Role of Estrogen in Androgen-Induced PCa in NBL Rats.

[pjoshea13]

New study below [1].

OK, so you are wondering how tall can those NBL rats be? How much a year do they earn? NBL rats are 'Noble' rats. Sometimes an abbreviation doesn't save much space & takes longer to say.

MC Bosland has been messing about with rats for 40 years. There are studies by others going back as far as 30 years where Noble rats were given testosterone [T] & estradiol [E2] to induce prostatic hyperplasia, etc. What's new about this study?

"Androgens are thought to cause prostate cancer, but the underlying mechanisms are unclear. Data from animal studies suggest that for androgens to cause prostate cancer, they must be aromatized to estrogen and act in concert with estrogen metabolites. We tested the hypothesis that androgen-receptor and estrogen receptor-mediated effects of androgen and estrogen are necessary, as well as genotoxicity of estrogen metabolites. NBL rats were treated with androgenic and estrogenic compounds for 16-75 weeks through slow-release silastic implants or pellets."

"5α-Dihydrotestosterone, which cannot be converted to estradiol or testosterone, did not cause a significant prostate cancer incidence (4%)."

"Testosterone alone {which can be converted to estradiol} induced cancer in the prostate of 37% of rats."

"Addition of estradiol to 5α-dihydrotestosterone treatment did not markedly enhance prostate cancer incidence (14%)"

"adding estradiol to testosterone treatment ... induced a 100% tumor incidence."

"results strongly support the hypothesis"

Going back 15 years, the literature was suggestive to me that in estrogen dominance, E2 drives proliferation while T is necessary but merely permissive. With T:E2 balance, though, T resumes its growth regulatory role.

But nobody seems to care about E2, or the fact the the T:E2 ratio is much reduced in men by the time they are diagnosed.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/308...

Horm Cancer. 2019 Mar 16. doi: 10.1007/s12672-019-00360-7. [Epub ahead of print]

Role of Estrogen in Androgen-Induced Prostate Carcinogenesis in NBL Rats.

Ozten N1, Vega K2,3, Liehr J4, Huang X2,5, Horton L2, Cavalieri EL6, Rogan EG6, Bosland MC7,8.

Author information

Abstract

Androgens are thought to cause prostate cancer, but the underlying mechanisms are unclear. Data from animal studies suggest that for androgens to cause prostate cancer, they must be aromatized to estrogen and act in concert with estrogen metabolites. We tested the hypothesis that androgen-receptor and estrogen receptor-mediated effects of androgen and estrogen are necessary, as well as genotoxicity of estrogen metabolites. NBL rats were treated with androgenic and estrogenic compounds for 16-75 weeks through slow-release silastic implants or pellets. Testosterone alone induced cancer in the prostate of 37% of rats. 5α-Dihydrotestosterone, which cannot be converted to estradiol or testosterone, did not cause a significant prostate cancer incidence (4%). Addition of estradiol to 5α-dihydrotestosterone treatment did not markedly enhance prostate cancer incidence (14%), unlike adding estradiol to testosterone treatment which induced a 100% tumor incidence. Testosterone plus estradiol treatment induced a DNA adduct detectable by 32P-postlabeling, oxidative DNA damage (8-hydroxyguanosine), and lipid peroxidation at the site within the prostate where this treatment causes cancers, preceding later cancer formation. The non-estrogenic 4-hydroxy metabolite of estradiol, when combined with testosterone, induced prostatic dysplasia within 16 weeks and, after long-term treatment, a very low incidence of prostate cancer (21%). When an estrogen that cannot be hydroxylated (2-fluoroestradiol) was added to this combined treatment with testosterone and 4-hydroxyestradiol, dysplasia frequency after 16 weeks was doubled. These results strongly support the hypothesis, but additional definitive studies are needed which may identify new targets to interfere with these mechanisms that are clinically feasible in humans.

KEYWORDS:

Androgen; Estrogen; Hormonal carcinogenesis; Prostate cancer

PMID: 30877616 DOI: 10.1007/s12672-019-00360-7

[NPfisherman]

I believe you have endorsed UltraSoy extract because of its high levels of genistein...for people on ADT--castrate sensitive--this should provide no increased risk of worsening prostate cancer--Correct? and could even be helpful ??....However, in the instance of castrate resistance, should not all soy products be avoided--because as T levels rise, the estrogen like properties of any soy product could make things worse?? Or, am I overthinking this... (this disease makes me overthink everything...)

Thanks in advance for your insight/ advice on this issue...

Fish

[pjoshea13 in reply to NPfisherman]

Phytoestrogens have a low affinity for the nasty alpha estrogen receptor [ERalpha] but a high affinity for protective ERbeta binding.

In CRPC, ADT typically continues. In the absence of testosterone [T], estradiol [E2] can bind to ERalpha but cannot cause growth. E2 requires T and the androgen receptor [AR] for it to be a problem.

-Patrick

[cujoe in reply to pjoshea13]

Thanks to Patrick and the rest for posting all this new info today. But I'm afraid my head is spinning quite a bit as I try to connect the many dots.

So, assuming someone is NOT on ADT (but has been briefly in the past), has no prostate, has a PSA <0.1, with T in the 300-600 range . . . should that person avoid ALL soy products?? Thanks in advance - cujoe

[pjoshea13 in reply to cujoe]

There are breast & prostate lab studies that note a biphasic effect of genistein. Growth-promoting at physiological levels from dietary soy, but protective at pharmaceutical levels. That turned me off soy food products. You have no prostate, but think of your breasts.

Am I correct in inferring that you eat a lot of soy-based food?

-Patrick

[cujoe in reply to pjoshea13]

Not any more. Over time I have eliminated most heavily processed food in general, and soy isolates in particular. And while I might eat tofu and/or miso soup at a restaurant a half dozen times a year, I haven't used it at all in the self-prepared food that is 90 % of what I eat day in and out. (Anyone who reads labels on processed foods knows that soy is used in a seemingly endless variety of processed food-like substances.)

The only soy I consciously consume now is soy milk which I mix 40/40/20 with almond milk and coconut WATER. As I try to limit my calcium to no more than the daily RDA, I go for oganic/non-gmo store-branded soy/almond milks, since calcium is not boosted 50% above that of dairy milk like it is with all refrigerated national brands.

The best guidelines on diet still seems to me to still be those stated in Michael Pollan's book, In Defense of Food; i.e., "Eat Food, Not Too Much, Mostly Plants". Combine that with his "Food Rules" and no matter what diet you choose, you will be making better dietary decisions.

Michael Pollan’s 64 Food Rules are listed here:

vdocuments.site/food-rules-...

and you can read the full book here:

vdocuments.site/michael-pol...

Be Well - cujoe

PS. Patrick, I also like your Wasa bread crisps - and since they come from Europe, I trust that the grains used are not sprayed with Glyphosate as is most non-organic wheat and many other grains here in the US. Would you like some toxic herbicide with your sandwich, sir??

[cesanon]

Wow. Isn't that something 100 percent!

[mcp1941]

I am so confused about soy products. I am on Eligard and Erleada and my brain just isn't working 100%. I don't even try to read and understand abstracts any more. Too confusing! When I was seeing Dr. Myers he said to stay away from soy products. I think it was yesterday there was a thread about genistein. I wrote down the info about the LE Ultra soy extract. My wife saw the note and warned me about soy products. Now I'm not sure if I should order that produce. Help!

Mike P

[pjoshea13 in reply to mcp1941]

Hi Mike,

I think Dr. Myers was right in advising you against soy products in general - I don't know if he would have included the LE product.

I can't advise anyone to use high-dose genistein, although I do use the LE Ultra soy extract. And I wouldn't want your wife to get mad with me. LOL

-Patrick

[mcp1941 in reply to pjoshea13]

I completely understand about "advising". Now I just have to convince my wife that it is OK to take Ultra Soy Extract. My wife is an attack dog when it comes to following my treatment.

Thanks Patrick

[jdm3]

I'm glad you mention Avodart.... The article suggests "5α-Dihydrotestosterone, which cannot be converted to estradiol or testosterone, did not cause a significant prostate cancer incidence." To me this implies that minimizing the conversion of T to DHT with Avodart/Proscar is not necessary. The issue is the E2 and T balance.

That being said, I am about to stop ADT (eeeeek) and plan to start Avodart as my T recovers because..... well, just because a lot of anecdotal data seem to suggest Avodart might be a good idea. I also take DIM and plan to monitor my E2 levels.

Cheers,

Josh

[pjoshea13 in reply to jdm3]

Josh,

For men (or rats) without PCa, DHT (the 'powerful' androgen) is not a threat. When it is produced in prostate cells, it is quickly cleared. It has a narrow window in which to promote growth.

For someone who has been on ADT, a lot of things are altered. One must tread carefully. It is prudent to limit T conversion to DHT.

The recovery period for T is slow, so E2 dominance is an issue. DIM is a good idea, but it doesn't address an unfavorable E2:T ratio. E2>30 needs Arimidex IMO, but if T is low, I'd be trying to get E2<20 (but >12). Of course, T supplementation would speed you past a bad E2:T.

-Patrick

[j-o-h-n]

Aw Rats!

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 03/18/2019 1:27 PM DST

[Hidden]

There is something I don't understand: if estrogen is bad, how can some be doing well on estrogen patches instead of ADT for years? And what about DES therapy? Nobody could tell me their estrogen levels during therapy, but should be like premenopausal woman, so still quite high.

[pjoshea13 in reply to Hidden]

Testosterone [T] is needed for growth. With a huge dose of estrogen [E2], T production is shut down. In this case, E2 cannot spur growth.

With regular ADT, doctors are not concerned with E2, but they should be. A certain amount is needed for bone health. (E2 is mostly made from T in men.)

E2 is dangerous, IMO, when the E2:T ratio is out of balance. i.e. where there is estrogen dominance. This can be the case before ADT. & when on an ADT holiday.

-Patrick