PHILADELPHIA—Daily treatment with estriol and glatiramer acetate may reduce multiple sclerosis (MS) relapses significantly, compared with placebo and glatiramer acetate, according to research presented at the 66th Annual Meeting of the American Academy of Neurology. The difference may become evident within 12 months of treatment. Cognitive scores also may improve within 12 months of treatment with estriol and glatiramer acetate, compared with placebo plus glatiramer acetate.
A previous study of women with MS who were not pregnant indicated that the pregnancy hormone estriol was associated with a significant decrease in the number and volume of gadolinium-enhancing lesions on MRI. To examine the hormone’s effect on relapse rate, Rhonda Voskuhl, MD, Jack H. Skirball Chair of MS Research at the University of California, Los Angeles (UCLA), and colleagues conducted a randomized controlled trial of women with relapsing-remitting MS.
Comparing Estriol With Placebo in Patients With Active MS
Eligible patients were between ages 18 and 50, had active disease, and had an Expanded Disability Status Scale (EDSS) score between 0 and 4.5. Women who were pregnant, breastfeeding, taking hormone replacement therapy, or taking oral contraceptives were excluded from the trial.
Patients were randomized to glatiramer acetate injections (20 mg/day) and oral estriol (8 mg/day) or to glatiramer acetate injections and placebo. Gynecologists examined the patients before, during, and after the study. Each patient was examined at three- to six-month intervals during the trial. Patients also underwent mammograms before and after the study. In addition, at baseline, three months, six months, 12 months, 18 months, and 24 months, the investigators measured participants’ estriol levels, administered the EDSS, and administered the MS Functional Composite.
A total of 82 patients received glatiramer acetate plus estriol, and 76 patients received glatiramer acetate plus placebo. The trial’s dropout rate was 29%. Baseline characteristics were similar in both patient groups. Participants’ mean age was approximately 38, and their mean EDSS score was 2.2.
Estriol Was Associated With Reduced Relapse Rate
At 12 months, the annualized relapse rate was 47% lower among patients receiving estriol and glatiramer acetate, compared with patients receiving placebo and glatiramer acetate. After month 12, the group receiving estriol and glatiramer acetate had few relapses and few gadolinium-enhancing lesions on MRI, and the group’s annualized relapse rate remained stable and low at 24 months. Participants receiving placebo and glatiramer acetate had fewer relapses at month 24 than at baseline, and the difference in annualized relapse rate between the two groups decreased to 32%.
After 12 months of treatment, scores on the Paced Auditory Serial Addition Test (PASAT) at 3 and 2 seconds improved by approximately 6% (ie, 3 points), compared with scores at baseline, among patients receiving estriol and glatiramer acetate. The change largely resulted from a 12% improvement (ie, six to seven points) among participants scoring less than 55 at baseline, which reflected cognitive disability. The investigators observed no change in patients who scored higher than 55 (ie, those with little cognitive disability) at baseline. After 24 months of treatment, patients receiving estriol plus glatiramer acetate continued to have high PASAT scores, and participants receiving placebo plus glatiramer acetate began to improve.
Dr. Voskuhl is conducting an ongoing study at UCLA, the University of New Mexico, the University of Pennsylvania, and the University of Colorado that involves treatment with estriol in combination with most of the currently approved treatments for MS, including injectables and newer oral treatments. The goal of the study is to examine the effect of estriol on cognition.