Several forms of estrogen occur naturally in a woman's body. The ovary produces a form named estradiol, which is converted into another important estrogen called estrone. Estriol is yet another form of estrogen metabolized from estradiol, weaker than the other two, but still active.
The estrogen tablets prescribed for menopausal symptoms usually contain estradiol, estrone, or a combination of the two. Some alternative medicine physicians have popularized the use of estriol as an alternative, and there is no doubt that estriol is also effective for symptoms of menopause. However, despite claims that it is safer than other forms of estrogen, the balance of evidence suggests that, in fact, estriol presents precisely the same risks (see Safety Issues below).
Estriol is manufactured in the body from estrone, estradiol, and androstenedione. When taken as a drug, it is manufactured synthetically, or extracted from animal products.
The usual dose of estriol is 2 to 8 mg taken once daily. Estriol is also commonly sold in combination with other forms of estrogen.
Like more common forms of estrogen, estriol is used for the treatment of menopausal symptoms. Double-blind, placebo-controlled studies and other controlled trials have found oral or vaginal estriol effective for symptoms of menopause, including hot flashes, night sweats, insomnia, vaginal dryness, and recurrent urinary tract infections. Estriol may also help prevent osteoporosis.1-9
Estriol might cause less vaginal bleeding as a side effect than other forms of estrogen, although this has not been definitively established.10,11
Some alternative practitioners claim that estriol actually fights cancer, as opposed to estrogen, which increases risk of some cancers. However, this claim is based on exaggerated interpretations of very weak studies.12,13,14 It is more likely that estriol increases cancer risk in much the same way as other forms of estrogen (see Safety Issues, below).
Like other forms of estrogen, oral estriol stimulates the growth of uterine tissue. This leads to risk of uterine cancer. In a placebo-controlled study of 1,110 women, uterine tissue stimulation was seen among women given estriol orally (1 to 2 mg daily) as compared to those given placebo.15 Another large study found that oral estriol increased the risk of uterine cancer.16 In a third study of 48 women, estriol (1 mg twice daily) caused uterine tissue stimulation.17 In contrast, a 12-month double-blind trial of oral estriol (2 mg daily) in 68 Japanese women found no effect on the uterus.18 It may be that the high levels of soy in the Japanese diet altered the results.
To protect the uterus, estriol—like other forms of estrogen—needs to be balanced with progesterone. Additionally, one study suggests that estriol is less likely to affect the uterus when taken in a once-daily dose rather than in multiple daily doses.19
However, the uterus isn't the only organ at risk of cancer. Test tube studies suggest that estriol is just as likely to cause breast cancer as any other form of estrogen.20 While this preliminary evidence doesn't constitute proof, it does raise alarm bells. Until proven otherwise, estriol must be regarded as increasing breast cancer risk.
As with other forms of estrogen, vaginal estriol preparations are safer than oral preparations.21,22
1. Takahashi K, Manabe A, Okada M, et al. Efficacy and safety of oral estriol for managing postmenopausal symptoms. Maturitas. 2000;34:169-177.
2. Minaguchi H, Uemura T, Shirasu K, et al. Effect of estriol on bone loss in postmenopausal Japanese women: a multicenter prospective open study. J Obstet Gynaecol Res. 1996;22:259-265.
3. Itoi H, Minakami H, Sato I. Comparison of the long-term effects of oral estriol with the effects of conjugated estrogen, 1-alpha-hydroxyvitamin D3 and calcium lactate on vertebral bone loss in early menopausal women. Maturitas. 1997;28:11-17.
4. Hayashi T, Ito I, Kano H, et al. Estriol (E3) replacement improves endothelial function and bone mineral density in very elderly women. J Gerontol A Biol Sci Med Sci. 2000;55:B183-B190.
5. Dugal R, Hesla K, Sordal T, et al. Comparison of usefulness of estradiol vaginal tablets and estriol vagitories for treatment of vaginal atrophy. Acta Obstet Gynecol Scand. 2000;79:293-297.
6. Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med. 1993;329:753-756.
7. van der Linden MC, Gerretsen G, Brandhorst MS, et al. The effect of estriol on the cytology of urethra and vagina in postmenopausal women with genito-urinary symptoms. Eur J Obstet Gynecol Reprod Biol. 1993;51:29-33.
8. Holland EF, Leather AT, Studd JW. Increase in bone mass of older postmenopausal women with low mineral bone density after one year of percutaneous oestradiol implants. Br J Obstet Gynaecol. 1995;102:238-242.
9. Nozaki M, Hashimoto K, Inoue Y, et al. Usefulness of estriol for the treatment of bone loss in postmenopausal women [in Japanese; English abstract]. Nippon Sanka Fujinka Gakkai Zasshi. 1996;48:83-88.
10. Minaguchi H, Uemura T, Shirasu K, et al. Effect of estriol on bone loss in postmenopausal Japanese women: a multicenter prospective open study. J Obstet Gynaecol Res. 1996;22:259-265.
11. Takahashi K, Manabe A, Okada M, et al. Efficacy and safety of oral estriol for managing postmenopausal symptoms. Maturitas. 2000;34:169-177.
12. Lemon HM, Kumar PF, Peterson C, et al. Inhibition of radiogenic mammary carcinoma in rats by estriol or tamoxifen. Cancer. 1989;63:1685-1692.
13. Lemon HM, Wotiz HH, Parsons L, et al. Reduced estriol excretion in patients with breast cancer prior to endocrine therapy. JAMA. 1966;196:1128-1136.
14. Lemon HM. Pathophysiologic considerations in the treatment of menopausal patients with oestrogens; the role of oestriol in the prevention of mammary carcinoma. Acta Endocrinol Suppl (Copenh). 1980;233:17-27.
15. Granberg S, Ylostalo P, Wikland M, et al. Endometrial sonographic and histologic findings in women with and without hormonal replacement therapy suffering from postmenopausal bleeding. Maturitas. 1997;27:35-40.
16. Weiderpass E, Baron JA, Adami HO, et al. Low-potency oestrogen and risk of endometrial cancer: a case-control study. Lancet. 1999;353:1824-1828.
17. Montoneri C, Zarbo G, Garofalo A, et al. Effects of estriol administration on human postmenopausal endometrium. Clin Exp Obstet Gynecol. 1987;14:178-181.
18. Takahashi K, Manabe A, Okada M, et al. Efficacy and safety of oral estriol for managing postmenopausal symptoms. Maturitas. 2000;34:169-177.
19. Punnonen R, Soderstrom KO. The effect of oral estriol succinate therapy on the endometrial morphology in postmenopausal women: the significance of fractionation of the dose. Eur J Obstet Gynecol Reprod Biol. 1983;14:217-224.
20. Lippman M, Monaco ME, Bolan G. Effects of estrone, estradiol and estriol on hormone-responsive human breast cancer in long-term tissue culture. Cancer Res. 1977;37:1901-1907.
21. Vooijs GP, Geurts TB. Review of the endometrial safety during intravaginal treatment with estriol. Eur J Obstet Gynecol Reprod Biol. 1995;62:101-106.
22. Weiderpass E, Baron JA, Adami HO, et al. Low-potency oestrogen and risk of endometrial cancer: a case-control study. Lancet. 1999;353:1824-1828.
Last reviewed December 2015 by EBSCO CAM Review Board
Last Updated: 12/15/2015
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