The Health Benefits of Estriol

This estrogen may be an effective option for MS and menopause

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Estriol is the main estrogen involved in pregnancy and is produced naturally by the placenta and fetus. Bio-identical estriol—a chemically-derived form of the hormone that is identical in molecular structure to natural estriol (available in cream form)—is FDA-approved for treating menopausal symptoms.

In addition to this, early research into the effects of estriol on reducing relapse rates in pregnant women with multiple sclerosis (MS) has put a spotlight on the potential use of synthetic estriol for MS disease management in all patients. More research is needed.

How a Hormone in Pregnancy May Help Your MS
Kelvin Murray/Getty Images

Health Benefits

There are many different hormones in the body, but all of them function as chemical messengers. In some cases, you may be acutely aware of hormonal changes. In others, it may be less obvious to you that hormones are playing a role in how you feel and what you're experiencing. In the case of estriol, can be true and replacement may benefit you in ways that are both surprising and not.

Menopausal Symptoms

During menopause, changes occur in the lower urinary tract and vagina as a result of the cessation of the production of estrogens by the ovaries. About 40 percent to 45 percent of menopausal women experience symptoms related to vaginal atrophy, including urinary tract infections, vaginal infections, and vaginal dryness. Menopausal women may also experience hot flashes and other symptoms related to hormonal changes.

One study found that estriol cream applied intravaginally prevented recurring UTIs by reducing vaginal pH and altering the makeup of vaginal flora. Another study of 206 postmenopausal women found that 1 milligram (mg) daily of intravaginal estriol in addition to pelvic floor rehabilitation was effective in reducing symptoms of urogenital aging, including vaginal dryness. Furthermore, in a 2017 review, 2 mg of daily oral estriol reduced hot flashes, insomnia, and night sweats in postmenopausal women.

Multiple Sclerosis

The immune system begins to eat away at the protective covering of nerves in patients with multiple sclerosis, leading to all kinds of symptoms related to degraded communication between the brain and the rest of the body. Most people with MS experience symptoms that partially or completely improve, only to return during a relapse.

Natural estriol plays a strong role in protecting the central nervous system during pregnancy by binding to estrogen receptors in the immune system, brain, and spinal cord, and the increase in this hormone is what is believed to be behind decreased MS relapses in expecting mothers with the disease. As such, synthetic estriol has begun to be investigated as a potential treatment option for all MS patients.

A 2017 review found that estriol protects against many inflammatory autoimmune disease markers. Estriol was found to reduce relapse rates for MS and also improve related cognitive function, fatigue, and brain atrophy. Women with MS were found to have decreased relapse rates at the time points when estriol levels were highest in their pregnancies, with those relapse rates rebounding after delivery.

In one promising 2016 study, 164 women between the ages of 18 to 50 with relapsing-remitting MS were randomized to receive a combination of the disease-modifying therapy Copaxone (glatiramer acetate) with 8 mg of estriol daily or Copaxone alone. Results of the study showed that after 12 months, there was a significant decrease in annual relapse rates in the estriol group, as well as a decrease in fatigue.

At the end of two years, the decrease in annual relapse rates between those taking estriol and those taking placebo was much less significant, but these results still indicate that estriol may be effective in ameliorating MS symptoms in the short-term. Ongoing research is focusing on just that.

Possible Side Effects

A systematic review conducted in 2017 of intravaginal estriol cream found that the majority of adverse events reported included localized discomfort and mild breast pain. Taking estriol may also decrease production of breast milk.

Risk Considerations

A heightened risk of endometrial hyperplasia has been raised as a possible concern, but the connection is not conclusive. The aforementioned review found one study that claimed estriol does not pose this risk, and another in which a biopsy found endometrial hyperplasia in one person after six months of estriol therapy.

There is also some concern that taking an estrogen might increase the risk of developing breast fibrocystic disease, breast cancer, or a thickened uterine lining. However, one study found no major differences in incidence of these issues between women who took estriol and those who did not. The only major distinction between the two groups was that irregular menstrual cycles were more common in the women who took estriol.

Estriol appears to confer less risk than some of the other estrogens. However, estriol may be contraindicated for those with estrogen-dependent malignant tumors.


According to the electronic Medicines Compendium, metabolism of estrogens can be increased when combined with drugs such as hydantoin anticonvulsants or other substances known to trigger drug-metabolizing enzymes, such as herbal formulations that contain St John's Wort. Increased metabolism of estrogens may lead to changes in uterine bleeding profile as well as decrease the effectiveness of estriol.

Estriol may increase the effects of corticosteroids, theophyllines, troleandomycin, and succinylcholine.

Dosage and Preparation

A dose of 0.5 mg of estriol in 0.5 mg of cream was studied and approved as a prescription medication by the European Medicines Agency (EMA) under the brand name Ovestin.

One study of colposcopy results and urethral pressure readings found that using a dose as low as .005% intravaginal estriol cream improved urogenital atrophy and incontinence. Oral estriol and topical estriol act on the body in similar dosage ranges and both have been investigated clinically.

8 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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  2. Rueda C, Osorio AM, Avellaneda AC, Pinzón CE, Restrepo OI. The efficacy and safety of estriol to treat vulvovaginal atrophy in postmenopausal women: a systematic literature review. Climacteric. 2017;20(4):321-330. doi:10.1080/13697137.2017.1329291

  3. Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med. 1993;329(11):753-6. doi:10.1056/NEJM199309093291102

  4. Capobianco G, Donolo E, Borghero G, Dessole F, Cherchi PL, Dessole S. Effects of intravaginal estriol and pelvic floor rehabilitation on urogenital aging in postmenopausal women. Arch Gynecol Obstet. 2012;285(2):397-403. doi:10.1007/s00404-011-1955-1

  5. Voskuhl RR, Wang H, Wu TC, et al. Estriol combined with glatiramer acetate for women with relapsing-remitting multiple sclerosis: a randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2016;15(1):35-46. doi:10.1016/S1474-4422(15)00322-1

  6. electronic Medicines Compendium. Ovestin 1 mg cream.

  7. Holtorf, K. The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy?Postgrad Med. 2009 Jan;121(1):73-85. doi:10.3810/pgm.2009.01.1949

  8. Cano A1, Estévez J, Usandizaga R, Gallo JL, Guinot M, Delgado JL, Castellanos E, Moral E, Nieto C, del Prado JM, Ferrer J. The therapeutic effect of a new ultra low concentration estriol gel formulation (0.005% estriol vaginal gel) on symptoms and signs of postmenopausal vaginal atrophy: results from a pivotal phase III studyMenopause. 2012. 19(10):1130-9. doi:10.1097/gme.0b013e3182518e9a

By Colleen Doherty, MD
 Colleen Doherty, MD, is a board-certified internist living with multiple sclerosis.