Estriol Uses and Side Effects

This estrogen may help MS and menopause symptoms, but more research is needed

Estriol is the main estrogen hormone involved in pregnancy. A lab-made estriol cream, known as bio-identical estriol, is sometimes used for menopause and multiple sclerosis. However, estriol is not approved by the Food and Drug Administration (FDA), and the agency warns that there is not enough evidence to confirm that it is safe or effective.

Preliminary research suggests that estriol may help with some menopausal symptoms or reduce relapse rates in pregnant people with multiple sclerosis (MS), but more research is needed.

The article explores estradiol's potential uses and possible side effects.

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

Potential Uses of Estriol

Drugs that contain estriol are compounded drugs, which are not FDA-approved.

A compounded pharmacy prepares medications individually for each person, not in high volume like most commercial drugs. Compounded drugs for menopausal symptoms are often mixes of multiple hormones.

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, more research into its potential uses and to evaluate safety and efficacy are needed.

Is Estriol the Same As Estradiol?

No. A lab-made form of estradiol, the main estrogen hormone of the reproductive years, is more potent than estriol. It is FDA approved and commonly prescribed for menopausal symptoms.

Menopause Symptoms

During menopause, changes occur in the lower urinary tract and vagina as a result of ovaries no longer producing estrogens. About 40% to 45% of menopausal women experience symptoms related to vaginal atrophy, including urinary tract infections, vaginal infections, and vaginal dryness.

People transitioning to menopause may also experience hot flashes and other symptoms related to hormonal changes.

A 2018 research review published in 2018 found that an ultra-low dose of .03 (mg) of estriol combined with the probiotic Lactobacillus acidophilus considerably improved symptoms of vaginal atrophy and quality of life for menopausal women. The authors also noted that the combination therapy was well tolerated with a low overall risk of side effects.

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.

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 those with MS.

Studies on Estriol and MS Relapse

A review published in 2017 in the journal Menopause found that estriol protected 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 a 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. 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 reducing MS symptoms in the short-term. Ongoing research is focusing on just that.

Possible Side Effects

A 2017 systematic review of studies on 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 (a precancerous condition) has been raised as a possible concern, but the connection is not conclusive. The 2017 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 may be contraindicated for those with estrogen-dependent malignant tumors.

Interactions

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 also increase the effects of medications such as:

  • Corticosteroids
  • Theophyllines
  • Troleandomycin
  • 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 published in 2012 in the journal Menopause found that using a dose as low as .005% intravaginal estriol cream improved urogenital atrophy and incontinence. Oral estriol and topical estriol may act on the body in similar dosage ranges.

Summary

Preliminary studies suggest that a lab-made form of estriol, an estrogen hormone, may be helpful for menopausal symptoms or may improve relapse rates for those with MS. However, estriol is not FDA approved and more research into side effects, dosage, safety, and efficacy are needed.

9 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. Ali ES, Mangold C, Peiris AN. Estriol: emerging clinical benefits. Menopause. 2017;24(9):1081-1085. doi:10.1097/GME.0000000000000855

  3. Food and Drug Administration. Menopause: medicines to help you.

  4. 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

  5. Mueck AO, Ruan X, Prasauskas V, Grob P, Ortmann O. Treatment of vaginal atrophy with estriol and lactobacilli combination: a clinical reviewClimacteric. 2018;21(2):140-147. doi:10.1080/13697137.2017.1421923

  6. 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

  7. electronic Medicines Compendium. Ovestin 1 mg cream.

  8. 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

  9. Cano A, Estévez J, Usandizaga R, et al. 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):1130-1139. doi:10.1097/gme.0b013e3182518e9a

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