"Estrogens represent a under-recognized contributor in CaP development and progression."
This was blindingly evident at least 15 years ago. Now & then someone says so, but it never makes any difference. & doctors seem quite content to have aging male patients live with testosterone < 350 ng/dL & estradiol > 30 ng/mL.
Department of Urology, University of Illinois at Chicago, Chicago, IL, USA.
2
Department of Urology, Vanderbilt University, Nashville, TN, USA.
3
Department of Urology, University of Illinois at Chicago, Chicago, IL, USA. Mabern1@uic.edu.
Abstract
BACKGROUND:
Hormonal influences such as androgens and estrogens are known contributors in the development and progression of prostate cancer (CaP). While much of the research to the hormonal nature of CaP has focused on androgens, estrogens also have critical roles in CaP development, physiology as well as a potential therapeutic intervention.
METHODS:
In this review, we provide a critical literature review of the current basic science and clinical evidence for the interaction between estrogens and CaP.
RESULTS:
Estrogenic influences in CaP include synthetic, endogenous, fungi and plant-derived compounds, and represent a family of sex hormones, which cross hydrophobic cell membranes and bind to membrane-associated receptors and estrogen receptors that localize to the nucleus triggering changes in gene expression in various organ systems.
CONCLUSIONS:
Estrogens represent a under-recognized contributor in CaP development and progression. Further research in this topic may provide opportunities for identification of environmental influencers as well as providing novel therapeutic targets in the treatment of CaP.
PMID: 30131606 DOI: 10.1038/s41391-018-0081-6
Written by
pjoshea13
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Chris Woollams of Canceractive, amongst others, has been warning of the problems associated with high Estrogen, and particularly Estradiol levels, for years.
Yes, I have the same question (Dr. Myers liked to add small amounts via estradiol patches to patients on ADT. I also remember reading about a trial that's ongoing in the UK using large doses of estradiol as an alternative therapy to ADT.
Do the findings above contradict these approaches? Very curious...
DEAR Researcher, Life’s impossibilities! Last checkup, a T measurement was ordered but not done by the lab. It will be three months before we see the MO again. DHT and E2 are not ordered. With the expense and iffy, to say the least, results of Z + P and Xgeva injections beginning, we trust, in September, we cannot afford to fly off to Johns Hopkins, for example, to begin a new protocol. I haven’t finished reading all your posts this past month so might have missed this, but are you currently taking high levels of estrogenic supplements to inhibit PCa growth? (Les briefly tried Estradiol patches but abandoned them due to breast growth and discomfort.) At the moment we can only brag about matchless, monstrous zucchini growth. Froze twelve pints of shredded yesterday which will likely be discovered in the freezers after our passing.
I wish. One could search, but zucchini quality would suffer looking for the non-existent. Smiles back. Finally, we get rain. Les is downstairs near those freezers reconstructing a wren house. At his request, I spent a half hour looking for a usable plane but unearthed only a couple too fine to use. Mrs. S
Wow! That’s some business. Are you joking? What is not funny is what I discovered in another reply of yours regarding lung melanoma and half a million for Keytruda. Trusting you have the world’s best insurance. As you may have read elsewhere, our friend’s doctors were able to wrangle free Keytruda for her which resulted in reduction by half of lung tumors and a couple more years of life. Wishing you and your wife well at MSK!
Thank you for your wishes and wishing you both well as well (that was well done if I say so myself). Yep, Keytruda is really expensive ($30K per treatment X 15 I've had = $450K based upon my computer calculator). Thank goodness I have full Insurance coverage... otherwise I'd have to go back to my old job robbing banks. 3 words that will make you rich "stick em up". God speed for your friend with their lung cancer.
I just finished a year in a clinical trial using an estradoil cream applied daily. Some breast growth (minor) and minor breast sensitivity. No other side effects. T & PSA >0. Not sure what the future holds but seemed to work well for me.
Genistein from soy products has been shown to have a biphasic effect on PCa & BCa cells. At low levels (as from the diet) genistein promotes growth. High levels (from supplements) might inhibit growth.
Good question! Leswell’s MO recommends “popping” edamame at night, as the good doctor does for whatever reason, in order to alleviate our mutual hot flashes. We’ve only tried it a few times and liked the taste. Our quantity is probably just the right amount of phytoestrogens to enhance PCa growth. Mrs. S
Sorry Patrick but I am now confused as to whether or not I should introduce some servings of soy to my husband because I just watched Dr Greger’s video:
First, I should reveal that my view of Greger is somewhat negative. His role in life is to promote veganism by quoting studies that seem to support a vegan lifestyle. The problem is that he overstates the case when it comes to PCa.
The first paper he mentions is by Dean Ornish [1].
In this 2005 study, the men had Gleason scores of 6 or less. The intervention diet was an extreme low-fat (10%) diet, very high in fiber. In effect, it was also a calorie reduction diet. Those men saw a PSA decline of 4%. PSAs were restricted to the 4-10 range. 4% of 4-10 is a 0.16-0.4 reduction. These men had intact prostates & some of the PSA drop could have been due to improvement in BPH or cancer - we don't know - but for PSA to drop from 10.0 to 9.6 after a year in a Gleason 6 is not impressive. Would there also be a PSA drop in Gleason 7-10 men? Or men with PSA>10? The study was met with indifference in the PCa groups I belonged to.
Greger doesn't mention, or course, but Ornish used a "near vegan" diet that included fish oil. Vegans were furious.
...
A vegan diet can be unintentionally deficient in one of a number of nutrients, but it is also a diet that can be manipulated for intentional deficiency.
The insulin-like growth factor I is often upregulated in aggressive PCa. However, protein-restricted diets cause the body to limit growth factors. There are no complete proteins in a vegan diet except from soy, so protein availability can be controled by limiting intake of a selected essential amino acid & limiting soy intake.
From the fourth of the Ornish studies mentioned by Greger [2]:
"... given the recent literature indicating that high intake of protein rich in essential amino acids (animal or soy protein) may increase IGF-1, it may be prudent for men with early stage prostate cancer not to exceed dietary protein recommendations"
...
You wrote:
"He said little serving is good and more than 7 servings is bad. But yours is exactly opposite"
Greger is referring to soy protein. I was referring to genistein, a phytoestrogen found in soy. Soy-based supplements do not contain the protein.
Greger is warning men with PCa to limit soy intake. This can lead to control of IGF-I & that might trump the potential negative effect of low levels of genistein.
When I wrote: "testosterone < 350 ng/dL & estradiol > 30 ng/mL", I was referring to aging men without PCa. i.e. men with age-related drift of T downward & E2 upward. Doctors seem to think it is a natural situation with no health consequences.
Your "T is <.1 and Estradiol is > 1500" is an artificial situation due to treatment, where E2 cannot cause proliferation because of the near absence of T.
The E2 patch is a reasonable ADT approach - just as oral DES was for decades, but much safer.
As you are probably aware Estrogen patches are not a risk of liver damage, significantly reduces cardiac issues compared to most other ADT therapies and no night sweats etc.
It's also a very cheap therapy for those on a budget or uninsured. Unfortunately in Ontario OHIP doesn't recognize it as an approved therapy so OHIP won't cover it.
It seems like the near absence of T due to ADT trumps just about everything. Is that fair to say? Obviously we want to eat well, exercise, supplement within reason, stay vigilant, etc... But generally I just sort of assume that while I am on effective ADT it is time to learn and dial in a protocol that will hopefully maintain durable remission once I stop ADT. Then the E2, DHT, and other factors become critical.
"the near absence of T due to ADT trumps just about everything"? Yes. IMO.
When you stop ADT, it generally takes many months for T to recover. As T rises through the hypogonadal range, T becomes growth-permissive. This is when I believe that estrogen dominance can become an issue. At high levels of T, we rise above estrogen dominance. My own feeling is that after ADT, most men would benefit from immediate T replacement.
(Dr. Myers has said that in the IADT off phase, an increase in T above 350 ng/dL has no additional effect on PSA. This is in line with Dr. Morgentaler's Saturation Model.)
I have seen T described as being biphasic - promoting growth at lower levels but resisting it at high levels. I think that is incorrect & that the E2:T ratio is responsible for that impression.
Thanks Patrick. This is all so interesting. I just wish my health and longevity didn't depend on understanding all this and making the right decisions :-).
Estrogen patches are proven alternative hormone therapy to treat prostate cancer. I did it for 1 year on the Dr Meyers protocol with other drugs and had my longest remission ever. Helped recover from osteoporosis, eliminated all hot flashes, improved memory, a little sex drive, more energy, and better skin. My current oncologist suggests I continue 0.05 (Half of a 0.1 patch) to keep testosterone in check, help with osteoporosis, and keep hot flashes away , which I am doing.
Great discussion “abmicro” and everyone! Maybe we’ll reconsider the E patch inasmuch as there is nothing but tomato sauce, zucchini, and Jack’s pizza in the freezers. I like your results abmicro, improved bones and memory in particular. Mrs. S
i have been on T injections for almost 10 years because my level was 66 when it should have been between between 600-900. During this period, my Pca spot grew from the size of a BB to the size of a english pea, and psa varied from 8 to 15 to 21 to 32 an back to 18 with a gleason score only changing at 3/4 =7 to 4/3 =7 before I recently decided on focal laser ablation. I used the study from Sloan-Kettering as well as the study from Dr Abraham Morgantaler, his book " Testosterone for Life. My Urologist agreed with my choice to keep my levels high so I could feel great, work in the heavy equipment an strenuous power utility business plus perform well in my private life. The Pca that had developed was the slow type, which is gone now. Also, during this time I chose to change my diet to less sugar, increase my alkalinity with different foods, buying a "Tyent" alkaline ionizing water machine, adding minerals marketed thru "Xooma Worldwide" that also helped with water alkalinity, the addition of numerous vitamins an low THC hemp oil from "Hempworx".
I’m on a ADT3 holiday after 13 months but PSA is rising rapidly as it has each time I’ve gone on holiday with latest reading of .8 up from .3 two months prior. I’m waiting for GA PSMA 68 ct pet in October at UCSF. I’ve had oligomets since SRT in 2014.
I’ve read extensively about TRT from Friedman and Morgentaler wondering if it applies in my case. My RO has said “no way” and Morgentaler told me it’s not recommended. What are your thoughts?
Well, I would go with Morgentaler, but I wonder what it is about your case that makes him say that? Perhaps it's because your past holidays have been brief?
One expects PSA to rise as T goes from near zero through the hypogonadal range up to Morgentaler's saturation point (which I believe is closer to 250 than 350 ng/dL.) Without knowing how fast your T recovery is, it's hard to interpret a PSA increase.
But it's what happens after saturation that's important. If you now have androgen receptors [AR] that have gained function (amplification), TRT will not be a good idea. In a more likely situation, perhaps, where PCa cells have simply gained more copies of AR, restoration of T will knock down those inflated numbers.
In essence, your PSADT (doubling time) during the transition to AR/T saturation is irrelevant. PSADT after saturation is what needs to be tracked. Does it settle down or does it shorten?
Do you know what your T was at the end of your prior holiday?
Looks like you didn't see much of a T recovery before the prior holiday ended. Your PSA wasn't very high when you went back on ADT, but I suppose you were following a protocol.
Might be interesting to switch to BAT (Denmeade at Johns Hopkins). After all, another ADT cycle might get you into CRPC.
But getting back to your T levels: what is not widely understood by men on intermittent ADT is that T doesn't quickly bounce back, & rarely to the previous high, which often was not very high anyway. Dr. Freedland has said that that the ADT holidays are largely a continuation of T deprivation. TRT would give men the improved QOL that is expected from a holiday. Might it shorten the holiday much? For some, perhaps. But it would also speed men through periods of low T with estrogen dominance.
Each time when PSA climbed after “ holiday” to a level where scan would be effective I had a scan which found oligomets ( see my profile) which I treated with radiation and ADT3 . I’m doing the same thing now. Ga 68 PSMA ct pet is scheduled for Oct 18 at UCSF.
You’re right I’ve never really benefited from stopping ADT3. I was determined to be hypogonadal for 12 years before dx with PCa and was on trt with androgel which brought T to 750s. I also had BPH which I treated with finasteride . Meanwhile all that time I was baking Gleason 9 PCa in the oven.
Thanks for the link to the CT . It seems that they felt that trying and failing Zytiga was a necessary pre-condition before trying BAT. I’ve not yet tried second level ADT as I’m waiting for PSMA scan to see where PCa has found its new home. But I’ll get in touch with the CT sponsor anyway.
I started out with LEF's Ultra Soy. At that time (14+ years ago) LEF was suggesting the current dose (5 caps) but I think 4 times a day. Couldn't handle that so took the 5 caps only once a day. A few years later they dropped the dose to once daily.
It's a dose that seems designed exclusively for cancer. there is no othe reason to aim this high:
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