# Estriol

Category: Hormones

Also known as: E3

Estriol (E3) is a so-called "weak" estrogen that Ray Peat argued is not protective, but rather a slightly weaker variant of estradiol that produces the same toxic effects at a proportionally higher dose. Peat emphasized that estriol is about 10 times weaker than estradiol, but…

9 passages · 2 authors · 1997–2023 · Most-cited: [Ray Peat](https://bioenergeticoracle.com/md/voices/ray-peat/index.md)

Canonical page: https://bioenergeticoracle.com/concepts/estriol

## Synthesis

**Estriol (E3)** is a so-called "weak" estrogen that Ray Peat argued is not protective, but rather a slightly weaker variant of **estradiol** that produces the same toxic effects at a proportionally higher dose. [Source 1, 3, 6] Peat emphasized that estriol is about 10 times weaker than estradiol, but that people simply use 10 times more to achieve an equivalent effect, making it functionally identical in its capacity for harm. [Source 1, 4] He stated plainly that "they're all interchangeable. It just takes a bigger dose of either estrone or estriol to have exactly the same effect as estradiol." [Source 6]

The notion that estriol is a benign or protective estrogen was a central target of Peat's critique. He traced the idea to a 1978 JAMA editorial promoting estriol for cancer resistance, which he dismissed as "aggressively stupid." [Source 3] Peat cited evidence that estriol stimulates the growth of human breast cancer cells in culture and overcomes the antiestrogenic effects of tamoxifen, leading researchers to conclude that "the data do not support an antiestrogenic role for estriol in human breast cancer." [Source 2, 7] He further noted that the elevated conversion of estradiol to estriol, via *16-hydroxylation*, is a hormonal feature found in women with breast cancer and in men who had a myocardial infarction, suggesting that high estriol is a *consequence of disease*, not a cause of protection. [Source 5, 7]

Peat explained that during a healthy pregnancy, the placenta converts the highly toxic estradiol into the more water-soluble estriol, which is *more quickly excreted* in the urine, making a high estriol level an index of rapid estradiol detoxification rather than a beneficial hormone in itself. [Source 5, 7, 8] A surge in estriol preceding labor was interpreted by Peat as likely reflecting the mother's increased production of **adrenal androgens** during stress, analogous to the hormonal dynamics of polycystic ovary syndrome. [Source 5, 7] He maintained that the decline of estriol in a failing pregnancy is a consequence of fetal sickness, not its cause. [Source 5, 7]

Despite its reputation as a weak estrogen, Peat documented that estriol exerts potent systemic effects. Intravaginal administration of 5 mg suppressed **LH** within two hours and **FSH** within five hours, while oral dosing produced estrogenic changes in the vaginal epithelium. [Source 2, 3, 7] Its *anti-progestational activity* is approximately the same as estradiol's, and when placed locally in the uterus of a rabbit, only 1.25 mcg was sufficient to prevent implantation and destroy the blastocyst. [Source 2, 3, 7] Subcutaneous administration induced abortions and stillbirths. [Source 2, 3, 5] Peat also warned that topical application for cosmetic purposes merely causes the skin to take up water, plumping it while altering collagen, an effect he characterized as "pro-aging." [Source 4] Georgi Dinkov has extended this critique by arguing that locally applied estriol inevitably distributes systemically, citing the phenomenon of *microchimerism* as evidence that molecules far larger than estriol traverse the body, and noting that even weak estrogens applied to the skin can drive melanoma formation. [Source 9]

## People also ask

### How does estriol compare to estradiol in its harmful effects?

Peat argued that estriol is about 10 times weaker than estradiol, but people simply use 10 times more to achieve an equivalent effect, making it functionally identical in its capacity for harm.

### Why did Peat reject the idea that estriol protects against breast cancer?

Peat cited evidence that estriol stimulates the growth of human breast cancer cells in culture and overcomes the antiestrogenic effects of tamoxifen, leading researchers to conclude the data do not support a protective role.

### What systemic effects can estriol have despite being considered weak?

The corpus describes that intravaginal estriol suppressed LH and FSH within hours, its anti-progestational activity is similar to estradiol's, and a small uterine dose prevented implantation and destroyed the blastocyst in rabbits.

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## Cited passages

Passage numbers match the `[Source N]` markers in the synthesis above.

### Source 1 — Ask the Herb Doctor: Language and Criticism, Estrogen (Part 1)

Ray Peat · Interview · Jun 16, 2017

> ## Caller: Bioidentical Hormones and Cycling
>
> **Ray Peat:** They all have the same effects but at different doses. Estriol (E3) is about 10 times weaker than estradiol (E2). But it is still harmful if you don't interrupt it.
>
> **Caller:** How long do I interrupt it for?
>
> **Ray Peat:** Something approaching the body's two weeks is probably ideal, but I think a week with a progesterone supplement is probably safe enough.
>
> **Caller:** So you don't see much difference between synthetic and bioidentical?
>
> **Ray Peat:** Estradiol is the powerful natural one. Ethinyl estradiol (synthetic) has an added group that makes it stay in the body 17 times longer. E2 is the strongest natural one.
>
> **Sarah Murray:** Why don't you try cutting out the E2 and just using the E3 for two weeks out of the month, while using the progesterone the whole cycle? You might find you don't have hot flashes at all.

### Source 2 — From PMS to Menopause: Female Hormones in Context

Ray Peat · Book · 1997

> **Ray Peat:** (Dmowski, et al., 1977.) Since the effect was local, the body weight of the animal doesn't make much difference, when thinking about the probable effect of a similar local concentration of the hormone on human tissues. The anti-progestational activity of estriol and estradiol are approximately the same. (Tamotsu and Pincus, 1958.) When 5 mg. of estriol was given to women intravaginally, this very large dose suppressed LH within 2 hours, and suppressed FSH in 5 hours. Given orally, 8 mg. had similar effects on LH and FSH after 30 days, and also had an estrogenic effect on the vaginal epithelium. These quick systemic effects of a "weak estrogen" are essentially those of a strong estrogen, except for the size of the dose. (Schiff, et al., 1978.) When administered subcutaneously, estriol induced abortions and stillbirths (Velardo, et al.) Another indication of the strength of an estrogen is its ability to cause the uterus to enlarge. Estriol is slightly weaker, in terms of milligrams required to cause a certain rate of uterine enlargement, than estradiol. (Clark, et al., 1979.) But isn't the important question whether or not the weak estrogen imitates all of the effects of estradiol, including carcinogenesis and blood clotting, in addition to any special harmful effects it might have? When added to long-term culture of human breast cancer cells, estriol stimulated their growth, and overcame the antiestrogenic effects of tamoxifen, even at concentrations hundreds of times lower than that of tamoxifen.

### Source 3 — Estriol, DES, DDT.

Ray Peat · Article · 2010 · https://raypeat.com/articles/aging/estriol-des-ddt.shtml

> DES is a "weak" estrogen, in the sense that it doesn't compete with natural estrogens for the "estrogen receptors." (Estriol binds more strongly to receptors than DES does: "Cytosolic and nuclear estrogen receptors in the genital tract of the rhesus monkey," J. Steroid Bioch. 8(2), 151-155, 1977.) Pills formerly contained from 5 to 250 mg. of DES. The 1984 PDR lists doses for hypogonadism and ovarian failure as 0.2 to 0.5 mg. daily. In general, dosage of estrogens decreased by a factor of 100 after the 1960s.
>
> An aggressively stupid editorial by Alvin H. Follingstad, from the Jan. 2, 1978, issue of JAMA, pages 29-30, "Estriol, the forgotten estrogen?" is being circulated to promote the use of estriol, or the phytoestrogens. It argues that women who secrete larger amounts of estriol are resistant to cancer.
>
> By some tests, estriol is a "weak estrogen," by others it is a powerful estrogen.
>
> When estriol was placed in the uterus of a rabbit, only 1.25 mcg. was sufficient to prevent implantation and destroy the blastocyst. (Dmowski, et al., 1977.) Since the effect was local, the body weight of the animal doesn't make much difference, when thinking about the probable effect of a similar local concentration of the hormone on human tissues. The anti-progestational activity of estriol and estradiol are approximately the same. (Tamotsu and Pincus, 1958.)
>
> When 5 mg. of estriol was given to women intravaginally, this very large dose suppressed LH within 2 hours, and suppressed FSH in 5 hours. Given orally, 8 mg. had similar effects on LH and FSH after 30 days, and also had an estrogenic effect on the vaginal epithelium. These quick systemic effects of a "weak estrogen" are essentially those of a strong estrogen, except for the size of the dose. (Schiff, et al., 1978.)

### Source 4 — One Radio Network: What is a virus anyway?

Ray Peat · Interview · Mar 16, 2020

> ## Rapid Fire Questions
>
> **Patrick Timpone:** Any fiction books or movies?
>
> **Ray Peat:** None come to the top of my head.
>
> **Patrick Timpone:** Tell us about your newsletter.
>
> **Ray Peat:** You can email raypeatsnewsletter@gmail.com. The latest one is about Gilbert Ling's work. He died last fall. He was one of my early influences in biology. He gave a clear, consistent explanation of cell function, whereas the standard theories are essentially impossible fantasies.
>
> **Patrick Timpone:** Can estriol be used topically for wrinkles?
>
> **Ray Peat:** It makes the skin take up water, so it plumps up, but it alters the collagen. Estriol is the weakest estrogen, but people use 10 times more to get the effect, which ends up being the same as estradiol—pro-aging. It makes the skin swell with water, looking smooth and shiny, but it isn't good.
>
> **Patrick Timpone:** What soap do you use?
>
> **Ray Peat:** Pure coconut soap.
>
> **Patrick Timpone:** Role of norepinephrine/adrenaline?
>
> **Ray Peat:** Adrenaline has been maligned. It activates other stress hormones like cortisol, so if it persists, it is harmful. However, things that momentarily increase adrenaline can be helpful if stopped soon enough. Thyroid has a relaxing function. When you first take thyroid, if you have been overproducing adrenaline to compensate for hypothyroidism, you might experience a stress reaction. Having sugar and salt while adjusting to thyroid helps keep adrenaline under control.

### Source 5 — Estriol, DES, DDT.

Ray Peat · Article · 2010 · https://raypeat.com/articles/aging/estriol-des-ddt.shtml

> The decreased output of hormones when the fetal-placental system is dying is a natural consequence, since the placenta produces hormones, and during pregnancy converts estradiol to estriol. Since estradiol in excess kills the fetus, its conversion by the placenta to estriol is in accord with the evidence showing that estriol is the more quickly excreted form. (G. S. Rao, 1973.) The conversion of 16-hydroxy androstenedione and 16-hydroxy-DHEA into estriol by the placenta (Vega Ramos, 1973) would also cause fetal exhaustion or death to result in lower estriol production. But a recent observation that a surge of estriol production precedes the onset of labor, and that its premature occurrence can identify women at risk of premature delivery (McGregor, et al., 1995) suggests that the estriol surge might reflect the mother's increased production of adrenal androgens during stress. (This would be analogous to the situation in the polycystic ovary syndrome, in which excessive estradiol drives the adrenals to produce androgens.)
>
> Estetrol, which has one more hydroxyl group than estriol, is a "more sensitive and reliable indicator of fetal morbidity than estriol during toxemic pregnancies," because it starts to decrease earlier, or decreases more, than estriol. (Kundu, et al., 1978.) This seems to make it even clearer that the decline of estriol is a consequence, not a cause, of fetal sickness or death.
>
> A 1994 publication (B. Zumoff, "Hormonal profiles in women with breast cancer," Obstet. Gynecol. Clin. North. Am. (U.S.) 21(4), 751-772) reported that there are four hormonal features in women with breast cancer: diminished androgen production, luteal inadequacy, increased 16-hydroxylation of estradiol, and increased prolactin. The 16-hydroxylation converts estradiol into estriol.
>
> A new technique for radiographically locating a hormone-dependent breast cancer is based on the fact that estriol-sulfate is a major metabolite of estradiol.

### Source 6 — #86 - The Estrogen Industry, the magic of progesterone and the importance of thyroid with Dr Ray Peat & Kate Deering

Ray Peat · Interview · Jan 31, 2022

> **Ray Peat:** Estradiol is considered about 10 times. as potent as Estrone, but really that depends on your general health and amount of progesterone. And it's about three or four times as active as Estriol. But they're all interchangeable. It just takes a bigger dose of either estrone or estriol to have exactly the same effect as estradiol.
>
> **Kate Deering:** So my understanding is that while in your youth, you have more estradiol. And then I was under the understanding as you go through menopause, it's estrone that is more potent in your system, or is that not correct?
>
> **Ray Peat:** It increases with aging, but the measurements have all been done in the blood, which... very little to do with the actual tissue exposure to the effect of estrogen. Because with aging, your progesterone goes down and the estrogen increasingly stays inside cells and intensifies its activity. when you seem to have a disappearance of estrogen and menopause, if you add progesterone, suddenly you can measure a normal amount of estrogen as it's leaving the inside of the cells being detoxified and carried to the kidneys for excretion. That shows the progesterone is able to mobilize it out of your cells in a detoxified form.

### Source 7 — From PMS to Menopause: Female Hormones in Context

Ray Peat · Book · 1997

> **Ray Peat:** "The data do not support an antiestrogenic role for estriol in human breast cancer." (Lippman, et al., 1977.) Studies of the urinary output of estriol/estradiol in women with or without breast cancer do not reliably show the claimed association between low estriol/estradiol and cancer, and the stimulating effect of estriol on the growth of cancer cells suggests that any alteration of the estrogen ratio is likely to be a consequence of the disease, rather than a cause. The conversion of estradiol to other estrogens occurs mainly in the liver, in the non-pregnant woman, as does the further metabolism of the estrogens into glucuronides and sulfates. The hormonal conditions leading to and associated with breast cancer all affect the liver and its metabolic systems. The hydroxylating enzymes are also affected by toxins. Hypothyroidism (low T3), low progesterone, pregnenolone, DHEA, etiocholanolone, and high prolactin, growth hormone, and cortisol are associated with the chronic high estrogen and breast cancer physiologies, and modify the liver's regulatory ability. The decreased output of hormones when the fetal-placental system is dying is a natural consequence, since the placenta produces hormones, and during pregnancy converts estradiol to estriol. Since estradiol in excess kills the fetus, its conversion by the placenta to estriol is in accord with the evidence showing that estriol is the more quickly excreted form. (G. S. Rao, 1973.) The conversion of 16-hydroxy androstenedione and 16-hydroxy-DHEA into estriol by the placenta (Vega Ramos, 1973) would also cause fetal exhaustion or death to result in lower estriol production. But a recent observation that a surge of estriol production precedes the onset of labor, and that its premature occurrence can identify women at risk of premature delivery (McGregor, et al., 1995) suggests that the estriol surge might reflect the mother's increased production of adrenal androgens during stress.

### Source 8 — Ask the Herb Doctor: Hormone Replacement Therapy

Ray Peat · Interview · Apr 20, 2013 · http://l-i-g-h-t.com/files/herb-doctors-hormone-replacement-therapy-60-mins.mp4

> ## Caller: Types of Estrogen
>
> **Caller:** I haven't heard mention of the three different types of estrogen in our bodies. They have a hugely disparate impact on our bodies. Please inform us of that.
>
> **Ray Peat:** There are probably a dozen important types of estrogen, but the three main types—estriol, estrone, and estradiol—are the best known. Those all have pretty much the same effects but at different potencies. If you can turn your most potent estradiol into the others, you're protected against some of the most toxic effects. During pregnancy, enzymes are detoxifying estrogen by many different routes. The index of a healthy pregnancy is when the estriol is high because that means you're destroying your estradiol very quickly.
>
> **Sarah Murray:** So the estradiol is the most dangerous form.
>
> **Ray Peat:** And these different forms are exactly the issue that Elwood Jensen denied happened. He said estradiol can't turn into estrone and estriol, but in fact, that's a major way of activating or inactivating estrogen according to the cell's energy system.
>
> **Sarah Murray:** So the only reason you'd want high estriol is because that would tell us that the estradiol is being detoxified, not that high estriol in itself is protective.

### Source 9 — Hormones Hiding in Your Tissues w/Georgi Dinkov

Georgi Dinkov · Interview · Jun 23, 2023

> **Kitty Martone:** you know that the whole concept of the estriol being being put i'm hearing this a lot that a lot of doctors are saying if you apply estriol to like the labia it's going to stay in that area so you don't have to worry and i'm i'm thinking wait i mean i learned this in basic chemistry and and just a basic biology which is that anything you ingest through the skin through the you know through the respiratory tract has to go through at least second pass at the liver. It's going to go through at least the second phase of detox at the liver. It won't go through first pass if it's topical, but it's going to go through the liver. And depending on what the status of your phase two liver detox is, is going to determine what you do with your estrogen. And then of course, phase three, if you're recycling, you can completely turn that into something potent, right?
>
> **Georgi Dinkov:** Yep, yep. You want to shut the doctor down? So there is this thing called microchimerism. And basically, they found out that women that have died and they did autopsy, they found samples of DNA from their husbands in their brains. So how the hell does this thing get there? Well, you can imagine. when the husband is ejaculating, that thing travels and that's a much larger molecule than estriol. So if that thing can make its way through the entire body and get lodged into the brain, then estriol is a given that is going to get eventually get metabolized and distributed. I think what they're trying to say is, okay, look, the highest concentrations will be in the labia because that's where you apply it. And little by little, it gets excreted. It gets transferred by the bloodstream through the liver and the second phase detox pathway. takes care of it, the glucuronidation and whatever, the sulfation, and then you pee it out, right? Yeah, but this process of diffusing through the body, it's very obvious that it's far from harmless. And there are many studies showing that you can actually get skin cancer from the local application of even a very weak estrogen. And if that's the case, then I don't see how applying it to the labia will be any different. Melanomas are known to form... in places of the skin that don't see any sunlight. So melanoma, no matter how much they scare us with melanoma, melanoma is not a sun-driven cancer. The basal cell carcinoma and the squamous cell carcinoma, which almost never kill because they don't spread, they're the ones that are tied to UV light damaging the DNA in the skin, but not melanoma. Most people get melanomas like at the bottom of their soles, between their legs. like somewhere behind the ear on the scalp, like where there's a lot of hair. And melanoma is known to be estrogenically driven. I posted this study a long time ago on the forum.

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