My onco continues to resist prescribing low dose E2 to help minimize some of my ADT SEs. Following my last appointment he suggested progesterone as an alternative.
- Has anybody here had success with using progesterone while on ADT?
- Any reasons to steer clear of progesterone?
Thanks
Can you ask your MO for studies to back up the use of progesterone during ADT?
We have some decent data and mechanisms of action for estrogen during ADT. I haven't seen much of anything for progesterone.
Without data it is risky to tamper with your hormones.
I will ask.
My concern is I have read that progesterone can promote oncogenic effects in prostate cancer. Not being a doctor or a scientist I don't try to interpret the research unless the findings are obvious.
It hasn't been proven but so far the evidence doesn't look too good for progesterone. A clinical trial examined the therapeutic use of a progesterone receptor antagonist for CRPC.
I use a modified BAT program. Almost like clockwork I become irritable and have joint pains when my testosterone is low. And almost like clockwork, after I slap on a 0.1 mg/day estrogen patch the issues go away within hours.
What is the difference please between estradiol and progesterone for low-dose estrogen add-back? (Recall that side effects that might be ameliorated by estrogen restoration include especially devastating acceleration of bone loss!)
Some progesterone converts to 17-OH-Progesterone to Androstenedione to Estrone to Estradiol.
So if you want to increase estradiol to reduce bone loss, you could dose up progesterone, or better, 17-OH-Progesterone, or even better Androstenedione, or even better Estrone. Or skip the mess and go straight to Estradiol.
If you decide to go up the chain be careful. Weak evidence exists that progesterone and most of its derivatives are harmful for PCa patients. Estrone might be the worst of the villains in the chain.
If you use a low dose estradiol patch (e.g. Climara) you don't have to deal with the unknowns of the other hormones.
But, if you try estradiol and it doesn't work for you, and you try progesterone and it does work then I would favor my QoL and take the progesterone.
Warrior - this is good information you have shared.
Based on what you wrote though, why wouldn't anyone just go straight for an Estradiol patch "to avoid bone loss"?
Because as you say with progesterone there's "a mess", "villains", "harmful derivatives" and "unknowns". Quality of life is mentioned, but only seems to be associated with estradiol.
And given that estradiol is available by a simple patch, and that millions of women already use it, why not go right to that? Progesterone seems like a dodgy detour.
From my vague memory I looked up "Occam's razor": "If you have two competing ideas to explain the same phenomenon, you should prefer the simpler one" 😃 In the absence of any other information, I think William of Ockham would prescribe the patch.
John, I agree. From my reading there seems to be a higher risk from progesterone than from E2, but according to many oncologists the science isn't in yet to support prescribing Estradiol. Don't know if this is a carryover from when estrogen was replaced by ADT as a treatment, or just an abundance of caution.
This is getting really interesting here Carlos. I'm getting the impression that many oncologists could be out of date. And ignoring something that is very beneficial, low risk, and low cost. And with lots of evidence.
1. I believe they're still confusion between E2 as ADT replacement and as estrogen add back.
2. There may be lingering prejudice because of the side effects of oral E2.
3. The focus for winning the battle against prostate cancer (testosterone suppression and resistance especially) overwhelms questions of side effects such as estrogen suppression.
4. The money isn't there of course.
5. I'm interested in whether the comparison between estradiol add back on the one hand and prednisone add back for glucocorticoids on the other hand etc. is useful and powerful. I think it is.
6. As for an abundance of caution, estradiol is used by millions of people worldwide every day for exactly estrogen add back. They are women of course. Seems to me one could go to one's physician and say I have low estrogen, which even men need, and then the physician prescribes it! (One should admit that the risks might be extended however to a subtle involvement with the prostate cancer process. From what I read this could be a serious issue, in the long term, if you want to use estradiol as ADT replacement.)
I've realized most of my comments on HU are as replies and then they get lost. I think I need to repost them as root comments.
John:
Feedback I have received from earlier posts and comments have convinced me that this is indeed a significant issue. If E2 can keep us healthier (QoL), we will be stronger for future treatment. In addition, I have heard from several men whose mental SEs caused them to discontinue ADT, even when they new it would shorten their lives. That's where I had come to before finally getting my onco to change me to Firmagon.
I think there should be a mini online conference or something (2 hours?). Maybe we have a reputable clinician speak? A short agenda and short PDF takeaway for physicians.
AGENDA: define topic and clarify confusions, summary powerful benefit, inventory of pros and cons, simplified science, actual good quality vetted references, the damage of low estrogen for men, protocols for administration and ongoing, brief history of the topic and why not a higher priority etc.
There should be sponsors. And a pre-conference review with knowledgeable people and experts to make sure the whole thing is on-message. Networking.
Okay I think it could be done in 3 hours. Also part of the project plan would include follow-up and leverage. Of course this all assumes that the proposition is viable!
Good idea John, but not sure how to go about initiating something like this. Five years ago I would have been all over the idea, but my cognition and motivation have really been hammered by 3 years of ADT.
That was me in 2019. Willing to die rather than continue ADT. Four months was very hard. I haven't heard of anyone who handled it worse than me.
My MO and I think that we might have found a way out.
PCW, Thanks. What is the way out that you have found? Is it low dose Estrogen?
Low dose estrogen certainly helps.
But the way out is not SOC. We only have one good trial to rely on (BATMAN).
I'm following a modified BAT program.
Re: reason 2: I lost count of the number of men who told me that they asked their MO for transdermal estrogen and were told that estrogen increases CVD risks.
We have clinical data for the use of estrogen for ADT. I am not aware of clinical data for estrogen add-back. For that we have science (biological mechanisms and well-studied effects of estrogen on bone, muscle, mental health and joints).
My MO is open to ideas that do not have 100% proof. Fortunately for me she is very empirically driven. Some MOs want the guarantee before they prescribe. My candid opinion is that some MOs are not very bright.
(Sad - I'm still thinking about the MO who prescribed two weeks of Casodex to remove the T flare that Orgovyx causes)
I won't judge the intelligence of my MO (but not shy at all about judging my Uro's IQ), even though I am sure that he has judged mine. I'm sure that my MO has filed me under "annoying patients with lots of questions."
Intelligence aside, I do think that he is exceedingly cautious, that's why it threw me when he offered progesteron.
In case this is not clear to people, your example of your MO prescribing Casodex as an example of not being very bright is because Orgovyx, along with other GnRH antagonists, does not cause testosterone flare. Is this correct understanding of your point?
100% agree.
Try estrogen, if it doesn't work think about alternatives.
Megace is sometimes used to lessen hot flashes. The downside is it's an appetite enhancer - expect to gain a lot of weight. It also causes gynecomastia, as estrogen does.
Thanks TA.
I may be looking at the wrong treatment, but I have really struggled with some of the SEs from ADT. After 2 years of first Lupron and then Eligard, I could no longer tolerate the effects they had on my mental health. I suffered from irrational thoughts, difficulty regulating my emotions, and severe cognitive impairment. I have always been very even tempered and light hearted, but during that time I stayed angry, got aggressive quickly, and avoided driving out of fear of a road rage incident. My anxieties dominated my mornings, and I was ready to quit ADT.
My oncologist switched me to Firmagon and I’m tolerating it better, but I still don’t feel like myself as my thinking and memory are greatly diminished, and my emotional swings and anxiety are a part of my daily life.
I don't think progesterone will help with that. Maybe a mood stabilizer?
Hi Carlosbach,
I recognize myself in what you are writing. I had to start therapy and go on anti depressants for the first time in my life while on ADT.
I highly recommend therapy - as well as anti depressant (not SSRI) if needed.
Ditto for my husband. Processing the emotions that surfaced due to ADT with a therapist resolved it, and he's fine tho still on ADT. I have my husband back. It sure was a crazy-maker, so I feel for you.
Sorry to hear that your husband also struggled. I know what my poor wife went through, and it was unfair to her for sure.
Thanks Mike. I am working with a counsellor, but during my final 4 months on Eligard it felt like my brain could no longer process correctly. I would wake up in the morning and lay in bed while I tried to count backwards from 10. Some mornings I could not get past 10, 9, 8, 7 without getting lost in dark thoughts. Since changing to Firmagon, I can easily wake up and count backwards from a hundred. Something drastic happened to my thinking and emotional regulation after a couple of years on Leuprolides.
Carlos, that sounds horrible - I’m glad Firmagon works better for you.
Thanks Mike, it was the worst 4 months of my life
I had the same experience. I went on Effexor and am much better. My wife agrees!
Thanks. I'm on the lowest dose, but may increase the doseage. In addition to the mental SEs, I am also concerened about the other side effects that E2 purportedly helps with (bone density, cv events, etc)
If you are on Effexor, the lowest dose won't do it. I'm on 112.5 and am going to 150. I think that will do it. For bone density, I take Prolia.
good info, thanks
Please explain why you suggest an antidepressant that is not an SSRI
Hi LifeQuality,
This is of course individual and something a doctor should help decide, but since SSRI tend to lower your libido - which already is taking a hammering by ADT - perhaps an alternative is better.
I started ADT in Feb 2021. Side effects, namely hot flashes and fatigue, became intolerable. In Nov that year I mentioned this to my Oncologist and he suggested medroxyprogesterone. Within a week the hot flashes had greatly reduced both in intensity and frequency. The fatigue used to be like running into a brick wall but now is just low level tiredness.
No side effects, that I am aware of, from taking medroxyprogesterone, just huge relief that I can now sleep comfortably for up to 4 hours without waking from hot flash. Still get slight effects (hot flash), but as I said it is nowhere near as bad as it was previously.
I used to have to sleep in a separate room from my wife with just a sheet over me and a fan blowing. We’re back to sharing a bed.
Not sure of diff between medroxyprogesterone and progesterone, if any.
Thanks RickyR. Good info.
Hi, Carlosbach - curious as to your onco's professed reasons for denying you the low dose estradiol patch, as we are considering talking to our onco about it primarily for bone health. Luckily, Eric's SE's from ADT are (so far) very mild, almost a year in. Thanks, friend.
HW, my onco is very much about SOC. I have shared with him info from this forum, Dr. Wassersug, etc., but so far no luck. I have Kaiser, so he is the only one available to me at this time. I am trying to change insurers, but having difficulty getting past the underwriting.
Doctors, as a rule follow SOC. They will not prescribe E2 patches for fear of a lawsuit should things go south.
While on Orgovyx for two years I choose to try a bioidentical BI-EST 5.0 which helped to mitigate the hot flashes and possibly bone loss. The challenge is getting just the right dose to bring your E2 within an acceptable range. Stopped Orgovyx because of lack of libido, fatigue and brain fog...QOL!
Request your doctor include E2 in your lab work to see where you are at. I think the range is between 12-30.
Not recommending, just letting you know what I tried.
Thanks Ex. I have been experimenting with creams. I've asked for a referal to an edocronologist, so fingers crossed.
I tried an Endocrinologists. Initial consultation was with a PA who seemed receptive to the E2 patches. Ordered labs which I immediately got. Several days later the PA called me to say they would not help me.
Hope you have better luck.
>Request your doctor include E2 in your lab work to see where you are at. I think the range is between 12-30.
Make sure you get the Ultrasensitive E2 blood test, the standard test won't return the actual number if your E2 is very low. Try asking your Primary Care if your MO isn't receptive. My understanding is that you should be shooting for about 20 while using the E2 patch.
Thanks, I have an appointment with my primary care doctor next week. I’ll follow up with him then
I would hold out for, or seek other prescriber for, estradiol patches. Progesterone would not be a substitute for me for reasons PCaWarrior listed. Cardiovascular risk is not increased even for high doses such as used in PATCH trial. If MO is inflexible in spite of evidence of clear benefiits, then I would request transfer to a different MO. Or go to a Naturopath or other avenue to obtain it. ptotects your bones, protects your brain function and helps wiith ADT siide effects.
Thanks MB, I appreciate you sharing your expertise on this topic. I'm not giving up, just looking for info.
In my last visit my onco showed a little more flexibility, but I do want to make a switch of my care provider.
When my very conservative MO retired quite a few years back, I went to the most experienced oncology nurses in the center and asked which MO was the most progressive, smart and open minded. Ended up with my current most-excellent MO for the last 10 years.
Good idea. Thanks
Low dose estradiol patches may be obtained inexpensively via mail order through pharmacies in India
Might be how I have to go. I am trying to work everything through with my MO because of my experience with other cancer sufferers who went off book to their detriment
Would you mind sharing link(s) of pharmacies in India? TIA
I've used indiamart.com/.
I don't trust the products though. My doctors prescribe me what I need. If they didn't I would likely try pushhealth.com/ or similar places.
My husbands onco also not willing to prescribe add back E2. Concerned about cv impact. To be fair he did contact Prof Langley who headed up the Patch trial and her response was - not part of the trial yet reported so no evidence to say it helps. Well of course, but if full dose E2 didn't do extra harm cardio wise then why resist trying low dose add back? We haven't got anywhere with this and hubby is really suffering from ADT SE - massive exhaustion and brain fog. It's holding down PSA (0.2 with prostate) and clear CT and Bone scans and that's brilliant but at Great cost in QOL. I thought it worth a punt but no go here in the UK. We are too scared so far to go off piste but getting desperate so considering the India option. He is on decapeptyl (plus abi/pred) would switch to Firmagon help I wonder?
Sorry to hear about your husband’s SEs. Also sorry that you have to deal with how his difficulties impact you.
I can’t say if a switch to Firmagon will help. Firmagon is an antagonist, so it works differently on the brain. After switching my hot flashes definitely lessened, my thinking is clearer, and I have some of my energy back. Firmagon does have some downsides. I have to go in every 28 days for an injection. Following the injection, I have a low-grade fever for 2 to 5 days, with some swelling and fever in the injection area. Also my body hair and body of or is returning. my wife had gotten acustomed to my manscaped body, so that’s not a hit.
Best of luck
What I would say to my MO is the following:
1. I cannot continue to do ADT. It is destroying my QoL.
2. However, I am willing to try a low dose estrogen patch along with ADT.
3. So, is the risk of going off ADT permanently less or greater than the risk of staying on ADT but adding a low-dose estrogen patch?
A post of 2 years ago....
Progesterone Receptor.
pjoshea13 profile image
pjoshea13•
2 years ago•11 Replies
ADTMan posted "Progesteronr Bad" yesterday [1]
The article cited refers to a new study - see [2] for full text.
"Inhibiting 3βHSD1 to eliminate the oncogenic effects of progesterone in prostate cancer"
It might be helpful to glance at the steroidogenesis chart at this point [3].
Steroidogenesis begins with cholesterol & the two main early hormones produced are pregnenolone (the so-called 'grandmother' of all steroid hormones) & progesterone.
Abiraterone inhibits the enzyme that converts those hormones into downstream androgens such as DHEA, testosterone [T] & DHT. This presumable leads to higher than normal levels of pregnenolone & progesterone. Does that matter?
The new study claims that progesterone is indeed bad for PCa patients.
"To inhibit the conversion of pregnenolone to progesterone, steroidogenic enzyme 3βHSD1 is a promising target ... Currently, there is no 3βHSD1 inhibitor available in clinic." However, the natural isoflavone (a flavonoid) biochanin A turns out to be an inhibitor.
Biochanin A can be found in soy or red cover extracts, e.g. [4].
Statin drugs might lower pregnenolone & progesterone by reducing cholesterol.
***
I have a couple of progersterone threads going back 4 years, but this is a fresh start.
When I was diagnosed in 2004, there were men who were using 'natural' progesterone based on the writings of Dr. John Lee. Lee had died in 2003 but he remained influential, although I never succumbed. He still has a website. LOL
"Mifepristone is a steroidal antiprogestogen." "In the presence of progesterone, mifepristone acts as a competitive progesterone receptor antagonist" [5]
In a 2010 mouse study [6], there was some indication that a progesterone receptor antagonist might have a place in PCa therapy:
"There was a significant reduction of adverse events (i.e. a tumor >1 cm or bleeding from the penis) in those with prostate cancer treated with mifepristone."
A 2015 Norwegian paper [7] reported that "High progesterone receptor density in tumor cells of the prostate cancer tumor is an independent negative prognostic factor for clinical failure."
"The progesterone receptor (PGR) exists in two isoforms, PGR-A and PGR-B, and both are transcribed from the same gene. It belongs to the same receptor family as the androgen- and oestrogen receptors, which are expressed in both stromal and tumor cells of the PCa tissue. Currently, there is a general agreement of PGR presence in the stromal cells of PCa. Results regarding PGR’s presence in tumor cells, however, are conflicting. Thus, the importance of PGR in the human prostate and in prostate carcinogenesis has never been adequately explained. As a consequence we sought to evaluate the expression of PGR in both tumor cells derived from epithelia (TE) and tumor stromal cells (TS) in malignant prostatectomy specimens and found the PGR density level in both TE and TS to be associated with PCa progression."
Using radical prostatectomy tissue, it was "found that a high density level of PGR in TE is an independent prognostic factor for progression to CF in PCa. Further, high PGR density levels are significant for progression to CF in patients with Gleason score ≥ 7."
In 2018, Thea Grinstad followed up with [8]:
"Progesterone Receptors in Prostate Cancer: Progesterone receptor B is the isoform associated with disease progression"
***
The literature on PCa & progesterone is a bit muddy, but I'm inclined to follow Grinstad & be wary of the role of the progesterone receptor in PCa. I most certainly do not intend to purchase natural progesterone (sorry Dr, Lee.).
Is there a role for Mifepristone?
Abiraterone basically inhibits production of all of the major steroid hormones except pregnenolone & progesterone. Do we need to eradicate progesterone as well? Is that safe? How much biochanin A is required to make a difference. I doubt that this could be done with a Michael Milkin all-soy diet. Ugh!
-Patrick
[1] healthunlocked.com/advanced...
[2] cell.com/cell-reports-medic...
[3] en.wikipedia.org/wiki/Stero...
[4] amazon.com/Natures-Answer-C...
[5] en.wikipedia.org/wiki/Mifep...
[6] pubmed.ncbi.nlm.nih.gov/211...
[7] pubmed.ncbi.nlm.nih.gov/257...
(full text) journals.plos.org/plosone/a...
[8] ncbi.nlm.nih.gov/labs/pmc/a...
Written by
pjoshea13 profile image
pjoshea13
United States
Related Tags
prostate cancerprogesteronetestosteronedheaoestrogenabirateroneprostatectomyradical prostatectomypregnenolonemifepristone
Good Luck, Good Health and Good Humor.
j-o-h-n Thursday 10/19/2023 5:07 PM DST
Awesome info. I really appreciate your looking this up.
Me too. Well done and thanks John
You're welcome...........
Good Luck, Good Health and Good Humor.
j-o-h-n Thursday 10/19/2023 7:06 PM DST
Many months later, thanks to another poster on this forum, I learned that estradiol cream is for the asking at any drugstore. Just look up "estradiol cream" on Google and you'll get a lot of common products. Bought by women.
What am I missing here? I've spent months researching patches and maybe persuading a physician to give me a prescription. And all kinds of discussions here. And reading papers. And apparently that's true dial cream is available over the counter! (Note added later - apparently this is not true in Canada.)
Three things to consider:
1. AVAILABILITY - Is retail OTC estradiol cream the estradiol cream we are looking for? (Note added later - apparently this is not true in Canada.)
2. REGIME -What would be a responsible regime for self-administration? How much, how many square millimeters etc? And what about regular blood tests. Apparently one of our colleagues gets estrogen included in his regular blood panel.
3. SAFETY - And then back to the safety question. Review literature seems to imply that e2 transdermal is safe. There is some subtle discussion about e2 alpha and e2 beta receptors - one suppresses prostate cancer but the other promotes it. The review consensus, without any RCTs, is that low-dose estradiol alleviates symptoms and doesn't seem to be a risk for promoting progression.
I'm posting this 8 months after the original thread - who knows if anyone will see it? (See update in warning note below.)
--------------------------------
WARNING NOTE, JUNE 30TH, 2024 - I've been doing a lot of reading about estradiol. My latest position is that there are risks and I am not ready to try low-dose transdermal estradiol yet. It's a very complex subject and there does seem to be the risk of stimulating progression. This despite clear benefits. (Apparently estradiol has nearly equal affinty for both the ERα and ERβ estrogen receptors. One retards and the other promotes progression! More research needed! The latest thread is pursuing what can target ERβ for activation more or less exclusively. Hello Equol.)
Thanks J.I.M. I had the same questions. Fortunately, my bodies response to ADT has leveled out and my QOL has improved.
Thanks for staying with this
Thanks Carlos! I've seen quite a few of your posts on these things. I just added a new comment to the end of the above post. My pendulum has swung to paranoia again and I'm not doing anything. It's a rabbit hole of complexity.
Statins and Prostate Cancer
PSA Anxiety and Intermittent ADT for Metastatic Prostate Cancer 
JorgeW - Prostate Cancer
Supplements for metastatic prostate cancer 
Confused about doublet therapy vs triplet therapy for prostate cancer
