Skin Patches vs. Traditional Hormone Therapy: A New Option for Metastatic Prostate Cancer?

[Maxone73]

I feel like...we will soon be all moved to estradiol!

A phase 2 study from the STAMPEDE trial found that transdermal estradiol (tE2) patches, when combined with androgen receptor pathway inhibitors (ARPIs), reduce PSA levels as effectively as luteinizing hormone-releasing hormone analogues (LHRHa) in metastatic prostate cancer.

Patients using tE2 had fewer hot flashes and lower hypertension rates than those on LHRHa, though breast tissue enlargement was more common. Estradiol may also help preserve bone density and lower treatment costs, making it a potentially safer and more accessible option for hormone suppression.

With further research, tE2 patches could emerge as a new standard in androgen deprivation therapy (ADT), improving both efficacy and quality of life for patients.

prostatewarriors.com/2025/0...

[janebob99]

Not to mention at a much lower cost !

[KocoPr in reply to janebob99]

Lol! That is an understatement!!!

[KocoPr in reply to janebob99]

Bob, do we know how fast tE2 patches lower T. I suppose during my ADT cycle of BAT i could use tE2 and darolutamide, then jump back on high T after one week ok clearing daro.

I wonder how the mechanism of action go. If I remember correctly this high dose of estrogen will lower androgen to castrate levels and the cancer cells androgen receptors will take up this estrogen and translocate to nuclease for transcription or not translocate?

My other concern is i have several mutations in the estrogen metabolism pathways that cause me to have a unhealthy high unmetabolized estrogen see paper by ercole calivisri and Elleanor Rogan. They have been studied estrogen and cancer for many decades.

Depurinating estrogen-DNA adducts, generators of cancer initiation: their minimization leads to cancer prevention

pmc.ncbi.nlm.nih.gov/articl....

———

Here is one of their older papers

pubmed.ncbi.nlm.nih.gov/172...

[janebob99 in reply to KocoPr]

Here's data that show testosterone levels drop precipitously over 2 weeks after initiation of estradiol patch therapy.

Regard your question about does estrogen cause cancer, all I can say is look to the 14-year PATCH study that showed metastasis-free and overall survival probabilities for E2 patch ADT were not worse than Lupron-based ADT, for over 750+ E2 patch users in the Phase-III study. That is pretty strong evidence against the hypothesis that estrogen causes prostate cancer.

Estradiol ADT works by reducing testosterone levels by disrupting the HPA axis signaling in a similar manner to LHRH agents, like Lupron. I'm not aware of estrogen being taken up and translocated to nuclease for transcription. I suppose it's possible, but I've never seen anything like that discussed.

Estrogen patches

[KocoPr in reply to janebob99]

Excellent discussion on E2. I enjoy this.

Oh i do not believe E2 patch is bad for prostate cancer once you already have it. What i am saying is unmetabolized estrogens before they even become E2 can CAUSE breast and prostate cancer.

Im a believer in the recent article on low testosterone can cause the dimerization of the androgen receptors to leading to mono activation of the AR which causes mutation transcription. That and this low T and unmetabolized estrogens creating and environment where prostate cancers can begin.

I definitely believe in the E2 patch and am thinking of alternating it with my high T BAT cycle.

Bob do you have a private group like on FB ? I am on your huge email group but it is difficult sometimes to follow threads or even create new threads.

[janebob99 in reply to KocoPr]

Hi, John.

I'm not a big Facebook user. So far, I just manage the large E2 email list. But, I understand what you are saying about following threads. I have so many projects going on that I can't start something new on Facebook.

I understand now what you are saying about hormones that can CAUSE cancers. Very interesting, and beyond my training.

Bob

[edfriedman in reply to janebob99]

Actually, it is an irrefutable fact that estradiol causes prostate cancer. It is impossible to develop prostate cancer without properly functioning estrogen receptor-alpha.

See: faseb.onlinelibrary.wiley.c...

They point out that prostate cancer results from very high local levels of estradiol (from high aromatase activity), acting on estrogen receptor-alpha, and not from serum levels of estradiol.

Also, although there is almost no estrogen receptor-alpha expressed in normal prostate epithelial cells, 94% of CRPC expresses estrogen receptor-alpha. They talk about ER in that article, but that was before estrogen receptor-beta was discovered, so that ER refers to estrogen receptor-alpha.

See: ncbi.nlm.nih.gov/pmc/articl...

Ordinarily, there is much more estrogen receptor-beta than estrogen receptor-alpha in early stages of prostate cancer, which means that estradiol is usually beneficial in those cases because estrogen receptor-beta helps increase the rate of cell death whereas estrogen receptor-alpha decreases the rate of cell death. However, in time, as mutations occur, in the presence of high levels of estradiol, any mutation that increases the amount of estrogen receptor-alpha greatly increrases the selective growth advantage for those cells.

[janebob99 in reply to edfriedman]

Thanks, Ed. Very interesting.

I naturally had high estrogen levels and high DHT levels, but low Testosterone, FSH, and LH levels (due to a pituitary microadenoma), for most of my adult life. Maybe that's what caused my PCa...

[Bacana in reply to edfriedman]

So because my husband is CRPC, he should not do transdermal E2?

[edfriedman in reply to Bacana]

I am not a physician so I cannot offer medical advice.

In theory, E2 (which binds equally well to ER-alpha and to ER-beta) is initially beneficial because ordinarily there is much more ER-beta than ER-alpha. However, continued use of E2 will give PCa with more ER-alpha a selective growth advantage so that they eventually take over the population and thrive in the presence of E2. Using a traditional form of ADT with the addition of transdermal estriol (which binds to ER-beta 3 times more strongly than to ER-alpha) seems like a reasonable option.

[Bacana in reply to edfriedman]

Interesting, we’ll look into this, thanks!

[PCaWarrior in reply to edfriedman]

So, theoretically, if one were to do ADT, use tE2 until signs of CRPC. Then switch to a GnRH drug? Perhaps combine with Zytiga.

Or of course just skip all the sides and use a modified BAT.

Edit: I should have read further down. Looks like you already answered this.

[PCaWarrior in reply to KocoPr]

It's variable. Average is as Bob stated. But in my own case it took over a month (T tests at 4 weeks and then at 5).

[pakb]

Interesting! Thank you. Wondering if they'd move someone like my husband- 8 years this August on ADT- to the patch. And wonder if it'd re-challenge (if that's the correct term) the cancer. He doesnt really have side effects anymore- very few hot flashes etc. But for bone and heart health perhaps. And his PSA is fairly steady but fluctuated in last 2 years. From 2 to .8 and back to 2 last month. Never been below .8 in the 7.5 years. Great info again Maxone73

[janebob99 in reply to pakb]

It's worth asking your MO to switch from Lupron ADT to tE2 ADT. The results of head-to-head Lupron vs tE2 PATCH study for ADT of both M0 and M1 men support that this is a safe and effective route to take. Show those papers to your MO.

[pakb in reply to janebob99]

My husband's oncology team is pretty open to our suggestions. We have great conversations about studies etc. His MO and the PA were at the conference last week so glad they keep up with research. Thanks!

[KocoPr in reply to pakb]

Don’t forget brain health. Testosterone is also converted to estrogen in the brain and with low T the brain suffers from lack of estrogen.

[pakb in reply to KocoPr]

Yes- just now noticing a few brain fog moments. He has continued to work successfully during the almost 8 years of treatment. But I know he's worried about it. He's just 57.

[dhccpa]

This is an exciting development. Expect major pushback.

[KocoPr in reply to dhccpa]

Big time pushback is right! I am surprised this trial was allowed to complete.

[dhccpa in reply to KocoPr]

Yes, an interesting experiment.