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

Maxone73 profile image
16 Replies

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...

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Maxone73 profile image
Maxone73
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janebob99 profile image
janebob99

Not to mention at a much lower cost !

KocoPr profile image
KocoPr in reply tojanebob99

Lol! That is an understatement!!!

KocoPr profile image
KocoPr in reply tojanebob99

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 profile image
janebob99 in reply toKocoPr

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 profile image
KocoPr in reply tojanebob99

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 profile image
janebob99 in reply toKocoPr

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 profile image
edfriedman in reply tojanebob99

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 profile image
janebob99 in reply toedfriedman

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...

pakb profile image
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 profile image
janebob99 in reply topakb

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 profile image
pakb in reply tojanebob99

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 profile image
KocoPr in reply topakb

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 profile image
pakb in reply toKocoPr

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 profile image
dhccpa

This is an exciting development. Expect major pushback.

KocoPr profile image
KocoPr in reply todhccpa

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

dhccpa profile image
dhccpa in reply toKocoPr

Yes, an interesting experiment.

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