Back in 2004 the research on PubMed indicated that the androgen receptor [AR} was generally wild-type at diagnosis and that AR alterations were a consequence of castration therapy. Conversely, the estrogen environment was generally screwed up at diagnosis. The protective beta estrogen receptor [ERbeta] was down-regulated, while the growth-promoting ERalpha was up-regulated.
In addition, men with low testosterone had a poorer prognosis. It seemed that testosterone at high-normal levels could continue to regulate growth, while testosterone at low levels was growth-permissive, depending on the ERalpha:ERbeta situation.
Also, it seemed that for many aging men, estrogen levels were creeping up while testosterone was falling, year by year (considered normal who believe in the 'andropause'.) The male body responds to elevated estrogen by reducing testosterone production (because most male estrogen comes from the aromatization of androgen by the aromatase enzyme.)
So I figured that the estradiol:testosterone [E2:T] ratio might have significance. And that ratio does have significance in a number of studies - but none related to the prostate.
In the new study the E2:DHT ratio is used. Fair enough; that may be more significant than E2:T. E2 is the most powerful estrogen (how do women put up with it? LOL), while DHT is the most powerful androgen.)
"Imbalance in the estrogen/androgen ratio may affect prostate fibrosis through the TGF-β/Smad signaling pathway"
From 2020 [2]
"Prostatic inflammation has been suggested to be a major etiological factor for benign prostatic hyper-plasia (BPH) and lower urinary tract symptoms (LUTS). End stage of inflammatory diseases results in fibrosis, characterized by the excessive deposition of collagen. Growing evidence shows that the degree of inflammation is correlated with symptoms severity and disease progression of BPH"
That study reported that "Resveratrol reduces inflammation-related Prostate Fibrosis"
It is acknowledged that inflammation plays a role in PCa.
Almost any polyphenol or combination at the right dose will reduce inflammation, because their target is nuclear factor kappaB [NF-kB], but what is causing the fibrosis?
From the new study [1]:
"An imbalance in the estrogen/androgen ratio may affect prostate fibrosis. E2 may activate the degree of prostate fibrosis. In contrast to the effect of E2, DHT may inhibit the degree of prostate fibrosis, which might involve the TGF-β/Smad signaling pathway."
It is said that at a certain age, men start to have higher estradiol levels than their wives - certainly higher than when they married. But the PCa experts continue to view E2 as a female thing - nothing to do with men at all. It is an under-studied subject.
Apparently psychologists have noticed that as we age, men begin to adopt more personality attributes traditionally associated with women. We find our feminine side.
And vice versa. My wife certainly has become more assertive and "Alpha" with age.
Are you implying that the study is of 'dubious internet provenance'? Explain.
Do men become 'feminine' with age? Men lose 1-2% of their testosterone every year, beginning in the early 30's. That is undoubtedly going to have an impact on a lot of things, but testosterone [T] alone does not define masculinity.
For many years I was on a cycle of 3 months T followed by 3 months castration. There was a feeling of well-being in the T phase. Libido took a while to kick in; seems that T injections don't flip a libido switch. None of my habits changed. The castrate phase was fine (it was short) but with less sunshine somehow.
My wife says that I became more edgy in the week after T injections.
In the castrated phase, did I feel feminine? I don't really know what that means. You have moved in another direction - please elucidate.
What defines a feminized man? You are going to have to give examples of feminine behaviour and every woman here is going to jump all over you. LOL
Perhaps rather than describing it as "more feminine" it might be better to describe it as "less masculine," in the animalistic sense of becoming less aggressively "toxic."
Younger males seem far more prone to be attracted to "stimulating" activities like bar fights, fast cars, fast women, etc.
I am not young (58) love bars, have a fast car and enjoy the company of young women. I have a wife and two young female companions I travel with but no children. So guess it isn't happening to me
Or maybe it has... I'm guessing you don't love bars because it's where you pick fights, you don't drive your car in ways that cost you your license, and... well, you've already given some descriptions of your relationship, and it doesn't sound like a "fast women" scenario to me at all. Sounds downright "slow" -- mature, stable and longer-term -- and NONtoxic!
Not really, I have been in two fights in the last 6 months in bars over disrespect of women and it is not uncommon for me to drive 130 on way to Vegas or Phoenix. Doctor put me on meds to make me less aggressive. Not proud of it but it is where I am in my life.
"for many aging men, estrogen levels were creeping up while testosterone was falling"
I am still confused by what process this occurs, if in fact "most male estrogen comes from the aromatization of androgen." In other words, if E2 comes from T, how does lowering T end up increasing E2? It seems like BOTH should get lower as T gets lower.
Does it have anything to do with the propensity for aging men to be adding fat and losing muscle?
The problem is visceral fat. You can have belly fat that you can pinch & that's not so bad, but internal fat (such as periprostatic fat) is hormonally active. It is able to secrete estradiol.
Visceral fat can occur in slim people. Follow a very low fat diet (high carb) diet with lots of fiber & it is likely to be lowish calorie but with glucose spikes, where excess triglycerides get dumped around intermal organs. Slim outside; fat inside.
For those not on a low-fat diet, it is the high-carb low-fat snacks, etc. that do the same thing. US supermarkets are full of LO/NO-Fat products that did not exist when we were young (& slim).
When estradiol [E2] goes a bit high, the body will increase SHBG, wich preferentially binds to T, & reduce T production. This does not address the visceral fat problem, so the man goes into a downward spiral where lean mass decreases & fat increases. Men our age are generally out of the breeding/child rearing years, so evolution has done nothing to help us survive longer. We are surplus to requirements. Women have the "grandmother gene" - they are often still active with grandchildren. That buys them 5 more years than us.
& diets often have no effect on visceral fat.
One can tackle the glucose spikes with Metformin.
We should certainly reverse any insulin resistance.
One can follow Barry Sears ZONE approach where every meal & snack has the proper carb:fat:protein ratio that does not result in a glucose spike.
Perhaps with a ketogenic diet? ...
"Although visceral fat is usually more difficult to shed than subcutaneous fat, some studies have shown that a low carb or ketogenic diet are effective for visceral fat loss."
Patrick,Couldn't understand much of what I was reading until the conclusion: “Conclusions: An imbalance in the estrogen/androgen ratio may affect prostate fibrosis. E2 may activate the degree of prostate fibrosis. In contrast to the effect of E2, DHT may inhibit the degree of prostate fibrosis, which might involve the TGF-β/Smad signaling pathway.”
Yes. An understudied subject that requires more inquiry.
A lot of the Men here on BAT. or mBAT are using E2 patches to help in the balance of High to Low T. Somehow this all ties together.
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.
Early Results from Transdermal Estrogen PATCH trial - 2
Study reports direct targets of ivermectin in prostate cancer
AST/ALT ratios. How much should we be paying attention to this? 
The human microbiome and its link in prostate cancer risk and pathogenesis
