I have reposted this from last year for the benefit of those of you who may have missed it.
Transdermal oestradiol for androgen suppression in prostatecancer: long-term cardiovascular outcomes from the randomised Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme.
Summary
Background Androgen suppression is a central component of prostate cancer management but causes substantial long-term toxicity. Transdermal administration of oestradiol (tE2) circumvents first-pass hepatic metabolism and, therefore, should avoid the cardiovascular toxicity seen with oral oestrogen and the oestrogen-depletion effects seen with luteinising hormone releasing hormone agonists (LHRHa). We present long-term cardiovascular follow-up data from the Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme.
Methods PATCH is a seamless phase 2/3, randomised, multicentre trial programme at 52 study sites in the UK. Men with locally advanced or metastatic prostate cancer were randomly allocated (1:2 from August, 2007 then 1:1 from February, 2011) to either LHRHa according to local practice or tE2 patches (four 100 µg patches per 24 h, changed twice weekly, reducing to three patches twice weekly if castrate at 4 weeks [defined as testosterone ≤1·7 nmol/L]). Randomisation was done using a computer-based minimisation algorithm and was stratified by several factors, including disease stage, age, smoking status, and family history of cardiac disease. The primary outcome of this analysis was cardiovascular morbidity and mortality. Cardiovascular events, including heart failure, acute coronary syndrome, thromboembolic stroke, and other thromboembolic events, were confirmed using predefined criteria and source data. Sudden or unexpected deaths were attributed to a cardiovascular category if a confirmatory post-mortem report was available and as other relevant events if no post-mortem report was available. PATCH is registered with the ISRCTN registry, ISRCTN70406718; the study is ongoing and adaptive. Findings Between Aug 14, 2007, and July 30, 2019, 1694 men were randomly allocated either LHRHa (n=790) or tE2 patches (n=904). Overall, median follow-up was 3·9 (IQR 2·4–7·0) years. Respective castration rates at 1 month and 3 months were 65% and 93% among patients assigned LHRHa and 83% and 93% among those allocated tE2.
157 events from 145 men met predefined cardiovascular criteria, with a further ten sudden deaths with no postmortem report (total 167 events in 153 men). 26 (2%) of 1694 patients had fatal cardiovascular events, 15 (2%) of 790 assigned LHRHa and 11 (1%) of 904 allocated tE2. The time to first cardiovascular event did not differ between treatments (hazard ratio 1·11, 95% CI 0·80–1·53; p=0·54 [including sudden deaths without post-mortem report]; 1·20, 0·86–1·68; p=0·29 [confirmed group only]). 30 (34%) of 89 cardiovascular events in patients assigned tE2 occurred more than 3 months after tE2 was stopped or changed to LHRHa. The most frequent adverse events were gynaecomastia (all grades), with 279 (38%) events in 730 patients who received LHRHa versus 690 (86%) in 807 patients who received tE2 (p<0·0001) and hot flushes (all grades) in 628 (86%) of those who received LHRHa versus 280 (35%) who received tE2 (p<0·0001).
Interpretation Long-term data comparing tE2 patches with LHRHa show no evidence of a difference between treatments in cardiovascular mortality or morbidity. Oestrogens administered transdermally should be reconsidered for androgen suppression in the management of prostate cancer.
Funding Cancer Research UK, and Medical Research Council Clinical Trials Unit at University College London.
Written by
E2-Guy
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My understanding is consistent with yours; however, the majority of men that are using tE2 as opposed to LHRH agonists such as Lupron or Zoladex appear to be experiencing a more comfortable lifestyle with fewer side effects. The study did mention that the "Long-term data comparing tE2 patches with LHRHa show no evidence of a difference between treatments in cardiovascular mortality or morbidity." Other than the significant reduction of hot flashes mentioned, most men don't appear to have the fatigue, bone density loss (since E2 is greatly responsible for bone health), muscle mass loss, and mood swings. After almost four years on tE2, my life has not been negatively affected in any way whatsoever. One example is that my ALP was way above the normal high, and is now consistently in the 80s. No one has complained about me exhibiting mood changes. I am experiencing no fatigue, and my gym routine (obviously not what it was like 20 years ago) is still not disappointing. I can't benchpress 300 pound 'babes' like Nalakrats with his 17 inch biceps routinely does, and I'm certainly not stupid enough to try arm-wrestling with him as he has challenged me to do, but I think that I'm doing OK for a 78 year old buzzard! Actually, today is exactly two months from what I hope will be my 79th orbit around the sun.
The other day I was looking through some old family photos and stumbled across this 35 year old photo of my son and me, so I took a pic of my arm just to see how much I have deteriorated.
TE2 achieved the same rate of castrate T levels at 93% by 3 months, and half the long term cardiovascular adverse events rate. Sounds like the winner to me. Better preservation of bone density is the kicker. Tamoxifen prevents development of the gynecomastia.
This is very interesting and I admire that you have doggedly pursued this for yourself and shared your experiences with us. Your stamina at 78 is amazing as well as that head of hair!
They left out a KEY factor - how did the men FEEL on the two treatments? Maybe I missed it, but I don't see that in the write up.
I had Lupron (3 years), and I felt terrible. Exhausted, fatigued, low energy, hot flashes, and rapidly deteriorating bone density. Most of those are symptoms of not having ANY sex hormones, specifically not testosterone, but also no estrogen. Men and women have both, just at very different levels.
Estradiol patches end up suppressing testosterone, yes, but importantly it is REPLACED as our sex hormone. The body is ok with either sex hormone really, as long as it is at a sufficient level.
Running a man's body on estradiol is a little like running a car on ethanol instead of gasoline. They both work, but a little differently.
I feel GREAT on estradiol patches! Good energy, good mood, bone density is fine, no hot flashes, better sense of smell than I can ever remember, and memory doing very well. And full disclosure - yes, I developed gynecomastia, a common side effect. I'm more careful in my clothing choices, and it's not a problem.
This study is so abstract, only looking at very basic "measurables". Don't overlook how important it is to FEEL our best too.
Hello VHRGuy. I am considering trying transdermal estrogen. I currently recieve Zoladez once a month. My PSA has been at . 19 for several years. Can you you combine zoladex with oestradiol?
I'm not an expert on various ramifications of hormone therapies. Having said that, Dr. Charles "Snuffy" Myers gave his patients on long term testosterone suppression estradiol patches to offset the side effects of not having testosterone.
The patches at a sufficient dose themselves can apparently successfully suppress testosterone, which is what the PATCH study was exploring as I understand it.
So yeah, I think it wouldn't be a problem at all to add at least a low dose of transdermal estradiol patch. Dr. Myers suggested 0.025-0.050 mg/day patches, changed twice weekly.
I'm on quite a bit higher dose than that so that I feel my best, and I DO! (For what it's worth, I also had surgery to remove the twin sources of my testosterone, so I don't need any testosterone suppression anymore.)
Thanks so much for VJRguy. Im going to talk to my oncologist. Im in the public health system in El Salvador and the doctors here seem reluctant to divert from SOC.
Yes, I hope that your doctors are open minded. It is a bit out of mainstream to add estradiol. Some doctors are reluctant because of some cardiovascular issues when they tried estrogens many years ago. However, those trials were NOT using today's technology. They were using equine (horse) estrogen, from pregnant mare's urine, and were not "bioidentical" to human estrogens. Also, the oral route, with pills, has other issues due to liver metabolism of estrogen taken by that method.
The transdermal estradiol, bioidentical, and NOT taken orally thus bypassing liver metabolism, are a new approach. I would suggest obtaining a copy of the PATCH trial to discuss with your doctor. Maybe this would be helpful!
My MO never billed for my Eligard injections, the hospital billed me. I'm not convinced the doctors make any money on the injection, regardless of cost...The hospital enjoys the proceeds IMO.
It's hard to minimize my medical cynicism, but I can't help but agree there is a profit motive involved. Pharma gets HUGE money for the drug. Medical facility/Doctor make money from administering the drug. My Lupron Depot bill was something over $400 for administering the shot, and around $2500 for the injectable, for a 6 month shot.
The medical system is making a LOT of money from guys on permanent T suppression. For around the same cost as ONE of those injections, a simple surgery can permanently suppress testosterone production by removing the sources. But then the medical community loses the years of ADT medication profits they would otherwise receive.
As an interim measure though, a decent level of transdermal estradiol will do the job pretty well, at far lower cost. I pay out-of-pocket for my estradiol patches. With a GoodRX coupon, my patches cost me about $145 for a 3 month supply. Injections would be even less, and can supply higher doses if the bloodwork suggests that.
Just a thought... for those on permanent continuous T suppression, there are other ways than frightfully expensive LHRH agonists/antagonists.
Thank you Patrick for posting this! Nal mentioned that you found a source for DES. You obviously are the 'Guru' of PCa research! I have more faith in your findings than most doctors.
Something to note: "Respective castration rates at 3 months were 93% among patients assigned LHRHa and 93% among those allocated tE2."
What's going on with those 7% of guys in either group (of which I am apparently a member) where the expected feedback mechanism fails, and does not sufficiently lower T levels?
I guess it must be be related to abnormalities in hormonal signaling, perhaps involving estrogen receptors, but really don't know.
After tE2 failed to get me to low enough T, I went on Firmagon (GnRH antagonist). After a few months we added abi+pred, and THEN switched the ADT drug to Lupron (LHRH agonist). T dropped to 4, nearly right away.
So I have never tried to reach castrate T on a LHRH agonist alone. My current T of <3 could result just from the abiraterone.
I have read that even a small percentage of men using Firmagon (GnRH antagonist) can fail to reach castrate T at 3 months, but that number is much lower than the 7% mentioned for the two modes discussed in PATCH.
I've been on Transdermal Estrogen patches since Sept 2016 and Tst and PSA have decreased over time and both are now unmeasurable at <.4 and <.008 respectively. ALT is low and steady and several years ago had a reference baseline for DHT and Chromogranin A if needed in the future. Had a bone density scan last month and apparently all is fine and I'm not shrinking at all or getting brittle bones which is nice to know.
No cardiac issues, night sweats or any other issues at all apart from slight man boobs I can live with. As someone else said this study does not seem to have evaluated QoL criteria which is a significant component of any therapy option.
FYI I believe this Report is of preliminary outcomes and final is not yet released as I nag my Oncologist in our meeting every three months and he's not seen it yet. I am looking forward to release of the final report as it may prompt my public healthcare insurance in Ontario to add it to their formulary and so remove my prescription costs for this.
It's all good and urge every guy to look into this option as it works and no downsides.
It's great to hear that you are having success with tE2 (a natural hormone, not the typical, chemical ADT) therapy! 'VHRguy' pretty much 'hit the nail on the head' in his reply above. I really feel sorry for all of the guys who are experiencing the numerous, nasty side effects generated by Lupron/Zoladex injections. I'm sure their doctors know damn well that transdermal E2 is a simple, effective and safe form of ADT; however, there is little money in self-administered patches or gels. Fortunately I can buy most pharmaceuticals here without a prescription, and get blood tests by myself...haven't been to a doctor in 4½ years. My total cost of PCa treatment is less than $20/month.
Wishing you continued success with this effective (however, not SOC) therapy,
Spare a thought for us over protected men suffering in the dark down here in OZ, the backwater of the world, because they will not approve these patches.One would have to wonder why?
This Transdermal Estrogen patch could replace the Zoladex shots that I get every three months. I have my appointment with the Oncologist coming up in March and I will definitely ask for this treatment. I am still castrate sensitive, does this determine if the patch works. Does it make any difference if you high volume of Mets. Like Peter I live in Canada and I am sure this is not standard of care and I would have to pay for it up front. Thanks
I have been using E2 gel (instead of The Patch) which Richard Wassersug (who also lives in Canada) has been using for over 20 years. He just told me that the price has recently doubled from about $50 to $100/tube. A tube (less than $20 here) lasts me about 3 weeks. Since you are still "CR", I would hope that it will help.
Yes but maley2711, the evidence here is obvious with men using it, but I take your point.We will have to wait many years for that evidence to be approved, or is it just all about money? It is cheaper than all the other treatments & their side effects.
I don't care if it is ever approved...it is doing the job for me without the all too common side effects of Lupron & Zoladex. It probably never will be approved in The US since there is no money in it!
i'm sure everyone is different. i was on estradiol .1 mg/day to attempt to reduce hot flashes. my blood pressure which has always been very good shot up. not sure yet if it was the estradiol but had not added anything new at that point.
Perhaps using it in conjunction with Lupron or Zoladex could be a problem; however, .1 mg/day is such a small dose that I question it would do anything. I use about 3 mg/day and my BP is always normal.
After reading the tE2 paper in Lancet and reading the replies to my ADT question posted Monday, I decided to postpone my 1st Lupron shot until my MO could walk me thru the pros and cons of Lupron vs tE2 therapy. My PCP who focuses on endocrinology supported the delay so I can get more info. If I decide to go the tE2 route, my PCP will help if my MO is unsupportive. This feels like info overload, but I am fortunate that with 0.4 PSA I have time to carefully consider my therapy options.
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