Bravo bringing up estradiol! The OP by "Horse" highlights the most common discourse around estradiol.
For anyone interested in this topic though it's worth understanding the two uses of estradiol in the context of prostate cancer.
These two uses are (1) high-dose estradiol as ADTreplacement for today's common ADT therapies [the topic above] and (2) low-dose estradiol as estrogenadd-back where estrogen has been suppressed as a side effect of today's ADT therapies. These two uses of estradiol are very different.
Note: When reading literature about estradiol and ADT it's not always clear which topic one is reading about. There is much more on estradiol as ADT replacement than estradiol as add-back therapy. (Interestingly there's a lot on estradiol in the context of therapies for women.)
(1) The use of high-dose estradiol "as ADT" in the context of prostate cancer has been tried in the past. It seems to have been stopped because of the development of better ADT therapies and because estradiol-based ADT via the oral route had nasty side effects where cardiovascular problems are concerned.
These problems have apparently been significantly ameliorated now because of the development of transdermal estradiol delivery via patch or cream, instead of via the digestive system. If I understand this correctly, estradiol is the subject of the PATCH study referenced by the previous reply. (This is not my interest - my main reason for commenting here is to ensure that the two distinctive uses of estradiol are on the table. From what I have read as a lay person, estradiol-as-ADT leads me to be wary of the long-term risks of this proposed therapy.)
(2) The use of estradiol on the other hand, at much lower doses, "in support of estrogen add-back", also seems to have potential. I'm interested because this proposed use seems to be justified in the same way that prednisone is prescribed with an ARPI to restart the production of glucocorticoids such as cortisol. All sorts of bad things happen in the body when you don't have cortisol etc. So prednisone is a great way of solving this problem. And no one seems to question that prednisone add-back is a good idea. As for the risks of higher estrogen levels, it doesn't seem to be a concern because prostate cancer isn't driven by estrogen.
But why would a man with prostate cancer want to return estrogens to the normal low level?
Because there are again all sorts of nasty side effects from not having a normal level of estrogen. Not having testosterone is one thing and then we just add to our body-out-of-whack problems by depleting estrogen too! The number one side effect of estrogen suppression is osteoporosis; apparently cognition may be negatively impacted too.
There's lots of literature on estradiol add-back for women in circumstances of various female medical problems. And there were a few isolated articles about estradiol add-back for men in circumstances of prostate cancer. But not much to go on yet.
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So here's a summary about estradiol for estrogen restoration in circumstances of prostate cancer therapies:
A) low dose estradiol can perform the function of estrogen restoration.
B) this is now safe to deliver via transdermal patches or creams and the previous concerns about nasty metabolites are gone.
C) at the low doses required to achieve estrogen add-back, this has nothing to do with high-dose ADT therapy replacement.
D) there is a significant benefit in restoring normal levels of estrogen specifically where bone loss and possibly cognition is concerned.
E) it would be interesting to have any experts comment on the validity of the comparison between the use of prednisone to restore glucocorticoids and the proposed use of estradiol to restore estrogens. Is the comparison between prednisone and estrogen therapies in the context of prostate cancer helpful and correct? Specifically are the circumstances, mechanisms, safety, results etc. as comparable as I am suggesting?
F) if this all makes sense it would be great to have some clinicians come up with a usage protocol in terms of mechanisms, dosage, timing, practices, blood marker tests and frequency etc. Or strong arguments why it's a bad idea.
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Maybe though this is just simpler than we imagine: men normally have some estrogen. It's important. And as an unintended side effect of prostate cancer therapies it is suppressed. And it's easy if one is careful just to restore normal estrogen levels. No big deal. And there's some important benefits from doing this. Very important benefits! Maybe it's not really a hard question at all.
Perhaps forum friend "Wassersug" could share some insights? Or pointers to research? Or also corrections, e.g. in terms of my references above to glucocorticoids -- which is a rather simplistic and even partial description of what prednisone does.
[I think I'll share this as a full post at a later date.]
‘From what I have read as a lay person, estradiol-as-ADT leads me to be wary of the long-term risks of this proposed therapy.’
I think for many men (like the OP) the long term side effects of the existing therapy are hideous enough for them to take that chance without hesitation.
The LHRH drugs (Lupron etc) are generally well tolerated by those fit and strong. This is the good news. The bad news is the fit and strong comprise about 15% of cancer patients over 65. Lupron greatly exacerbates virtually all major co morbidities.
ADT is hard on every man, but with relatively few exceptions, its side effects target those in poor health disproportionately. This is partly why there is such a clamor for alternatives.
I wonder how many Pca patients on Lupron will die from CVD, strokes, suicide etc while the Patch study rolls on. I know the data is important, but for many ‘lesser of evils’ probably applies here.
Fantastic comment London!! And great context and analysis!
(And for any reader: the biggest difference you can make is in the volume of exercise you do, both for strength and aerobics. Can't be mentioned too often.)
Very good summary JohnITM. Estrogen is essential to bone and brain health. With ADT there is always estrogen deficiency since it is made (aromatized) from testosterone. Low dose replacement via estradiol patch should be standard for all on ADT and is safe via this route.
MB - you aware of any jurisdictions where low dose estrogen replacement via estradiol patch is in place or even standard of care? There doesn't seem to be much literature on this yet.
POST FROM 7 YEARS AGO!!! (note: I redacted the UserID).
Transdermal Estrogen Versus Lupron
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7 years ago•1 Reply
Dr Myers latest vblog post [1], below.
He has previously spoken about very low dose estradiol [E2] (when on Lupron) for preserving bone health. Here he is speaking of high E2 doses to suppress testosterone [T].
In essence, since male E2 is largely a result of the aromatization of T, the male body responds to elevated E2, by cutting back on T production. Rather than use a fixed E2 dose, Dr. Myers monitors T & adjusts E2 accordingly.
Myers preferentially uses E2 in older men who might do very badly on Lupron, & on men who cannot tolerate the Lupron class of drugs, but he doesn't answer the question of E2 effectiveness versus Lupron. The Phase III PATCH UK clinical trial is expected to do that, although accrual is apparently slow.
Fantastic note j-o-h-n! I see in your second paragraph that the two separate uses of estradiol are both covered:
"He has previously spoken about very low dose estradiol [E2] (when on Lupron) for preserving bone health. Here he is speaking of high E2 doses to suppress testosterone [T]."
This is a major topic of my earlier note here -- the fact that there are TWO almost completely different applications of estradiol/estrogen/E2 as therapies in the context of prostate cancer. And the justifications and purposes of the two therapies are also very different. Personally I found it confusing in the begnning and I think a lot of people learning about this for the first time may also find the it confusing.
From the 40s until the 80s, oral estrogen was used for ADT. Oral estrogen has to be broken down in the liver and leads to cardiovascular risks.
Along came Lupron. We logically adopted it because the CVD risks were low.
But now we have transdermal formulas. However, Lupron (and other GnRH drugs) was already in the seat.
Transdermal formulas do not carry undue CVD risks. This has been shown in PATCH and in other studies.
In 2019 I used 0.3 mg/day - 0.4 mg/day of transdermal estrogen in lieu of Lupron. It worked. My testosterone was undetectable. I don't like ADT so stopped later that year. My PSA was <0.01.
We use this in our practice frequently. Doesn't get much attention in the US as it is easy, readily available and inexpensive, so no push or support from pharma or urologists. The ongoing PATCH trial data as it has been coming out from Europe is compelling and supportive of its use. Less ADT side effects and supportive rather than detrimental for bone health. Find an integrative oncologist if you would like to pursue this.
I'm 71 diagnosed with PC six years ago. Following RP PSA climbed from 1 to 12. Started high dosage Estrogen patches and both PSA and Testosterone went to Undetectable in eight months. No CV issues, no sweats only enhanced gynomasticia
Annoying side effect but in the absence of any other events I would rate QoL with Transdermal Estrogen patches as very high.
Gynecomastica (gynomastica or male breast growth) can be prevented by a single dose of radiation to each breast. This is preventative and cannot reverse breast growth, so must be done beforehand. Breast reduction surgery is also an option at any time.
FYI following RP and 35 sessions of radiation started on high level Estrogen patches for nearly 6 years. Initially using x4 100mg patches and changed 2 daily to maintain estrogen level between 1000-1500 and PSA dropped from 14 to .1 in ten months and Testosterone had dropped from .5 to .1 in five months. I had a script from my MO for twice monthly blood work to monitor very closely and he included FSH, LH and Alanine Aminotranferase to look for any adverse effect.
Since then patches have been gradually titrated to a lower concentration and PSA has been <.008 and Testosterone <.1 simply because lab reagents can't measure any lower. Interestingly on one reduction of Estrogen patch level PSA immediately rose very incrementally just to confirm the cancer is still active in metastasis and so returned to the previous level of estrogen patches and all has been well since then.
I had done initial research on standard ADT and didn't like what I read on CV issues as well as significant arrhythmia and night sweats in peers of mine. I provided clinical papers on Estrogen patch therapy to my MO, we discussed and he agreed to go ahead with a therapy he had never tried. The results have been exceptional and we are both very impressed.
A recent bone scan confirmed no bone loss at all, no CV or night sweats and only side effect is more pronounced gynecomastia but at 71 years doesn't really both me one way or the other.
PeterCraig2, if you are being treated in the U.S. I would very much like for my medical oncologist to speak to yours. Could we exchange information, please? If you send a "friend" request (or respond to mine if I can figure out how to send one) we can have share information privately.
It occurred to me that there are two populations with recent experience with estrogen therapies. Post-menopausal women requiring estrogen to maintain bone health, etc (maybe not the levels required as a monotherapy to suppress prostate cancer, as we are discussing here) and male-to-female transgender persons (who are, I guess, likely to require levels of estrogen similar to or higher than those required to suppress prostate cancer).
Obviously, both populations' protocols are FDA approved in the United States.
This begs the questions,
"Can oncologists in the U.S. 1) prescribe transdermal estrogen for prostate cancer patients and 2) have it approved by the payer (insurance company or, in my case, the Veteran's Administration)?"
"What are the health effects of those treatments in those populations and what clinical trials given to them (especially the M-F transgender persons) are applicable to prostate cancer patients?" That is, "what can we learn from these populations?" Particularly about bad side effects.
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