Estriol and MS Relapse

This form of estrogen may be an effective option for disease management

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

Estriol is the main estrogen involved in pregnancy, produced naturally by the placenta and fetus. Chemically-derived forms of hormones that are identical in molecular structure to the hormones people make in their bodies are called bio-identical hormones. In Europe and Asia, bio-identical estriol is approved for treating menopausal symptoms, however it is not yet approved for this use in the US. More research is needed, but 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.

Health Benefits

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 new symptoms in batches, improving partially or completely before experiencing symptoms again during a relapse. 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 has begun to be investigated as a potential treatment option for this disease with the aim of increasing the time between relapses.

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 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 with relapse-remitting MS between the ages of 18 to 50 were randomized to receive a combination of the disease-modifying therapy Copaxone (glatiramer acetate) with 8 milligrams (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 and ought to be the focus of further research.

Menopausal Symptoms

During menopause, atrophic 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 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 make-up of vaginal flora. Another study of 206 postmenopausal women found that 1 mg daily of intravaginal estriol in addition to pelvic floor rehabilitation was effective in reducing symptoms of urogenital aging, including vaginal dryness. According to a 2017 review, 2 mg of daily oral estriol reduced hot flashes, insomnia, and night sweats in postmenopausal women.

Possible Side Effects

Precautions and Contraindications

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. The review found one study that claimed estriol does not pose a risk of endometrial hyperplasia and also one study in which a biopsy found endometrial hyperplasia in one person after 6 months of estriol therapy with a connection between the two being inconclusive.

There is 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 conditions between women who did take 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 than the women who did not. Estriol appears to confer less risk than some of the other estrogens, however estriol may be contraindicated for those with estrogen-dependent malignant tumors.

Taking estriol may decrease production of breast-milk.

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 which 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 corticostreoids, 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 EMA under the brand name Ovestin. One study of colposcopy and urethral pressure readings found that using a dose as low as .005 percent 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.

What to Look for

It's important to note that estriol is not currently approved by the U.S. Food and Drug Administration (FDA) for use in the United States, although it is used in Europe and Asia to treat menopausal symptoms like hot flashes and vaginal dryness.

Bio-identical hormones such as estriol are often available at compounding pharmacies, but the FDA maintains that compounded bio-identical hormone preparations are of unreliable potency and that there can be significant variation in a medicine’s content even within the same product, exposing women to potentially risky doses and combinations of hormones.

Further research into the beneficial effects of estriol on MS may eventually lead to it being approved as a treatment option in the US.

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