Dr. Myers used to test DHT & looked for it to be <5 ng/dL, so 1.7 looks good if those are your units.

Doctors aren't interested in estradiol [E2] for the most part. I have known a number of men with elevated E2 ask their doctors for Arimidex. The usual response being laughter, followed by "I only prescribe that for my female patients." As though E2 is irrelevant - even for bone health.

I don't think you can read anything into those PSA numbers at this stage.

Best, -Patrick

Break60 profile image
Break60 in reply to pjoshea13

Patrick

I agree re : Psa . I also take xgeva after my single bone met was found nearly a year ago and do weight training 3x weekly and golf 2x for muscle and bone strength . So far I’ve had very few mets and feel relatively fortunate. My RO ( Dattoli) treated Snuffy and prescribes to his treatment philosophy. Maybe that has kept met volume low and perhaps my low volume Gleason 9 also helped. As you can see from my profile I’ve had RP and lots of RT as well.

My biggest gripe about ADT is weight gain in gut and fatigue. Do you know of any way to stop the beer belly other than stop eating?

Thanks

Bob

pjoshea13 profile image
pjoshea13 in reply to Break60

Bob,

A short burst of intense exercise can have a profound effect on blood chemistry. Myers used to say that he could always tell which patients exercised.

-Patrick

Break60 profile image
Break60 in reply to pjoshea13

Yea without it I’d be a mess.

Break60 profile image
Break60 in reply to pjoshea13

Patrick:

Latest PSA came in at .162 down from .175. T is still 7.9. All other bloodwork is ok . Not sure what that PSA reading means though I'm happy it didn't rise. It's too low for CT Pet scan to be effective as I understand it. Does this mean I'm not castrate resistant ? Does it make any sense to add zytiga? What is the chance that I have a strain of PCa that doesn't produce PSA?

Bob

pjoshea13 profile image
pjoshea13 in reply to Break60

Bob,

I'm not a doctor, but your numbers look good to me. If PSA is not going up, don't worry about CRPC. & don't worry about cells no longer being PSA producers.

Regarding Zytiga, you need to ask your doctor that question.

-Patrick

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