Progest-e Or Not Progest-e, That Is The Question

[Peaterpeater]

Ray Peat has mentioned that it would be fine to dose progesterone continuously if you are overburdened with estrogen and/or you do not care about menstruating......or during menapause.

 

[alywest]

Ray Peat has mentioned that it would be fine to dose progesterone continuously if you are overburdened with estrogen and/or you do not care about menstruating......or during menapause.

I agree but that seems to contradict what the president of Kenogen wrote to me (above.) I'm really confused. I'm going to write that back to her.

 

[alywest]

Here is a post from @Blossom that I copied and pasted from another thread (I hope that's ok Blossom! This is really helpful!):

I asked Ray Peat about why it might be that I notice breast pain from taking bioidentical progesterone like Progest-e and this was his response:

"Have you had a blood test for vitamin D and TSH? High estrogen increases the conversion of progesterone to the 5- metabolite, but thyroid and progesterone lower estrogen, preventing the exaggeration of that pathway. A vitamin D deficiency disturbs many hormones, and can cause breast pain."
Here are the studies he attached:
Endocrinology. 2003 Dec;144(12):5650-7.
Distinct molecular pathways mediate progesterone-induced growth inhibition and
focal adhesion.
Lin VC(1), Woon CT, Aw SE, Guo C.
(1)Department of Clinical Research, Singapore General Hospital, School of
Biological Sciences, School, Singapore 637616. [email protected].
We have reported previously that reactivation of progesterone receptor (PR)
expression in estrogen receptor (ER)- and PR-negative MDA-MB-231 breast cancer
cells enabled progesterone to inhibit cell growth and invasiveness, and to induce
remarkable focal adhesions. The present study addressed molecular mechanisms that
mediate these anticancer effects of progesterone in the PR-transfected breast
cancer cells ABC28. In response to progesterone treatment are the marked
up-regulation of cyclin-dependent kinase inhibitor protein p21WAF1/CIP1 and
decreased expression of cyclin A, cyclin B1, and cyclin D1 that are required for
G1 progression and during cell mitosis. Progesterone also induced down-regulation
of phosphorylated MAPK (p42/44 MAPK). Furthermore, this study also demonstrated
that MEK inhibitor PD98059 that inhibits the phosphorylation of p42/44 MAPK also
caused reduction of cyclin D1 level and inhibition of cell proliferation. These
results suggest that inhibition of p42/44 MAPK pathway is part of the mechanisms
mediating progesterone's growth-inhibitory effect. On the other hand,
progesterone-induced focal adhesion is mediated by separate pathway. Whereas
PD98059 exhibited no effects on cell adhesion, inhibitory antibody to
beta1-integrin was able to reverse progesterone-induced focal adhesion and
progesterone-induced increase in the phosphorylation of focal adhesion kinase. On
the other hand, beta1-integrin antibody had no effect on progesterone-mediated
growth inhibition and on progesterone-mediated expression of cyclins p21CIP1/WAF1
and phosphorylation of P42/P44 MAPK. In the context of complex functions of
progesterone in breast cancer and reproductive organs, identification of distinct
pathways offers new strategies for designing therapeutic agents to target the
specific pathway so as to minimize the side effects.

J Steroid Biochem Mol Biol. 2005 Nov;97(3):278-88.
Membrane 5alpha-pregnane-3,20-dione (5alphaP) receptors in MCF-7 and MCF-10A
breast cancer cells are up-regulated by estradiol and 5alphaP and down-regulated
by the progesterone metabolites, 3alpha-dihydroprogesterone and
20alpha-dihydroprogesterone, with associated changes in cell proliferation and
detachment.
Pawlak KJ(1), Zhang G, Wiebe JP.
(1)Hormonal Regulatory Mechanisms Laboratory, Department of Biology, University
of Western Ontario, London, Canada.
Previous studies have shown that the progesterone metabolite,
5alpha-pregnane-3,20-dione (5alphaP), exhibits mitogenic and metastatic activity
in breast cell lines and that specific, high affinity receptors for 5alphaP are
located in the plasma membrane fractions of tumorigenic (ER/PR-positive) MCF-7
cells. The aim of this study was to determine the effects of the mitogenic
(estradiol; 5alphaP) and anti-mitogenic (3alpha-hydroxy-4-pregnen-20-one,
3alphaHP; 20alpha-hydroxy-4-pregnen-3-one, 20alphaHP) endogenous steroid hormones
on 5alphaP receptor (5alphaP-R) numbers and on cell proliferation and adhesion of
MCF-7 and MCF-10A cells. Exposure of MCF-7 cells for 24h to estradiol or 5alphaP
resulted in significant (p < 0.05-0.001) dose-dependent increases in 5alphaP-R
levels. Conversely, treatment with 3alphaHP or 20alphaHP resulted in significant
(p < 0.05-0.01) dose-dependent decreases in 5alphaP-R levels. Treatment with one
mitogenic and one anti-mitogenic hormone resulted in inhibition of the
mitogen-induced increases, whereas treatment with two mitogenic or two
anti-mitogenic hormones resulted in additive effects on 5alphaP-R numbers.
Treatments with cycloheximide and actinomycin D indicate that changes in
5alphaP-R levels depend upon transcription and translation. The non-tumorigenic
breast cell line, MCF-10A, was also shown to posses specific, high affinity
plasma membrane receptors for 5alphaP that were up-regulated by estradiol and
5alphaP and down-regulated by 3alphaHP. Estradiol binding was demonstrated in
MCF-10A cell membrane fractions and may explain the estradiol action in these
cells that lack intracellular ER. In both MCF-7 and MCF-10A cells, the increases
in 5alphaP-R due to estradiol or 5alphaP, and decreases due to 3alphaHP or
20alphaHP correlate with respective increases and decreases in cell proliferation
as well as detachment. These results show distribution of 5alphaP-R in several
cell types and they provide further evidence of the significance of progesterone
metabolites and their novel membrane-associated receptors in breast cancer
stimulation and control. The findings that 3alphaHP and 20alphaHP down-regulate
5alphaP-R and suppress mitogenic and metastatic activity suggest that these
endogenous anti-mitogenic progesterone metabolites deserve considerations in
designing new breast cancer therapeutic agents.

Biochem Biophys Res Commun. 2000 Jun 16;272(3):731-7.
Plasma membrane receptors for the cancer-regulating progesterone metabolites,
5alpha-pregnane-3,20-dione and 3alpha-hydroxy-4-pregnen-20-one in MCF-7 breast
cancer cells.
Weiler PJ(1), Wiebe JP.
(1)Hormonal Regulatory Mechanisms Laboratory, University of Western Ontario,
London, Canada.
Recent observations indicate that the progesterone metabolite,
5alpha-pregnane-3,20-dione (5alphaP), which is produced at higher levels in
tumorous breast tissue, promotes cell proliferation and detachment, whereas
3alpha-hydroxy-4-pregnen-20-one (3alphaHP), which is produced at higher levels in
nontumorous breast tissue, suppresses proliferation and detachment of MCF-7
breast cancer cells. The objective of the current study was to determine the
presence and characteristics of binding sites for these endogenous putative
cancer-regulating steroid hormones. Radiolabeled 5alphaP and 3alphaHP were used
in radioligand binding assays on MCF-7 cell (membrane, cytosolic, and nuclear)
fractions. Binding of [(3)H]5alphaP and [(3)H]3alphaHP was observed only in the
plasma membrane fraction, whereas estradiol binding sites were confirmed in the
cytosolic and nuclear fractions. The respective membrane binding sites exhibited
specificity for the 5alphaP and 3alphaHP ligands with no appreciable displacement
at 200- to 500-fold excess by other steroids. The association rate constants were
calculated as 0. 107/min and 0.0089/min and the dissociation rate constants were
0. 049 9 and 0.011 for 5alphaP and 3alphaHP, respectively. Saturation analyses
indicated single classes of molecules with dissociation constants of 4.5 and 4.87
nM and receptor densities of 486 and 629 fmol/mg protein, respectively, for
5alphaP and 3alphaHP. Exposure of MCF-7 cells to estradiol for 1, 24, 48, and 72
h resulted in 2.3, 4. 2-, 2.99-, and 1.7-fold increases, respectively, in 5alphaP
receptor density. 3alphaHP resulted in partial suppression of the
estradiol-mediated increase in 5alphaP receptor density. This is the first report
of receptors for the progesterone metabolites, 5alphaP and 3alphaHP, of their
occurrence in breast cancer cell membranes, and of the induction of 5alphaP
receptors by estradiol. The results provide further support for the potential
importance of progesterone metabolites in breast cancer.
Copyright 2000 Academic Press.

Breast Cancer Res. 2013 May 11;15(3):R38.
Progesterone metabolites regulate induction, growth, and suppression of estrogen-
and progesterone receptor-negative human breast cell tumors.
Wiebe JP(1), Zhang G(2,)(3), Welch I(4), Cadieux-Pitre HA(5).
(1)Department of Biology, The University of Western Ontario, London, Ontario,
N6A5B7, Canada. [email protected] (2)Department of Biology, The University of Western
Ontario, London, Ontario, N6A5B7, Canada. [email protected].
(3)Department of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry,
The University of Western Ontario, London, Ontario, N6A 5C1, Canada.
[email protected]. (4)Department of Animal Care & Veterinary Services
and Department of Physiology and Pharmacology, Medical Sciences Building, The
University of Western Ontario, London, Ontario, N6A 5C1, Canada. [email protected].
(5)Department of Animal Care & Veterinary Services, Medical Sciences Building,
The University of Western Ontario, London, Ontario, N6A 5C1, Canada.
[email protected].
INTRODUCTION: Of the nearly 1.4 million new cases of breast cancer diagnosed each
year, a large proportion is characterized as hormone receptor negative, lacking
estrogen receptors (ER) and/or progesterone receptors (PR). Patients with
receptor-negative tumors do not respond to current steroid hormone-based
therapies and generally have significantly higher risk of recurrence and
mortality compared with patients with tumors that are ER- and/or PR-positive.
Previous in vitro studies had shown that the progesterone metabolites,
5α-dihydroprogesterone (5αP) and 3α-dihydroprogesterone (3αHP), respectively,
exhibit procancer and anticancer effects on receptor-negative human breast cell
lines. Here in vivo studies were conducted to investigate the ability of 5αP and
3αHP to control initiation, growth, and regression of ER/PR-negative human breast
cell tumors.
METHODS: ER/PR-negative human breast cells (MDA-MB-231) were implanted into
mammary fat pads of immunosuppressed mice, and the effects of 5αP and 3αHP
treatments on tumor initiation, growth, suppression/regression, and
histopathology were assessed in five separate experiments. Specific
radioimmunoassays and gas chromatography-mass spectrometry were used to measure
5αP, 3αHP, and progesterone in mouse serum and tumors.
RESULTS: Onset and growth of ER/PR-negative human breast cell tumors were
significantly stimulated by 5αP and inhibited by 3αHP. When both hormones were
applied simultaneously, the stimulatory effects of 5αP were abrogated by the
inhibitory effects of 3αHP and vice versa. Treatment with 3αHP subsequent to
5αP-induced tumor initiation resulted in suppression of further tumorigenesis and
regression of existing tumors. The levels of 5αP in tumors, regardless of
treatment, were about 10-fold higher than the levels of 3αHP, and the 5αP:3αHP
ratios were about fivefold higher than in serum, indicating significant changes
in endogenous synthesis of these hormones in tumorous breast tissues.
CONCLUSIONS: The studies showed that estrogen/progesterone-insensitive breast
tumors are sensitive to, and controlled by, the progesterone metabolites 5αP and
3αHP. Tumorigenesis of ER/PR-negative breast cells is significantly enhanced by
5αP and suppressed by 3αHP, the outcome depending on the relative concentrations
of these two hormones in the microenvironment in the breast regions. The findings
show that the production of 5αP greatly exceeds that of 3αHP in ER/PR-negative
tumors and that treatment with 3αHP can effectively block tumorigenesis and cause
existing tumors to regress. The results provide the first hormonal theory to
explain tumorigenesis of ER/PR-negative breast tissues and support the hypothesis
that a high 3αHP-to-5αP concentration ratio in the microenvironment may foster
normalcy in noncancerous breast regions. The findings suggest new diagnostics
based on the relative levels of these hormones and new approaches to prevention
and treatment of breast cancers based on regulating the levels and action
mechanisms of anti- and pro-cancer progesterone metabolites.

 

[tara]

So I think I came across someone pointing out that Progest-e is not good, and that is why RP walked away from the company Kenogen despite the fact that he patented the process of dissolving the progesterone in vitamin e. That seems like a pretty significant stand to take and I'm surprised that people on this forum are still purchasing Progest-E.

I thought he had to separate himself from the product because there were legal issues about both discussing the effects of using progesterone and selling the product. So he separated himself from the production before there was any change to the formula. And then there was a change to the formula. The only negative thing I thought I'd read from Peat about the changed formula was that he thought it would be a bit less effective with the vit-E diluted with another oil.

 

[tara]

But one drop of this thick liquid is one drop. Are you really telling me you think this liquid should be coming out like a water drop. Not a chance. But one drop = 3mg. Why complicate things.

I think I read instruction that said look at the size of the first drop that comes out of the bottle when you first get it. That amount should give about 3mg. If subsequent drops are bigger, take that into account.

Maybe women need much more progesterone than men.

Yes, I think we typically produce more of it than men do.

 

[tara]

I agree but that seems to contradict what the president of Kenogen wrote to me (above.) I'm really confused. I'm going to write that back to her.

AIUI, Peat has said that if you keep supplementing progesterone continuously, the liver can get more efficicent at eliminating it. If you take it for a few days then a few days off on a cyclical pattern, you reset so that you are sensitive to the benefits again when you resume next time around.
He has said that if someone needs to take it continuously to keep on top of sufficiently severe symptoms, and not needing to maintain the usual menstrual cycle, it's OK to do that. These may seem contradictory. I'm guessing, maybe taking a very small dose continuously could give some ongoing benefit without triggering the increased elimination. But that's a guess.
I used it continuously for a while, and I think it may have had reduced effectiveness after a while. Then I reduced to a very regular low dose for a while, and then I stopped.

 

[marsaday]

AIUI, Peat has said that if you keep supplementing progesterone continuously, the liver can get more efficicent at eliminating it. If you take it for a few days then a few days off on a cyclical pattern, you reset so that you are sensitive to the benefits again when you resume next time around.
He has said that if someone needs to take it continuously to keep on top of sufficiently severe symptoms, and not needing to maintain the usual menstrual cycle, it's OK to do that. These may seem contradictory. I'm guessing, maybe taking a very small dose continuously could give some ongoing benefit without triggering the increased elimination. But that's a guess.
I used it continuously for a while, and I think it may have had reduced effectiveness after a while. Then I reduced to a very regular low dose for a while, and then I stopped.

Interesting point about the liver.

I am now using only one drop per day and find it more effective, plus i will sometimes miss it out and the effect when i resume in one or two days time is better. This must explain what is happening here.

It is nice to know i need less of the progesterone as time has moved on.

 

[Braveheart]

I thought he had to separate himself from the product because there were legal issues about both discussing the effects of using progesterone and selling the product. So he separated himself from the production before there was any change to the formula. And then there was a change to the formula. The only negative thing I thought I'd read from Peat about the changed formula was that he thought it would be a bit less effective with the vit-E diluted with another oil.

I recently asked him...10/25/2017

"Am looking for the "right" Progesterone for my aging body...is this it?"

https://www.longnaturalhealth.com/Dr-Peats-Progest-E-Complex-34-ml

His answer..."That's the right (I think the only good) progesterone product. You can also get it directly from the producer, Kenogen: [email protected].

I tried it, but went back to Progestene......why? ...because of better absorption and more accurate dosing...also got a bit of a strange headache...granted I didn't give it much of a trial...plus wondered about having to refridgerate?

 

[mr.mag]

So I think I came across someone pointing out that Progest-e is not good, and that is why RP walked away from the company Kenogen despite the fact that he patented the process of dissolving the progesterone in vitamin e. That seems like a pretty significant stand to take and I'm surprised that people on this forum are still purchasing Progest-E. So in wondering what in the product is not good that would cause RP to walk away like that and I saw that they decided to use 'soy isoflavones.'

Here is a quote from RP:

The estrogenic properties of legumes were studied when sheep farmers found that their sheep miscarried when they ate clover. (I think it's interesting how this terribly toxic effect has been neglected in recent decades.) All legumes have this property, and all parts of the plant seem to contain some of the active chemicals. In beans, several substances have been found to contribute to the effect. The estrogenic effects of the seed oils and the isoflavones have been studied the most, but the well-known antithyroid actions (again, involving the oils, the isoflavones, and other molecules found in legumes) have an indirect estrogen-promoting action, since hypothyroidism leads to hyperestrogenism. (Estrogens are known to be thyroid suppressors, so the problem tends to be self-accelerating.) ( Natural Estrogens )

Hmmm, seems a bit counterintuitive to use an estrogenic product in a progesterone oil. When I used PRogest-e I had a lot of breast pain but I attributed it to the estrogens being loosened from my tissues. Now that I use another oil, I don't have breast pain and feel that I'm making better progress in restoring the balance between progesterone and estrogen.

Thoughts?

I sent this to Ray and this is his response:

The first part is a complete fabrication. If the person making the statement, including the remark that “they had decided to use soy isoflavones,” can’t provide the source, it should be assumed to have been invented by that person. The second part is at best a non sequitur: Quoting something I had said about the estrogenic effects of the legumes, their isoflavones and polyunsaturated fatty acids, and then to say that an estrogenic product has been used in a progesterone oil. Progest-E Complex contains neither. Both pure vitamin E and progesterone are strongly antiestrogenic. Such lack of contact with reality should make a reader question the rest of the statement. Does the person use a pseudonym? The defamatory statements are clearly malicious, so I’m interested in knowing the identity of their author.

 

[alywest]

I sent this to Ray and this is his response:

The first part is a complete fabrication. If the person making the statement, including the remark that “they had decided to use soy isoflavones,” can’t provide the source, it should be assumed to have been invented by that person. The second part is at best a non sequitur: Quoting something I had said about the estrogenic effects of the legumes, their isoflavones and polyunsaturated fatty acids, and then to say that an estrogenic product has been used in a progesterone oil. Progest-E Complex contains neither. Both pure vitamin E and progesterone are strongly antiestrogenic. Such lack of contact with reality should make a reader question the rest of the statement. Does the person use a pseudonym? The defamatory statements are clearly malicious, so I’m interested in knowing the identity of their author.

The comment about soy isoflavones was on one of those watchdog consumer websites, I'm pretty sure I linked to it earlier in this thread. They said that Progest-E contained soy isoflavones.

 

[alywest]

Progest E Review (UPDATED 2018): Don't Buy Before You Read This!

 

[alywest]

Perhaps Ray Peat should urge Kenogen to take some sort of action against that website.

 

[lampofred]

Wow he got really angry... Irrationally angry actually. Lots of weird assumptions. I've never seen a response like that from him until now.

 

[Dhair]

Progest E Review (UPDATED 2018): Don't Buy Before You Read This!

To be clear, is this the source of the rumor?

Wow he got really angry... Irrationally angry actually. Lots of weird assumptions. I've never seen a response like that from him until now.

Read the link that alywest posted. The person who wrote that review is clearly trying to direct the reader's attention toward another product, and they have no understanding of progesterone, Ray Peat, or this forum. I was very annoyed reading it.
@alywest It would probably be a good idea to contact Ray and tell him that you didnt know that you had been misinformed and link him to the consumer review website post that started all this nonsense. It's not your fault, but someone did send him a quote of yours that is kind of out of context. The reviewer spreading these lies should be held accountable though.

 

[lampofred]

Read the link that alywest posted. The person who wrote that review is clearly trying to direct the reader's attention toward another product, and they have no understanding of progesterone, Ray Peat, or this forum. I was very annoyed reading it.
@alywest It would probably be a good idea to contact Ray and tell him that you didnt know that you had been misinformed and link him to the consumer review website post that started all this nonsense. It's not your fault, but someone did send him a quote of yours that is kind of out of context. The reviewer spreading these lies should be held accountable though.

I don't think he saw that link, only alywest's post. Way too much dopamine from thyroid, caffeine, and diet probably making him paranoid and suspicious lol. But I agree that the website that the link leads to is very stupid

 

[Peaterpeater]

I don't think he saw that link, only alywest's post. Way too much dopamine from thyroid, caffeine, and diet probably making him paranoid and suspicious lol. But I agree that the website that the link leads to is very stupid

LOL! I love Ray Peat. He is obviously very passionate about this subject; I mean Progest-E was his baby/brain child. So good for him to squash false statements so strongly. Way to go Peat!!

Aly, I agree with Dhair that it's not your fault and that you should send Ray that link directly in case he hasn't seen it.

 

[Peaterpeater]

Wow he got really angry... Irrationally angry actually. Lots of weird assumptions. I've never seen a response like that from him until now.

Yes, he was really angry but i don't think irrationally so. His assumptions are actually spot on.....but misplaced on Alywest. I believe that the statements on that website are "defamatory" and "malicious" towards Protest-E. They are trying to bring Protest-E's reputation down so they can sell their own product.

 

[Vinero]

I have ordered a bottle of progest-E around two weeks ago, and noticed when pushing the drops out on my finger that it was very light in color.
Almost clear like water. But it was still thick and sticky. Only the color was much lighter then all the progest-E bottles I have ordered before.
Has anyone else noticed this?
I am afraid they have changed the ingredients or something. I hope this is not the case as Progest-E has always worked so well.

 

[Herbie]

I bought a bottle of progest-e in 2016 and received a new bottle last week and its exactly the same as far as I can tell.

 

[Laura]

So I think I came across someone pointing out that Progest-e is not good, and that is why RP walked away from the company Kenogen despite the fact that he patented the process of dissolving the progesterone in vitamin e. That seems like a pretty significant stand to take and I'm surprised that people on this forum are still purchasing Progest-E. So in wondering what in the product is not good that would cause RP to walk away like that and I saw that they decided to use 'soy isoflavones.'

Here is a quote from RP:

The estrogenic properties of legumes were studied when sheep farmers found that their sheep miscarried when they ate clover. (I think it's interesting how this terribly toxic effect has been neglected in recent decades.) All legumes have this property, and all parts of the plant seem to contain some of the active chemicals. In beans, several substances have been found to contribute to the effect. The estrogenic effects of the seed oils and the isoflavones have been studied the most, but the well-known antithyroid actions (again, involving the oils, the isoflavones, and other molecules found in legumes) have an indirect estrogen-promoting action, since hypothyroidism leads to hyperestrogenism. (Estrogens are known to be thyroid suppressors, so the problem tends to be self-accelerating.) ( Natural Estrogens )

Hmmm, seems a bit counterintuitive to use an estrogenic product in a progesterone oil. When I used PRogest-e I had a lot of breast pain but I attributed it to the estrogens being loosened from my tissues. Now that I use another oil, I don't have breast pain and feel that I'm making better progress in restoring the balance between progesterone and estrogen.

Thoughts?

I am appalled to read this as Elaine Hollingsworth in Australia recommended it in her book Take Control of Your Health, l am still having hot flushes & bought 6 bottles since I am in Australia . l am having hormone testing soon but will never buy again