Emailing: Estriol

[Guest guest]

ESTRIOL Estriol (E-3) is one of the three active estrogens found in the body. Although a small amount may be secreted by the ovary, it is a converted estrogen. It is mainly converted in the liver from estrone (E-1) and also by a more circuitous route from estradiol (E-2). In the nonpregnancy state estriol is only a scant by product of estrone metabolism. During pregnancy, however, the placenta is the major source of estrogens; Estriol is produced in milligram quantities, while the other two estrogens and produced in microgram amounts.

Estriol made by the placenta is made from the hormone DHEA (dehydroepiandrosterone) supplied from either the mother or the adrenal cortex of the fetus. Because of fetal participation in estriol formation, estriol measurements can be a sensitive indicator of placenta and / or fetal well-being.

Estriol is considered the "forgotten" estrogen. Is has been labeled historically in the US as a weak or ineffective estrogen, while in Europe estriol has been recognized for its benefits and has been used for years. With articles and studies such as the one published in the New England Journal of Medicine stating that women using traditional estrogen therapy for five or more years have a 30 to 40% increased risk of cancer, the need to use a safer form of estrogen seems crucial. Estriol might be the estrogen of choice, considering it has not been associated with cancer activity in the female body.

POSSIBLE BENEFITS OF ESTRIOL

Estriol has a much less stimulating effect on the breast and uterine lining than estradiol and estrone. Estradiol is 1000 times more stimulating to the breast tissue than is estriol.

One of the most exciting things about estriol is the fact that not only does it not promote breast cancer, but considerable evidence exists to show that it protects against this disease.

In 1978, A. H. Follingstad, M.D. of Albuquerque, NM, wrote as article for the Journal of the American Medical Association, calling for the use of estriol instead of estrone and estradiol. In support of his position, he cited a group of post menopausal women with metastatic breast cancer. When given small doses of estriol, 37% of the women experienced either a remission or a complete arrest of the metastasized lesions.

In 1966, H. M. Lemon, M.D. demonstrated that women with breast cancer have lower estriol levels. Later he showed that women without breast cancer had naturally higher estriol levels (compared to estrone and estradiol) than those with breast cancer.

Doses of 2-4 mg. estriol is considered to be the equivalent of .625 and 1.25mg conjugated estrogen respectively.

Dr. n Whitaker, Publisher of the "Health and Healing " newsletter, says that estriol's anti-cancer effect is thought to be due to its anti-estrone characteristics. It apparently blocks the stimulatory effect of estrone on the breast.

Estriol as an estrogen supplement does not lose its unique identity when given orally as does estradiol. It remains estriol.

Estriol is thought to help prevent or stabilize the conversion of estradiol to estrone. Estrone being labeled by many researchers as the "villain" estrogen in the female body.

Estriol seems to be well tolerated when given orally.

It is also remarkable that estriol, different from estradiol, does not provoke endometrial proliferation and shedding when given in one dose a day. Thus, estriol is characteristically suitable for postmenopausal women who no longer want to have uterine bleeding and who have comparatively higher risk of endometrial hyperplasia.

A Taiwan study concluded that estriol was very effective in the improvement of major subjective climacteric complaints in 86% of patients, especially hot flush and insomnia within 3 months. The atrophic genital changes caused by estrogen deficiency were also improved satisfactorily. This study was not able to show that estriol will prevent bone loss.

Receptor binding studies have indicated that estriol has only low relative binding affinity to endometrial estrogen receptors (about 10% of Estradiol). whereas it has a relatively strong binding affinity to vaginal estrogen receptors (equal to Estradiol). This means that after a single dose of estriol, the binding to the endometrial estrogen receptor is too short to induce true proliferation, while its binding to the vaginal estrogen receptor is sufficient to exert a full vaginotropic effect. Because of estriol's strong vaginotropic effect it is though to be the estrogen most beneficial to the vagina, cervix, and vulva. In cases of postmenopausal vaginal drynes and atrophy, which predisposes a woman to vaginitis and cystitis, estriol supplementation would theoretically be the most effective (and safest) estrogen to use.

Of all the estrogens, estriol has the shortest receptor occupancy. Therefore providing a short duration of action in certain estrogen receptor tissue. A consequence of the short duration of action of estriol at the receptor level is that there are hardly any systemic effects. Studies indicate absence of effects on: blood pressure, body weight, liver function, hemostasis, lipid metabolism, and bone metabolism.

Current studies do not show estriol to have any cardioprotective effects through changes in lipid metabolism.

Literature searches produced only one study which showed that estriol had a postive effect on Bone Mineral Density. A Japanese study. Seventy -five natural postmenopausal women with a BMD of more that 10% below the peak bone density were treated for 50 weeks with 2mg/ day estriol cyclically (4 weeks on / 1 week off) and .8gm / day calcium lactate continuously. The BMD increased by 1.79% (p<0.01 vs. pretreatment) after 50 weeks.

The Japanese study also concluded that the parameters of lipid metabolism in their study showed no significant changes after 50 weeks.

The intravaginal administration of estriol prevents recurrent urinary tract infections in postmenopausal women, probably by modifying the vaginal flora.

It is suggested that Vitamin E administered daily with estriol therapy will improve Estriols activity in the body.

Oral doses of up to 16mg per day have been documented. The most common oral dosage range is 1-4mg per day.

Hybrid combinations using estriol as their main component have become very popular in estrogen replacement therapy. Such as Triestrogens (using all 3 natural estrogens) in a specific ratio and proportion. This ratio is generally 80% estriol, 10% estradiol and 10% estrone. And also Biestrogens (using 2 estrogens, generally Estriol and Estradiol). Again estriol usually being the major component. The thought here is to use an estrogen complex which has the protective effects of estriol on the breast and uterus while recognizing the benefits of estradiol and estrone for bones and cardiac protection. Also it is generally recognized that 2 or more drugs with the same pharmacologic action in the body when used together can elicit a greater response by acting synergistically, This synergism therefore allows a reduction of each single component while producing the same therapeutic effect. This generally results in fewer side effects and a better overall therapeutic response.

References

1. R. Lee, M.D. with Virginia Hopkins. What your Doctor may not tell you about

menopause. The breakthrough book on natural progesterone. Warner Books, Inc 1996

2. Tzay-Shing Yang M.D. et al., Efficacy and safety of estriol replacement therapy for climacteric women. Chin Med J (Taipei) 1995;55:386-91

3. A. H. Follingstad M.D. Estriol, the forgotten estrogen. JAMA, Jan. 2 1978 Vol 239 No.1

4. Hiroshi Minaguchi M.D. et al, Yokohama City University, School of Medicine, Yokohama, Japan. J. Obstet. Gynaecol. Res. Vol 22, No. 3: 259-265 1996

5. Raz, M.D., Walter E. Stamm, M.D. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N. England J. Med. 1993;329:753-6

6. G. P. Vooijs, T. B. P. Geurts, Review of the endometrial safety during intravaginal treatment with estriol. European Journal of Obstet. and Gynec. and Reprod. Biology 62 (1995) 101-106