Estriol Promising for Reduction of Multiple Sclerosis Relapse

Estriol, combined with glatiramer acetate, was associated with a reduced MS relapse rate.

The hormone estriol may be a promising treatment to reduce the rate of relapse in multiple sclerosis, according to data from a phase 2 trial.

The rate of multiple sclerosis (MS) relapse is known to decrease during pregnancy, when estriol levels are increased. In addition, previous preclinical and single-arm studies have shown estriol to be anti-inflammatory and neuroprotective, and effective for the reduction of gadolinium-enhancing lesions in people with MS.

Researchers led by Rhonda R. Voskuhl, MD, of the University of California David Geffen School of Medicine, sought to further test the effectiveness of estriol in a randomized, double-blind, placebo-controlled trial. The trial enrolled 164 patients (aged 18-50 years, 100% female) with relapsing-remitting MS from 16 neurology centers in the U.S. between June 2007 and January 2014. The women were randomized to either daily oral estriol (8 mg) or placebo, both in combination with injectable glatiramer acetate (20 mg) daily.  Relapses were confirmed using the Expanded Disability Status Scale score.

CLINICAL CHART: Multiple Sclerosis Treatments

In all, 83 patients were randomized to the estriol group and 81 to the placebo group. The annualized relapse rate for the estriol group was 0.25 relapses per year (95% CI 0.17–0.37) compared with 0.37 relapses per year (0.25–0.53) in the placebo group (adjusted rate ratio 0.63, 95% CI 0.37–1.05; P=0.077). The rate of adverse events did not substantially differ between groups, however irregular menses were more common in the estriol group (23% vs. 4%), but vaginal infections were less common (1% vs. 11%) compared to the placebo group. No differences were found in breast fibrocystic disease, uterine fibroids, or endometrial lining thickness as assessed by clinical exam, mammogram, uterine ultrasound, or endometrial lining biopsy.

Treatment with estriol plus glatiramer acetate met the study’s primary endpoint, which was annualized relapse rate after 24 months with a significance level of P=0.10. The researchers also noted that the treatment was well-tolerated over the 24 months, warranting further investigation of estriol for the reduction of MS relapse in a phase 3 trial. 


  1. Voskuhl RR, Wang H, Wu TCJ, et al. Estriol combined with glatiramer acetate for women with relapsing-remitting multiple sclerosis: a randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2015; doi:10.1016/S1474-4422(15)00322-1.