Does anyone know of recent studies, clinical trials or Standard of Care (SoC) protocols using or studying estrogen gels, sprays, ointments or patches as hormone therapy for Prostate Cancer, particularly micrometastatic cancer that has not spread beyond the pelvic region?
I am in discussions with my oncology team. Orgovyx or transdermal estrogen is being discussed. Orgovyx is SoC in the U.S. I am finding that estrogen has less objectionable side effects.
I seek 1) ways to convince my care team to use estrogen in my care and 2) any reasons I should NOT pursue this protocol (I don't want to "shoot myself in the foot" so to speak).
Thanks in advance.
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Lost_Sheep
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Tall_Allen says that there are no such trials. Perhaps he is not aware of the results of a Phase-II randomized trial (PATCH) comparing TransDermal Estrogen (TDE) to Lupron ADT in high risk men with PCa.
Aside from being equally effective at castrating men (to very low testosterone levels), TDE has much fewer side effect compared to Lupron, including: no osteoporosis, no bad lipid changes, no increased fat deposition, no increased insulin resistance, no memory loss, no hot flashes, and no decrease in libido.
TDE, however, does not stop muscle loss, loss of muscle strength, or ED. TDE also can cause increased gynecomastia (enlarged breasts). I don't know about fatigue or depression, however.
If you private chat me your email address, I will send you 10+ papers on TDE.
The Phase-III results of the PATCH trial will be published this Spring. Stay tuned!
You also may want to look up Professor Wassersug, who has been doing estrogen gel therapy for 20+ years and he swears by it. He's got some YouTube videos about ADT in general.
I plan on doing TDE myself instead of Lupron or Orogovyx ADT. I will meet with an endocrinologist next week to confirm this plan.
Bob
Estrogen, Testosterone, and PSA versus time for TDE therapy
I was referring to the Phase-II results, which have been published. I read that something like 67% of men were stage T3, which makes the data relevant to Lost_Sheep's situation.
All of the older papers regarding the use of Oral Estrogen (DES) are also relevant, in general. The main downside of the oral estrogen was blood clots and other cardiovascular effects
Sadly, survival wasn't very good with oral estrogens. It created fatal blood clots. That's why anti-androgens and later, GnRH agonists replaced them. Blood clots occurs because of cancer too, so we don't know why those men died.
That's interesting that cancer causes blood clots. I had an unprovoked pulmonary embolism last year (which coincides with the likely existence of my PCa). I'm on Xarelto now. Have you written anything about blood clots and PCa?
"Until we have that data, estrogen use is experimental." Yes, not Standard of Care (SoC) IN THE U.S.A..
As I understand it, it is commonly used elsewhere in the world with as good or better results than the SoC used in the U.S. But it is being studied in the U.S.
I found one paper that was intriguing because it sought to investigate whether transdermal estrogen could induce an immune system response through cytokine activity. A cohort of men destined for prostatectomy was recruited for 28 days of estrogen therapy, then the surgery. Comparison of their pre-treatment biopsies and post-op pathology (before and after the 28 days) unfortunately did not reveal the hoped-for results and the study was never published. I contacted the lead researcher and he confirmed this. He also wrote that estrogen does work as effectively as standard ADT, with fewer side effects which were primarily breast pain and enlargement.
What I desire is to use transdermal estrogen for my prostate cancer (unless there are contra-indications of which I am not aware), either in my clinical setting or in a clinical trial. And soon.
Any research that would support my argument with my oncologist (who is receptive to my input at present) would be helpful and appreciated.
Here's a paper by Hedlund, from 2008, about parenteral estrogen injection (IM) that shows no difference in 6-year cancer survival metrics, compared to standard ADT treatment, and no blood clots.
Here's a paper from Hedlund, about parenteral estrogen injection (IM) that shows no difference in 6-year cancer survival metrics, compared to standard ADT treatment, and no blood clots.
It is not compared to standard ADT treatments. It is compared to flutamide ± decapeptyl. Flutamide is never used anymore, and decapeptyl is not approved in the US for PCa.
Here's a small study from 2012 on the use of transdermal estrogen for castrate and chemotherapy - resistant prostate cancer. It was safe and well tolerated, they said. 40% of patients had a decrease in PSA, which is impressive, given the severity of their PCa.
Micrometastases are tumor cells or groups of tumor cells too small to be detected by current imaging tests. My May 25 2023 PSMA-PET scan detected no detectable cancer outside the prostate gland, but seminal vesicles and perineural invasion was detected. Obviously there was some escape of the cancer by the time of my surgery 5 months later. It was probably there at the time of the PSMA-PET, but too small to be seen.
Two lymph nodes examined from the protatectomy pathology were negative for cancer.
Thanks. I understand. That's always a possibility.
The plot I sent you earlier shows how fast and effectively estrogen patch/gel therapy lowers testosterone levels to castrate levels. (The influence of estrogen was discovered by Huggins in 1941). That's all the doctors care about (low T). It shouldn't matter if low-T is accomplished by Lupron or Estrogen...both achieve the same chemical result. The key difference is that estrogen has fewer side effects.
Show them that plot !
I plan on doing that with the endocrinologist next week.
The original published graphs and the papers that published them would be more helpful. Also more readable. You have my email address already and I have the .pdf files you sent. I suspect it is one of them. Help me out with a title, please?
I see that you are in the U.S.. Are you planning on estrogen therapy covered by insurance or will you be self-pay or am I missing something?
I'm having trouble getting a good link to the Ockrim paper. I'll keep looking. But, here's another paper that I just stumbled across. It's a review from 2008.
We have to remember that oral estrogen was the gold standard treatment for chemically treating PCa for decades before they invented Lupron. The problem with oral estrogen was formation of blood clots, which the new methods (transdermal patches or gels, or IM injections) don't have because the estrogen doesn't pass through the liver.
Great discussion. I was able to convince my MO to prescribe a low dose Estradiol patch for me about a year ago. It wasn't designed to lower PSA or treat the cancer but to address bone density concerns and hot flashes. I'd been on Lupron for 3 years at the time. Presnetly doing BAT. Interesting how modulating Hormones can cause the cancer to slow down it's march. Hopefully this approach can be used in an adaptive fashion for longer remissions.
last January I met with Dr. Denmeade. He said that I would be an excellent candidate for BAT. I used Propionate instead of Cypionate. He has a much shorter half life. I was indeed a responder.
Here's a paper about a pill form of estrogen that causes a complete remission of castration-resistant prostate cancer when used as mono therapy. Doctors don't seem to mind using it after ADT fails.
"Here's a paper about a pill form of estrogen that causes a complete remission of castration-resistant prostate cancer when used as mono therapy. Doctors don't seem to mind using it after ADT fails."
Yes, I read that this weekend. 80 year old man in otherwise good health. Prostate intact, no bone mets, but some lymph node involvement Gleason 4+5 and survived quite well from 2011 to 2013 where the trail ends. (Did he die of automobile accident?, Just quit coming? Move away?) Apparently clotting was a concern, so he went on a low-dose aspirin for blood thinning.
It was only one guy.
This paragraph from the study is concerning, however. It seems to indicate that this particular estrogen therapy usually has a short period of effectiveness ("several months"), making a two-year remission worthy of comment, hence this paper.
"Estrogens are sometimes used for castration-resistant prostate cancer (CRPC). However, the duration of the response to estrogens is limited to several months. We report a patient with metastatic prostate cancer who had complete remission for almost 2 years after administration of ethnylestradiol."
It also remains that blood clotting is problematic. I wonder also about this case being unique. It is not. I know of at least one man who has been using estrogen gel for two decades. So, why is this case valuable to this discussion? Is there something about oral ethnylestradiol?
Any oral form of estrogen, DES or ethnylestradiol, will have problems with blood clots because they go through the liver. That's what great about transdermal Estrogene, it doesn't go through the liver. I'm not sure what they mean by "the duration of the response to estrogens is limited to several months". Perhaps they stopped using estrogen after a few months? The PATCH study is looking at 5 and 10 year survival rates, but I don't know what duration of estrogen therapy they used. We'll find out soon.
I’ve been using estradiol patches , (3) .1 mg. changed weekly, since 2019. They’ve kept my testosterone <3.0. I read the PATCH trial in UK and asked my urologist about it and he agreed immediately to prescribe them. In 2021 I added Xtandi when psa started to increase. Psa has been <.1 since then. Man boobs are the only side effect of estradiol. Much much better than Lupron or other SOC ADT !
I have been advised that muscle loss (and concomitant fatigue) is also common among estradiol gel/patches. But easily counteracted by weight-bearing and aerobic exercise, diligently done (especially before starting the hormones). I have not found much research on the matter.
Can you shed any light from your doctor, your research or your personal experience?
TDE is used internationally by countries that offer national health care because it has been proven to drive T to castrate levels without the accompanying SEs of American pharmaceutical ADT drugs that are common in America. The principle reason for the use of TDE in countries with national health care is it’s low cost and proven benefits. TDE gel is manufactured from plants primarily in Israel and is a available OTC in many countries very inexpensively.
But, because of the long established links between the American pharmaceutical industry that manufactures the ADT drugs and the doctors who distribute their drugs, there is a financial disincentive to allow the use of TDE. A single settled lawsuit against Abbott Lab years ago for its manufacture of oral estrogen was settled instead of decided through a jury verdict.
This settlement essentially eliminated the distribution of estrogen within the American medical establishment overnight. The threat of medical malpractice litigation against doctors and their employers has caused a boycott on TDE. TDE essentially disappeared from pharmacy shelves. Good luck trying to get any doctor who adheres to the AMA SOC and whose employer is a COE or a large hospital group from giving you a prescription. You’ll need to obtain it OTC from another country. Wassersug is an American working and living in Canada. He is a fine source of information of the benefits of TDE.
I'd be very curious as to the different interactions between Estrodial and SOC Hormone treatment on the cancer dell. Could they be used sequentially or in some adaptive approach? Do their mechanisms effect the cancer differently?
T3bN0M0. PSMA-PET scan May 2023 showed no metastasis outside the gland, but clearly showed seminal vesicle involvement and perineural invasion. Prostatectomy late October 2023, the surgical pathology showed positive margins but the removed lymph nodes were negative. Gleason 5+4=9. Clearly I have some metastasis in the region.
PSA the day before surgery 13.3
PSAs since surgery,
1.33 (at the surgery center, same lab as the 13.3 test)
“I am finding that estrogen has less objectionable side effects.”
By ‘finding’ it, I assume you mean reading about it, folklore etc.
What side effects are you most concerned about?
ADT side effects vary greatly due to factors such as baseline testosterone, length of ADT course (whether fixed or lifelong), age (older men typically have naturally lower levels of T and often don’t feel sides as much), and simple heterogeneity.
However, the single greatest factor is biological health, specifically strength and cardiovascular fitness. Those who are more fit and strong have fewer and less severe side effects regardless of ADT type. Often none.
Keep in mind that regardless of which path you choose, substantial muscle wasting and accompanying fatigue will very likely occur without intervention (resistance training). At the very least this muscle loss is severe and very difficult to recover later if allowed to proceed.
Also as I’m sure you know, gynecomastia is very common with transdermal estrogen, though it can usually be successfully mitigated.
“I am finding that estrogen has less objectionable side effects.”
By ‘finding’ it, I assume you mean reading about it, folklore etc.
I don't think anything I found could be counted as folklore. I admit some compelling evidence is anecdotal, though (Including Professor Wassersug's 20 year tenure on transdermal estrogen). But most of my findings/discoveries are from medical journals. I have studiously avoided giving credence to popular press and any sources of questionable origin.
I am sure if I cited any spurious "evidence", it would undermine my efforts to be taken seriously by my medical care team, aside from the potential for actually leading my thought processes astray. So, I vet my sources carefully.
I am type 2 diabetic, so metabolic disturbance is a major concern. I am 75 (and hope use my good genes to match my parents' tenure of 90+ years), so bone density is a concern. Cognitive function, too. Anemia, sure. The only side effect of concern with estrogen is breast pain (mastodynia/mastalgia) and breast growth (gynecomastia). I care little for cosmetic body changes at my age and have discussed the mater with my partner-she says it makes no difference to her. Pain, I would not care for but as a tradeoff against diabetes or bone density loss, I will take that risk.
On the other hand, one of the members of a local support group is taking Orgovyx and has experienced only hot flashes (mild) and fatigue (which he attributes to the radiation he is taking at the same time). Of course, he is just one and his experience is still only 4 months along, so has no long-term results. Peer-reviewed medical journals carry more weight with me.
There still isn’t enough data to ‘find’ that transdermal estrogen has less objectionable side effects. For some it does no question. For you who knows?
Overall it is likely preferable, but many can’t obtain it, especially in the US. What is known is that most do not take the exercise piece seriously, especially weight training. Wassersug himself refers to it extensively in his writing and talks about it, but of course he is Canadian.
All I am saying is that strength and fitness habits have a considerably greater influence on side effects than delivery system of T deprivation.
Weight-bearing exercise and aerobic conditioning are a given. Is there any research that suggests hot flashes are mitigated by exercise? That seems most likely to me.
My main concerns, though, are osteoporosis and muscle loss (clearly weight-bearing exercise helps here),. Also, congnitive effects,
My libido has mostly been mental, so I think I can handle reduction in the physical libido loss.
I already had erectile problems, so that is not an issue. (Unfortunately my penile implant's reservoir was a casualty side effect of prostatectomy)
hot flashes? I live in Alaska, so might not be a problem at this time of year.
Blood lipids are currently under fair control, but both parents had heart problems (at 90 years). So this needs to be watched.
Insulin resistance - I am type 2 diabetic so this is a major concern.
Weight gain. Muscle gain is good. Fat gain (especially abdominal) is not.
Mood swings- I am a pretty calm guy, so not too worried. But habitually melancholy, so maybe I should be ?
Fatigue would be a problem, but I do not have a job, so maybe not. But snow shovelling, home maintenance and mowing may suffer.
Gynecomastia at 75 years of age and with a steady partner will not be a problem the breast pain sometimes associated with estrogen ADT might be.
Most of the research I have read suggest that transdermal estrogen lacks all those side effects except the breast growth and pain.
There is also some indication (but far from proof) that prostate cancer does not develop resistance to the treatment. I think this really does merit scrutiny.
Weight bearing exercise and aerobic conditioning may be a 'given', but it's also a given that most don't do it, or not nearly enough anyway. It is effective against all the side effects, though to widely varying degrees depending on overall health and what exercise is actually occurring, how frequently how intense etc. All probably also a 'given' to you but it always bears mentioning. If it were a drug it should be the first one off the shelf.
Again, expect fat gain unless exercising more and eating less. Metabolism is slowed so both are required to prevent it. It's good for preserving your cognitive ability and the mitigating the melancholy as well.
"Most of the research I have read suggest that transdermal estrogen lacks all those side effects except the breast growth and pain."
This is false. Do your homework.
With the estradiol you may fare better with the hot flashes and insulin resistance, as well as CVD issues.
The fatigue is another matter. Muscle loss is the driver of the fatigue, not what ADT drug you take. Same with fat gain. Testosterone suppression lowers metabolism, regardless of method.
Thanks for caring enough to take the time to reply. I appreciate your perspective and believe you are correct that exercise, a good diet, general robust health will enable a person to withstand/tolerate/reduce the side effects of ADT or any treatment, including surgery and advanced treatments like chemotherapy, etc. And the disease itself.
Your advice on my statement "Most of the research I have read suggest that transdermal estrogen lacks all those side effects except the breast growth and pain." that it is false, "This is false. Do your homework. " lacks specificity. I am doing the best homework I can think of. Do you have any advice about how to better my efforts?
Thanks for applying the light of scrutiny. All research needs that and I really do appreciate it.
Your diligence is being rewarded, and I can’t blame you a bit for pursuing the Estradiol. I imagine you have read Wassersug’s book or even perhaps talked with him? He is very accessible and obviously a good authority on the matter.
As long as you keep in mind that T suppression ‘is what it is’ it should be clear. The estradiol can only help so much. All the LHRH drugs act similarly on the muscles, and unless you intervene, the resulting fatigue can be very debilitating.
Lifting is the perfect antidote. Estrogen as ADT should be widely available for sure, but beyond the few positive differences it’s known for, there is no colder ice so to speak. Great luck to you!
London441, yes I have read Professor Wassersug's book AND talked with him. He has been very generous with his time. I even had contact with researcher and clinician at Fred Hutchinson Cancer Center in Seattle who had done an interesting research project on estradiol looking for how it might increase immune system suppression of prostate cancer.
I am unsure of the meaning of the phrase "there is no colder ice".
Just a humorous (depending on your view) way of saying improvements on a given model past a certain point are superfluous, of no consequence etc.
But I can agree that if any man has a superior experience, or even a positive placebo effect from any alternative form of ADT it's a plenty good thing. Certainly no doubt very unfortunate that Pca finds testosterone so life giving., and even more unfortunate that it eventually makes its own if deprived of it.
The capacity of prostate cancer to manufacture its own nutrients in the absence of its preferred nutrient (testosterone) has been mentioned in some of the literature I have read. Of course, this is how castrate-resistance develops.
There seems to be some mechanisms of estrogen that decreases prostate cancer's ability to do this. Not specifically mentioned as a feature in anything I have read. But an intriguing concept, yes?
Professor Wassersug's 20 year tenure on transdermal estradiol could be confirmation that at least one version of prostate cancer is unable to become castrate resistant (or that estradiol may have some mechanism that suppresses the cancer's ability to become castrate-resistant. If I were a researcher, I think I would propose looking in that direction.
Or it could be a placebo effect. The mind is a powerful organ and might be able to suppress the errant prostate cells all by itself. The mind does regulate many systems in pathways as yet not fully studied.
But I am not ready to hang my hat on hypnosis yet.
There are two different uses for transdermal Estradiol in the context of PCa. Here are some posts and replies mainly concerned with estradiol as "estrogen addback". Scroll up and down to see the full dialogues.
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.
The major side effect of transdermal estrogen therapy appears to be significant risk of gynecomastia from high doses of estrogen, as well as loss of muscle mass and muscle strength (because you are being castrated).
I'm suggesting that men go beyond their Urologist/MO and get the estrogen themselves from estrogel.com. Estrogel.com provides an MD that write prescriptions to Estrogel. Problem solved!
Thanks for the reference, Janebob99. I am not quite willing to go beyond my oncology team's recommendations If I cannot convince them, I will be going with medical advice.
I may be timid, but I consider this prudent. The U.S. Veteran's Administration is the payer for my medical care and I feel that going against medical advice (AMA) is risking more than I am willing to lose.
But, I will contact them to see if supporting data from their MD will persuade my oncology team to recommend it. So, thank you.
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