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Safety Issues
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. 1 Another large study found that oral estriol increased the risk of uterine cancer. 2 In a third study of 48 women, estriol (1 mg twice daily) caused uterine tissue stimulation. 3 In contrast, a 12-month double-blind trial of oral estriol (2 mg daily) in 68 Japanese women found no effect on the uterus. 4 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. 5 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. 6 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. 7
References
- Granberg S, Ylöstalo P, Wikland M, Karlsson B. Endometrial sonographic and histologic findings in women with and without hormonal replacement therapy suffering from postmenopausal bleeding. Maturitas. 27(1):35-40.
- Weiderpass E, Baron JA, Adami HO, Magnusson C, Lindgren A, Bergström R, Correia N, Persson I. Low-potency oestrogen and risk of endometrial cancer: a case-control study. Lancet. 353(9167):1824-8.
- Montoneri C, Zarbo G, Garofalo A, Giardinella S. Effects of estriol administration on human postmenopausal endometrium. Clin Exp Obstet Gynecol. 14(3-4):178-81.
- Takahashi K, Manabe A, Okada M, Kurioka H, Kanasaki H, Miyazaki K. Efficacy and safety of oral estriol for managing postmenopausal symptoms. Maturitas. 34(2):169-77.
- Punnonen R, Söderström 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. 14(4):217-24.
- 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. 37(6):1901-7.
- Vooijs GP, Geurts TB. Review of the endometrial safety during intravaginal treatment with estriol. Eur J Obstet Gynecol Reprod Biol. 62(1):101-6.
