Sept 20, 2002
Estriol given orally to nonpregnant women with relapsing remitting multiple sclerosis (MS) significantly reduces brain lesions, according to the results of a phase I trial reported in the September issue of the Annals of Neurology.
Dr. Rhonda Voskuhl from the University of California at Los Angeles, and colleagues note that animal experiments have shown that estriol can ameliorate MS and cause an immune shift. A significant decrease in relapses has also been noted in MS patients during pregnancy.
In their crossover trial, the researchers treated 12 female MS patients with estriol. Six patients had relapsing remitting disease and secondary progressive disease. Patients underwent repeat MRI and immune system testing during a 6-month pretreatment period, a 6-month estriol treatment period, a 6-month posttreatment period and a 4-month retreatment period.
All six patients with relapsing remitting MS who were treated with estriol at 8 mg/day showed significant decreases in delayed-type hypersensitivity responses to tetanus, interferon-gamma levels in peripheral blood mononuclear cells, and the number and volume of gadolinium-enhancing lesions.
Lesions increased to pretreatment levels when estriol therapy was stopped, but decreased again once estriol treatment was restarted, Dr. Voskuhl's team found.
Among the four women with secondary progressing MS who completed the trial, estriol treatment failed to produce any significant improvement in lesions or in immune response, they add.
"I am excited by the prospect of finding an easily administered treatment for MS based on a naturally occurring phenomenon in pregnancy," Dr. Voskuhl commented in a UCLA statement. "At present the only approved treatments are antiinflammatory drugs administered with injections."
"Our findings also hold promise for finding new treatments for a host of other autoimmune disorders that improve during pregnancy, such as rheumatoid arthritis," she added.
Ann Neurol 2002;52:000-000.
© 2002 Reuters Ltd
Sept. 24, 2002
Laurie Barclay, MD
In a phase I trial reported in online in advance of publication in the Annals of Neurology, estriol given in doses comparable to levels during pregnancy resulted in significant decreases in enhancing lesions in women with relapsing remitting multiple sclerosis (MS) but not in women with secondary progressive MS. When the hormone was discontinued the lesions recurred, but they again regressed with reinstitution of therapy.
"I am excited by the prospect of finding an easily administered treatment for MS based on a naturally occurring phenomenon in pregnancy," senior author Rhonda Voskuhl, an associate professor of neurology at the David Geffen School of Medicine at the University of California, Los Angeles, says in a news release. "Early treatment is crucial to preventing disabling symptoms. Finding an easily administered oral treatment is important, in part, because patients are less likely to delay treatment if it involves a pill rather than weekly or daily shots."
Earlier studies in pregnant women and animal models suggested that estriol might be beneficial in MS by causing an immune shift from T helper 1 to T helper 2. This study involved 12 women who were not pregnant, six with relapsing remitting MS and six with secondary progressive MS. All six women with relapsing remitting MS and four of the six with secondary progressive MS completed the trial of estriol treatment, 8 mg/day.
During estriol treatment, patients with relapsing remitting MS had a significant decrease in the number and volume of gadolinium-enhancing brain lesions seen on monthly magnetic resonance imaging. Although lesions recurred when estriol treatment was discontinued, they regressed when treatment was restarted.
While taking estriol, patients with relapsing remitting MS also had an an improvement in cognitive test scores and an increase in protective immune response, reflected in significant decreases in delayed-type hypersensitivity responses to tetanus and in interferon-gamma levels in peripheral blood mononuclear cells. Patients with secondary progressive MS had no measurable improvements on estriol therapy.
"Based on these results, a larger, placebo controlled trial of estriol is warranted in women with relapsing remitting MS," Voskuhl says. "If larger studies confirm the benefits of estriol treatment, further studies for longer periods of time will be needed to determine whether estriol can decrease relapse rates and disabling symptoms. Our findings also hold promise for finding new treatments for a host of other autoimmune disorders that improve during pregnancy, such as rheumatoid arthritis."
Ann Neurol. 2002;52:000-000
Reviewed by Gary D. Vogin, MD
Laurie Barclay, MD, is a staff writer with WebMD.
© 2002 Medscape