NCCN adds transdermal estradiol to its prostate cancer ADT guidelines

@marko49
Thanks Marko for the update 👍 , it is very much appreciated : ))).

You are kind of a "pioneer" in this area 🚀 : ))) and we are all rooting for you : )) !!!

@toomany Estradiol Initiative has a page with some charts about gels and patches. I haven't figured out how to interpret one of them yet. If you send in a question to the site they'll answer it. I attached the chart I'm referring to.
https://estradiolinitiative.org/for-clinicians/costs-and-effectiveness/

@toomany I've read from some people who have contacted Dr. Wasserburg directly at the estradiol initiative and he reportedly writes back quickly. He has used the gel/cream for years as has Dr Shellhammer. May be worth reaching out to them directly. There IS some very specific guidance on the site as well uner the section for medical practitioners.

@marko49 Dr. Wassersug says there is increasing interest showing up as questions to their website. I think they still personally answer but at some point if there are too many people inquiring they won't be able to keep this up....

@climateguy As always, my thanks for your continued insightful and helpful contributions here, but let me start by apologizing for the sheer length of what follows. It's a bit verbose, and above and beyond what the average forum member cares to know, but hopefully, it will be of some help to those interested in this topic of tE2-ADT.

Now, as you might expect, given my own demonstrated interest in the subject, I am familiar with the Estradiol Initiative website and much of the information provided there, and in-fact, I had previously viewed the specific chart that you've referenced here. However, I must say, I had not looked at it nearly as closely as I should have, because on second glance, it certainly does answer several key questions.

On its face, at least for me personally, the core subject of converting patch concentrations of tE2, to gel concentrations, would seem to be rather simple and straight-forward. By example, if the Patch/Stampede trial guidelines called for four (4) patches (marketed as delivering 0.1 mg of tE2), applied roughly twice weekly, then by extension, it would appear that a comparable gel application, would simply be 0.4 mg of total tE2, in a small volume of gel (lets say 0.4 mg/mL), with 1.0 mL volume of gel being applied, also twice weekly.

The problem is, I'm told by numerous sources including manufacturers and pharmacists, that for some unknown reason, the absorption dynamics differ from a patch to a gel, purportedly by a factor of 10x (i.e., tE2 in patches being absorbed 10x more efficiently than from gel). Unfortunately, none of these folks have been willing to stand by this estimated formulation factor, nor have any been able to provide documentation to support such a conversion factor. Perhaps more importantly, that 10x figure appears to differ exponentially from what is seen with commercially available gels, which are often (by example), 0.1% (i.e., 1.0 mg tE2 delivered per single mL of a gel packet weighing 1.0g). Needless to say, whatever the true or most accurate conversion factor may actually be, I remain reluctant to proceed with any special order gel formulation, until I can achieve more reliable clarification on the matter.

Lastly, regarding the graph of Serum E2 levels vs. Patch Strength and/or Gel Volume that you referenced here - while its helpful in several meaningful ways, this graph is also problematic on several levels: . . .

First and foremost, it lists 'by name' five (5) different brands of estradiol gels, many (if not most) of which, are available in different (variable) concentrations, which were not specifically identified as being used in the studies depicted on this graph. In other words, only the total volume of gel used was specified, NOT its concentration of tE2 (was it 0.025%, 0.01%, 0.06%, 0.1%, etc.?), making it essentially impossible to extrapolate to the patches used, which were specifically cited as delivering in units of ug/24 hours.

Secondly, of the total twenty-six (26) triangular and round multi-colored data points illustrated in the graph (red, blue, yellow, lime, dark green, etc.), all but three are for 'gels' of unspecified concentration, but more importantly, all 26 were data points from post-menopausal women (not male prostate patients). And while the results for the only three (3) remaining data points (which are in-fact associated with males), appear to be linear, they were from 'patch' use (not gel), and they were at relatively insignificant serum E2 levels, well above the 100 pg/mL range of testosterone, needed to achieve castration (<50 ng/dL).

Anyway, this next and final point doesn't help resolve the potential long-term availability issue often associated with patches, but if all else fails, there are commercial tE2 gel products readily available out there, that contain both practical volumes of gel (1.0 mL), and at suitably appropriate ('deliverable') levels of tE2 (0.1-1.0 mg), to effectively mirror the daily Patch/Stampede application protocol, depending upon the volume applied.

@toomany You could send a question in to Estradiol Initiative. (E2-I). Richard Wassersug has said he prefers gels. Richard has been very focused on helping PCa patients with questions about tE2 clarify their understanding.

Also, there is a reference list on a poster E2-I presented at AUA 2025. This poster contains the graph. I've assumed the reference list on the poster contains a paper that explains the graph. I haven't had time to check this out. I attached the poster.

I have been doing some research for E2-I and I could ask Richard, but he and all of the principals are extremely busy at the moment so I haven't bothered them. I'm also swamped with work, and I have a month's supply of patches.

@climateguy Thank you again, and yes, understood on all scores. Continued best wishes to you, and please know that like all others, you are appreciated here.👍

Before I get into the Estradiol Inititative (tE2-I), and the great folks involved there, I think its important to note that regardless of source, much of what one may hear, read or learn, regarding disease urgency and treatment approaches, or likely survivability, is of mixed relevance, depending upon one's own case specifics. That's rather self-evident.

For example, if I consult with eight different physicians, researchers and "specialists" in any given field of medicine, I'll likely get ten to twelve different opinions . . . either my situation is serious and urgent, or its not . . . I should be on this ADT, that ADT, or both . . . I should take this med or that, and I should plan on taking it for months, years, or for-life, etc., etc. My point being, no matter who we consult, or how many opinions we obtain, in the end, we and our decisions, stand alone. All we can hope for, is "guidance".

Now, that said, I have indeed communicated with Richard Wassersug (of the tE2-I), on multiple occasions. He has been consistently and incredibly giving and sharing of both his time and expertise, each and every time. And yes, he (himself) has been on transdermal estradiol (tE2) for decades, switching from patches to gel, once he firmly determined the proper dosage needed to keep his testosterone level at bay, which is precisely the approach that everyone should take.

However, as you have aptly indicated here, given the increased popularity of tE2-ADT as a treatment modality, he and the folks at the tE2-I, are very likely to be overwhelmed with recent inquiries. Further, while he is a perfectly gracious guy, who is happy to share his personal experience and professional "opinions", he himself will readily admit that he is not a licensed physician, and therefore, he cannot (strictly speaking), recommend the usage or dosage of any specific medication.

Hello
I have started estradiol patches 3 weeks ago because I didn't want the negative side effects from standard ADT. 4 patches at a time changed twice a week. I had 3 treatments of low dose breast radiation to help alleviate breast enlargement. Some mild soreness in that area but I've been told it subsides. Hoping for the best and wishing you the best.

Just to clarify, the gel or cream forms of estradiol require daily application in order to maintain steady blood levels. The patches release medication consistently for three and a half days.

I'm just about to start on tE2. I have a month's supply of patches. The reason I'm interested in gels is because of the national patch shortage. Since the NCCN guideline change on happened a few days ago, a significant new demand from PCa patients has yet to develop.

FDA and the patch manufacturers appear to be unaware there may be this new factor to consider when they attempt to predict what the future demand will be. As of now some predict several years of shortage for patches because of the difficulties of adding and getting FDA approval for new manufacturing facilities. So, things could be even worse than this.

So, if a guy wants to stay on tE2 and no patches can be found, gels will be the alternative. They are easy for compounding pharmacies to produce if brand name gels become scarce. Patch production is unlikely from compounding pharmacies.