Estriol as a therapeutic supplement

• PRINCIPAL PROPOSED USES: Menopausal symptoms, osteoporosis

DEFINITION: Natural substance of the human body used as a supplement to treat specific health conditions.

Overview

Several forms of estrogen occur naturally in a woman’s body. The ovaries produce the most common type of estrogen called estradiol (E2), which is converted into another important estrogen called estrone (E1). Estriol (E3), sometimes called oestriol, is another form of estrogen metabolized from estradiol that is weaker than than E1 and E2, but still biologically active. It is the main estrogen present in the blood of pregnant women, reaching its highest levels near the end of pregnancy, just before labor.

The estrogen tablets or creams prescribed for menopausal symptoms usually contain estradiol, estrone, or a combination of the two. Some alternative medicine physicians have popularized the use of estriol because of its positive effect on 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.

Requirements and Sources

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.

Therapeutic Dosages

The usual dose of estriol is 2 to 8 milligrams (mg) taken once daily. Estriol is also commonly sold in combination with other forms of estrogen.

Therapeutic Uses

Though the FDA has not approved estriol for the treatment of menopausal symptoms, many individuals and medical professionals recommend this use. 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. Estriol might cause less vaginal bleeding as a side effect than other forms of estrogen, although this has not been definitively established.

Some research indicates estriol may be potentially helpful in treating certain negative symptoms associated with breast cancer treatments using nonsteroidal aromatase inhibitors (NSAIs). In a twelve-week study of sixty-one women experiencing the vulvovaginal side effects of NSAIs, a 0.005 percent estriol vaginal gel appeared to improve symptoms without interfering with their cancer treatment.

Other research indicates that estriol may have applications for the development of therapies for progressive multiple sclerosis. One study found that the hormone reduced spinal cord inflammation and limited damage to the myelin sheath.

Other uses of estriol have been explored, including treating postpartum depression, menstrual migraines, and improving cognitive function. However, these uses have not been confirmed and remain under investigation.

Safety Issues

Like other forms of estrogen, oral estriol stimulates the growth of uterine tissue. This leads to the risk of uterine cancer. In a placebo-controlled study of 1,110 women, uterine tissue stimulation was seen among women given estriol orally (one to two mg daily) compared with those given a placebo. Another large study found that oral estriol increased the risk of uterine cancer. In a third study of forty-eight women, estriol (one mg twice daily) caused uterine tissue stimulation. In contrast, a twelve-month double-blind trial of oral estriol (two mg daily) in sixty-eight Japanese women found no effect on the uterus. 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.

However, the uterus is not the only organ at risk of cancer. Many studies suggest that estriol is just as likely to cause breast cancer and endometrial hyperplasia as any other form of estrogen. Because it is the weakest form of estrogen, estriol likely poses less of a risk for increasing blood pressure and forming blood clots. As with other forms of estrogen, vaginal estriol preparations are safer than oral preparations. Still, side effects occur, including breast pain, hair loss, headaches, vomiting, weight gain, yeast infections, and abnormal menstruation.

Bibliography

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Dugal, R., et al. “Comparison of Usefulness of Estradiol Vaginal Tablets and Estriol Vagitories for Treatment of Vaginal Atrophy.” Acta Obstetricia et Gynecologica Scandinavica, vol. 79, 2000, pp. 293-97, pubmed.ncbi.nlm.nih.gov/10746845. Accessed 10 Dec. 2025.

"Estriol." Cleveland Clinic, 6 May 2025, my.clevelandclinic.org/health/articles/22399-estriol. Accessed 10 Dec. 2025.

Gomez, Francisco P., et al. “Therapeutic Effects of Estrogens on Inflammatory Demyelination in a Mouse Model of Multiple Sclerosis.” Journal of Neuroimmunology, vol. 407, 2025, doi:10.1016/j.jneuroim.2025.578698. Accessed 10 Dec. 2025.

Hirschberg, Angelica Lindén, et al. “Efficacy and Safety of Ultra-Low Dose 0.005% Estriol Vaginal Gel for the Treatment of Vulvovaginal Atrophy in Postmenopausal Women with Early Breast Cancer Treated with Nonsteroidal Aromatase Inhibitors: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial.” Menopause (New York), vol. 27, no. 5, 2020, pp. 526-34, doi:10.1097/GME.0000000000001497. Accessed 10 Dec. 2025.

"Hormone Therapy: Is It Right for You?" Mayo Clinic, 18 Apr. 2025, www.mayoclinic.org/diseases-conditions/menopause/in-depth/hormone-therapy/art-20046372. Accessed 10 Dec. 2025.

"Multidisciplinary Study Finds Estrogen Could Aid in Therapies for Progressive Multiple Sclerosis." Texas A&M University School of Public Health, 13 Oct. 2025, stories.tamu.edu/news/2025/10/13/multidisciplinary-study-finds-estrogen-could-aid-in-therapies-for-progressive-multiple-sclerosis. Accessed 10 Dec. 2025.

Weiderpass, E., et al. “Low-Potency Oestrogen and Risk of Endometrial Cancer.” The Lancet, vol. 353, 1999, pp. 1824-28, www.thelancet.com/journals/lancet/article/PIIS0140-6736(98)10233-7/abstract. Accessed 10 Dec. 2025.