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We are talking about a metabolite of estradiol, belonging to the category of sex hormones.
Estriol, an estrogen that has been largely ignored by the general medical community, is one of the three main estrogens produced by the body.
Estriol was originally thought to be of little importance due to its weak estrogenic activity compared to estrone and estradiol. However, research has found that your weakness may very well be your strength.
Studies suggest that when the lower-strength estrogen, estriol, is administered topically, it does not increase the risk of hormone-dependent breast or endometrial (uterine lining) cancer.
However, having weaker estrogenic effects does not mean that estriol does not have any of the benefits that come with more potent estrogens.
Importance of estriol
Studies suggest that estriol reduces menopausal symptoms, such as hot flashes and vaginal dryness, but with a better safety profile compared to more potent estrogens.
This makes estriol a better choice for bioidentical hormone replacement treatment regimens.
Research suggests that estriol has benefits for bone density, heart health, multiple sclerosis, and urinary tract health.
The body naturally produces three estrogen hormones: estradiol, estrone, and estriol. Since estriol possesses the weakest estrogenic effects of the three, it has been largely overlooked by the medical community.
Many studies show that estriol offers a host of potential health benefits, without the dangers that sometimes accompany higher-strength estrogens and synthetic or horse-derived hormones.
Studies suggest that estriol helps relieve menopausal symptoms while benefiting bone and urinary health.
Estriol can also help improve cardiovascular risk factors and even shows promise for reducing multiple sclerosis brain injuries.
The most reliable way to measure estriol levels is through 24-hour urine collection.
Despite abundant evidence to the contrary, the FDA has recently stated that estriol is not safe.
The fear of cancer prevents many women from regaining youthful hormone levels. When applied topically (transdermally), estriol is not associated with an increased risk of cancer.
Other methods women can use to prevent hormone-related cancers include consuming plenty of vitamin D, cruciferous vegetables, soybeans, D-glucarate, and lignans, while minimizing high-fat meat and dairy products.
Hormone replacement therapy and estriol
If you are on hormone replacement therapy (HRT) and have never heard of estriol, you may be wondering why not.
Before the 1970s, estriol was thought to be important only during pregnancy. Estriol levels are elevated in pregnancy up to 1,000 times compared to normal non-pregnant levels.
In the 1960s, we saw the beginning of hormone replacement therapy with proprietary equine estrogens like Premarin® and synthetic progestins found in Provera®.
In the 1990s, a third of menopausal women were taking Premarin®.
Research found the highest incidence of breast cancer, the highest risk of blood clotting, and the highest cardiovascular risk associated with the use of these synthetic and horse-derived hormones (used in combination in the proprietary drug Prempro®).
The medical community began to wonder if using hormones from pregnant horses was a good idea.
In an effort to find a safer alternative, many patients and practitioners began looking for a “natural” hormone replacement treatment using bioidentical hormones, which are identical to those naturally produced in the body.
Bioidentical hormone replacement was pioneered in the 1980s as a treatment for menopause by Dr. Jonathan Wright.
Interest in estriol increased as estriol was found to be safer than synthetic and horse hormones in relation to cardiovascular health and potential cancer risk.
Unfortunately, many physicians have not embraced its use, and many bioidentical hormone replacement regimens use only estradiol, a more potent estrogen with higher associated risks.
The benefits of estriol can, in part, be explained by the mixed proestrogenic and anti-estrogenic effects of this interesting estrogen hormone.
Scientists Melamed et al. He investigated the mix of stimulant and non-stimulant effects posed by estriol on estrogen receptors.
When estriol is administered together with estradiol, the specific stimulation of estradiol to cells is decreased.
This little-appreciated scientific fact helps explain how estriol can reduce the pro-cancer effects of more potent estrogens, such as estradiol.
However, when estriol is given alone for a long period of time, it can produce a more complete proestrogenic effect, explaining why symptom relief is achieved when menopausal women take estriol.
Experimental studies suggest that both estriol and tamoxifen (a synthetic antiestrogenic) have protective effects against radiation-induced breast cancer.
Security concerns
Most of the research cited in this article used oral estrogen as the route of administration. However, for added safety, topical estriol would be a better option.
Several studies have shown that transdermal estrogen confers less risk to health as a route of administration than oral estrogen.
The clinical experience of many physicians in the past 20 to 30 years suggests that transdermal estrogen is also more effective for some women.
This is largely thought to be due to the ‘first pass effect’, which means that drugs taken by mouth are often metabolized first in the liver, before having any activity in the body.
Oral estrogen hormones are among these drugs that are first metabolized in the liver before exerting their effects in the body.
Doctors with experience in hormone replacement often observe that women treated with oral estrogens show high levels of estrogen metabolites in 24-hour urine samples, suggesting that the majority of orally ingested hormones are being excreted.
Additionally, several studies suggest that bioidentical estrogen has less health risk when administered with low doses of bioidentical progesterone.
In a prospective study funded by the US Army and conducted at the Institute of Public Health in Berkeley, California, researchers compared estriol levels during pregnancy with the incidence of breast cancer 40 years later.
The results revealed that of the 15,000 women enrolled in the study, those with the highest levels of estriol relative to other estrogens during pregnancy had the lowest risk of cancer.
In other words, as the relative level of estriol increased during pregnancy, the risk of breast cancer decreased 40 years later.
In fact, women with the highest level of estriol during pregnancy had a 58% lower risk of breast cancer compared to women with the lowest levels of serum estriol.
The authors also noted that Asian and Hispanic women had higher levels of estriol compared to other racial groups. Curiously,
Asian and Hispanic women have the lowest rates of breast cancer.
The authors concluded: “If confirmed, these results could lead to breast cancer prevention or treatment regimens that attempt to block the action of estradiol and estrogen using estriol, similar to the antiestrogenic synthetic tamoxifen-based treatment.”
Estriol reduces cardiovascular risk markers
In another study, Takahashi et al. He studied the safety of estriol treatment for menopausal symptoms.
Fifty-three women with natural or surgically induced menopause received 2 mg oral estriol / day for 12 months.
Endometrial and breast evaluations performed with endometrial biopsy and breast ultrasound, respectively, found normal results in all women.
The authors concluded that over a 12-month period, “estriol appeared to be safe and effective in relieving symptoms in menopausal women.”
In one investigation, 52 postmenopausal women were given oral estriol 2 mg, 4 mg, 6 mg, or 8 mg / day for six months.
In all patients, vasomotor symptoms of menopause (such as hot flashes) decreased.
Women who took the highest dose of 8 mg experienced the improvement. There were no signs of endometrial hyperplasia confirmed by endometrial biopsy during the six-month treatment period.
Mammograms were obtained in six of the patients who had breast hyperplasia at baseline and no further changes were observed.
Although the oral route of estriol administration appears relatively safe in the short term, the transdermal route is preferred for long-term use.
For example, Weiderpass et al. found an increased risk of atypical endometrial hyperplasia and endometrial cancer with oral use of estriol, but not with transdermal estriol for at least a five-year period.
Compared to using estriol without use, those who took oral estriol for at least five years had a significantly higher risk, compared to people who took no estriol.
Women who used topical estriol for at least five years had no increased risk. Several studies suggest that the use of a natural progesterone topical cream can further reduce the risk to the endometrium.
Henry Lemon, MD, a women’s cancer specialist, took this research one step further and developed the concept of the estrogen quotient – the ratio of estriol to the sum of estradiol and estrone (estriol / estrone + estradiol).
By looking at this ratio of “good” estrogen to “bad” estrogen, a doctor can assess the risk of breast cancer and prescribe a better-tailored estrogen replacement to reduce the risk of cancer.
The estrogen quotient can be assessed from a 24-hour urine hormone panel.
Mounting evidence suggests that estriol may offer protective benefits for the cardiovascular system.
For example, Takahashi et al. found that some naturally menopausal women who received 2 mg / day of oral estriol for 12 months had a significant decrease in systolic and diastolic blood pressure.
Another study compared the use of oral estriol at a dose of 2 mg / day for 10 months in 20 postmenopausal women and 29 elderly women.
Some of the older women had a decrease in total cholesterol and triglycerides and an increase in beneficial high-density lipoproteins (HDL).
Estriol improves bone mineral status in women with osteoporosis
A Japanese study that included 75 postmenopausal women found that:
After 50 weeks of treatment with cyclical oral estriol 2 mg / day and calcium lactate 800 mg / day, the women had an increase in bone mineral density, a decrease in menopausal symptoms, and no increased risk. endometrial hyperplasia (excessive tissue growth that can precede cancer).
Similarly, Nishibe et al. investigated the treatment of postmenopausal and elderly women with 2 mg / day of oral estriol and 1,000 mg / day of calcium lactate versus 1,000 mg / day of calcium lactate alone.
Bone mineral density increased significantly in women who received estriol, while women who did not take estriol experienced a decrease in bone mineral density.
Estriol reduces multiple sclerosis brain lesions
High levels of estriol during pregnancy are known to alleviate some autoimmune conditions due to its ability to change the immune response.
For example, Sicotte et al. at the Reed Neurological Research Center in Los Angeles, the effects of estriol doses at the pregnancy level (8 mg / day) in nonpregnant women with multiple sclerosis (MS) were investigated.
Brain MRI images showed a significant reduction in gadolinium-enhancing brain lesions of multiple sclerosis.
These injuries increased when treatment was stopped and decreased when treatment was restarted.
Gadolinium is a contrast agent used in certain MRI studies, gadolinium-enhanced lesions are associated with an increased inflammatory response that marks disease progression in MS patients.
A decrease in the number of these lesions observed on MRI with gadolinium contrast would be equivalent to a decrease in the progression of the disease.
This effect can also apply to men with autoimmune conditions. Another team of researchers at the Reed Neurological Research Center in Los Angeles found that treatment with estriol improves experimental autoimmune encephalomyelitis (EAE) in men, compared to treatment with placebo.
EAE is an experimental demyelinating inflammatory disease that shares many features with MS.
Estriol treatment also resulted in a decrease in pro-inflammatory immune markers.
This is very promising news for patients and their doctors who are struggling to treat challenging neurological conditions associated with inflammation.
Estriol protects urinary health in postmenopausal women
Postmenopausal women who suffer from recurrent urinary tract infections or incontinence will be pleased to know that estriol offers benefits in the context of these troublesome conditions.
In a prospective, randomized, placebo-controlled study, 88 women received 2 mg intravaginal estriol suppositories (once a day for two weeks, then twice a week for six months) or placebo.
Of the women in the estriol group, 68% reported improvement in incontinence symptoms. Furthermore, measurements of maximum mean urethral pressure and mean urethral closure pressure were significantly improved.
In another randomized, double-blind, placebo-controlled trial, women with recurrent urinary tract infections (UTIs) were given intravaginal estriol cream (containing 0.5 mg of estriol, once daily for two weeks, then twice a week for eight months) or a placebo.
The incidence of urinary tract infection was drastically reduced in the estriol group compared to placebo (0.5 versus 5.9 episodes per year).
Measurement of estriol
Hormones produced by the body are secreted in pulses, whereas hormones taken transdermally or orally will initially be very high and slowly decline throughout the day.
This scientific reality makes tests for estriol at a single point in time, such as saliva or serum tests, very inaccurate.
Estriol in particular does not last long in the blood. In fact, the half-life of estriol has been shown to be between 3.6 and 64 minutes.
The most accurate way to evaluate estriol is by collecting what is excreted during a 24-hour urine collection.
This form of testing ensures that we have an accurate value that is not affected by the fluctuations of the day, because we are measuring 24 hours of hormone production.
Estriol, once considered negligible and weak, actually has protective effects against stronger estrogens. For this reason, it is a relatively safer option for bioidentical hormone replacement therapy.
We have learned that safety is also increased by using topical rather than oral administration and by balancing estrogen with progesterone.
Estriol has benefits beyond treating typical postmenopausal symptoms.
Estriol offers potential benefit for people with MS, postmenopausal women prone to urinary tract infection or incontinence, and menopausal / postmenopausal women with osteoporosis.
It would be a great shame to lose this wonderful tool before it has been fully used.
Is the fear of cancer a reason to deprive yourself of hormones?
As women enter their menopausal years, they are faced with a difficult decision.
The body’s natural production of estrogen, progesterone, dehydroepiandrosterone, and other critical hormones necessary for maintaining health and vigor rapidly declines.
While the individual effects of menopause vary widely, most women suffer because their glands no longer produce the hormones necessary to regulate critical physiological processes.
Depression, irritability, and short-term memory lapses are common menopausal conditions, along with hot flashes, night sweats, and insomnia.
Cancer concern is the main reason women do not restore their hormones to more youthful levels. Like much of what we eat, estrogen and testosterone affect cell proliferation.
Does that mean that we should shrink, degenerate, and die from these sex hormone deficiencies that we all face as part of “normal” aging?
Based on data showing how people can reduce their cancer rate and favorably affect estrogen metabolism in a way that targets cancer prevention.
In other words, when consuming many cruciferous vegetables it is difficult to accept the argument that natural sex hormones should only be enjoyed by young people.
Large human population studies show huge reductions in cancer risk and specific protective mechanisms against negative estrogen pathways when vitamin D, cruciferous vegetables (a source of indole-3-carbinol or I3C), soy, D-Glucarate , and lignans are consumed.
Drastic reductions in cancer rate also occur when red meat, high-fat dairy products, and other harmful foods are reduced or eliminated from the diet.
