[Dynseli]

'Estriol: Safety and Efficacy' Review http://www.altmedrev.com/publications/3/2/101.pdf

Estradiol and Esterone can convert into each other. Very little of either converts into Estriol by the liver.

"Most estradiol, however, is bound to sex-hormone binding globulin (SHBG), so only a portion of the circulating estradiol is available for entry into cells. On the other hand, estriol has a much lower affinity for binding to SHBG; therefore, a greater percent is available for biological activity."

Androstenedione converts into estriol.

"While estriol appears to be safer than estrone and estradiol and, in some situations, provides some protection against carcinogenesis, it appears its use in breast cancer patients with active disease or with patients at high risk for breast cancer should be approached with caution."

[Dynseli]

'Oestetrol stimulates proliferation and oestrogen receptor expression in breast cancer cell lines: Comparison of four oestrogens.' abstract https://www.ncbi.nlm.nih.gov/pubmed/25213195

"Some current investigations suggest that the use of E4 in hormone therapy or contraception may have advantages in terms of breast cancer risk when compared to other oestrogens."

"Oestetrol was significantly less effective than E2 at the lower concentration."

"However, no difference was found regarding receptor expression [among estrogens]."

Oestetrol = Estetrol = 15-alpha-hydroxyoestriol = E4

Estriol = Oestriol = E3

[Dynseli]

'Effects of estriol on growth, gene expression and estrogen response element activation in human breast cancer cell lines.' abstract https://www.ncbi.nlm.nih.gov/pubmed/24529907

"Like E2, low levels of E3 were able to trigger a robust estrogenic response in breast cancer cells. Thus, our data suggest caution regarding use of E3 by breast cancer survivors."

[Dynseli]

From the chart in the top post:

Estradiol or Estrone + 16a-OHase --> Estriol

16α-Hydroxyandrostenedione + 17-OH-SDH or aromatase --> Estriol

The enzimes 16a-OHase, 17-OH-SDH, aromatase, and 3b-OH-SDH are important for the production of estriol.

3β-OH-SDH = 3b-Hydroxysteroid dehydrogenase
17-OH-SDH = 17-Hydroxysteroid dehydrogenase
16α-OHase = 16a-Hydroxylase

estrone (E1); estradiol (E2)

[Dynseli]

The chart in the top post shows the pathways from Dehydroepiandrosterone (DHEA), to Androstenedione, to testosterone, to estradiol, to estriol. It shows aromatases making conversions to estradiol, estrone, and estriol.

https://www.ncbi.nlm.nih.gov/mesh/?term=...ydroxylase Steroid 16-alpha-Hydroxylase, a liver enzyme, seems important in that can make different conversions on the way to estriol.

I wonder if blessed thistle which has a role in helping the liver, and is also a lactogogue has an effect in any way on an estriol pathway.

On the other hand, estriol may not be normal for the body to synthesize in large amounts, so it may possibly be irrelevant. Estriol is synthesized by a small amount by the liver, and also by a large amount by a placenta.

[Dynseli]

Liver metabolites of estradiol are E3, 16alpha-OHE1, 2-OHE2, E1, and two unidentified composition... Over 90% of estradiol is protein bound, mostly by SHBG - Determination of estradiol metabolites in human liver microsome by high performance liquid chromatography-electrochemistry detector.

Some metabolites of E2 are claimed to be carcinogenic, but E3 is a lot safer than estradiol.

Here is the pathway from DHEA to estradiol, estrone, and estriol:


Aromatase and the liver enzyme 16alpha-OHase are involved in many pathways to estriol.

According to Wikipedia - Estrogen "Though estriol is the most plentiful of the three estrogens it is also the weakest, whereas estradiol is the strongest with a potency of approximately 80 times that of estriol.[unverified]"

Although estriol is weaker, it is more plentiful, and 90% of estradiol is bound to SHBG. So do the math, Estriol is important for NBE. Approximately 10% of estradiol is free. Where as more estriol is free, and is 80 times less potent. Estriol already is about as effective as estradiol, for NBE because it is bioavailable.

10% of estradiol acting 80 times more than estriol. Whereas, let's assume 100% estriol is free, and is 1/80th as strong as estradiol. The free amounts of E2 to E3 become comparable, then.