Tall_Allen: Most of what I've read on tE2 is on castrate resistant patients. How can that be? How does it work at all if they're castrate resistant, meaning that their PSA is rising despite castrate levels of T?
Does it delay castrate resistance in castrate sensitive men? ADT author and patient Richard Wassersug has been on it 20 years.
What do the latest studies report on the efficacy, SEs, etc.?
Why isn't it FDA approved?
This is an extremely big deal for people who tolerate ADT SEs poorly and are facing with lifetime "sentences."
Thanks, as always.
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Horse12888
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The UK PATCH trial hasn't ended yet, but has not been terminated either, so it looks to be a success. The FDA isn't likely to approve transdermal estradiol before the study ends. imo
I found it interestind that in a UK study paper of last year [1]:
"Forty-one patients with CRPC and steroid-resistant prostate cancer were eligible for this dose-escalation study of transdermal estradiol. A starting dose of 50 mcg/24 hours was applied and increased if prostate-specific antigen (PSA) rose > 5 ng/mL in steps to 300 mcg/24 hours. The primary endpoint was PSA response, and secondary outcomes included incidence of thromboembolic events and progression-free survival. Patients who progressed were offered diethylstilbestrol."
{It has been known for some time that a significant percentage of CRPC men will respond to Diethylstilbestrol [DES] - but estradiol [E2]?}
"Five (13%) of 40 patients had > 50% PSA reduction for at least 1 month at any transdermal estradiol dose. No venous-thromboembolic events were observed, and responses plateaued at 200 mcg/24 hours. A correlation between PSA response and rising sex hormone binding globulin was seen.
{I'm surprised that it was as high as 13%.}
"Fifty percent of patients subsequently responded to low-dose diethylstilbestrol."
There are men in this group who have been able to switch to E2 (without having CRPC). Perhaps some will respond.
Incidentally, I was able to get a script for DES (in the U.S.)
It reduces testosterone, but whether it provides the same survival advantage and delays progression as the goserelix will eventually be determined. I believe it will, but that is just my personal belief - proof is required.
Even then, there will be many unanswered questions, like: are outcomes further improved by adding second-line androgen-axis inhibitors (Zytiga, Xtandi, or Erleada) that are proven to delay progression and increase surviva? Also, can tamoxifen still be used to prevent gynecomastia without impairing estrogen's oncological effectiveness?
As for the mCRPC situation, high dose estrogen provides 2 potential oncological benefits:
(1) it reduces testosterone production by acting on the hypothalamic-pituitary-testicular axis (remember, the upgraded androgen receptors of the cancer are more sensitive to testosterone in the mCRPC state).
(2) it may have a more direct effect via estrogen receptors (and possibly prolactin receptors)
The FDA and the NHS (UK) are only allowed to approve medicines for which there is documented proof of safety and efficacy. So far, there is good proof of safety, which was the big concern. Estrogen pills were killing men because of increased blood clots when it was first used in the 1950s. The transdermal estrogen doesn't have the same disadvantage. Some patients are using it without FDA approval.
Tall Allen, what can be the effect of high-dose transdermal estrogen on prolactin receptors?I ask since I will be starting tE2 and also considering starting cabergoline, a prolactin inhibiting drug.
Estrogen has a bigger anti-prolactin effect than cabergoline. Unless you are taking cabergoline for some other purpose than to inhibit prolactin, you are only increasing side effects by taking both.
Early on, before I had given up on sex, I was taking cabergoline to inhibit prolactin on the basis that someone said it would improve my capacity for sex. It didn't work for me, but did that make any sense whatsoever?
I was on Eligard, and even now, years later, my RP and its repair operation has rendered my penis no more sexually sensitive than my index finger.
Yeah, it, bromocryptine and apomorphine were promoted as aphrodisiacs for a while but only seemed to work in a minority of men. They based it on its dopaminergic properties. But I think they failed to consider that negative feedback quickly destroys any positive effects. Steroid hormones usually have both positive and negative effects and are biochemically tightly controlled. More is often not better and is frequently worse. (BTW- many fail to understand this about Vitamin D, a steroid)
Are you certain... searching I don't find prolactin-lowering effects of estrogen intake, on the contrary at times the opposite. However, I didn't find anything on prolactin and transdermal estrogen. Hoping and believing you are right so I don't have to use cabergoline.....
My understanding is that high doses of estrogen in men completely shuts off prolactin secretion by negative feedback to GnRH. This is similar to the way that Lupron (a GnRH agonist) works by causing a surge of testosterone.
Anti-prolactins have been tried in PCa and have failed to show any effect. I know that Leslie Costello has been promoting this. But he has so far failed to gain much support.
TA: I’m in a support group where one of the men plans to use E2 patches for ADT. He plans to also take cabergoline to reduce prolactin in order to prevent gynecomastia. Your comment raises the question of whether the typical estrogen patch level for PCa inhibits or stimulates prolactin. I found an article stating that estrogen therapy in post-menopausal women increases prolactin (journals.lww.com/menopausej..., so I’m curious about why you’re certain that the E2 level in the patch will be sufficient to suppress prolactin (as a super-agonist).
This is for men, not women. In men, excess estrogen causes inhibition of GnRH by negative feedback. (The estrogen set-point in women is obviously much higher) GnRH inhibition results in the complete shut-off of prolactin, LH, and testosterone. It is a much more effective way to reduce prolactin than taking cabergoline. In fact, if you try to decrease prolactin directly, it will probably result in a paradoxical surge of prolactin. Steroids are tightly controlled by negative feedback.
Prolactin causes milk production in mammary cells, but does not cause an increase in mammary cells - only estrogen does that.
Well, it appears that Snuffy Myers thinks cabergoline reduces gynecomastia in med using tEd for ADT. He prescribes a small amount3x per week, says it helps his patients but doesn’t eliminate it. It’s around 7:21 in this video from his site: askdrmyers.wordpress.com/20...
He can say whatever he wants. If it is real, he should publish. Snuffy says a lot of things - some true, some not. When women get pregnant, their breasts grow early on due to a surge of estrogen. Estrogen inhibits the action of prolactin. Breasts do not produce milk until after women give birth and the estrogen (and progesterone) goes back down, allowing prolactin to act.
Regarding FDA approvals, don't drug companies file the applications/petitions that include studies proving the drug is effective against the illness or condition it’s treating? In other words, the FDA does not go looking on its own for studies, but rather those studies must be actively compiled and presented as part of an approval process sought and initiated BY a drug company or other entity.
I can't imagine why any drug company would spend the time and money to seek approval for a cheap, generic treatment that would only serve to cannibalize sales of other potentially high-profit drugs. So it seems to me the question is not why E2 isn't yet approved for PC, but how and why will it EVER be?
E2 can of course be used off-label to treat PC, but if my understanding of the approval process in the US is close to being correct, there is no logical sequence of events that would result in PC treatment becoming an "approved indication" for the use of E2. (I expect the story will be different in the UK.)
Right. It is for this reason that we'll never know if there are food supplements or other remedies like CBDs that are effective in fighting this or any other disease.
As far as tE2 is concerned, speaking strictly for myself, I couldn't care less if it's FDA-approved, and, especially, that it's not the standard of care. If it's not inferior, or even if it's anywhere close, and it prevents my having to live the rest of my life in the physical and emotional condition that came with Eligard, it's a deal. I had to laugh when one of my MOs told me that it might cause heart attacks; he asked my why I found that funny, and I explained that I spent two years PRAYING for a heart attack.
I've been considering an LUPRON alternative for my CRPC for the last 9 months.Weight gain is mounting for my body and I disgusted with it. Disgusted with it's impact of my exercising. I just started a new Trimfast weight reduction medically supervised program 3 weeks ago.
Questions:
1. tE2 option for me would work as well as Lupron/Eligard?
2. Since I'm already on a Max blood thinner Rx dose daily Xarelto, I should be so concerned about venous-thromboembolic events?
3. Am considering advancing to stage of Orchiectomy, in lieu of continuing my Lupron/Eligard 90 day injections. Less SE's??
4. Am I on the wrong track for suggesting or urging my Med/ONC to go the tE2 path?
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