Quick answer: Estriol, or E3, is the gentlest of the three main estrogens, and it rises sharply during pregnancy while being made in much smaller amounts afterward as estrogen is broken down. Outside pregnancy, an estriol result reflects how much estrogen the body makes and how it is processed, and in one prospective study estriol itself was not significantly linked with postmenopausal breast cancer risk.
When people talk about estrogen, they usually mean estradiol, but the body actually makes three main estrogens. Estradiol, often written E2, is the strongest. Estrone, or E1, is the main estrogen after menopause. Estriol, or E3, is the gentlest of the three, and during pregnancy the placenta makes it in very large amounts. Outside pregnancy, estriol is made in much smaller amounts as estrogen is broken down along what is called the 16-hydroxylation pathway. My articles on estrogen metabolism and progesterone metabolites look at the wider picture, and this one focuses on estriol itself.
This article is educational. It explains what the marker reflects and how researchers connect it to the deeper mechanisms of aging, so you can have a more informed conversation with your own provider.
What does an estriol result reflect?
Estriol can be measured in blood or urine, and urine hormone panels often report it alongside estrone, estradiol and the estrogen metabolites from three main pathways, called the 2, 4 and 16 pathways after the place on the hormone where the liver adds a chemical group. Estriol sits near the end of the 16 pathway, so its level reflects both how much estrogen the body makes and how that estrogen is being broken down.
A higher estriol result outside pregnancy can reflect higher overall estrogen production, more estrogen moving down the 16 pathway, or the use of hormone products that contain estriol. A lower result is common after menopause, when the ovaries make much less estrogen overall. During pregnancy estriol is used in a completely different way, as one of the markers in prenatal blood screening, which is a separate topic from the hormone testing discussed here. Any hormone cream, patch or pill can change estrogen results, so it helps to tell your provider about everything you use before testing.
How does estriol connect to aging and root causes?
Estrogens are messengers, and the decline in estrogen around menopause is one of the clearest examples of how changes in hormone signaling between tissues shape aging. Estrogen helps keep the tissues of the vagina, bladder and urethra thick and well supplied with blood, and when it falls, those tissues thin and the local microbiome changes. The research below shows that in postmenopausal women with recurring urinary infections, protective lactobacilli were missing from every vaginal culture at the start, and the vaginal pH sat at about 5.5, which is less acidic than in younger women. That is a direct link between hormone signaling and the microbiome.
Estriol also has an immune side. Relapses of multiple sclerosis tend to drop during pregnancy, when estriol is highest, and that observation led researchers to study estriol as an immune-calming hormone. This connects estrogen signaling to chronic low-grade inflammation, although most of that work is still in early stages.
From a root-cause view, the more interesting question is often not how much estriol you have, but how estrogen as a whole is being processed. The liver breaks estrogen down through the 2, 4 and 16 pathways and then uses methylation to finish the job, which depends on nutrients such as folate, vitamin B12, vitamin B6 and magnesium. The gut then plays a role, because an enzyme from gut bacteria called beta-glucuronidase can release estrogen that the liver has packaged for removal, allowing it back into circulation. Fiber intake, alcohol, body fat, sleep, stress and blood sugar balance all influence how much estrogen is made and how it is cleared.
Everyday exposures matter here as well. Some plastic chemicals and other compounds can weakly mimic estrogen, and researchers are still working out how much they affect human hormone levels. Genetics plays a part too, since common variations in the liver enzymes that process estrogen differ from person to person. Supporting digestion, fiber, liver function and methylation is often more useful than focusing on estriol alone.
What does the research show about estriol?
A study of estrogen metabolism and breast cancer risk measured estriol directly. In 2013 in Breast Cancer Research, Falk and colleagues drew on 6,915 women who gave blood samples between 1977 and 1987 and were followed through 2002, comparing 215 postmenopausal women who developed breast cancer with 215 matched controls who were not using hormones. They measured 15 estrogens and metabolites with mass spectrometry. Estriol itself was not significantly linked with risk, and among the 16-pathway metabolites only 16-epiestriol showed a borderline trend. Women with higher levels of 2-pathway metabolites had lower risk, with odds ratios of 0.57 and 0.53 for the highest versus lowest quarter of two methylated 2-pathway metabolites. This was a modest-sized observational study based on a single blood draw taken years before any cancer appeared, so the authors called for larger pooled studies.
A randomized trial looked at estriol applied directly to vaginal tissue. In 1993 in the New England Journal of Medicine, Raz and Stamm enrolled 93 postmenopausal women with a history of recurrent urinary tract infections and randomized them to an intravaginal estriol cream or placebo for eight months. Urinary tract infections fell to 0.5 episodes per person per year with estriol compared with 5.9 with placebo. Lactobacilli reappeared in 22 of 36 women using estriol and in none of the 24 using placebo, and vaginal pH fell from 5.5 to 3.8. The limitations are real, since only 60 of the 93 women completed the eight months and side effects led 28 percent of the estriol group and 17 percent of the placebo group to stop.
A larger trial tested oral estriol at pregnancy-like doses. In 2016 in Lancet Neurology, Voskuhl and colleagues randomized 164 women aged 18 to 50 with relapsing-remitting multiple sclerosis at 16 academic centers to 8 milligrams of estriol a day or placebo, each added to a standard injectable medication, for 24 months. The yearly relapse rate was 0.25 with estriol and 0.37 with placebo, an adjusted rate ratio of 0.63. That result met the trial’s pre-set threshold for a phase 2 study, but the confidence interval crossed one, so it is promising rather than conclusive, and irregular menstrual cycles were more common with estriol, at 23 percent compared with 4 percent.
Human evidence on estriol as a blood or urine marker on its own is still limited, and most of the strongest trials studied estriol given as a hormone rather than natural levels. That is why I see an estriol result as one piece of the larger estrogen metabolism picture.
Related reading
If you would like to explore related topics, my articles on estrogen metabolism, progesterone metabolites and beta-glucuronidase go deeper. You can also see the specialty tests I commonly recommend on my functional labs page.
Common questions about Estriol
Is estriol a good or a bad estrogen?
Estriol is a weaker estrogen than estradiol, but research does not support a simple good or bad label. In one prospective study, estriol itself was not significantly linked with postmenopausal breast cancer risk, while the balance of the 2 pathway looked more informative.
Why is estriol so high during pregnancy?
The placenta makes large amounts of estriol during pregnancy. Researchers studied estriol in multiple sclerosis partly because relapses tend to drop during pregnancy, when estriol is at its highest.
Can hormone products change an estriol result?
Yes. Any hormone cream, patch or pill can change estrogen results, so it helps to tell your provider about everything you use before testing so the result can be read in context.
Sources
This article is for educational purposes only and is not medical advice. It does not replace an individual evaluation. Talk with your healthcare provider before making changes to your diet, exercise, supplements, or medications, especially if you are pregnant, nursing, or managing a health condition.
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