A Form of Estrogen That May Reduce MS Relapses

Phase 2 Studies Suggest High Dose Estriol May Be Beneficial in MS

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

Pregnant women with multiple sclerosis have a 70 percent reduced risk of having a relapse during the third trimester, and experts believe that the female sex hormone estriol may play a critical role in this protection.

Estriol is a type of estrogen that is unique to pregnancy. It is made by the placenta and reaches its highest levels during the third trimester. The exciting news is that scientists are looking closer at using estriol to treat people with MS, in the hopes it will slow their disease.

The Science Behind Using Estriol To Reduce MS Relapses

There are two phase 2 studies that suggest estriol may be effective in reducing MS relapses. Phase 2 studies are done to assess the safety of a medication and whether or not it could be beneficial. Phase 3 studies, which are larger and longer, are required for approval of a medication by the United States Food and Drug Administration (FDA). So this is all very early data, but nevertheless exciting.

In a two-year 2016 study in The Lancet Neurology, 164 women with relapsing-remitting MS (ages 18 to 50) were randomized to receive either 8mg of estriol daily or a placebo pill daily. Neither the participants nor the study investigators knew which pill was being distributed to which woman. The participants took the daily estriol pill or placebo pill along with their usual daily 20mg injection of Copaxone (glatiramer acetate)—which the participants had all recently started.

Results of the study showed that after 12 months, there was a significant decrease in annual relapse rates in the participants taking Copaxone and estriol, as compared to those taking Copaxone and placebo. But at the end of two years, the decrease in annual relapse rates between those taking estriol and those taking placebo was only moderately significant (if at all).

Whereas the study's results were initially promising, it's unclear why the same relapse reduction was not seen after two years, as it was seen after one year. Experts suggest that repeating the study with a larger number of participants would be helpful.

On another note, the Copaxone and estriol group did have significant improvements with their fatigue, compared with the Copaxone only group.

The good news is that estriol was well tolerated in the study. For instance, in terms of developing breast fibrocystic disease, breast cancer, or a thickened uterine lining (all concerns of taking a form of estrogen), there were no major differences between the 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. Vaginal infections were less common in the women who took estriol than the women who did not.

In another smaller 2002 study in The Annals of Neurology, ten non-pregnant women with MS were treated with 8mg daily of estriol and underwent monthly brain MRIs.

Results revealed a significant decrease in the number of gadolinium-enhancing lesions in the 6 months during treatment with estriol, as compared to the prior six months before estriol treatment.

In addition, when the women's estriol treatment was stopped for six months, the number of their gadolinium-enhancing lesions returned to pretreatment or baseline levels. But then after four months of restarting estriol, their lesion number again reduced on brain MRI—this back and forth evaluation really emphasizes the benefit of estriol in this small study.

Understanding Estriol's Role in MS

Estrogen is a sex hormone mostly produced by a woman's two ovaries and is responsible for developing her reproductive organs (uterus, vagina, fallopian tubes, ovaries). Estrogen also plays a critical role in menstruation, breast development, pregnancy, and bone health.

There are three different types of estrogen produced in the body:

  • estradiol
  • estrone
  • estriol

Unlike estradiol and estrone, estriol is unique to pregnancy and binds weakly to estrogen receptors (docking sites) located inside cells in the body.

In terms of benefiting multiple sclerosis, scientists believe that estriol plays a strong role in protecting the central nervous system. This is suggested by studies that demonstrate estriol binding to estrogen receptors in the immune system, brain, and spinal cord. In fact, giving estriol to mice with experimental autoimmune encephalitis, or EAE (the mouse model of MS), was found to prevent spinal cord inflammation and myelin loss—myelin being the protective nerve covering that is damaged in MS.

That being said, experts believe that estriol is more neuroprotective and less anti-inflammatory—meaning it protects the brain and spinal cord from myelin and nerve fiber (axon) loss, but does not prevent inflammation in the central nervous system. This is why it's likely that an anti-inflammatory medication (like one of the current disease-modifying therapies) would be needed in combination with estriol for treating MS.

What Does This Mean for Me?

It's important to note that estriol is not currently approved for use in the United States, although it is used to treat menopausal symptoms like hot flashes and vaginal dryness in Europe and Asia.

The take home message here is that while a promising MS treatment candidate, the science behind estriol and its role in protecting disease activity in MS has not been fully teased out. More research needs to be completed first, including phase 3 studies. Therapies take time to develop, which is a good thing in the end for your health and safety.


Bebo BF Jr, Fyfe-Johnson A, Adlard K, Beam AG, Vanderbark AA, Offner H. Low-dose estrogen therapy ameliorates experimental autoimmune encephalomyelitis in two different inbred mouse strains. J Immunol. 2001 Feb 1;166(3):2080-9.

Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T. Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group. N Engl J Med 1998 Jul 30;339(5):285-91.

Spence RD, and Voskuhl RR: Neuroprotective effects of estrogens and androgens in CNS inflammation and neurodegeneration. Front Neuroendocrinol 2012; 33: pp. 105-115.

Sicotte et al. Treatment of multiple sclerosis with the pregnancy hormone estriol. Ann Neurol 2002 Oct;52(4):421-8.

Voskuhl RR et al. Estriol combined with glatiramer acetate for women with relapsing-remitting multiple sclerosis: a randomized, placebo-controlled, phase 2 trial. Lancet Neurol. 2016 Jan;15(1):35-46.

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