Estriol Cream - The Forgotten Estrogen

By Community Drug compounding pharmacy.

Estriol may offer many benefits for post menopausal women without the side effects. The primary forms of estrogen include three substances - estrone, estradiol and estriol.

During pregnancy, Estriol is produced in much greater quantities than estrone and estradiol. 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.

In the 1966 Journal of the American Medical Association by 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 excretion of estriol. He also observed that women without breast cancer have naturally higher estriol levels, compared with estrone and estradiol levels, than women with breast cancer. Vegetarian and Asian women have high levels of estriol, and these women are at much lower risk of breast cancer than are other women. Estriol's anti-cancer effect is probably related to its anti-estrone properties it blocks the stimulatory effect of estrone by occupying the estrogen receptor sites on the breast cells.

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 Estriol). This means that after a single does of estriol, the binding to the endometrial estrogen receptor is too short to induce true proliferation, while it's binding to the vaginal estrogen receptor is sufficient to exert a full vaginotropc effect. Because of estriol's strong vaginotropic effect it is thought to be the estrogen most beneficial to the vagina, cervix, and vulva. In cases of postmenopausal vaginal dryness and atrophy, which predisposes a woman to vaginitis and cyctitis, estriol supplementation would theoretically be the most effective (and safest) estrogen to use.

The intra-vaginal administration of estriol prevents recurrent urinary tract infections in postmenopausal women, by modifying the vaginal flora and significantly lowering vaginal pH. Lactobacilli (absent prior to therapy) reappeared after one month in 61% of patients given estriol but in no patient receiving placebo. ((Cardozo et al, 1998: Rax & Stamm, NEJM 1993; 329:753-6)

It is suggested that Vitamin E administered daily with estriol therapy will improve Estriol 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 Tri-estrogens (using all 3 natural estrogens) in a specific proportion. This ratio is generally 80% estriol, 10% estridiol and 10% estrone. And also Bi-estrogens (using 2 estrogens, generally Estriol and Estradiol). Again estriol usually being the major component. 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 beter overall therapeutic response. A Taiwan study concluded that estriol was very effective in the improvement of major subjective climeratic complaints in 86% of patients, especially hot flash and insomnia within 3 months. The atrophic genital changes caused by estrogen deficiency were also improved satisfactorily.

1. John R. Lee MD 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 MD. et al., Efficacy and safety of estriol replacement therapy of climacteric women. China Medical Journal of Taipei 1995;55:386-91

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

4 Hiroshi Minaguchi MD et al, Yokohama City University, School of Medicine, Yokohama, Japan Journal of Obstetrics and Gynecology Research. Vol 22, No.1:259-265 1996

5. Raul Raz, MD., Walter E. Stamm, MD. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. New England Journal of Medicine. 1993;329:753-6

6. G. P. Voooijs, T. B. P. Geurts, Review of the endometrial safety during intravaginal treatment with estriol. European Journal of Obstetrics and Gynecology and Reproduction Biology 62 (1995) 101-106




Authored by the Community DrugExit Site compounding pharmacy.

Wendy Wells

Reviewed by Wendy Wells January 2013
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Menopause Topics
Life-stages, perimenopause, treatment safety, bio-identical hormones, progesterone cream, and estriol lotion.