ESTRIOL (E3) - It's weakness is its strength

• Health Benefits of ESTRIOL
• How to supplement ESTRIOL
• ESTRIOL may not have its protective role if CONTINUOUSLY supplied

What is ESTRIOL ?

ESTRIOL is one of the 3 main estrogen hormones -  the other two are  ESTRADIOL and  ESTRONE.

Health Benefits of ESTRIOL

ESTRIOL provides a safe form of HRT

ESTRIOL prevents menopausal symptoms.    E.g. hot flashes, without causing unwanted side effects common to conventional estrogen replacement therapy.

-   Vaginal dryness, atrophy (leading to vaginitis and cystitis).   Beneficial acid-producing vaginal Lactobacilli depend on the presence of estrogen. ESTRIOL has a binding affinity to vaginal ERs equal to ESTRADIOL, sufficient to exert a full effect on the vagina after a single dose. For postmenopausal vaginal dryness and atrophy, which can lead to vaginitis and cystitis, ESTRIOL supplementation is theoretically the most effective and safest estrogen choice.

ESTRIOL improves vaginal flora in postmenopausal women

Study shows ESTRIOL modifies the vaginal flora and significantly lowers vaginal pH (from 5.5 to 3.8).

• -   ESTRIOL recolonized Lactobacilli (absent prior to therapy) in the vagina after only one month.   In 61% of postmenopausal women given ESTRIOL, but in none receiving placebo.

• -   Additionally, the prevalence of Enterobacteriaceae (fecal bacteria) colonization fell from 67% to 31%.    No change observed in those receiving placebo.  (Cardozo et al,1998)

Prevent recurrent UTIs in postmenopausal women

• The intravaginal administration of ESTRIOL prevents recurrent UTIs in postmenopausal women
• Intra-vaginally applied ESTRIOL cream significantly reduced UTI incidences in women with recurrent UTIs - in a randomized, double blind, placebo-controlled study the group of women using intravaginal ESTRIOL cream (containing 0.5 mg ESTRIOL, once daily for two weeks, then twice weekly for eight months) had dramatically reduced incidence of UTI compared with placebo (0.5 versus 5.9 episodes per year). Raz & Stamm, 1993)

ESTRIOL reduces incontinence in postmenopausal women

• The intravaginal administration of ESTRIOL reduced incontinence in postmenopausal women.    In a randomized, placebo-controlled study, 88 women were given 2 mg intravaginal ESTRIOL suppositories (once daily for two weeks, then twice weekly for six months) or placebo. Of the women in the ESTRIOL group, 68% reported improvement in symptoms of incontinence. In addition, measurements of mean maximal urethral pressure and mean urethral closure pressure were significantly improved. Dessole et al, 2004

ESTRIOL (E3) protective against breast and uterine cancers

ESTRIOL may offer cancer-protective benefits for post menopausal women without the side effects of ESTRADIOL

ESTRIOL's WEAKNESS IS ITS STRENGTH.

ESTRIOL has a much less stimulating effect on the breast than ESTRONE and ESTRADIOL (which is 1000 times more stimulating to breast tissue)

• ESTRIOL blocks ESTRONE and ESTRADIOL activity.    ESTRIOL binds to estrogen receptors (ERs) on the breast cells, but has much weaker activity. Thus, it actually blocks the stronger ESTRONE and ESTRADIOL from binding to those cells and subjecting them to the subsequent higher estrogenic activity.

• ESTRIOL ▲ correlates with cancer▼.    In the 1966 Journal of the American Medical Association H.M. Lemmon, M.D. reported a study showing that higher levels of ESTRIOL in the body correlate with remission of breast cancer. Dr. Lemmon demonstrated that women with breast cancer had reduced urinary ESTRIOL excretion. He also observed that women without breast cancer have naturally higher ESTRIOL levels, compared to ESTRONE and ESTRADIOL levels, than women with breast cancer.

• Vegetarian and Asian women have high levels of ESTRIOL (presumed to be the result of a high intake of phytoestrogenic soy) and these women are at much lower risk of breast cancer than other women

ESTRIOL has a much less stimulating effect on uterine lining than ESTRADIOL

• Receptor binding studies have indicated that ESTRIOL has a binding affinity to endometrial estrogen receptors only about 10% of ESTRADIOL.   After a single dose (as opposed to a continuously supplied dose) of ESTRIOL, the binding to the endometrial estrogen receptor is too short to induce proliferation

ESTRIOL arrests breast cancer

• Unlike the stronger estrogens ESTRADIOL or ESTRONE, ESTRIOL has not been shown to stimulate the uterus or breast cells either.    In either animal studies or human clinical trials.
• A clinical trial of 2.5 to 5 mg per day of ESTRIOL therapy in 28 premenopausal and postmenopausal breast cancer patients demonstrated that ESTRIOL induced remission or arrest of metastatic tumors in six (37%) of the women.

ESTRIOL improves skin

Estrogens are needed for producing the proteins collagen and elastin.    These give skin its elasticity and structure, and also hyaluronic acid, responsible for holding moisture in the skin.

• -   Collagen is lost at a rate of ~30% in first 5 years after menopause.    Then ~ 2.1%/year over 20 years.

• -   Mid/Late 1990's studies demonstrated that ESTRIOL face cream is very effective at reversing wrinkles and other skin aging problems occurring at menopause

• -   You need a "Goldilocks" Dose" of ESTRIOL.    i.e. it must be just right, because estrogen levels too high or too low give lower collagen levels.

Estrogen replacement therapy significantly increases dermal skin thickness.   Determined by various studies.

• Estrogen therapy in castrated mice increased GAG content by 70% in 2 weeks.     In women, increases in GAGs lead to skin thickness increases that are much higher than from collagen content increases alone;

ESTRIOL may support the cardiovascular system

• Some menopausal women taking oral ESTRIOL experienced a significant decrease in both systolic and diastolic blood pressure.   These women took 2 mg/day oral ESTRIOL for 12 months. (Takahashi et al, 2000)
• Some elderly women taking ESTRIOL decreased their total cholesterol and triglycerides and increased their levels of beneficial HDL cholesterol.   The study evaluated 20 postmenopausal and 29 elderly women taking an oral Estriol dose of 2 mg/day for 10 months. Nishibe et al, 1996

ESTRIOL improves bone mineral status in women with osteoporosis

• Japanese study of 75 postmenopausal women supplementing ESTRIOL showed increases in bone mineral density, a decrease in menopausal symptoms, and no increased risk of endometrial hyperplasia (tissue overgrowth that may precede cancer).   After 50 weeks of taking 2 mg/day of ORAL estriol cyclically and 800 mg/day of calcium lactate. (Minaguchi et al, 1996)
• Another study found that supplementing estriol in addition to calcium lactate significantly increased bone mineral density compared to calcium supplement alone.    Postmenopausal and elderly women took 2 mg/day of ORAL estriol and 1,000 mg/day of calcium lactate versus 1,000 mg/day calcium lactate alone. (Nishibe et al, 1996)

How to supplement ESTRIOL

Estriol is available as an oral supplement.   However, via this route, the ESTRIOL must navigate through the digestive system and the liver will "dump" approximately 75% of the estriol into the body's elimination channels. A typical 2-5mg dose will thus yield only about 0.5mg. of ESTRIOL whilst also burdening the liver.

Estriol is better delivered topically or intravaginally using an estriol cream.   The skin does not absorb ESTRIOL quite as well as ESTRADIOL or ESTRONE, but studies have shown that topical delivery is about 20 times more efficient than oral delivery. The skin and vaginal membranes also provide quite a steady supply of ESTRIOL until it clears the body - usually in 2 days.

Where to apply ESTRIOL cream?

It would make sense to apply cream in the area where it is needed.   If in the reproductive area, then rubbed inside the vagina or into the testicle skin. Alternatively, if using it to treat facial wrinkles, then apply to the face and neck.

Estrogen receptors have been identified in the vulva, vagina, bladder, urethra, pelvic floor musculature, and endopelvic fascia.    ESTRIOLhas a binding affinity to vaginal ERs equal to ESTRADIOL.   Number of ERs varies by location:

• Vaginal epithelium has highest ER concentration.    Also, the vagina has a high ER : PR ratio; in contrast,the vulva has high PR: ER ratio;
• Cervix, uterine body and fallopian tubes.     Have high ER density

ER and PR concentration remains stable postmenopause.    However, AR (androgen receptor) concentration decreases by about half ;

Combine ESTRIOL therapy with . . .

PROGESTERONE.    To prevent hormone imbalance, any supplemental estrogen should be used together with Natural PROGESTERONE . According to Dr. Lee, most women become deficient in PROGESTERONE long before estrogen levels drop to the point of causing symptoms.

Vitamin E.    Administered at 400 IU / day with ESTRIOL therapy will improve ESTRIOL activity and effectiveness

How much and how often?

Use 0.5 mg - 0.75 mg topical or intravaginal ESTRIOL  cream every other day or just a few times a week (responding to amount needed to control symptoms)     See ESTRIOL Health Benefits for doses used in studies for specific problems.

• Why every other day?    ESTRIOL does not clear the body as fast as the other estrogens, usially taking 2 days. Thus, one dose will last  2 days for most women. Using more could result in excessively high doses in your body.
• Example Cream: Life-Flo ® Estriol cream.    One full press of the pump contains 0.75mg natural ESTRIOL USP;

Take a break from using ESTRIOL at the same time you take a break from PROGESTERONE.    E.g. If you are postmenopausal or have had a hysterectomy, you use PROGESTERONE for only 3 weeks out of the month

 

ESTRIOL may not have its protective role if CONTINUOUSLY supplied (E.g. by implants)

Potency of ESTRADIOL is not much different to ESTRONE and ESTRIOL WHEN THEY ARE CONTINUOUSLY SUPPLIED (E.g. by implants or a patch) - Earlier work from the Clark laboratory maintained that physiological Estrogens, other than ESTRADIOL, were not weak when their concentrations were maintained continuously by implants (as opposed to single injections), in which case, they could actually elicit tissue growth of the uterus.  Anderson JN etal, 1975

Also, continuous administration of ESTRIOL was shown to induce breast tumors in rodents, whereas a single injection failed to induce tumors in susceptible rodent strains and appeared to block such induction by ESTRADIOL and ESTRONE.

In the 1940's, Alexander Lipshuts demonstrated that a CONTINUOUS, WEAK estrogenic stimulus was immensely effective in producing first fibromas, then cancer, in one organ after another.   The effect was not limited to the reproductive system. For example, the brain and liver, which also have estrogen receptors, may grow tumors too. Townsend Letters, 1997

ESTRIOL has been suggested as having a protective role in breast cancer based on the observation that oriental women who have a high ESTRIOL / (ESTRADIOL + ESTRONE) ratio in their blood also have a low incidence of breast cancer.

• Soy bean (containing phytoestrogens) has also been suggested as being protective in breast cancer.   On the basis that Japanese women who consume much more soy bean than Western women have lower incidence of breast cancer.
• However, in the past, oriental women took much less medical drugs including painkillers compared to women in Western societies.   Today, oriental breast cancer incidence has gone up significantly in recent years even though soy bean products are still consumed there much more than in Western societies - a trend that may in part be due to increased consumption of medications. The American Liver Foundation stated that the amount of medicine consumed has increased greatly with resulting dangers to the liver. The elevated estrogen level caused by a weak liver may not be detected in blood tests because blood estrogen levels do not necessarily reflect estrogen levels in tissues and estrogen levels in the tissues cannot be measured

 

References

Anderson, J. N., Peck, E. J., Jr., and Clark, J. H. (1975) estrogen-induced uterine responses and growth: relationship to receptor estrogen binding by uterine nuclei. Endocrinology 96, 160-167

Cardozo L, Bachmann G, McClish D, Fonda D, Birgerson L. (1998) Meta-analysis of estrogen therapy in the management of urogenital atrophy in postmenopausal women: second report of the hormone and urogenital therapy committee. Obstet Gynecol ;92:722-7.

Dessole S, Rubattu G, Ambrosini G et al (2004 Jan) Efficacy of low-dose intravaginal estriol on urogenital aging in postmenopausal women. Menopause. ;11(1):49-56.

Minaguchi H, Uemura T, Shirasu K, et al (1996 Jun) Effect of estriol on bone loss in postmenopausal Japanese women: a multicenter prospective open study. J Obstet Gynaecol Res.;22(3):259-65.

Nishibe A, Morimoto S, Hirota K, et al (1996 May) Effect of estriol and bone mineral density of lumbar vertebrae in elderly and postmenopausal women. Nippon Ronen Igakkai Zasshi. 33(5):353-9.

Raz R, Stamm WE (1993) A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections.N Engl J Med ;329:753-7.

Takahashi K, Okada M, Ozaki T, et al (2000 May) Safety and efficacy of oestriol for symptoms of natural or surgically induced menopause. Hum Reprod.; 15(5):1028-36.

Townsend Letters for Doctors and Patients (January, 1997 issue), Ray Peat, a renowned biologist in the U.S.

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