Breast Cancer Survivors Who Use Estrogenic Botanical Supplements Have Lower Serum Estrogen Levels

rzero

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Breast cancer survivors who use estrogenic botanical supplements have lower serum estrogen levels than non users

The authors seem to agree that lower serum estrogen is correlated to lower breast cancer risk, but the part I found interesting is the ambiguity surrounding whether particular supplements are estrogenic or anti-estrogenic. The study caught my eye as I have been looking into diosgenin (wild yam extract), which seems to be widely referred to as a phytoestrogen but in some studies shows clear androgenic effects.

Some quotes:
Women reporting use of any estrogenic botanical supplement had significantly lower levels of estrone (20.8 v 23.6 pg/mL), estradiol (12.8 v 14.7 pg/mL), free estradiol (0.29 v 0.35 pg/mL), and DHEAS (47.7 v 56.2 ug/dL) compared to women reporting no use.
The biologic theory behind this inverse association is that phytoestrogens, because they are weak estrogens, may stimulate the synthesis and release of SHBG, thus reducing the amount of available estradiol [37]; and they may also inhibit enzymes involved in estrogen synthesis and metabolism [8].
We are aware of one study that has evaluated the effect of EBS on breast cancer development. Rebbeck [40] et al conducted a case-control study that asked participants about their use of hormonal supplements. They found the risk of breast cancer was significantly lower among women who reported use of any estrogenic supplements compared to women reporting no use. Additionally, the use of black cohosh had a significant protective effect for breast cancer. The authors hypothesize this association may be due to the hormonal (antiestrogenic) effects of black cohosh or to its antiproliferative properties.
The conflicting results described above may be due to the difficulty in defining a supplement as estrogenic. Black cohosh, for example, can be classified as estrogenic or non-estrogenic, depending on which study is cited [41-43].
 
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Fidelio

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Most phytoestrogens are actually net anti-estrogenic as they are very weak agonists of ER.

Same reason why DHEA is net anti-androgenic.
 

rzero

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Most phytoestrogens are actually net anti-estrogenic as they are very weak agonists of ER.

Same reason why DHEA is net anti-androgenic.
Interesting. I don't hear that often on this board.
 

LeeLemonoil

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Lots of variables. Phytoestrogens displacing more powerful physiological estrogens this lowering the harmful effects of ER agonism in some tissues.

In estrogen sensitive cancer this is likely positive. But does that mean that eating phytoestrogens when you have a „good“ hormonal situation is recommendable?
I don’t know. Those compounds like diosgenin are interesting for sure
 

JKX

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Agree with @LeeLemonoil

You'll be there forever and a day trying to determine useful outcomes from the first study, the women filled in a questionnaire. Too many variables present to draw any useful conclusion.

DHEA is net anti-androgenic? I would question that statement. It increases expression of AR. Perhaps you are referring to studies using crazy high dosages?

Disogenin is a source of several hormones. Its been used and is used to derive everything from estrogens and cortisol to progesterone. Difficult to predict what the effect of ingesting the extract would have.
 

Fidelio

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DHEA is net anti-androgenic? I would question that statement. It increases expression of AR. Perhaps you are referring to studies using crazy high dosages?
DHEA is a partial agonist of the AR. Meaning it binds and prevents other agonists from binding and exerting transcriptional activity. The issue is however is that it is so weak as an AR agonist that you just end up taking up places that T could otherwise bind to. Instead T hangs around in serum and converts to e2 via aromatase or DHT via 5ar. Neither one optimal outside normal range in my opinion.
 

Iqa

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I’ve started looking into phytoestrogens recently to see if maybe the presence of an estrogen mimic in the body would increase androgen production to compensate. Sort of like how artificial sugar activates our reward pathways like real sugar.

Anyways, here are some articles that I thought were interesting:

Effects of dietary phytoestrogens on plasma testosterone and triiodothyronine (T3) levels in male goat kids
Effects of dietary phytoestrogens on plasma testosterone and triiodothyronine (T3) levels in male goat kids

Dual effects of phytoestrogens result in u-shaped dose-response curves.
Dual effects of phytoestrogens result in u-shaped dose-response curves.

Modulation of Aromatase by Phytoestrogens
https://www.researchgate.net/publication/287811027_Modulation_of_Aromatase_by_Phytoestrogens

Effects of Dietary Phytoestrogens on Hormones throughout a Human Lifespan: A Review
Effects of Dietary Phytoestrogens on Hormones throughout a Human Lifespan: A Review

It looks like the estrogen reduction tends to be in women for most of the studies but many researchers seem to focus on soy products and flax which have there own issues when it comes to thyroid disruption. Right now, I’m experimenting with whole mint leaves as a source of phytoestrogens. Based on the second study above, I think low concentrations would be found in whole foods and essential oils or extracts would be more estrogenic.
 

rzero

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I’ve started looking into phytoestrogens recently to see if maybe the presence of an estrogen mimic in the body would increase androgen production to compensate. Sort of like how artificial sugar activates our reward pathways like real sugar.

Anyways, here are some articles that I thought were interesting:

Effects of dietary phytoestrogens on plasma testosterone and triiodothyronine (T3) levels in male goat kids
Effects of dietary phytoestrogens on plasma testosterone and triiodothyronine (T3) levels in male goat kids

Dual effects of phytoestrogens result in u-shaped dose-response curves.
Dual effects of phytoestrogens result in u-shaped dose-response curves.

Modulation of Aromatase by Phytoestrogens
https://www.researchgate.net/publication/287811027_Modulation_of_Aromatase_by_Phytoestrogens

Effects of Dietary Phytoestrogens on Hormones throughout a Human Lifespan: A Review
Effects of Dietary Phytoestrogens on Hormones throughout a Human Lifespan: A Review

It looks like the estrogen reduction tends to be in women for most of the studies but many researchers seem to focus on soy products and flax which have there own issues when it comes to thyroid disruption. Right now, I’m experimenting with whole mint leaves as a source of phytoestrogens. Based on the second study above, I think low concentrations would be found in whole foods and essential oils or extracts would be more estrogenic.
Very interesting. Thanks for the links.
 

Fidelio

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I’ve started looking into phytoestrogens recently to see if maybe the presence of an estrogen mimic in the body would increase androgen production to compensate. Sort of like how artificial sugar activates our reward pathways like
That’s not how the HPTA axis works. In fact estrogen is directly inhibitory to the pituitary and hence androgen production. Regardless it doesn’t matter because within physiological levels of hormones androgen levels are fully saturated. Artificially boosting your total t from 600ng/dl to 800ng/dl will have zero noticeable effect on your physiology, mood, strength, etc.
Unless you are legitimately hypogonadal you’re chasing an exercise in futility. Is there health benefits to mint? Sure. But using them to ‘boost androgens’ is a waste of time.
 

Inaut

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My favourite herbalist (James Sloan) has always said that phytoestrogens -due to their weaker affinity, bind with estrogen receptors allowing for excretion from the body more easily. Not sure about any of it but he's written about it if you search for him....
 

haidut

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When you administer strong estrogen agonists, it is quite natural for serum estrogens to fall. The same effects is seen on testosterone/DHT if you administer a strong AAS such as say trenbolone. There is nothing weak about the phytoestrogens. Some of them like daidzein and genistein have HIGHER affinity for ER-alpha than even estradiol. The isoflavones (daizdein and genistein are two such chemicals) are almost universally estrogenic, and powerfully so. Resveratrol is a stilbenoid and another example of a powerful phytoestrogen.
Isoflavone - Wikipedia
Phytoestrogen - Wikipedia

The flavones, on the other hand, are anti-estrogenic and this is due to the phenyl ring being further away from the ketone group than in the case of isoflavones. Notable examples include apigenin and naringenin, which have now been classified as phytoprogestogens due both to their anti-estrogenic effects and their ability to activate the progesterone receptor (PR).
Flavones - Wikipedia
Phytoprogestogen - Wikipedia


Structurally, it is very hard to have a chemical that activates both ER and PR, so if the flavones activate PR (and that has been confirmed) you can have reasonable assurance that they are NOT estrogenic, which has also been confirmed already in both in-vitro and in-vivo studies. In fact, most of the flavones are relatively potent anti-estrogens, especially naringenin, followed closely by apigenin. On the other hand, the isoflavones activating ER and not PR is a reasonable assurance they are estrogenic and that has also been confirmed both in-virto and in-vivo.

@rzero @Fidelio @LeeLemonoil
 

haidut

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@haidut what’s the difference between naringin and naringenin

@Broken man explained it - naringin is the glycoside of naringenin and gets metabolized into naringenin when ingested but that process is very inefficient and little free natingenin gets absorbed when ingesting naringin. Also, less than 50% of the naringin is the naringenin moiety so even if the conversion/absorption was efficient you'd be getting less than half of the naringin dose as naringenin.
 

lampofred

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Progesterone releases estrogen from tissues and so causes serum estrogens to go up while they are being detoxified. So I could see a situation in which taking something estrogenic shuts off the detox process and decreases estrogens in the serum, while increasing them inside tissues. Admittedly sounds a bit convoluted though.
 

jb116

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Progesterone releases estrogen from tissues and so causes serum estrogens to go up while they are being detoxified. So I could see a situation in which taking something estrogenic shuts off the detox process and decreases estrogens in the serum, while increasing them inside tissues. Admittedly sounds a bit convoluted though.
This is the most likely scenario.
 

Spartan300

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Assuming this is the case then I'm wondering whether anyone here been brave enough to push through the detox phase and come out the other side?

Whenever I've tried prog it's not been a good experience. Makes me really emotional.....
 

Broken man

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Assuming this is the case then I'm wondering whether anyone here been brave enough to push through the detox phase and come out the other side?

Whenever I've tried prog it's not been a good experience. Makes me really emotional.....
Can't progesterone be converted to estrogen?
 

rzero

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When you administer strong estrogen agonists, it is quite natural for serum estrogens to fall. The same effects is seen on testosterone/DHT if you administer a strong AAS such as say trenbolone. There is nothing weak about the phytoestrogens. Some of them like daidzein and genistein have HIGHER affinity for ER-alpha than even estradiol. The isoflavones (daizdein and genistein are two such chemicals) are almost universally estrogenic, and powerfully so. Resveratrol is a stilbenoid and another example of a powerful phytoestrogen.
Isoflavone - Wikipedia
Phytoestrogen - Wikipedia

The flavones, on the other hand, are anti-estrogenic and this is due to the phenyl ring being further away from the ketone group than in the case of isoflavones. Notable examples include apigenin and naringenin, which have now been classified as phytoprogestogens due both to their anti-estrogenic effects and their ability to activate the progesterone receptor (PR).
Flavones - Wikipedia
Phytoprogestogen - Wikipedia


Structurally, it is very hard to have a chemical that activates both ER and PR, so if the flavones activate PR (and that has been confirmed) you can have reasonable assurance that they are NOT estrogenic, which has also been confirmed already in both in-vitro and in-vivo studies. In fact, most of the flavones are relatively potent anti-estrogens, especially naringenin, followed closely by apigenin. On the other hand, the isoflavones activating ER and not PR is a reasonable assurance they are estrogenic and that has also been confirmed both in-virto and in-vivo.

@rzero @Fidelio @LeeLemonoil
Ah, I see diosgenin is listed as a phytoprogestogen.
 
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