Estriol as a therapeutic supplement
Estriol is a naturally occurring estrogen in the human body, primarily produced during pregnancy and considered weaker than other forms of estrogen like estradiol and estrone. It has gained attention as a therapeutic supplement, particularly for managing menopausal symptoms such as hot flashes, night sweats, and vaginal dryness. Despite its popularity among some healthcare providers, the FDA has not approved estriol specifically for menopausal treatment, though various studies suggest its efficacy. Estriol is also noted for potentially aiding in the prevention of osteoporosis and alleviating symptoms associated with breast cancer treatments involving aromatase inhibitors.
While some believe that estriol may have a favorable safety profile compared to other estrogens, research indicates it presents similar risks, including the stimulation of uterine tissue leading to potential uterine cancer, breast cancer, and endometrial hyperplasia. The recommended therapeutic dosage of estriol typically ranges from two to eight milligrams daily, and it is often available in various forms, including vaginal gels. Users should be aware of potential side effects, which can include breast pain, hair loss, and abnormal menstruation. As with any hormonal treatment, it is important to consult healthcare professionals to weigh the benefits and risks associated with estriol use.
Estriol as a therapeutic supplement
DEFINITION: Natural substance of the human body used as a supplement to treat specific health conditions.
PRINCIPAL PROPOSED USES: Menopausal symptoms, osteoporosis
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 the other two but still active. It is the main estrogen present in pregnant women's blood, reaching its highest level just before labor and delivery.
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 two to eight 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 helpful in treating some negative symptoms associated with breast cancer treatments involving 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 improved their symptoms without interfering with their cancer treatment.
Some research indicates estriol may be helpful in treating some negative symptoms associated with 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 improved their symptoms without interfering with their cancer treatment.
Other uses of estriol have been explored, including treating postpartum depression, multiple sclerosis, menstrual migraines, and improving cognitive function. However, these uses have not been confirmed.
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
Ali, Emad S., et al. “Estriol: Emerging Clinical Benefits.” Menopause (New York), vol. 24, no. 9, 2017, pp. 1081-5. doi:10.1097/GME.0000000000000855.
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. 293-297.
"Estriol." Cleveland Clinic, 18 Feb. 2022, my.clevelandclinic.org/health/articles/22399-estriol. Accessed 20 Sept. 2024.
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. 526-534. doi:10.1097/GME.0000000000001497.
"Hormone Therapy: Is it Right for You?" Mayo Clinic, 6 Dec. 2022, www.mayoclinic.org/diseases-conditions/menopause/in-depth/hormone-therapy/art-20046372. Accessed 20 Aug. 2023.
Takahashi, K., et al. “Efficacy and Safety of Oral Estriol for Managing Postmenopausal Symptoms.” Maturitas, vol. 34, 2000, pp. 169-177.
Weiderpass, E., et al. “Low-Potency Oestrogen and Risk of Endometrial Cancer.” The Lancet, vol. 353, 1999, pp. 1824-1828.